E-Poster

Abstract No: ABS004: Strongyloidiasis masquerading as Addison’s disease

M. Sriram

People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India

E-mail: shriram.mudraje@gmail.com

A 20-year-old man presented with complaints of weight loss of 25 kg, anorexia, vomiting and generalized darkening of complexion for 6 months. He complained of abdominal discomfort, fullness and pain after meals followed by vomiting. There was no history of diarrhea, fever, night sweats or jaundice. Stools were not bulky or oily. He was hospitalized before but nothing significant was found except for mucosal thickening in stomach and duodenum in gastroscopy. His Chest X ray, thyroid function tests, plasma glucose and abdominal sonography were found normal during previous admission. Serology for HIV was non-reactive. Family history was non-contributory. Patient had no addictions. Patient was shifted to endocrine ward with suspected diagnosis of Addison's disease. Patient looked cachexic, with sunken eyes and coarse hair. However, serum 8AM cortisol was normal. But Vitamin B12 was low. Patient belonged to rural background and was going to fields for defecation. His stools examination showed larvae of strongyloides. After antihelminthic drugs he showed improvement in appetite and regained 24 kg of weight in next 4 months. Skin complexion also became normal.

Keywords: Addison's disease, hyperpigmentation, strongyloidiasis, Vitamin B12 deficiency

Abstract No: ABS006: Correlation between acne and insulin resistance; Experience from central India

Prachi Srivastava

People’s College of Medical Sciences and Research Center, Bhopal, Madhya Pradesh, India

E-mail: drjaideepkhare919@gmail.com

Introduction: Acne is a common dermatological condition primarily seen in teenage and adolescent patients and is a major concern for cosmological issues. Along with environmental factors, proliferation of basal keratinocytes in the sebaceous-pilosebaceous unit, abnormal desquamation of follicular corneocytes and metabolic abnormalities play a significant role in pathogenesis of acne development.

Aim: To study causal relation between Acne Vulgaris and Insulin Resistance by calculating HOMA-IR and identify relation between insulin resistance and severity of acne.

Materials and Methods: This was a retrospective study, where the data of patients with persistent Acne Vulgaris who were referred to the Endocrine department for evaluation of the hormonal and metabolic causes for acne vulgaris was analysed. The patient’s clinical records were evaluated in whom there was no significant hormonal or metabolic abnormality was identified known to cause persistent acne were included after proper consent and HOMA IR was calculated.

Results: Of several patients of persistent acne, 150 patients were included in our study with the male to female ratio was 23:27. The mean age of patients was 33.2 years. The mean HOMA IR in our acne patients was 1.62 ranging from 0.9 -3.7. 64 (42.67%) patients had HOMA IR more 2.0, thereby suggesting insulin resistance.

Conclusion: Our study suggests prevalence of Insulin Resistance in 42.67% patients with acne thereby providing the possibility of use of insulin modifiers as an adjunct acne treatment and stratify possible risk of metabolic syndrome in patients with acne. Also recommended is the control of dietary factors and lifestyle modification for the management of acne with insulin resistance.

Keywords: Acne grades, acne, HOMA-IR, insulin resistance, metabolic syndrome

Abstract No: ABS010: A rare case of somatotrophic macroadenoma presenting with atypical manifestations

Varnan Chandrawanshi, Rajesh Verma

Mahatma Gandhi Memorial Medical College, Indore, Madhya Pradesh, India

E-mail: varnan2021@gmail.com

Introduction: Acromegaly is a rare condition that usually results from hypersecretion of GH, with subsequent raised IGF1. Prevalence- 30 cases per million population, Pituitary adenoma- around 33% non functional, Among functional- Lactotroph> Somatotrophic adenoma, Adenoma- increased hormone secretion, mass effect, stalk effect, Acromegaly-a/w CVS, Bone, soft tissue involvement etc.

History and Examination: 26 years old married female, a homemaker presented with c/o–Irregular menses f/b amenorrhea for 2 years, intermittent headache along with gradual progressive blurring of vision for 1 year. Patient also noticed increase in her footwear size over 2 years She also removed her ring due to increase in the size of her hands in last 2 years, Took multiple treatments for irregular cycles, NO history of acne, excessive hair growth, weight gain, galactorrhea or OCP use. No significant comorbidities or family history, No h/o previous hospitalization, surgery or blood transfusion. General Examination: Macroglossia present, Broad fleshy nose, Increased distance between 2 incisors, Spade like hands, Broad foot, Deep voice, CNS Examination-HMF-Intact, Cranial nerves- Optic nerve-Visual acuity-6/36 in right eye, 6/60 in left eye. Rest S/E-WNL, Confrontation test & Perimetry s/o Bitemporal Hemianopia

Diagnosis and Treatment: Patient diagnosed with Acromegaly d/t Somatotrophic Macroadenoma with secondary Hypothyroidism with Hypogonadotropic Hypogonadism with impaired glucose tolerance, Patient was started with Octreotide depot injection with oral Cabergoline twice weekly with planned debulking neurosurgery. Diagnosis often delayed- slow progression of signs over many years, Sellar expansion features- carefully monitored.

Conclusions and Learning: Sellar masses- neurological symptoms, abnormalities related to under or oversecretion of pituitary hormones, or as an incidental finding on radiologic examination performed for some other reason. A somatotroph macroadenoma due to its size can cause decreased secretion of other pituitary hormones. A suspicion of pituitary adenoma should be thoroughly investigated both radiologically and biochemically. A patient of Acromegaly should be assessed for cardiovascular, neurological, hormonal, metabolic and neoplastic complications.

Abstract No: ABS020: Phenotype of lipodystrophy

Supreeth Chandrashekar, Saksham Pandey, S. K. Singh, N. K. Agrawal, Ritesh Kumar, Avina Bishnoi, Subhash Kumar, M. Reshma

IMS, BHU, Varanasi, Uttar Pradesh, India

E-mail: Supreeth.c91@gmail.com

Background: Lipodystrophy is a heterogenous condition which can be acquired or congenital rare disorders having less prevalence which occurs more common in individuals taking antiretroviral therapy. In a way, Lipodystrophy is similar to diabetes mellitus where all the complications of type 2 diabetes obese phenotype like severe insulin resistance, hypertension dyslipidaemia are seen in addition to abnormal distribution of fat or total absence of fat, menstural irregularities, cardiomyopathy, hepatic steatosis, hirsuitism, PCOS, cognitive defect, umbilical hernia. Addressing the complications is the most important aspect of managing Lipodystrophy syndromes.

Case Summary: Patient 1: 18 year old presented to us for diabetes with symptoms of polyuria, polydipsia for 5 months with history of polyphagia without gain in weight for 5 years. on examination found to have coarse facies, acromegaloid appearance, acanthosis nigricans over neck and axilla, muscular prominence, prominent veins of forearm and legs, umbilical hernia, hirsuitism, oligomenorrhoea, clitoromegaly, hepatomegaly and generalised loss of fat. Patient 2: 21 year old presented to us for menstural cycle abnormalities with increased body and facial hair for 2 years with the history of loss of fat from face, neck and chest with increased fat accumulation over arms and legs. On examination apart from abnormal fat distribution no abnormal findings were found. Patient 3: 25 year old female presented to us with the history of delayed menarche at 18 years and oligomenorrhoea since then with increased facial and body hair, increased appetite without weight gain, starting at the age of 15 years. On examination found to have los of fat from face hands, legs with sparing of trunk. She also had umbilical hernia, no acanthosis nigricans noted, hepatomegaly, hirsuitism and clitoromegaly.

Summary: Phenotype can reveal multiple entities in answering pathology that caused the Lipodystrophy.

Abstract No: ABS033: Study of correlation between computed tomography density of liver and pancreas with beta cell insufficiency in patientS with transfusion dependent thalassemia

Prabhat Ranjan, Animesh Maiti, Anirban Sinha

Department of Endocrinology and Metabolism, Medical College and Hospital, Kolkata

E-mail: prabhatranjan4dec@gmail.com

Background: Endocrine complication including diabetes in thalassemia patients are common especially in transfusion dependent thalassemia (TDT) patients due to deposition of iron in various endocrine glands leading to dysfunction. MRI has been used to detect iron overload in TDT. In best of my knowledge no study has been done on CT scan density and pancreatic or liver iron deposition in diabetic patients. Aim was to identify relationship between beta cell function and pancreatic architecture (volume and density in HU) on CT scan of pancreas. To find out the relative contribution of insulin resistance and beta cell insufficiency for diabetes in transfusion dependent thalassemia patients.

Materials and Methods: 30 patients form single center with transfusion dependent thalassemia on regular blood transfusion with or without chelation therapy, with or without splenectomy with diabetes were taken. Exclusion Criteria: Patients with normal blood sugar or prediabetes, end stage renal disease or liver disease and or who did not give the consent.

Results: Mean age of thalassemia diagnosis was 4.38 years and that of diabetes was 16.53 years. Majority of patients had no family history of diabetes (76%) and were splenectomised (80%). All patients were on insulin for their diabetes management and 80% were on metformin and 80% on chelation therapy. All patients had fasting c-peptide <0.7 ng/ml and stimulated c-peptide, 1 ng/ml suggestive of beta cell deficiency. All patients had low pancreatic volume (14.23 6.37). Significant correlation was found between ferritin level and density of liver on CT.

Conclusion: The predominant mechanism for diabetes in transfusion-dependent thalassemia (TDT) patients in our study is beta cell destruction. NCCT abdomen showed a small pancreatic volume, and a positive correlation was found between serum ferritin levels and liver density. No significant correlation was found between either HOMA-IR or HOMA-B with liver or pancreas density.

Abstract No: ABS035: Evaluation of hypothalamic-pituitary-adrenal axis after short course of systemic steroids

Pooja Ashok Jadhao, Jaya Bhanu Kanwar, Swayamsidha Mangaraj, Jayshree Swain, S. L. Sravya

IMS and SUM Medical College and Hospital, Bhubaneswar, Odisha, India

E-mail: poojadhao@gmail.com

Introduction: Effect of short-term steroid therapy (with any dose) on the hypothalamic-pituitary-adrenal (HPA) axis has not been systematically evaluated previously. In our study we have examined the temporal pattern of HPA axis suppression and recovery after a short course of glucocorticoids and identified its predictors.

Materials and Methods: A total of 229 patients, prescribed steroids for a short duration between 5 to 45 days for various underlying conditions were recruited; of whom 121 completed the study. Testing of the HPA axis was done by 8 am baseline serum cortisol (BC) level, and when required 1-µg ACTH stimulated cortisol (SC); at baseline before starting steroid therapy and after completion of therapy on day 3, 10, 17, 24 and 31.

Results: The mean age of our study group was 45.07±14.61 years and mean serum cortisol before starting steroid treatment was 11.12±2.91 µg/dl. The mean cumulative prednisolone equivalent dose of steroid received and duration of therapy was 858.6±134.64 mg (ranging from 100 mg to 6250 mg) and 15.98±9.51 days respectively. HPA axis suppression was seen in 57 (47%) subjects on day 3 after completion of steroid course; diagnosed by BC in 43 subjects and by SC in 14 subjects. On day 10, 18 (31.5%) subjects had persistent HPA axis suppression while 39 (68.5%) recovered. On day 17, 4 (7%) subjects had persistent HPA axis suppression while 14 (24.5%) recovered. All patients had recovery of HPA axis by day 31. Logistic regression analysis showed HPA axis suppression on day 3 after completion of steroid therapy negatively correlated with age (p=0.018), baseline cortisol before therapy (p=0.036) and tapering of steroid dose (p=0.049).

Conclusion: After short course of steroid therapy, HPA axis suppression is transient and it recovers in majority by one month after completion of steroid therapy. Cumulative dose of steroid, duration of steroid therapy or type of steroid used did not predict HPA axis suppression after short course of steroid therapy.

Abstract No: ABS040: Clinical and etiological profile of hyperprolactinemia

Shah Smit Tushar

St. John’s Medical College Hospital

E-mail: smittusharshah@gmail.com

Introduction: Hyperprolactinemia is a common disorder encountered in clinical endocrinology. In addition to hypothalamo-pituitary disorder, hyperprolactinemia is also seen with use of various drugs, clinical conditions like hypothyroidism, chronic kidney disease, chronic liver disease, pregnancy, lactation. Hyperprolactinemia is also an important treatable cause of infertility. Hyperprolactinemia presents with varied clinical presentations ranging from asymptomatic to infertility, galactorrhea, headache etc. Treatment of hyperprolactinemia with drugs or surgery provides excellent results and most patients do well.

Aim and Objectives: To study the etiological profile of hyperprolactinemia. To identify the clinical manifestations of various causes of hyperprolactinemia. To study the treatment interventions & outcomes in the subset with prolactinomas.

Materials and Methods: Data was collected form the patients coming to Endocrine OPD at St. John’s Medical College Hospital, Bengaluru with hyperprolactinemia. The patients’ demographic, clinical, laboratory, radiologic and treatment data was collected. The symptoms of hyperprolactinemia, drug history, history of the comorbidities was collected. The data collected was entered and analysed using Microsoft Excel 2010 software.

Results: A total of 50 subjects with hyperprolactinemia were included in the present study between April 2023 – August 2023. The study included 38 females and 12 males. Majority of the subjects were in the age group of 31-40 years. Most of the subjects presented with multiple complaints. The most common complaint among males was Headache (66.6%) followed by visual disturbances in 50%. Loss of libido, infertility, galactorrhea were other complaints noted. Most females (89.47%) suffered from galactorrhea followed by menstrual cycle irregularity (amenorrhea + oligomenorrhea) 78.95%. Other complaints among females were headache, visual disturbances and infertility. The most common etiology of hyperprolactinemia was use of drugs (56%) followed by prolactinoma (38%). Hypothyroidism and PCOS were the other causes noted. Among the drugs causing hyperprolactinemia, Domperidone (with and without PPI) was the most common drug – 53.57% followed by Oral Contraceptive pills in 17.86% cases. Next was PPI – responsible for 14.29% cases, Risperidone in 7.14%, Olanzapine and Sertraline in 3.57% cases.

Conclusion: Hyperprolactinemia presents with a varied etiological and clinical profile and usually easy to treat after correct identification of the cause.

REFERENCES

1. Serri O, Chik CL, Ur E, Ezzat S. Diagnosis and management of hyperprolactinemia. CMAJ 2003;169:575-81.

2. Lundberg PO, Osterman PO, Wide L. Serum prolactin in patients with hypothalamus and pituitary disorders. J Neurosurg 1981;55:194-9.

3. Molitch ME, Thorner MO, Wilson C. Management of prolactinomas. J Clin Endocrinol Metab 1997;82:996-1000.

4. Vilar L, Freitas MC, Naves LA, Casulari LA, Azevedo M, Montenegro R Jr., et al. Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients. J Endocrinol Invest 2008;31:436-44.

Abstract No: ABS051: Thyrotoxic periodic paralysis (TPP)

Y. N. Krishna Reddy

A. J. Hospital, Mangalore, Karnataka, India

E-mail: neilyavasani@gmail.com

Background: The main characteristic features of thyrotoxic periodic paralysis (TPP) are elevated thyroid hormones, hypokalemia and proximal muscle weakness or paralysis. Thyrotoxic periodic paralysis is a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and can be secondary to thyrotoxicosis.

Results: We have reported five cases of hypokalemic paralysis secondary to thyrotoxicosis. In all cases thyroid profile revealed suppressed TSH <(0.01mIU/ml). T4 levels were above 14mcg/dl. Serum potassium levels were low in all the five cases. Clinical diagnosis of hypokalemic paralysis was made and were treated symptomatically. All underwent technituim 99 scan which showed diffuse increased uptake suggestive of graves disease. Subsequently, they were started on anti thyroid drugs and beta-blockers. All five cases had complete neuromuscular recovery after correction of potassium levels.

Discussion: TPP is an uncommon disorder characterised by simultaneous thyrotoxicosis, hypokalaemia and paralysis that occurs primarily in males of South Asian descent. The overall incidence of TPP in Chinese and Japanese thyrotoxic patients is 1.8% and 1.9% respectively. Here we report five cases of TPP which were confirmed by biochemistry and nuclear imaging, who improved after correction of thyroid status.

Conclusion: Although the association of thyrotoxicosis and periodic paralysis has been well known, TPP is often not recognized when first seen because of rarity. When a young male initially seen with severe lower limb weakness or paralysis, TPP should be kept as a differential diagnosis before diagnosing as a Guillan barre syndrome. The diagnosis of TPP should not be missed since it is a curable disorder that resolves when euthyroid state is achieved.

Abstract No: ABS063: Kearns Sayre Syndrome: A rare cause of mitochondrial diabetes and hypogonadotropic hypogonadism

M. Sriram

People’s College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India

E-mail: shriram.mudraje@gmail.com

Kearns Sayre syndrome is a rare mitochondrial myopathy which usually presents before the age of 20 years with ptosis, external ophthalmoplegia, pigmentary retinopathy, diabetes and cardiac conduction abnormalities. Here we report a 18 year old female presenting with fever, cough, secondary amenorrhoea, diabetes, ptosis, external opthalmoplegia, dysdiadochokinesia and ataxia. Respiratory system examination revealed reduced chest expansion on right side. Right mammary and infra-axillary areas were woody dull to percuss and crepitations and bronchial breath sounds with post-tussive suction were heard. Complete hemogram showed hemoglobin of 9.5g/dL (Normal: 12-14g/dL) and Erythrocyte-Sedimentation-Rate of 65mm/hour (Normal: 0-20mm/hour). Other parameters of hemogram were normal. Renal function tests, serum electrolytes, serum calcium, serum amylase, serum lipase and thyroid function tests were normal. Random blood sugar was 542mg/dL. Urine analysis showed ketones 3+, sugars 3+ and albumin 2+. Arterial blood gas analysis was normal. Liver function test showed low albumin (2.42g/dL; Normal: 3.2-5.5g/dL) and raised Alkaline phosphatase levels (123 IU/L; Normal:<110IU/L). Serum triglycerides were 202mg/dL (Normal:<150mg/dL) and other lipid profile parameters were normal. Serology for HIV was non-reactive. Follicle-stimulating-hormone was 0.2mIU/mL (Normal: 3-10mIU/mL) and luteinizing-hormone of 0.3mIU/mL (Normal: 5-25mIU/mL). Serum prolactin levels and 8AM-Cortisol were normal. Sputum for Acid-fast bacilli was negative, however sputum CBNAAT (Cartridge based nucleic acid amplification test) showed sensitive strain of Mycobacterium tuberculosis. Electrcardiogram showed intraventricular conduction abnormalities. 2D-echocardiography revealed global left ventricular hypokinesia with ejection fraction of 40% and mild mitral valve prolapse. Ophthalmological fundoscopy revealed pigmentary retinopathy. Ultrasound abdomen and pelvis was normal. MRI Brain and orbit with contrast was normal.

Final Diagnosis: A final diagnosis of Kearns Sayre Syndrome with Pulmonary Tuberculosis was made as the patient had ptosis, external ophthalmoplegia, ataxia, intraventricular conduction abnormalities, diabetes, hypogonadotropic hypogonadism, pigmentary retinopathy and age of onset being less than 20 years.

Outcome and Follow-up: Patient’s glycemic control was achieved with basal-bolus insulin. Fever and cough subsided. Her appetite improved and she gained weight. She regained her menstrual cycles with combined pills. At 2 months, her sputum CBNAAT came negative and she completed ATT at the end of 6 months.

Abstract No: ABS075: The role of neck ultrasonography and nuclear imaging in the diagnosis of congenital hypothyroidism

S. Palanivel, S. Sridhar, N. Vasanthiy

Madurai Medical College, Madurai, Tamil Nadu, India

E-mail: drpalanivel84@gmail.com

Background: Congenital hypothyroidism (CH) -preventable cause of mental retardation, if identified and treated early. Two important causes of CH are thyroid dysgenesis and dyshormonogenesis. Imaging -an integral part in diagnostic workup to identify exact etiology.

Methods: A prospective study conducted over three years. The clinical, ultrasonographic and Technicism-99 imaging of congenital hypothyroid children with age group ranges from day three of life to nine years were analyzed. Statistical analysis were done using SPSS-2023.

Results: 62 CH children were included for final analysis. Mean age was 22.16 (±21.03) months with equal male to female ratio. There was a significant association between parental consanguinity and congenital hypothyroidism (P = 0.006). Ultrasonography of neck was done in all, whereas Tc99 scintigraphy report available in 35 (56.4%) cases. In USG, 43 (69.3%) children had thyroid at anatomical position, 16 (25.8%) cases had absent gland and 3 (4.9%) had ectopic gland. Among 35 children, who underwent scintigraphy, 10 (28.6%) had agenesis, 3 (8.6%) with ectopic thyroid and 1 (2.8%) case had hemiagenesis with dyshormonogenesis. After excluding the structural abnormalities in nuclear imaging the remaining 21 (60%) were possibly dyshormonogenic. On comparing various etiological groups of congenital hypothyroidism, mean age of presentation was 8 months in thyroid agenesis group, 45 months in ectopic thyroid group and 23.5 months in dyshormonogenesis group. Median baseline TSH at diagnosis was 214 (IQR-134, 216) uIU/ml, 374 (IQR-351, 395) uIU/ml and 121 (IQR-110, 132) uIU/ml among thyroid agenesis, ectopic thyroid and dyshormonogenesis groups respectively. The median FT4 was 0.85 (IQR-0.7, 0.9) ng/dl, 0.75 (0.7, 0.95) ng/dl and 0.9 (IQR-0.7, 1.1) ng/dl in agenesis, ectopic thyroid and dyshormonogenesis groups respectively. Three cases were diagnosed as apparent athyreosis.

Conclusion: Dyshormonogenesis is more frequently reported as compared to agenesis in our study in contrast to western literature. High rate of consanguineous marriage in our setting could possibly be attributed. Due to long term requirement of thyroxine therapy, imaging is an ideal tool to assess the natural history, progression, dose requirement and treatment response.

Abstract No: ABS081: A short case series of neonatal diabetes – Does it always need to be insulin??

P. Sinju Sankar, S. Sridhar, R. Priyanka, N. Vasanthiy

Madurai Medical College, Madurai, Tamil Nadu, India

E-mail: sankar.sinju@gmail.com

Background: Neonatal diabetes mellitus is the onset of diabetes before 6 months of age due to monogenic defect. It occurs in approximately 1 in 90,000-160,000 live births and there are more than 20 known genetic causes of neonatal diabetes mellites. It can be permanent or temporary. Early recognition and genetic testing are important for predicting the clinical course, evaluating for additional features and guiding appropriate cost-effective treatment.

Methods: A short case-series of 5 neonatal diabetes infants diagnosed & followed up over a period of 3 years in our hospital. Genetic analysis was done for all the patients. The aim of our study is to implicate the role of genetics in prognosis and treatment of neonatal diabetes.

Results: In our cohort, 60% were females (3 out of 5). Gestational age was full-term in 60% (3 out of 5) and preterm in 40% (2 out of 5). Consanguinity was present in 60% (3 out of 5). Mean age at presentation was 35 days. Most common presentation was DKA. Majority of patients were having permanent neonatal diabetes and KCNJ11 was the common mutation identified in our cohort 40% (2 out of 5) and were treated with sulfonylureas. 1 out of 5 (20%) patients had transient neonatal diabetes due to uniparental disomy at 6q24 region. 1 out of 5 (20%) patients had homozygous mutation in EIF2AK3 gene which is associated with Wolcott Rallison syndrome.

Conclusion: From this study, we observed that neonatal diabetes may not always present with acidosis. Genetic analysis should be done as soon as neonatal diabetes is diagnosed. Certain forms of neonatal diabetes like ABCC8 and KCNJ11 may respond to sulfonyl urea thus preventing lifelong insulin therapy. Genetic analysis may also help in differentiating temporary and permanent neonatal diabetes and to look for associated defects.

Abstract No: ABS087: Fungal infections in endocrinological disorders

Ayushi Singhal, Subhash B. Yadav

SGPGI, Lucknow, Uttar Pradesh, India

E-mail: ayushi.singhal56@gmail.com

Background: Invasive fungal infections are associated with significant morbidity and mortality in immunocompromised individuals. Fungal involvement of the adrenals, pituitary, thyroid, pancreas and gonads is well recognized. Immune dysfunction is responsible for causing fungal infections in Cushing’s and diabetes.

Aims and Objective: We present two cases of endocrinological disorders harbouring fungal diseases. The first case was that of a 28-year-old male who presented with cushingoid features, acute onset breathlessness and chest discomfort found to have pituitary macroadenoma and hydropneumothorax. The second case was that of a 65-year-old diabetic male with uncontrolled blood sugar and longstanding history of fever, weight loss and hoarseness of voice with presence of vocal cord nodule and growth on video laryngoscopy.

Results: In our first case of Cushing’s disease, Intercostal drainage tube was inserted in view of hydropneumothorax. Mucoromycetes was detected in pleural fluid, for which liposomal amphotericin B given (later continued on posaconazole). For hypercortisolism, ketoconazole was given till stabilisation followed by transsphenoidal surgery of pituitary adenoma. Patient also had invasive candidiasis for which he was put on Fluconazole. The second case was found to have laryngeal, hepatic, splenic, adrenal masses, and histologically showed presence of histoplasma. Adrenal insufficiency was absent. For disseminated histoplasmosis liposomal amphotericin B was given (followed by itraconazole).

Conclusion: Infection in Cushing’s has been regarded as second most common cause of mortality. Various case reports of invasive fungal infections in cushing’s have been reported but our first case is unusual case of pulmonary mucormycosis with invasive candidiasis in endogenous hypercortisolism. Early suspicion and screening for the infections and definitive management of hypercortisolism should be done to prevent further life-threatening deterioration. Uncontrolled diabetes can be a risk factor for disseminated histoplasmosis in otherwise immunocompetent individuals secondary to defective cellular immunity and treatment for same should be done aggressively.

Abstract No: ABS089: Immune check point inhibitor (ICI) induced endocrine dysfunction a case series from a tertiary care centre

Devika Nandakumar, Remya Rajan, Nitin Kapoor, Kripa Elizabeth Cherian, Felix Jebasingh, Thomas Paul, Nihal Thomas, Ashish Singh, H. S. Asha

Christian Medical College, Vellore, Tamil Nadu, India

E-mail: devikanandan.95@gmail.com

Background: The development of immunotherapy has revolutionized the therapy for many cancers, however the same has resulted in a specific toxicity profile including endocrine immune-related adverse events (IRAE). Hypophysitis, thyroiditis, insulin dependent diabetes mellitus and adrenalitis are the common endocrine manifestations.

Methods: We describe a series of ten patients with IRAE associated with immune check point inhibitor (ICI) therapy managed at our centre- including their clinical characteristics, endocrine dysfunction, biochemical and radiological features.

Results: The ICIs implicated in IRAE in our series included nivolumab and pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA4 inhibitor). Out of the 10 patients, eight patients had thyroid dysfunction. Among them, five patients had isolated thyroid dysfunction and other five had associated hypophysitis as well. Thyroid dysfunction was the first manifestation of IRAE in six patients. Two patients had thyrotoxicosis followed by hypothyroidism, while six patients had primary hypothyroidism at presentation. All five patients with isolated thyroid dysfunction were on nivolumab (PD-1 inhibitor). Five patients had hypophysitis and among them two had isolated hypophysitis and other three had associated thyroid dysfunction. Four patients with hypophysitis had isolated ACTH deficiency and one patient also had secondary hypogonadism. All patients with hypophysitis had hyponatremia and four of five patients were symptomatic. Insulin dependent diabetes was present in one patient on nivolumab therapy, and he also had thyroiditis and hypophysitis.

Conclusion: Thyroid dysfunction was the most common IRAE in our cohort, and PD-1 inhibitor therapy was associated with this endocrinopathy. Isolated ACTH deficiency was the most common manifestation of ICI associated hypophysitis. Periodic monitoring of patients on ICI therapy for endocrine dysfunction would help in early diagnosis and treatment of IRAE, to prevent complications.

Abstract No: ABS097: Variant Turner Syndrome with Xq deletion associated with premature ovarian failure

Deorukhkar Prathamesh Ramesh, Archana Juneja, Dheeraj Kapoor, Nisha Kaimal

Kokilaben Dhirubhai Ambani Hospital and Medical Research Centre, Mumbai, Maharashtra, India

E-mail: prathameshdeorukhkar1111@gmail.com

Introduction: Turner Syndrome is a common genetic cause of premature ovarian failure (POF) in which a complete or near complete loss of the second X chromosome occurs. Two critical regions in the X chromosome for POF have been documented which are Xq13-Xq21 (CR1) and Xq23-Xq27 (CR2). We describe a case of variant Turner Syndrome with a terminal deletion on the long arm of chromosome X at band Xq21 in all the metaphases analysed.

Case: A 41-year-old female presented to the emergency department with acute onset of right sided weakness and clumsiness of the right hand. She had sustained a fracture of her coccyx and D10 vertebra just prior to admission. Her random glucose was 352 mg/dl. D3 hydroxybutyrate was 0.28 mmol/L, urine ketones were negative. She was a known case of primary hypothyroidism on thyroxine. On examination, she was found to have short stature with a height of 141 cm, which was below the third centile. She was born at term gestation of a non-consanguineous union. Further history revealed normal schooling; menarche at 13 years of age and subsequent secondary amenorrhea at 33 years of age. MRI brain revealed multiple acute infarcts. Hba1c was 12.7%, FSH 33.7 mIU/ml, LH 17.9 mIU/ml, estradiol < 10 pg/ml, total cholesterol 321 mg/dl and LDL was 229 mg/dl. Kidneys were normal on ultrasound. 2-D Echo was normal. DXA scan confirmed osteoporosis. She recovered uneventfully with physiotherapy and antiplatelets. Chromosomal analysis was done in view of her short stature and premature ovarian failure; which revealed a karyotype of 46,X,del (X)(q21); establishing the clinical diagnosis as variant Turner Syndrome.

Conclusion: Routine cytogenetic analysis plays a pivotal role in the identification and treatment of chromosomal abnormalities. This case highlights the importance of early genetic diagnosis offering consequential opportunities for growth hormone therapy, fertility treatments, screening for cardiovascular disease risk factors and timely preventive interventions.

Abstract No: ABS098: The curious case of a vanishing hypothyroidism!

Harini Jayaraman

A. J. Institute of Medical Sciences, Mangalore, Karnataka, India

E-mail: harini610.j@gmail.com

Background: Consumptive Hypothyroidism (CH) is a severe form of hypothyroidism that occurs due to the expression of high levels of type 3 deiodinase (D3) in tumors.

Introduction: Cavernous Haemangiomas (CAH) and arteriovenous malformation (AVM) express high levels of type 3 iodothyronine deiodinase. This selenoenzyme, usually present in the human placenta and brain, catalyzes the inner-ring deiodination of T4 into inactive reverse T3 (rT3) and T3 to 3,3′-diiodothyronine (T2). In CAH, AVM tumoral D3 can cause a unique form of hypothyroidism with degradation in thyroid hormone at rates that exceed the synthetic capacity of the thyroid gland.

Case: We present a 36-year-old lady who reported to the Department of Plastic Surgery with pain and swelling in the right proximal thigh for five years, heightened over a period of six months. She was diagnosed with hypothyroidism six years back, on thyroxine 100 mcg. Soft Tissue Ultrasonography of the Right Thigh done was suggestive of CAH in the Right Proximal thigh, measuring 8.9 cm x 7.6 cm seen in the medial aspect of the proximal thigh, with lesion consisting of extensive dilated vascular channels, low-velocity venous type flow mass superficial to the muscular plane. The patient underwent an excision biopsy and AVM repair. Histopathology was consistent with clinical diagnosis and features suggestive of AVM. The dosage of Thyroxine was reduced to 25 mcg on follow-up (based on TSH levels) post-procedure and subsequently stopped as the patient was euthyroid.

Discussion and Conclusion: In adults, CH is rare. Vascular, Fibrous, and Gastrointestinal stromal tumors each account for 33% of total cases. Prompt diagnosis, higher-dose thyroid hormone replacement, and tumour-directed therapy are keys to optimizing outcomes. Recognition of CH, a rare disease, is imperative as the patients can be off Thyroxine after definitive treatment of the primary aetiology.

Abstract No: ABS101: HAIR-AN syndrome: A neglected clinical entity in middle aged females leading to severe depression

Pooja Ashok Jadhao, Jayshree Swain, Jaya Bhanu Kanwar, Swayamsidha Mangaraj, S. L. Sravya

IMS and SUM Medical College and Hospital, Bhubaneswar, Odisha, India

E-mail: poojadhao@gmail.com

Background: The HAIR-AN syndrome is an underdiagnosed multisystem endocrinopathy comprising of features of hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN); commonly presenting in adolescents. It is associated with adverse cosmetic and psychosocial effects along with significant metabolic and cardiovascular morbidity.

Case Description: A 43-year-old female presented with complains of excessive hair growth and acne over face for last 10 years. She had irregular cycles followed by amenorrhoea since last 11 years beginning at the age of 32 years. She did not seek consultation for these complains and suffered from progressive depression for over a decade. On examination, she had BMI of 36 kg/m², waist hip ratio of 1.02, severe acanthosis nigricans on nape of neck, axillae, groin, and sub-mammary regions, significant hirsutism (Ferriman-Gallwey score 21), severe acne on her face and back, muscular physique and clitoromegaly (clitoral index 0.81 cm²). On evaluation TSH, prolactin was normal with elevated serum testosterone (158 ng/dl), androstenedione (6.16 ng/ml), normal DHEAS level (37.2 mg/dl), FSH 8.15 mIU/L (premenopausal), basal and stimulated 17-hydroxy progesterone-2.2 and 5.4 ng/dl respectively. Ultrasound Abdomen revealed bilateral polycystic ovarian morphology. CT abdomen revealed normal adrenals with polycystic ovaries and stromal oedema. Fasting serum insulin was significantly increased (116 mIU/L) and fasting glucose (123 mg/dl) was impaired. She was counselled regarding depression, weight loss and started on metformin, combination estrogen and antiandrogenic progesterone and spironolactone with escalating doses. She was advised cosmetic laser therapy for severe hirsutism. After 4 months of therapy, FG score reduced to 8, cycles have resumed and she reports feeling happy and self-confident.

Conclusion: HAIR-AN syndrome should not be neglected in middle aged females who have achieved fertility and should be a differential diagnosis in patients presenting with hirsutism and amenorrhoea even at a later age. A delayed diagnosis owing to lack of awareness may lead to disastrous metabolic complications of insulin resistance and severe psychosocial hazards.

Abstract No: ABS102: A rare FGFR1 mutation in a family of idiopathic hypogonadotropic hypogonadism

Teli Brij Rajesh, Jaya Bhanu Kanwar, Jayshree Swain, Swayamsidha Mangaraj, Lavanya Kasukurti

Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India

E-mail: brijteli@yahoo.com

Background: Idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by complete or partial failure of pubertal development. The clinical presentation is quite heterogeneous, and over 30 genetic mutations have been described to cause IHH.

Aim: This study aims to study the genetic defect in two siblings with delayed puberty, and an affected maternal uncle.

Case Report: A 20-year-old male presented with complaints of small-sized genitalia and failure to develop secondary sexual characteristics. On examination, he had SMR-P2B1, absent facial/axillary hair, testicular volume-10cc (bilateral), SPL-5cm. He was born out of non-consanguinous marriage at full term via normal delivery; had normal developmental milestones and intelligence. He had no history of anosmia/hyposmia, headache, seizures, visual disturbance, hearing loss, or movement disorders. He had decreased sexual interest and absent nocturnal erections. His height was 167 cm, weight 57 kg, arm span 176 cm, upper-to-lower segment ratio 0.87. On investigation, he had normal thyroid function and electrolytes, S.Prolactin 9.3 ng/ml, 8AM-cortisol 9.35 ug/dl, total testosterone-20.9 ng/dl, baseline FSH-1.1 mIU/ml, LH-1.23 mIU/ml, GnRH stimulated FSH-2.67 & LH-6.51 mIU/ml. He had bone age of 14 years (chronological age 20 years). He also had a 16-year-old younger brother with delayed puberty, who had SMR-A0P1B1, testicular volume <1cc (bilateral), SPL-3.5 cm, total testo-2.5 ng/dl, basal/stimulated FSH-1.44/8.69 & LH-0.38/6.14 mIU/ml, with bone age of 12 years. They had an infertile 40-year-old uncle, who when evaluated was also found to have hypogonadotropic hypogonadism. All 3 had normal brain scans and were diagnosed as IHH. When subjected to clinical exome sequencing, all 3 patients had heterozygous nonsense variant in exon 15 of the FGFR1 gene (chr8:g.38414626G>A) that resulted in a stop codon and premature truncation of the protein at codon 661 (p.Arg661Ter).

Conclusion: Genetic screening of patients with IHH can provide useful insights into familial mutations even in symptomatic family members previously undiagnosed, and thus guide the further treatment and prognosis.

Abstract No: ABS104: A case of primary adrenal insufficiency unfolding itself as a rare synrome

Nancy

People’s College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India

E-mail: nancygarg54@gmail.com

Background: X-linked adrenoleukodystrophy leads to demyelination of the nervous system, adrenal insufficiency, and accumulation of long-chain fatty acids. X-ALD is panethnic and affects approximately 1:20,000 males. Most young patients with X-linked adrenoleukodystrophy develop seizures and progressive neurologic deficits, and die within the first two decades of life. Phenotypes include the rapidly progressive childhood, adolescent, and adult cerebral forms; adrenomyeloneuropathy, which presents as slowly progressive paraparesis in adults; and Addison disease without neurologic manifestations.

Case Presentation: An eleven year old male child presented to us with complaints of pigmentation of skin, decreased appetite and weight loss from last one year. He also had visual disturbances and learning disabilities from last six months. On further probing it was revealed that he had gait disturbances and would often stumble upon objects due to decreased visual field in the temporal half. There was neither any history of similar complaints in siblings or other family members nor any still births or male child deaths in the family. Investigations revealed the diagnosis of adrenal insufficiency and MRI done was suggestive of diffuse demyelination. For further confirmation blood sample for determination of very long chain fatty acids was sent which revealed accumulation of C26 fatty acids, thus confirming the diagnosis of adrenoleukodystrophy. He was treated with hydrocortisone, fludrocortisone and anti-oxidants, and was referred for bone marrow transplant evaluation.

Abstract No: ABS109: Hypoglycemia: A case series

M. S. Gokul

Gauhati Medical College, Guwahati, Assam, India

E-mail: mudagalguru@gmail.com

Background: Central hypothyroidism is caused by insufficient stimulation of the thyroid gland due to decreased production of TSH by pituitary or hypothalamic cause. A diagnosis of Central hypothyroidism is difficult because serum TSH levels can be low, normal or even elevated. Pituitary adenoma can be a cause of this. Seizures are very rare presentation of Pituitary macroadenoma. Here is a case of pituitary adenoma presented with Seizures and features of hypothyroidism.

Case Report: A 42-year-old male, initially presented with neck pain and headache, underwent ayurvedic treatment for 10 days. He also had associated fatigue, tiredness and hiccups. He was referred to our hospital for further evaluation. On examination his pulse was 50/min, regular. Systemic examination was with in normal limits. Blood investigations revealed hyponatremia (112), low serum osmolality (236) and high urinary sodium (164). Thyroid functions showed decreased TSH and T3 levels. CT head was normal. He developed Generalized tonic clonic seizures. In view of SIADH he was treated with Fluid restriction, Sodium correction, Tolvaptan and antiepileptic measures. MRI imaging of head revealed homogenous lesion with suprasellar extension (16x10x9.6 mm), suggestive of pituitary macroadenoma. Neurosurgery opinion was sought and surgical resection was advised. He clinically improved and was discharged with plan for surgical resection in near date.

Discussion: Central hypothyroidism is characterized by insufficient thyroid gland stimulation by TSH, due to pituitary dysfunction. Pituitary tumors can cause central hypothyroidism by compressing pituitary thyrotropes. Generalized seizures are also comparatively rare presentation of pituitary adenoma.

Conclusion: Central hypothyroidism in adults can be caused by pituitary macroadenoma. Fatigue and peripheral edema are the most specific clinical features. Diagnosis is to be established by presence of low -normal TSH on the background of low normal thyroid hormones.

Abstract No: ABS113: Residual symptoms and signs of hypothyroidism in biochemically euthyroid patients on levothyroxine and its comparison to serum T3

Abhijeet Balabhau jawanjal, Altaf Naushad, Chitra Selvan, Pramila Kalra

M S Ramaiah Medical College, Bengaluru, Karnataka, India

E-mail: abhijawanjal.aj@gmail.com

Sella – suprasellar masses are a common presentation in the Endocrinology outpatient department. There are a wide range of causes for Sellar masses which could range from infiltrative, inflammatory to neoplastic causes. Sellar masses have to be investigated and evaluated with a detailed history, a thorough hormonal evaluation, imaging of the hypothalamic pituitary region and in some cases which are not straight forward, histopathological assessment by Biopsy. There are wide range of differentials which must be assessed before coming to a final diagnosis. Some of these can be pituitary macroadenoma, optic pathway glioma, pituitary infiltration, and pituitary metastasis. The case described in this paper is of an elderly lady who presented with headache and vomiting. MRI Brain done revealed an enlarged Sella with a 16 X 17 X 19 mm nodule with solid and cystic components suggestive of a pituitary macroadenoma. A Hormonal evaluation done revealed hypogonadotropic hypogonadism and hyperprolactinemia. Endoscopic Trans- nasal and Trans- sphenoidal resection of the tumor was done and a biopsy was taken, which revealed Pituicytoma. Pituicytoma is a rare entity with only 78 cases reported in the literature so far. We report a case of a rare disease presenting as headache and vomiting with pituitary dysfunction.

Abstract No: ABS114: Everything you see may not be true

Umamaheswara R. Golamari, P. R. Manjunath, Pramila Kalra

M S Ramaiah Medical College, Bengaluru, Karnataka, India

E-mail: mahesh.golamari@gmail.com

Introduction: CAH-X chimeras (CYP21A1P-TNXA/TNXB) are caused by recombination between TNXA and TNXB, null the entire CYP21A2 and replace the 3′ of neighboring TNXB with the pseudogene TNXA. This contiguous deletion is hence termed CAH-X, named for both CYP21A2 and TNXB defects.

Case Report: A 38 day old term male baby born out of second degree consanguineous marriage was admitted for not gaining weight and poor feeding since day 20 of life, appearing yellowish since day 3 of life, not passing stools since 5 days, passage of high coloured urine since 5 days and H/o vomiting, non-bilious occasionally since Day 25 of life. Baby was evaluated for hyperbilirubinemia, hyponatremia, hyperkalemia and bulky adrenal glands, 17[OH] progesterone was sent, it was >154 ng/ml. Hence, referred to endocrinolgy for further management. On examination baby’s BP was 78/42mmHg (<50^th percentile), GRBS was 76mg/dl, SPL-3.2 cm, bilateral testes present in scrotum, TV- 1cc bilaterally. Scrotum developed normally, No hyperpigmentation noted. On biochemical testing, baby’s electrolytes were 122/6.1/88, 8amcortisol was 48.7mcg/dl, 17 (OH)P 400ng/ml, ACTH 49.6pg/ml, Aldosterone 10.5mg/dl, PRA 312ng/ml/hr, karyotype XY. Patient was planned for ACTH stimulated steroid profile [LC-MS/MS] in view of high cortisol levels and clinical exome sequencing was sent. Baby was treated with T. Fludrocortisone 100 mcg 1-0-1/2, T.Hisone 1mg-1mg-1mg, oral salt 1 gm in divided doses/day, stress dose of steroids advised. Clinical Exome sequencing shows CYP11B1 deficiency, heterozygous with uncertain significance which was discordant to 21 alpha (OH) deficiency as shown in ACTH stimulated steroid profile [LC-MS/MS]. Hence sent for MLPA gene detection, which showed homozygous positive for complete CYP21A2 gene deletion extending further to exon 35 of TNXB gene.

Conclusion: High cortisol levels might be due to assay interference with 21-deoxy cortisol commonly seen with immunoassays. If MPLA methodology is used, an up-to-date version now simultaneously checks “30 kb deletion” and a CAH-X chimera of haploinsufficiency.

Abstract No: ABS116: A rare case of naso-cranial phosphaturic mesenchymal tumor – The causative tumor localized a decade after the diagnosis of tumor induced osteomalacia (TIO)

Naga Bhagya Sri Mangam, Prasun Deb

Krishna Institute of Medical Sciences, Secunderabad, Telangana, India

E-mail: nagabhagyasrimangam@gmail.com

Background: A 41 years male Mr.X presented with leg pains for 2 years which were not responding to calcium and vitamin D supplementation.

Methods: Investigations revealed low serum phosphorous (1.9mg/dl), normal calcium (9.6mg/dl) and 25 (OD) vitamin D (35ng/ml), elevated serum alkaline phosphatase (694 IU/ml), and low PTH (5 pg/ml). Phosphaturia was established by calculating TmP-GFR, which was low; i.e, 0.7 mmol/L (normal range for age and sex= 0.99-1.34 mmol/L). PET-CT was negative for metabolically active soft tissue or solid organ disease. Bone scan was suggestive of metabolic superscan with increased tracer uptake in the left proximal fibula, left neck of femur and bilateral calcaneum. Patient improved symptomatically with phosphate and calcitriol supplementation. Ten years after this diagnosis he developed epistaxis. CT scan of PNS revealed right nasal cavity lesion extending into right ethmoidal and frontal sinuses, it was eroding ipsilateral cribriform plate with intracranial extension. MRI PNS and Brain showed expansile lesion in right nasal cavity extending into cribriform fossa and right basifrontal region with compression of gyri and minimal perilesional edema. Surgical excision was done by transcranial and transnasal approach but in-toto removal of tumor was not possible as it was locally aggressive. HPE was suggestive of phosphaturic mesenchymal tumor, MIB-1 was 4-5% (i.e, high risk for local recurrence).

Results: Post surgery FGF23 levels were elevated (348.8 pg/ml) but dose requirements of phosphorous (2gms of elemental phosphorus pre-operative to 1 gm post-operative) and calcitriol (0.75mcg pre-operative to 0.25mcg post-operative) had decreased. The patient is scheduled for radiotherapy and further follow-up with imaging yearly for growth of the residual tumor.

Conclusion: In TIO, repeated imaging-68Ga-DOTATATE-PET/wholebodyCT/MRI (every 1-2 years) may be required to localize the causative tumor. When complete resection is not possible, novel modalities such as burosumab, radiotherapy of tumor or PRRT may improve the outcome. Follow-up imaging for relapse/recurrence is required for aggressive tumors.

Abstract No: ABS118: Childhood adreno-cortical carcinoma presenting as isolated precocious pubarche

Aiman Mohammadi, N. Ravi Kumar, Uzma Tabasum, Chaitanya Jyothi

Niloufer Hospital, Osmania Medical College, Hyderabad, Telangana, India

E-mail: aimanmohammadi007@gmail.com

Background: Adrenocortical carcinoma is a very rare aggressive malignancy with an annual incidence of 0.2-0.38 cases per million pediatric population, with a female predominance. They have a bimodal distribution; the first peak is in children less than five years and second around the fifth decade. The tumors have varied presentation, either virilizing forms or presentation with Cushing’s syndrome, or both.

Methods: This is a case report of a 1 year 8 months old female child presented with development of pubic hair from past 8 months and axillary hair from past 2 months as noticed by her mother. On examination, anthropometry was within normal limits. Sexual Maturity Staging was Breast- stage1, Axillary hair- stage2 and Pubic Hair – stage4. Genital examination showed female genitalia with separate urethral and genital opening and anogenital ratio of 0.4. There was clitoromegaly with clitoral index – 48mm square. Vaginal mucosa was shiny and pink and no inguinal or abdominal masses were palpable.

Results: Bone age was 18months. Ultrasound abdomen showed a lobulated heterogenous lesion in left suprarenal region. Enzyme assay showed elevated Testosterone, DHEA and DHEAS with normal estrogen, LH and FSH. Serum cortisol was also elevated with low ACTH, it was non suppressible after overnight Dexamethasone test. Histopathology of resected specimen showed conventional type of Adrenocortical carcinoma. PET scan revealed metastasis in lungs.

Discussion: The case is a functional adrenal tumor presenting as virilization and sub clinical Cushing syndrome with distant metastasis to lungs categorizing as Stage4 Adrenocortical carcinoma.

Abstract No: ABS119: Hyperprolactinemia in patients referred to a tertiary care hospital: A new drug mimics tumour levels

D. M. Mahesh, C. P. Shajeerali, K. Chethan Dev, Praveen Kumar, Akshay K. Nair

Aster CMI Hospital, Bengaluru, Karnataka, India

E-mail: drmahesh.dm@asterhospital.com

Introduction: Etiology of Hyperprolactinemia includes pituitary adenomas, drugs, etc. Pituitary adenomas are the common type of benign neoplasm accounting for 40% of total pituitary adenomas.[¹,²] Among drugs, Classes of medications that cause hyperprolactinemia include antidepressants, antihypertensive agents, and prokinetics.

Materials and Methods: The patients with hyperprolactinemia were identified in the out-patient department of Endocrinology, Aster CMI Hospital. We prospectively collected data like demographic details, clinical presentation, family history, drugs taken, and laboratory reports. Patients were screened through MRI brain for the presence or absence of pituitary adenoma.

Results: A total of 58 cases (15 males and 43 females) with hyperprolactinemia were referred for endocrinology evaluation from March 2019 – March 2023. Out of the 58 cases, 44 were due to pituitary adenoma. Prolactin levels normalized in 3-6 months in those with adenoma and within a week for those with drug induced hyperprolactinemia, but one patient had resistant prolactinoma. There were 5 cases of non-functioning pituitary adenoma with stalk effect (prolactin= 40-55 ng/ml), 14 cases of macroadenoma (prolactin= 750-1600 ng/ml), and 25 cases of microadenoma (prolactin= 50-300 ng/ml) among the 44 cases of pituitary adenomas. Six of the fourteen patients with macroadenoma opted for surgery. 25 cases of microadenoma were under medical treatment. Among the 14 cases of non-tumour causes, 11 were drug-induced hyperprolactinemia, with prolactin levels greater than 100 ng/ml caused by levosulpiride (5 cases) and risperidone (1 case), and prolactin levels less than 100 ng/ml caused by levosulpiride (1 case), domperidone (3 cases), and risperidone (1 case). 3 cases had idiopathic hyperprolactinemia.

Conclusion: With excellent response to cabergoline therapy prolactinomas are most common etiology among patients referred to endocrinology department in a tertiary care centre. However among medications, less commonly known levosulpiride is being increasingly identified as a common cause for hyperprolactinemia with prolactin levels >100 ng/ml. however, it is not listed as a common cause of drug induced hyperprolactinemia and prolactin levels must be monitored while treating a patient with levosulpiride.

Abstract No: ABS120: Analysing the effect of current therapy on HbA1c trend during post covid era in a tertiary care hospital

D. M. Mahesh, C. P. Shajeerali, K. Chethan Dev, Praveen Kumar, Akshay K. Nair

Aster CMI Hospital, Bengaluru, Karnataka, India

E-mail: drmahesh.dm@asterhospital.com

Introduction: The glycosylated haemoglobin (HbA1c) levels in individuals with type 2 diabetes mellitus (T2DM) who are taking insulin and oral hypoglycaemic agents (OHA) may vary. People living with type 2 DM are more vulnerable to various forms of both short- and long-term complications, which often lead to their premature death. During post covid era we are seeing a spike in hospital acquired infection in both acute and chronic illness patients with diabetes mellitus. Hba1c is an effective way to determine the effectiveness of therapy received by the patient pre-admission.

Objective: To analyse the effect of current therapy on HbA1c trend during post covid era.

Methods: The study was conducted in the in-patient setting of Aster CMI hospital for a period of one year from Apr 2022 – Mar 2023 after second wave of Covid-19 pandemic. Patients with type 2 diabetes mellitus and who are either alone or in combination therapy with insulin and oral hypoglycaemic agents were included in the study.

Results: A total of 292 patients (189 males and 103 females) with T2DM were analysed out of which 148 patients (51%) were on OHAs (single or multiple), 79 patients (27%) were on insulin + OHAs and 32 patients (11%) were only on insulin treatment for T2DM. The average Hba1C value of these groups were found to be 8.6±2.2% with average age of 63.1±10.7 years, 9.2±2.2% with average age of 64.9±10.9 years and 8.8±1.7% with average age of 62.8±15.3 years respectively.

Conclusion: Insulin is considered as the miracle agent which can be used for attaining desired glycaemic control in patients with acute or chronic illness. Therapeutic inertia is often cited as a reason of delaying insulin use. In our study we found that despite insulin initiation the glycaemic control was still insufficient. This indicates that starting insulin is inadequate unless followed up with appropriate education for follow up with titration and intensification of insulin. The role of diabetic education is paramount to achieve this goal. Hence, we need Diabetes Educators need to provide access for all patients not just in speciality clinics.

Abstract No: ABS121: Thyroid ectopia; a rarity, yet warrants attention

K. Sanjana Rai, Madhuri Patil

St John’s Medical College

E-mail: sanjurai.k@gmail.com

Background: Ectopic thyroid tissue is a rare entity resulting from developmental defect at early stages of thyroid gland embryogenesis, during its passage from the floor of the primitive foregut to its final pre-tracheal position. In this case series we studied 21 cases of ectopic thyroid and dyshormonogenesis. Of which 3 cases (14.3%) were male and remaining 18 cases (85.7%) were females; resulting in male to female distribution ratio of 1:6. The age of the patients at presentation ranged from birth to 50 years. 11 cases (52.4%) were detected at birth, infancy and early childhood (less than 5 years). 4 cases (19%) were diagnosed between 6 years to puberty. 6 cases (28.5%) presented late at puberty [2 cases (9.6%)] and adulthood [4 cases (19%)]. Most common site of presentation in the series was lingual [13 cases (61.9%)] followed by suprahyoid [3 cases (14.3%)]. 2 cases (9.5%) presented with sublingual, 1 case (4.8%) each presented with subhyoid, mediastinal and right paratracheal location. Most common mode of presentation was congenital hypothyroidism [11 cases (52.4%)] followed by neck swelling [5 cases (23.8%)]. Rare modes of presentation included dysphagia, mediastinal mass and hyperthyroidism [1 case (4.8%) each]. All cases underwent routine blood thyroid profile followed by radiological investigations like ultrasonography [11 cases (52.4%)], radionuclide scintigraphy [9 cases (42.9%)], CT scan [1 case (4.8%)] and FNAC [4 cases (19%)]. Except for one case of thyrotoxicosis, Thyrotropin (TSH) levels in these cases ranged from 7.44µIU/mL to >100µIU/mL. 1 out of 21 cases presented with thyrotoxicosis. This particular case was diagnosed to have eutopic thyroid tissue present in the usual pretracheal area which further showed Grave’s pattern on Technetium scan. Treatment with radio-iodine therapy was advised. Cases that presented with hypothyroidism received L-thyroxine replacement therapy.

Conclusion: Although rarely seen in practice, ectopic thyroid demands vigilant clinical evaluation for its diagnosis. Furthermore, the often-aberrant histological nature of tissue resulting in dyshormonogenesis with otherwise rare malignant changes and pressure symptoms needs to be identified and treated promptly with medical or surgical modalities.

Abstract No: ABS131: Prevalence of non-alcoholic fatty liver disease and correlation of anthropometric indices with fibroscan parameters in type 2 diabetes mellitus at a tertiary care center

Kasukurti Lavanya, Brij Teli, Jayshree Swain, J. B. Kanwar, S. Mangaraj

IMS and SUM Hospital, Bhubaneswar, Odisha, India

E-mail: drlavy99@gmail.com

Background: Type 2 diabetes mellitus are at increased risk of NAFLD (prevalence-55%–68%), with rapid progression and high risk of steatohepatitis and liver-related mortality. The degree of fibrosis represents the strongest predictor of mortality. Fibroscan a validated non-invasive tool measures both hepatic stiffness (liver stiffness measurement LSM) and steatosis (controlled attenuation parameter CAP). There are few NAFLD prevalence studies with fibroscan and also regarding role of anthropometric indices in predicting NAFLD in India.

Materials and Methods: A total of 600 T2DM patients (age>18yrs) were enrolled in the study after exclusion of significant alcohol consumption, prior diagnosis of NAFLD, Acute hepatitis, CLD, CKD and heart failure, causative drugs, seropositive status for hepatitis B, C. Anthropometric indices including Weight (wt), Height (Ht), body mass index (BMI), Waist (WC), Hip Circumferences (HC), waist hip ratio (WHR), were assessed for 200 subjects. Fibro-scan was done by a single observer (VCTE 402-3.5 MHz Probe). The optimal cutoff for high CAP was taken as > 237 dB/m (high CAP) for steatosis and LSM >7 kPa (high LSM) for fibrosis.

Results: Out of the 600 individuals enrolled in the study, 243 (40.5%) were females 357 (59.5%) were males with mean age of 53.28 ± 11.56 years. A total of 84% patients had steatosis (CAP >237), 36.9% had fibrosis (LSM>7). Grade 3 steatosis and advanced fibrosis were seen 180 patients (30%) and 56 (9.3%) respectively. Steatosis (CAP) showed a positive correlation with Wt (r=0.44, p<0.01), BMI (p<0.01, r=0.27), WC (p<0.001), r=0.39), HC (p<0.01, r=0.4), and WHR (p<0.04 r=0.19). Similarly, fibrosis (LSM) showed a positive correlation with weight (p<0.001, r=0.22), BMI (p<0.01, r=0.16), WC (p<0.03, r=0.21), HC (p<0.04, r=0.20), WHR (p<0.05 r=0.13). The duration of diabetes and age had no significant correlation with hepatic steatosis or fibrosis.

Conclusion: Prevalence of NAFLD in T2DM is high. Hepatic fibrosis and steatosis are strongly associated with anthropometric indices irrespective of age and duration of diabetes. Hence, central obesity in T2DM can be considered as a surrogate marker for NAFLD. Early screening and risk mitigation will reduce future morbidity and mortality.

Abstract No: ABS135: Diagnosis and management of a case of primary adrenal lymphoma, a rare entity with poor prognosis

N. Siddhartha Chakravarthy

Apollo Hospitals, Hyderabad, Telangana, India

E-mail: sidhu80@gmail.com

Background: Primary adrenal lymphoma is a rare malignancy with poor prognosis. There are no standard treatment protocols for this disorder. We present a case of primary adrenal lymphoma (PAL), diagnosed on evaluation for features of adrenal insufficiency. A tissue diagnosis was made and the patient was treated with chemotherapy followed by radiation. She is doing well at 6 months of follow up.

Methods: A 58 year old lady presented with features of adrenal insufficiency. CECT revealed large bilateral adrenal masses. LDH and CRP levels were markedly elevated. CT guided biopsy of the adrenal gland showed malignant round cells positive for CD 20, Bcl2, Bcl6, C-myc, Mum-1, reported as high grade B-cell non-Hodgkin lymphoma. The patient was treated with replacement doses of hydrocortisone, fludrocortisone and was started on chemotherapy with the R –CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen. Chemotherapy was followed by radiation to bilateral adrenal glands.

Results: Blood investigations and PET CT were repeated after 6 cycles of chemotherapy given over 2 months, followed by Radiation therapy. LDH levels showed a marked decrease at 6 months. Repeat FDG PET CT showed a reduction in the size of the adrenals with no metabolic activity.

Conclusion: PAL is a rare adrenal malignancy constituting 1% of non-Hodgkins lymphomas (NHL). It is a rapidly progressive disease with poor prognosis, therefore a high index of suspicion and early diagnosis is important. Chemotherapy with R-CHOP is shown to result in higher overall and disease free survival.

Abstract No: ABS144: Grave’s disease with medullary thyroid carcinoma – A case report

Prashant Hubballi

SGPGI, Lucknow, Uttar Pradesh, India

E-mail: prashhubli17@gmail.com

Background: Thyroid cancer is occasionally associated with hyperthyroidism. Among thyroid malignancies, the most common histological type is papillary followed by follicular. Medullary thyroid cancer (MTC) is rarely associated with Graves disease or other forms of hyperthyroidism. Until 2004, only 11 similar cases were reported in the literature.

Methods: Type of study- Observational study. A case report of the patient presented to SGPGI, Lucknow in 2022. Data recorded- Clinical, biochemical and radiological characteristics of the patients.

Results: A 53 year old postmenopausal lady with no comorbidities presented with c/o b/l upper limb tremor x 3 months, weight loss x 1.5 months fT4 28.5pmol/L TSH <0.014 TRAB 4.18 (>1.75iu/l s/o Graves disease), Calcium 9.4 Calcitonin <2 pg/ml, Urinary metanephrines and normetanephrines 78/587 mcg/24 hrs respectively, USG thyroid- TIRADS IV and TIRADS II lesions + Thyroid nuclear scan- Diffuse uptake, FNAC- s/o medullary thyroid carcinoma, Underwent total thyroidectomy (robotic).

Conclusion: Graves disease should not be considered protective for any thyroid cancer, as it was believed earlier. The simultaneous existence of Graves disease and MTC seems to be very rare. Until now, the coexistence of Graves diseases and MTC seems to be incidentally. Even the presence of MTC in Graves disease is extremely rare; however, a complete clinical and laboratory evaluation in patients with Graves disease should be performed, especially when a multinodular goiter is also presented. Thus, an early diagnosis and appropriate management of MCT could be done.

Abstract No: ABS146: A diverse clinical spectrum of skeletal dysplasia and genotype – Phenotype correlation

S. Palanivel, S. Sridhar, N. Vasanthiy

Madurai Medical College, Madurai, Tamil Nadu, India

E-mail: drpalanivel84@gmail.com

Background: Skeletal dysplasias (osteochondrodysplasias) -heterogeneous group of disorders with abnormal cartilage /bone growth. These are rare individually, but collectively common (approximate incidence -one in 5000 births). Very limited studies in India.

Methods: Prospective study, included individuals with skeletal dysplasia over 1 year (June 2022 to May 2023). Complete history, pedigree and anthropometric assessment done. Skeletal survey was done to diagnose the pattern of family. Genetic analysis with next generation genome sequencing (NGS) done for all patients.

Results: Case-1: 10-year male presented with disproportionate short limb dwarfism since 2.5years, progressive deformity of limbs and excessive joint mobility. He had craniofacial dysmorphism, rhizomelia. Skeletal survey -multiple epiphyseal dysplasia family. WES confirmed – Pseudoachandroplasia (COMP mutation). Case-2: 15-year adolescent with short stature, progressive coarsening of face, corneal clouding, deformities. Radiological survey -dysostosis multiplex family. WES confirmed ARSB mutation suggestive of Maroteaux Lamy. Case-3: 34-year male presented with headache, progressive hearing/ visual impairment. Examination revealed tall stature, coarse facies, syndactyly. Skeletal survey revealed increased density/sclerosis. Diagnosed as Sclerosteosis. Case-4: 14-years male, presented with short stature, macrocephaly, prominent forehead, depressed nose, short finger, stubby fingers, and hypertelorism since birth. Skeletal survey suggestive of achondroplasia family and confirmed by WES (FGFR3 mutation). Case-5: 3-year boy, presented with recurrent fractures since1 month of age. Blue sclera was present. WES -Osteogenesis imperfecta type-1 (COL1A1 mutation). Case-6: 11-year old boy with short stature &craniofacial dysmorphism. Skeletal survey -suggestive of osteopetrosis family (pycnodysostosis). WES confirmed mutation CTSK gene. Case-7: 7-years male with short trunk short stature and limb deformities, progressive kyphoscoliosis. Skeletal and dental abnormalities as well as skeletal survey were suggestive of metatropic dysplasia family.

Conclusion: Suspect skeletal dysplasia, when disproportionate short stature/recurrent fractures/deformity. Skeletal survey is key to diagnosis. Localizing the bones (axial /appendicular /both), pattern of shortening, bone density and complications will help us to reach skeletal dysplasia family. Subtle differences within a family need to be identified to get exact diagnosis and confirm by NGS.

Abstract No: ABS150: “Is the Gen-Y generation better at self-care and spousal support in diabetic patients than other generations?: A mixed methods study”

Anulekha Mary John, Austin Koshy, Mariyamma Joseph, Alice David

Believers Church Medical College, Thiruvalla, Kerala, India

E-mail: anulekhageorge@gmail.com

Background: Better glycemic control is possible with better diabetes-related support from the spouse. However, we do not know if there is generational difference in diabetes-care. This study aims to examine both self-care and spousal support across various age cohorts by comparing the various domains of diabetic care and to examine the strategies/tech-bits used for self-care across the age cohorts using qualitative study design.

Methodology: Crosssectional design with following age cohorts were considered: i. Gen Y/ Millennials (1981-1996) ; 26-41 years, ii. Gen X (1965-1980) ; 42-57 years, iii. Baby boomers (1946-1964) ; 58-76 years and iv. War babies (1928-1945) ; 77-94 years. Patients who are married and come together were included. The Spousal Support Scale and The Self Care Scale will be used to estimate the level of care and sampling to redundancy was used for qualitative analysis. Mean scores were compared across the various age-cohorts using ANOVA. Each age-cohort was compared to Gen-Y using student t test.

Results: Gen-Y and War babies were not significantly different for either Spousal Care Score (p=0.3) or for Self Care Score (p=0.5). However, Gen-Y was significantly different from Gen-X both for Spousal Care Score (p=0.01) and for Self Care Score (p<0.0001). Similarly Gen-Y was significantly different from Baby Boomers both for Spousal Care Score (p=0.006) and for Self Care Score (p<0.0001).

Conclusions: Gen-Y were different from GEN-X and BABY BOOMERS but similar to that of WAR BABIES but one cohort had very little time to cope and the other had much longer time to cope. Hypothesis that GEN-Y generation has the maximum self care was true considering they scored the maximum of average self care score; however WAR BABIES had the highest average spousal care score which made them considerably dependent on their spouse than other age cohorts.

Abstract No: ABS155: Correlation of bone resorption markers and bone mineral density with thyroid hormone levels and duration of disease manifestation in drug naive hyperthyroid patients and to determine the change in both after achievement of biochemical and clinical euthyroidism

Marrapu Venkata Vivek, A. K. Baliarsinha, Deepak Kumar Dash, Debarchan Jena

SCB Medical College Cuttack, Odisha, India

E-mail: vivekvenkat2010@gmail.com

Background: This study aimed to investigate i) degree of osteopenia or osteoporosis with level of thyroid hormones and duration of disease. ii) To determine the change in bone resorption markers and bone mineral density after achieving biochemical and clinical euthyroid state.

Methods: Hyperthyroid individuals of Graves’ disease, who are newly diagnosed and drug naive, presenting to Dept. of Endocrinology, SCBMCH between July 2022 to August 2023 were included. Thyroid profile, bone mineral density and bone resorption markers are collected at baseline and compared after 6 months of treatment.

Results: The mean age of patients with active GD (N = 15) was 33 ± 9 years. The female: male ratio was 3:2 The mean lumbar spine BMD, femoral neck BMD, total hip BMD were significantly reduced and a greater degree of osteopenia observed in patients having longer duration of disease. None of the patients showed BMD in Osteoporosis range. C terminal cross linked telopeptide was significantly higher which is not significantly associated with disease duration, but other bone metabolism markers like Osteocalcin, ALP were normal. After treatment CTX returned rapidly to normal values in all patients, and all other bone metabolism markers remained in the normal range. During treatment (n = 9) a significant gain in femoral and lumbar spine BMD (SDS) was observed (P <.001), and none of the patients showed osteopenia.

Conclusion: In conclusion, severe osteopenia was observed at diagnosis in patients with Graves’ disease but was rapidly corrected after 6 months of treatment. Initial reduced bone mass with high bone turnover caused by hyperthyroidism was corrected after achieving euthyroid conditions. These findings indicate that early diagnosis and management can be effective for osteoporosis prevention.

Abstract No: ABS157: Rare monosynaptic presentation of Graves’ disease in an adult male

S. L. Sravya, Jayshree Swain, Swayamsidha Mangaraj, Jayabhanu Kanwar, Pooja Jadhao

IMS and SUM Hospital, Bhubaneswar, Odisha, India

Introduction: Graves’ disease (GD) is characterized by thyrotoxicosis, goitre and orbitopathy. Uncommonly, presents with THYROTOXIC PERIODIC PARALYSIS (TPP) characterized by hypokalaemia. Here we present a case of GD presenting as normokalaemia PP.

Case Description: 54 years male presented with recurrent episodes of transient flaccid paralysis of lower limbs with falls, recovered spontaneously. History of weight loss of 5kgs over 6months without other symptoms of thyrotoxicosis. On examination, fine tremors, tachycardia, onycholysis and palmar erythema were seen. But no goitre or orbitopathy. Proximal muscle weakness was present, but reflexes were normal at presentation. Nerve conduction studies of lower limbs were within normal limits. Biochemically, Serum potassium 4.04mEq/L, creatinine phosphokinase was normal, FT3- 12.47pg/ml, FT4- 4.06ng/dl, TSH – 0.01IU/ml. Anti-TPO antibody- 24IU/ML (negative). Euglycemic and normal renal parameters. VitaminB12 -398pg/ml, vitaminD-32ng/ml. Ultrasonogram showed slightly enlarged thyroid with increased vascularity, peak systolic velocity 52cm/sec. Technetium 99 uptake scan showed absolute thyroid uptake of 3.5% and thyroid parotid ratio of 6.1%. Patient was started on carbimazole and beta blockers. On 2 years follow-up, patient never had paralytic episodes.

Discussion: Incidence of TPP in thyrotoxic patients is about 1.9%, usually affecting adult Asian men. Many of them do not have features of thyrotoxicosis. The attack is characterized by transient muscle weakness affecting the proximal muscles, with diminished deep tendon reflexes and complete recovery between attacks. Attacks are precipitated by carbohydrate-rich food, alcohol or exercise. The hallmark of TPP is hypokalaemia, but in the recovery stage, serum potassium may be normal as in our case. Due to subtle features of thyrotoxicosis and rarity of TPP, it is difficult to diagnose at presentation. Immediate therapy with potassium supplementation and β-adrenergic blockers can prevent serious cardiopulmonary complications and hasten recovery.

Conclusion: Periodic paralysis should be evaluated for thyrotoxicosis despite normokalaemia and treatment of thyrotoxicosis prevents the recurrence of TPP.

Abstract No: ABS162: The Unique phenotypes associated with a novel mutation in the LHX3 gene

B. Sanjana Gayatri, Beatrice Anne, Sumana Kunnuru, Jyothi Wadhwa, Glady Thomas, Divyasree Namburi, K. Bhoomika

Nizams Institute of Medical Sciences, Hyderabad, Telangana, India

E-mail: bsanjanagayatri@gmail.com

Background: The LHX3, a LIM-homeodomain transcription factor gene is required for normal pituitary, auditory system and motor neuron development. LHX3 mutations are associated with growth hormone, prolactin, gonadotropin, and TSH deficiency; abnormal pituitary morphology; and may be accompanied with limited neck rotation and sensorineural hearing loss.

Methods: We report the clinical, endocrinological, radiological and molecular features of two patients from unrelated families. Clinically they presented with dysmorphic facial features, short stature and developmental delay. They were not associated with limited neck rotation. They were diagnosed with Growth hormone deficiency, central hypothyroidism and mild sensorineural hearing loss was noted on auditory testing with normal cortisol levels. On sellar imaging, the anterior pituitary gland was found to be hypoplastic in them. Levothyroxine and growth hormone therapy was started and improvement in growth velocity was seen.

Results: Mutation analysis of the LHX3 gene revealed a homozygous mutation in exon4, c.503A>C (p.Gln168pro). The parents of the patients are heterozygotes, indicating a recessive mode of action for the deletion allele.

Conclusions: LHX3 mutations are a rare cause of Combined pituitary hormone deficiency. Whereas most patients have a severe hormone deficiency manifesting after birth, the milder forms can be observed, and limited neck rotation is not a universal feature of patients with LHX3 mutations. All patients should have regular monitoring of biochemical and auditory testing. This study extends the range of phenotypes found in LHX3-associated diseases and highlights the importance of molecular study diagnosis in patients with combined pituitary hormone deficiency.

Abstract No: ABS175: Atypical Cushing disease in a young male: Evolution of a corticotroph adenoma from an initial non-functioning adenoma-possibly a silent corticotroph adenoma

Krishna Veni Nutakki, Prasun Deb, Smitha Nalla, M. Bhagyasri

Department of Endocrinology, KIMS, Hyderabad, Telangana, India

E-mail: krishnaveni.nutakki@gmail.com

Background: Silent corticotroph adenoma (SCA) represents an uncommon subset of nonfunctioning pituitary adenomas (NFAs). This subpopulation of NFA is characterized by a lack of hypercortisolemia, no clinical evidence of Cushing disease (CD), and positive immunostaining for adrenocorticotropic hormone (ACTH). Transformation of SCA into active CD though rare, has been reported in the literature. Here in we report a case of a young male who underwent pituitary surgery for a presumed NFA but later developed Cushing syndrome.

Case: A 34-year-old male presented with headache, left-eye ptosis and visual disturbance. Three years ago, he was evaluated for gradual visual disturbance, right eye and diagnosed with pituitary macroadenoma. There were no clinical features suggestive of hormonal hypersecretion or hypopituitarism. Hormonal investigations were unremarkable except for new-onset DM and he was diagnosed as a case of NFA. Following that he underwent trans-sphenoidal surgery and histopathology revealed pituitary adenoma with MIB-1 3-4%. However, immunohistochemical study was not done on that instance. He was later lost to follow up. In the intervening period, he developed HTN and gained weight. He didn’t have typical cushings facies but there was mild proximal muscle weakness and evident fungal infection on extremities. Midnight cortisol (58.6mcg/dl) and midnight ACTH (336.2pg/ml) were elevated. LDDST was non suppressible, but HDDST was suppressible consistent with ACTH-dependent pituitary cushings. MRI showed a recurrent pituitary macroadenoma (5.4.3) with extensive invasion. Patient underwent redo-TSH. He had made significant subjective and objective improvement with reduction of weight and HTN and his vision also improved to significant extent.

Discussion: SCAs are more aggressive with earlier recurrence and more likely to transform into active coritocotroph adenoma than other NFAs. Appropriate biochemical and immunohistochemical subtyping of a NFA can often pick up SCA which in rare instances can transform into a hormonally active tumour.

Abstract No: ABS176: Cystic ectopic parathyroid adenomas masquerading as nodular thyroid disease

Krishna Veni Nutakki, Smitha Nalla, Prasun Deb

Department of Endocrinology, KIMS, Hyderabad, Telangana, India

E-mail: krishnaveni.nutakki@gmail.com

Solid parathyroid adenomas account for most cases of PHPT. We describe 2 cases with presentation consistent with PHPT with intra-thyroidal nodule-like lesions with negative SESTAMIBI imaging and inconclusive FNAC.

Case: Case1 is a 56-year male who presented with ARF. Case2 is a 60 year male who presented with generalized weakness and ARF. In both, serum biochemistry revealed hypercalcemia, hyperparathyroidism and hypophosphatemia consistent with primary hyperparathyroidism. Hypercalcemia was managed with iv hydration and denosumab. Renal failure improved in both cases as calcium levels decreased. In case1 Neck-sonogram revealed a predominantly cystic intra-thyroidal lesion which turned out inconclusive on FNAC. In case2, USG showed a heterogeneous solid-cystic thyroid nodule with FNAC reported as follicular neoplasm (Bethesda3). SESTAMIBI scan (with thyroid-subtraction) was negative in both cases.

In case 1, repeat USG after 3 months identified definitive parathyroid adenoma (4.3) notable for its intra-thyroidal location S/O cystic ectopic parathyroid adenoma.

Both patients underwent open-neck exploration with adenoma embedded in the thyroidal gland, case1 with a definitive pre-op diagnosis and case2 with suspicion of an intra thyroidal parathyroid adenoma. Resolution of elevated calcium and PTH levels and histopathological confirmation of parathyroid adenoma were noted in both cases.

Discussion: Although rare, Ectopic parathyroid adenomas are a well-reported cause of PHPT. Ectopic adenomas can be located anywhere from the base of the tongue to the mediastinum (most frequent location) including within the thyroid gland (0.7-6%). On imaging, they can appear similar to other structures, including benign thyroid nodules. During surgery, they can be challenging to find, being embedded in the thyroid. The possibility of ectopic parathyroid is to be considered in the presence of PHPT or normocalcaemic-hyperparathyroidism, and concomitant nodular thyroid disease. Systematic blood sampling for Calcium, PTH and role of PTH levels in cystic aspirate from suspicious nodules need to be explored.

Abstract No: ABS181: A case of hyperthyroidism with young onset hypertension

B. Sravya, R. N. Mehrotra

Apollo Hospital, Hyderabad, Telangana, India

E-mail: honeysravs1994@gmail.com

Case Report: 32 year old female who presented with complaints of weight loss of 4 to 5 kgs, sweatings, increased appetite, palpitations, sweatings, anxious for about a month. Past medical history of hypertension diagnosed at 24 years of age, h/o occasional palpitations and sweatings. H/O preterm delivery emergency LSCS in view of high BP, had seizures, intraop Hypertensive crisis managed with antiepileptics, antihypertensives. Was on tab nifedipine 20 mg BID, metoprolol 50 mg OD. Family history of brain tumour in paternal aunt, CKD at 34years on Hemodialysis in cousin. On general examination weight of 47.7 kgs, pulse rate 102/min regular, BP 160/100 mm of hg in right upperlimb, 150/90 mm of hg in left upper limb, eyes mild right upperlid retraction, with lid lag present, no evidence of any swelling, redness noted, diffuse firm thyroid gland on palpation. On evaluation CBP, electrolytes were normal, TSH 0.001 miu/l, free T3 16.78 pg/ml /9 2-4.4), free T4 4.2 ng/dl (0.9-1.6), TRAB positive >40 IU, started on tab carbimazole 20 mg/day. On regular follow up, inspite clinical and biochemical improvement in thyrotoxic symptoms, Clinic and home BP readings were high. On reviewing she was evaluated for hypertension in the pat, 2Decho, bilateral renal artery Doppler, USG abdomen were normal. On further evaluation for secondary endocrine causes of hypertension her 24 hour urinary cortisol, plasma renin activity, plasma aldosterone werenormal.24 hour urinary fractionated normetanephrines 4877 mcg (73 – 808), 24 hour urinary fractionated metanephrines 55.37 mcg (74- 297), Plasma free metanephrines 25.10 ng/l (7.9 – 88.7), Plasma free normetanephrines 1270 ng/l (<135). On radiological investigation CT abdomen triphasic study 26 x 23 mm brilliantly enhancing mass lesion with central non/hypo enhancing area within the left adrenal gland, Partial double moiety in the right kidney with fusion of ureter at the proximal 1/3^rd. Adequate preoperative preparation with alpha blocker phenoxy benzamine 10mg twice a day increased to 50 mg in divided doses Beta blockers added after adequate alpha blockade, Tab carbimazole 5 mg OD continued. Adequate extra salt intake advised, hydration maintained, Blood pressure, PR monitored regularly. Robotic left adrenelectomy done, no intraoperative hypertensive crisis. Postoperatively managed with IV fluids and supportive care. Histopathology report shows Microscopic description – Sections show neoplastic tissue composed of nests of neoplastic cells with enlarged moderately pleomorphic vesicular nuclei and eosinophilic cytoplasm. Focally significant nuclear atypia is identified, mitotic activity is not seen. A zell ballen pattern is recognised at places. IHC – Neoplastic cells are positive for chromogranin

On follow up visits, patient is off antihypertensives with normal bloodpressure 120/80 mm of hg, PR 86/min, tapering doses of carbimazole with clinical and biochemically euthyroid, freeT3 2.59pg/ml (2-4.4), free T4 0.72 ng/dl (0.9-1.7), TSH 0.9 (0.27 -4.2), repeat 24 hour urinary fractionated metanephrines 22.58 mcg (74- 297), 24 hr urinary normetanephrines 147.89 mcg (73- 808) .

Discussion: We reported a case of patient with graves disease accompanied by adrenal pheochromacytoma. Graves disease is considered to be an autoimmune disease. A combination of environmental and genetic factors, including polymorphisms in HLA-DR, CTLA-4, and PTPN22, contributes to susceptibility to Graves’ disease. The association of pheochromocytoma and Graves’ disease is exceptional. Paschke et al and Abe et al reported relapse of Graves disease in patients with pheochromocytoma. They suggested that increased catecholamines in pheochromocytoma act as an exacerbating factor for Graves disease. Pheochromocytoma is usually revealed by paroxysmal or permanent arterial hypertension (AHT) associated with a symptomatic triad of headache, sweating, and palpitations. Prevalence is 0.1-0.6%, incidence is 2-8 cases per 1 million people. These tumors may arise sporadically or may be inherited as features of multiple endocrine neoplasia type 2 or several other pheochromocytoma-associated syndromes VHL, NF1. The thyroid gland is richly innervated by autonomic nerves, an increase in circulating catecholamines stimulates basal thyroid hormone secretion. In some patients, adverse events precede the onset of Graves’ disease, suggesting that stress plays an important role as an initiating factor for the disease through catecholamines. Additionally, it is assumed that catecholamines may modulate the immune system, inhibit Th1 cells and drive a Th2 shift. Graves disease is thought to be a Th2-driven disease. The definitive mechanism, however, is not well understood. On the diagnostic level, the overlapping of symptoms involved for the most part in the two pathologies of hypercathecholaminemia can mislead the diagnosis of one or another of the two pathologies, while the outcome of one or the other may be fatal during any invasive procedure.

Conclusion: The continuing presence of the sympathomimetic features of hyperthyroidism, despite adequate antithyroid medication, should prompt the clinician to consider the possibility of an associated pheochromocytoma.

Abstract No: ABS183: “Uncommon Vascular Complications in Pheochromocytoma” Insights from Three Intriguing Cases”

S. Lekshmi, Ega Lakshman Kumar, T. Srujana, K. Neelaveni, Rakesh Sahay

Osmania Medical College, Hyderabad, Telangana, India

E-mail: dr.lekshmi.sudhan@gmail.com

Background: Pheochromocytomas are rare catecholamine-secreting tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. While traditionally associated with classic symptoms such as paroxysmal hypertension, headaches, and palpitations, the spectrum of presentations has expanded to include atypical manifestations, often leading to diagnostic challenges.

Case Details: C1: The first case involves a 20-year-old male who presented with left-sided abdominal pain. Hypertension, coupled with hypertensive retinopathy, prompted further investigation. Biochemical tests revealed a pheochromocytoma, and abdominal imaging uncovered a left adrenal mass along with non-enhancing upper pole of the left kidney, indicative of ischemia. The patient underwent successful left adrenalectomy, and postoperative imaging demonstrated the remarkable reversal of renal ischemia. C2: The second case unfolds as a 40-year-old female with gangrene affecting three lateral toes of her left foot. Known to have hypertension, her evaluation revealed a left adrenal pheochromocytoma. The patient underwent left adrenalectomy and disarticulation of toes. C3: In the third case, a 27-year-old male presented with left hemiplegia and hypertension. Neuroimaging revealed hemorrhage in the right capsuloganglionic area. Further evaluation led to the discovery of a mass in the right paraaortic area, and elevated 24-hour urinary normetanephrine levels confirmed the diagnosis of retroperitoneal paraganglioma.

Conclusion: These cases collectively highlight the diverse and uncommon vascular complications associated with pheochromocytoma, emphasizing the importance of considering this rare entity in the differential diagnosis of atypical presentations. Understanding the varied clinical scenarios and associated complications is crucial for prompt diagnosis, appropriate management, and improved patient outcomes. This paper aims to provide insights into the complexities of vascular manifestations in pheochromocytoma through the narratives of these three intriguing cases.

Abstract No: ABS187: Retroperitoneal abdominal ganglioneuroma masquerading as paraganglioma/pheochromocytoma – SAFES 2023

Sridevi Paladugu, Sravya Barla

Apollo Hospitals, Hyderabad, Telangana, India

E-mail: sridevip018@gmail.com

An 18 years old female resident of Somalia came with the complaints of right flank pain, dull, intermittent, increasing in severity over past eight months, with no radiation no relief with any particular position. On evaluation, was found to have right retroperitoneal mass, and was referred to us. There was history of headache, palpitations on and off, not associated with sweatings. There were complaints of vomitings on and off and easy fatiguability. There was no history of fever, weight loss and her appetite normal. On evaluation her BP was 120/80 checked multiple times, with no postural changes. Biochemical investigations showed 24 hours urine metanephrines- 102.05 mcg/24 hours (< 350mcg/24hr) and 24 hours urine normetanephrine 1010 mcg/24 hours (<600mcg/24hr). Her routine investigations were normal. USG abdomen – large well defined heteroechoic mass lesion measuring 16 x 10 mm in suprarenal region under right inferior liver margin, there are calcific foci within, no evidence of vascularity on Doppler. CECT abdomen showed 15.6cmx14.7cmx15cm large hypodense lesion which was not separate from the right adrenal gland, with multiple calcifications, multiple thick irregular enhancing septations. In view of the large size of the lesion Gallium Dotanoc scan was done, which showed surprisingly no uptake in the retroperitoneal lesion. She underwent surgery with removal of the whole lesion after adequate alpha and beta blockade. Preoperative, intraoperative and post operative BP remained stable. Histopathology showed Ganglioneuroma MIBI index 1%.

Conclusion: This case was worked up and managed as Paraganglioma/Pheochromocytoma. The histopathology revealed that it was a Ganglioneuroma. The ganglioneuromas are rare benign tumours of the neural crest arising in the paravertebral sympathetic chain and can have varied locations in the chest, mediastinum, abdomen, adrenal gland. Most often these are silent but can be secretory in nature in which case they usually present with the symptoms of catecholamine excess. They are known to secrete metanephrines, normetanephrines, dopamine etc.

Abstract No: ABS188: Tumour induced osteomalacia (TIO)

K. Sruthi, Manjunath Goroshi

Jawaharlal Nehru Medical College, Belagavi, Karnataka, India

E-mail: reddysruthi94@yahoo.com

Introduction: Rare disease <400 reported cases. Acquired hypophosphatemic osteomalacia due to a phosphaturic factor produced by tumor. Organ specific action of FGF23 on the kidneys causing phosphaturia and inappropriately low 1,25(OH)2 vit.D levels.

Case History: Case1- 34-year male with pain in left hip joint since 4 years. Fixation was done. But pain persisted with progressive difficulty in ambulation, he developed pain in right hip joint. He was completely bed ridden in 1 year. S. calcium- 8.4mg/dl; S. phosphorous- 0.6mg/dl; Hypophosphatemia was diagnosed. FGF23- 224 RU/ml.25OH vitamin D – 38. 68Ga DOTA NOC PET CT was done, lesion was localized in right acetabulum. Radio frequency ablation was done. Oral phosphorous & D supplementations were started. Calcium & phosphorous levels improved. After 2 years his serum calcium and vitamin D levels were 9.8 mg/dl and 4.5 mg/dl respectively. Case 2: 45-year male with pain in left hip joint since 2 years, progressive difficulty in ambulating, pain in right hip joint since 1 year, associated with generalized body aches, weakness and complete bed ridden from 6 months. S.ca -8.9, PO4 - 1.8, ALP- 420, 25OH vit D- 18, FGF 23- 284.5 RU/ ml. 68 GA DOTA NOC PET CT localized 6 cm lesion in right thigh. Surgical tumour resection was done. Post operatively PO4 improved.

Conclusion: TIO is a rare entity and high degree of suspicion is required for diagnosis. They can be localized with FDG PET/CT scan and somatostatin receptor based functional scans. Surgical excision:- Treatment of choice. Wide resection with tumor free margins. Medical management:- During Initial phases, Non-localisable lesion, Incomplete removal of causative lesion/ Difficult to treat, Secondary TIO. (Phosphorus and calcitriol supplementation) (Target- Normalization of ALP. Low end of age specific normal range of phosphorus) RFA:- effective, less invasive, difficult to access locations.

Abstract No: ABS192: Adrenal insufficiency with hypertension in an infant: A clinical dilemma unravelled

Prasadh Rao, Uma Devi

Madras Medical College, Chennai, Tamil Nadu, India

E-mail: prasadhrao20@gmail.com

Background: DAX 1 mutation causes adrenal insufficiency with hypotension and WNK1 mutation is associated with hypertension and hyperkalemia. A combination of these two mutations in a infant presented with confusing clinical picture, finally mystery unraveled with genetics. we present the case report of this rare clinical combination of two syndromes AHC and Gordons syndrome.

Methods: A 9-month-old male infant referred to us for Hypertension. He is first born of 3-degree consanguinity and old history revealed, the infant presented with vomiting and failure to thrive on day 12 of life with hyperpigmentation with no genital ambiguity. Started on hydrocortisone and fludrocortisone and discharged. At 2 months admitted with pneumonia and adrenal crises, started iv hydrocortisone, and tapered to maintenance dose and discharged. Similar admission at 6 months age. At present admission revealed hyperkalemia, metabolic acidosis, and normal sodium with Bp 106/64 mm Hg which is more than 95^th percentile. We reduced dose of steroids and stopped fludrocortisone in view of hypertension, on day 3 he developed adrenal crises recurrent vomiting, hyponatremia, hyperkalemia, and metabolic acidosis with high BP. Restarted on hydrocortisone. Still patient had high BP and hyperkalemia.

Results: Day 12 of life 17 OHP was 11.6 ng/ml. current 17 OHP is 1ng/ml. MLPA/microarray ruled out CAH at 6 months. Aldosterone 1.6 (1`.7-23 ng/dl) direct renin 2.4 (2.8-39 uIU/ml). Na: 138meq/L and K: 6.2 Meq/L on admission. After stopping steroids na:119 and k:6.4 meq/l and steroids restarted. genetics yielded DAX1 mutation and WNK1 mutation. Treatment started with Thiazide and blood pressure normalized and hyperkalemia normalized.

Conclusion: Combination of two rare syndromes always a confusing scenario. Adrenal insufficiency in a male we should suspect DAX1, measurement of LH and FSH would help us diagnose in infancy as they also fail to have mini puberty. A suspicion of Gordons syndrome has to be sought in instances with hyperkalemia and hypertension. Diagnosis and treatment would have been difficult without genetics in this scenario.

Abstract No: ABS193: Metabolic and endocrine workup in obesity patients

K. D. Modi, B. Christina, Pratyusha Segu, Kunal Modi

Dr Modi’s Clinic, Care Hospital, Hyderabad, Telangana, India

E-mail: drkdmodi@yahoo.co.in

Background: Defining diabetes and impaired glucose tolerance (IGT) by oral glucose tolerance test (OGTT) versus HbA1C can create a minor mismatch. Metabolic and endocrine workup in obese individuals with a special focus on comparing glycemic criteria for diabetes & IGT with OGTT & HbA1C was performed.

Methods: Patients (n=285, M/F: 43/242) presented for obesity at our clinic in the last 2 years were analysed. The mean age was 31.62 + 9.72 years and the mean body mass index (BMI) was 34.7 + 16.43 kg /m2. Twenty-five out of 285 (8.7%) patients’ age was < 18 years and were analysed as childhood obesity group. Anthropometric workup, OGTT, HbA1C, Lipids, uric acid, Serum TSH & overnight Dex suppression test (O-DST) were done in all. IGT & diabetes were defined as per WHO criteria. For HbA1C, the cutoff for normal, IGT and diabetes was decided as values <5.7%, 5.8-6.4% and >6.5% respectively.

Results: The Table 1 shows comparative figures for glycemic parameters. High LDL (>130 mg/dl), high Triglycerides (>150 mg/dl) and low HDL (<40mg/dl) were seen in 116 (41%), 130 (46%) and 96 (34%) patients respectively. Overnight DST was suppressed in all. Seventeen (6%) had Serum TSH > 10 (Overt primary hypothyroidism) while 30 (10.5%) had subclinical hypothyroidism. Among the childhood obesity group (n=25), 3/25 were diagnosed with diabetes as per OGTT criteria while 2 had HbA1C >6.5%. Subclinical hypothyroidism was seen in 3/25 while overt hypothyroidism in 1/25. Dyslipidemia was present in 10/25 children.

Conclusion: OGTT detected more IGT patients in comparison to IGT defined by HbA1C criteria. Newly detected diabetes cases were more in the HbA1C-defined group. However, these differences were not statistically significant. Metabolic abnormalities were common among childhood obesity patients.

Abstract No: ABS194: Tissue the issue, a rare presentation of parathyroid carcinoma

G. Dhanunjaya, Anil Satyaraddi, G. Dhanunjaya

S. Nijalingappa Medical College, Bagalkot, Karnataka, India

E-mail: dhanunjayag1997@gmail.com

Introduction: Parathyroid carcinoma accounts for less than 0.005% of all malignancies reported as cancers worldwide and accounts for less than 1% of cases of primary hyperparathyroidism, manifested by severe hypercalcemia and up to 50% of patients will have concomitant kidney, bone disease.

Materials and Methods: A 48year male presented with Bilateral lower limb weakness, Fatiguability, Difficulty in getting up from squatting position and reduced appetite since 6months. CNS examination normal. Bio chemical investigations showed very high serum calcium levels of 23.4mg/dl and on further evaluation serum Parathormone levels were >1500pg/ml. USG Neck S/O Left inferior parathyroid adenoma, USG abdomen S/O Non obstructive right renal calculus. MRI Neck S/O parathyroid adenoma with mild Retrosternal extension. USG guided FNAC of lesion S/O DDs 1) Oxyphil cell neoplasm of parathyroid origin 2) Hurthle cell neoplasm of thyroid origin. A provisional diagnosis of Parathyroid adenoma was made. Patient was treated with Inj Zolendronate 5mg over 45mins and Inj CALCITONIN 4units/kg 2 doses 12 hours apart, calcium levels reduced to 12.8mg%. Patient was clinically unstable to shift for sestamibi scan. Patient was taken for Parathyroidectomy, mass of 6×6cm excised and sent for histopathology opinion. Immediate Post op values: Calcium 9.6mg/dl, PTH 119.8pg/ml which showed normalisation. 12 hrs after surgery values: Calcium 10.6, PTH 33.7pg/ml. Patient recovered well, discharged without any complications. HPR is suggestive of Parathyroid carcinoma (extracapsular lympho-vascular invasion) with supportive evidence of IHC markers showing negative for TTF1 and thyroglobulin. Post op Sestamibi scan no evidence of residual tumor.

Conclusion: Parathyroid carcinoma is very rare endocrine malignancy (0.005%). Patients suffering from Hyperparathyroidism has to be thoroughly evaluated, because etiology of parathyroid cancers is largely unknown. Careful histopathological evaluation can differentiate adenoma from carcinomas which can be treated early and effectively if proved as carcinomas.

Abstract No: ABS196: Comparing the efficacy of targeted genetic screening strategy and whole exome sequencing (WES) in 21-hydroxylase deficiency: Insights from case studies

Lavanya Ravichandran, H. S. Asha, A. Rekha, Sumita Danda, Nihal Thomas, Aaron Chapla

Christian Medical College, Vellore, Tamil Nadu, India

E-mail: lavanyaravichandran1992@gmail.com

Background: Congenital Adrenal Hyperplasia (CAH) includes a heterogeneous group of autosomal recessive disorders resulting from molecular defects in adrenal steroidogenesis. The most common yet severe form of CAH is 21-hydroxylase (21-OH) deficiency. Genetics of 21 hydroxylase deficiency is complex due to pseudogene derived large rearrangements and point mutations in the CYP21A2 gene that contribute to 90% of the cases. With the recent advances in sequencing technology, Whole exome sequencing has been increasingly utilized by clinicians and geneticists in diagnosis and carrier screening of various disorders.

Aim and Objectives: We discuss the utility and challenges of NGS strategies in CAH genetics and the advantage of targeted genetic screening over WES through the lessons learnt from our cohort.

Methods: We describe three families who underwent WES from external commercial labs and also was tested at MEL, CMC, Vellore with a targeted genetic strategy: A step wise protocol involving long range PCRs and restriction digestion to enrich the functional gene CYP21A2 without pseudogene interference and identify large rearrangements and gene conversion. Followed by this, Allele Specific PCR (ASPCR) is utilized to genotype common pesudogene derived point (hotspot) mutations. Those who are negative for large rearrangements and hotspot mutations were subjected to targeted panel of NGS with seven genes in CAH. All the results were validated with Sanger sequencing.

Results: The results of WES vs. targeted genetic strategy in three families is given in the below Table 1. WES in family 1 in two siblings with severe salt wasting phenotype of CAH turned out to be negative for CYP21A2 mutations. However with a comprehensive approach in our lab, both the siblings were found to be compound heterozygous for large 30 kb deletion with chimera 1 and I172N hotspot mutation. WES in Family 2 with a couple seeking carrier testing for CAH in both the partners had negative results in the female partner while male partner was identified as a carrier for CYP21A2:Ala392Thr. However in our lab we identified that female partner was a carrier for CYP21A2:c.-113G>A in the promoter region utilizing targeted NGS. On the other hand the husband was negative for the CYP21A2:Ala392Thr variant identified through WES. These results were again validated with Sanger sequencing. WES in family 3 with a couple seeking carrier testing for CAH in both the partners had negative results. However using targeted genetic screening approach, we identified heterozygous CYP21A2:Gly111ValfsTer21 and Gln319Ter in the husband and wife respectively.

Discussion: CAH – 21 hydroxylase deficiency is a complex genetic disorder often requiring a comprehensive genetic testing approach with a combination of molecular techniques. NGS analysis in CAH is extremely challenging with sequencing reads aligning to pseudogene region. Further large CNVs cannot be detected. The major limitation in exome/genome sequencing is with achieving optimal coverage of the target region. This might result in missing of clinically significant variants resulting in false negative results. Also insufficient depth of coverage might result in false positive results as seen in the male partner of family 2. Targeted NGS is advantageous over WES in achieving optimal coverage and depth to reliably identify variants. Thus a direct whole exome sequencing is not recommended in CAH diagnosis/ carrier screening. A step wise approach with simple long range PCR and ASPCR can identify mutations in >85% of the cases which is more cost effective and comprehensive. Only those negative for these mutations would require a targeted NGS whereas WES is suitable for nonspecific phenotype or when targeted panel yields negative results.

Abstract No: ABS197: Advancing genetic diagnosis in CAH patients: A call for partner screening in genetic counseling and prenatal diagnosis

Shriti Paul, Lavanya Ravichandran, H. S. Asha, Nitin Kapoor, Nihal Thomas, Aaron Chapla

Christian Medical College, Vellore, Tamil Nadu, India

E-mail: shritipaul1309@gmail.com

Background: Congenital Adrenal Hyperplasia (CAH) affects the synthesis of adrenal steroids and is inherited in an autosomal recessive pattern. CYP21A2 gene mutation that results in 21 hydroxylase deficiency is the leading cause of CAH. The consanguinity rates and prevalence of CAH in India are very high compared to the West. However, genetic testing is not widely available for diagnosis or carrier screening due to pseudogene-imposed challenges in the molecular analysis of the CYP21A2 gene. This study aims to perform carrier screening of spouse/ fiancée of CAH-affected individuals to provide genetic counseling and enable subsequent prenatal diagnosis.

Methods: A total of eight couples were included in the study and each of these couples had one partner affected with CAH and a confirmed genetic diagnosis. For carrier screening in the asymptomatic partner, cost-effective genetic testing utilizing Allele-Specific PCR for hotspot mutations in the CYP21A2 gene followed by comprehensive Next Generation Sequencing for 7 genes- CYP21A2, CYP11B1, CYP17A1, CYP19A1, StAR, HSD3B2, and POR was carried out. The positive results were validated with Sanger sequencing.

Results: Two out of eight asymptomatic partners were positive for CYP21A2 mutation. In couple MEL 001, the asymptomatic husband was heterozygous positive for large gene conversion while the affected wife was positive for I172N hotspot mutation. Prenatal Diagnosis (PND) was carried out in their foetus who was found only to be a carrier for I172N and was followed up with New Born Screening (NBS). In couple MEL 007, the asymptomatic wife was a heterozygous carrier for large 30kb deletion with chimeric gene (CH-8) while the husband affected with CAH was positive for I2G mutation. All the other partners screened were negative for disease-causing variants in the CAH panel of genes tested.

Discussion: Through our genetic screening strategy, we were able to identify two couples at 50% risk of having CAH-affected progeny. The couples were provided with genetic counselling and PND followed by NBS was possible in couple MEL 001. With the high prevalence of CAH and the consanguinity rate in India, there is a need for carrier testing in partners of affected CAH individuals in routine clinical practice. This will identify couples at risk, and aid in pregnancy planning, PND, and management followed by NBS. Further, these cost-effective strategies can also enable carrier screening and NBS in larger cohorts across the country.

Abstract No: ABS202: Pyknodysostosis: A case series

D. Venkateswarlu

Jawaharlal Nehru Medical College, Belagavi, Karnataka, India

E-mail: venky.1806.co.in@gmail.com

Background: Pyknodysostosis is a rare genetic disease characterized by osteosclerosis and bone fragility with varying clinical manifestations. We report 4 cases with the typical clinical and radiological characteristics of the pyknodysostosis.

Case Presentation: Case-1 is a 10-year-old girl with disproportionate short stature, short terminal phalanges in both hands and feet, dysplastic nails and koilonychia. She had frontal bossing, beaked nose, dental caries, impacted and misaligned teeth. Case-2 (12-year-old boy) and Case-3 (10-year-old boy) are siblings presented with similar clinical phenotype. X-ray of hands and feet showed sclerotic bones, tapered phalanges with terminal acro-osteolysis in all three patients. On the basis of clinical and radiological features a diagnosis of pyknodysostosis was made. Case-4 is a 25-year-old male presented with deformities in upper limbs and fracture neck of right femur. On examination, he had cubitus varus. His X-ray of the forearm showed sclerotic bones with interosseus calcification and terminal acro-osteolysis. X-ray of hip with femur showed sclerotic bones and fracture neck of femur on right side.

Conclusion: Disproportionate short stature with normal biochemistry with typical radiological characteristics should alert the clinician to think of pyknodysostosis to avoid unnecessary investigations. Early diagnosis is important to plan the treatment, to prevent complications and to provide better quality of life to the patients.

Abstract No: ABS203: Rathke’s cleft cyst masking ACTH secreting pituitary adenoma: A case report

D. Venkateswarlu

Jawaharlal Nehru Medical College, Belagavi, Karnataka, India

E-mail: venky.1806.co.in@gmail.com

Background: The association between Rathke’s cleft cyst (RCC) and pituitary adenoma was found in 0.5-1.9% cases in literature, co-occurrence with ACTH-producing pituitary adenoma being rarer. We herein describe a rare condition of Cushing’s disease that coexisted with RCC.

Case Presentation: Fifty-three year old female presented with generalized weakness, swelling of feet, facial puffiness, easy bruising and proximal myopathy for 9 months. She was a known diabetic and hypertensive for 10 years, with history of left UV and subclavian thrombosis. On examination, she had central obesity, round facies, bilateral pitting pedal edema, skin bruising, and proximal myopathy. Investigations revealed hypokalemia (Serum potassium: 2.9 mEq/L). Workup for Cushing’s syndrome revealed an elevated 8am serum cortisol (45.3 mcg/dl), midnight serum cortisol (30.37 mcg/dl) and a non-suppressible cortisol post-ONDST (5.7 mcg/dl). Plasma ACTH was 137.6 pg/ml. Other pituitary hormones were within normal limits. MRI pituitary features were consistent with RCC. Ga 68 DOTA scan didn’t show any source of ectopic ACTH secretion. IPSS localized the source of ACTH excess to pituitary (Stimulated Right central/Peripheral Ratio: 4.75). In view of evidence of pituitary ACTH excess, patient underwent trans-nasal trans-sphenoidal pituitary adenomectomy. Histopathology of the specimen revealed Crooke cell adenoma (ACTH-positive on IHC). Postoperatively patient developed adrenal insufficiency and was started on steroid replacement. Patient’s symptoms have improved significantly at the three month follow-up.

Conclusion: Presence of discriminatory clinical features and biochemical workup forms the basis for diagnosis of Cushing syndrome. MRI pituitary with dynamic contrast has sensitivity and specificity of 60% and 87% respectively for adenoma localization. Presence of RCC on MRI in a patient with ACTH-dependent Cushing’s syndrome should alert the clinician for occult pituitary adenoma. IPSS is invaluable for accurate localization of ACTH-excess in such cases to institute appropriate management.

Abstract No: ABS205: A rare co-occurrence of papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC)

R. Vishnu, Kirandeep Kaur, Kalyani Sridharan

AIIMS, Rishikesh, Uttarakhand, India

E-mail: vishnumavoor1@gmail.com

Background: Thyroid cancer is the most common endocrine malignancy. Co-occurrence of Papillary thyroid carcinoma (PTC) and Medullary thyroid carcinoma (MTC) is rare. We report such a rare co-occurrence in a patient and discuss the challenges in management.

Case Details: A 42-year-old lady presented with a painless neck swelling and dysphagia for 3 months. Neck examination revealed firm non-tender nodules in both thyroid lobes. Thyroid function test was normal and ultrasound neck showed bilateral TIRADS 4 lesions (1X1 cm right side; 2X2 cm left side). FNAC from both nodules revealed Bethesda IV lesions (follicular neoplasm). The patient underwent total thyroidectomy and bilateral central compartment lymph node dissection. Histopathology showed MTC with nodal metastasis in right lobe and PTC in the left lobe. The first serum calcitonin, done post operatively was 307 pg/ml. As part of metastatic work up bone scan, CECT chest, abdomen and FDG PET done, which showed metastasis in bone and mediastinal lymph nodes. The bone and mediastinal nodes also showed Ga 68 DOTANOC uptake suggesting the metastatic disease to be from MTC. Post operative whole body iodine scan showed remnant uptake only in the thyroid bed and patient underwent RAI ablation twice. Post op thyroglobulin is within normal range. Patient was started on cabozantinib for metastatic MTC with good response which was later stopped due to side effects. The patient currently has stable disease and is on follow-up.

Discussion: Concomitant MTC and PTC are rare, accounting for only 0.15% of thyroid cancers. In the past 30 years, a total of only 18 cases have been reported in the literature. The management is challenging as both the components need to be managed individually. The prognosis of the disease depends upon the extent of more aggressive MTC.

Conclusion: The concurrent occurrence of PTC and MTC in the same patient is rare. The management and follow up of such cases are often challenging.

Abstract No: ABS208: Unveiling the enigma: A case report of lymphocytic infundibulo-neuro-hypophysitis in a postmenopausal woman

V. Aarthi Devi

Osmania Medical College, Hyderabad, Telangana, India

E-mail: aarthivijay18@gmail.com

Background: Lymphocytic hypophysitis is a rare autoimmune disease, seen most frequently in women, with a F:M of ~9:1, and often in the postpartum period or the third trimester of pregnancy. Lymphocytic Infundibulo-neuro-hypophysitis (LINH) is one of its rarer variants, that typically presents as acute onset diabetes insipidus (DI).

Case Details: A 48 year old postmenopausal female, a K/C/O Diabetes Mellitus, well controlled with oral medications, presented with polyuria and polydipsia for 3 months, without symptoms of headache and visual disturbances. Quantification of 24-hour urine volume and osmolality was confirmative of polyuria. Water deprivation test and Desmopressin trial was suggestive of Central Diabetes Insipidus. Other pituitary hormone axis evaluation was normal, except for mildly elevated serum prolactin. MRI brain showed loss of the pituitary bright spot and stalk thickening. The screening for other secondary causes of hypophysitis was normal. The patient is currently on treatment with oral Desmopressin.

Conclusion: LINH in postmenopausal females is a very rare entity. Conservative treatment is the mainstay of treatment in the absence of compressive symptoms. Long-term follow-up with serial neuroimaging and hormonal assessment after diagnosis of LINH is mandatory.

Abstract No: ABS211: Robinow syndrome: A rare case report

S. Anushri, G. Arun, K. V. S. Harikumar, Shaikh Naseemuddin Nayeemuddin

ESIC Medical College and Hospital, Hyderabad, Telangana, India

E-mail: dranusridhar@gmail.com

Background: Robinow syndrome is a rare disease with dysmorphic characteristics. The incidence is found to be of 1:500 000 with equal incidence in males and females. The syndrome is also known as Robinow-Silverman-Smith syndrome. It can be seen in dominant and recessive forms with moderate abnormalities in dominant and recessive group have more skeletal abnormalities. This is a case report of a baby presenting with features of CAH (congenital adrenal hyperplasia) later found to have Robinow syndrome.

Methods: 1 day old term male boy with birth weight 2.2 kg presented with microphallus and empty scrotum. BP was normal and there were no episodes of hypoglycemia vomiting. Clinical examination showed microphallus with stretched penile length (SPL) – 0.5 cmm, bilateral empty underdeveloped scrotum with decreased pigmentation, impalpable testis, penoscrotal webbing, meatus at the end of penoscrotal area with good urine stream. Investigations showed low cortisol with hyponatremia and hyperkalemia with elevated 17 hydroxy progesterone. MRI pelvis showed an oval hyperintense structure (phallus) with bilateral testis in the lower inguinal region. Karyotyping showed 46 XY. Clinical diagnosis of XY DSD (disorders of sexual differentiation) with CAH. Around 8 months of age we noted dysmorphic facial features. Examination showed depressed nasal bridge, widened eyes large anterior fontanelle (AF), short and stout nose, tented upper limb, gum hypertrophy, mesomelia, low set ears and cryptorchidism.

Results: Due to high suspicion of syndromic features, genetic testing was adviced. Genetic testing with whole genomic sequencing showed heterozygous pathogenic variant involving gene WNT5A and diagnosis being autosomal dominant Robinow syndrome.

Conclusion: Robinow syndrome is a very rare disease presenting with dysmorphic features and skeletal abnormalities. A high index of suspicion is required for diagnosis to offer genetic testing

Abstract No: ABS213: Correlation between acanthosis nigricans neck severity scoring with insulin resistance and parameters of metabolic syndrome

Sruthy Jayadevan

Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, Kerala, India

E-mail: sruthy.jayadevan@gmail.com

Introduction: Acanthosis nigricans, the velvety pigmentation of neck, axilla, knuckles and other surfaces is seen in obesity, diabetes, malignancies, drugs, pineal tumors, and other endocrine disorders. It is considered a cutaneous marker of tissue insulin resistance.

Aims and Objectives: To determine the prevalence of acanthosis nigricans in type 2 diabetes mellitus and its correlation of acanthosis neck grading with various anthropometric measurements BMI, waist circumference, waist hip ratio and insulin resistance by HOMA-IR and other metabolic parameters.

Materials and Methods: From the newly diagnosed type 2 DM patients attending the endocrinology/medicine OPD of Pushpagiri medical college, 125 consecutive males and 125 consecutive females were screened for the study. Acanthosis was graded based on standard scale of 0-4 (0: Not visible, grade 1 Present: clearly present on close visual inspection, not visible to the casual observer, extent not measurable. grade 2, Mild: limited to the base of the skull, does not extend to the lateral margin of the neck, grade 3: extending to the lateral margins, not visible from the front, and grade 4: extending anteriorly). Anthropometric data were obtained and insulin resistance calculated as HOMA-IR from fasting insulin and fasting blood sugar values. Other parameters of metabolic syndrome and obesity- HDL, Triglycerides, Uric acid levels were estimated.

Results: The average age of the study population was 40.1 years, with male to female ratio of 0.89. The prevalence of acanthosis in males was 56.2% and in females was 74.1%. The acanthosis neck severity grading had a statistically significant correlation with fasting glucose levels, fasting insulin levels, and insulin resistance values calculated by HOMA-IR (P < 0.05). Acanthosis severity scoring had statistically significant correlation with triglyceride values, and uric acid levels. The correlation showed a trend towards significance with waist circumference, but not with BMI.

Conclusion: Acanthosis nigricans neck severity grading correlates well with insulin resistance and can be used as a clinical surrogate for assessment of severity of insulin resistance.

Abstract No: ABS214: Two swords in one sheath

Bhoomika Kauloorkar

NIMS, Hyderabad, Telangana, India

E-mail: bhoomi.bannu@gmail.com

Maturity-onset diabetes of the young (MODY) is a rare subtype of diabetes, affecting 1-5% of diabetes cases, typically emerging before the age of 25 and notably lacking beta-cell autoimmunity. Unlike the majority of diabetes cases, fewer than 1% of MODY individuals exhibit positive autoantibodies like glutamate decarboxylase (GAD) and islet antigen-2 (IA-2). This description highlights a unique case involving two siblings who developed diabetes at a young age, subsequently facing complications and nephropathy. Genetic testing, encompassing whole exome sequencing and mitochondrial genome sequencing, revealed a heterozygous variant in the ABCC8 gene (C.4799630; P-Arg 1600His), which is associated with a specific form of MODY known as MODY12. Remarkably, both siblings displayed both type 1 diabetes autoimmunity and a mutation linked to MODY 12 within the ABCC8 gene. This juxtaposition suggests a possible explanation for their early onset of progressive insulin deficiency. This case underscores the intricacies of diabetes diagnosis, particularly when multiple factors are at play. It emphasizes the significance of genetic testing, especially when autoantibodies and family histories suggest a potential overlap between MODY and autoimmune diabetes. It also sheds light on the intricate relationship between genetics and diabetes presentation, offering valuable insights into disease mechanisms and management for rare cases like these.

Abstract No: ABS215: Remarkable reversal of diabetes mellitus and hypertension after surgical paraganglioma removal: A rare case report

Basharat Quyoom Dar

SSH, GMC, Srinagar, Jammu and Kashmir, India

E-mail: basharatdar1992@gmail.com

Catecholamine secreting tumours with Hypertension and Diabetes mellitus are rare, and surgical removal of the offending tumour can result in complete remission of the clinical manifestations. Here we have a patient, A 26 year-old female, with Diabetes mellitus who presented with recurring symptoms including headaches, flushing, palpitations, and sweating over a span of 5 years. The patient also exhibited Hypertension with a significant postural drop. Laboratory analysis revealed elevated plasma free normetanephrine levels. Imaging indicated a large retroperitoneal lesion, suspected to be a paraganglioma. Treatment commenced with pre-operative preparation with alpha followed by beta blockade, resulting in blood pressure control & Insulin for glycemic control. The patient underwent surgical intervention with removal of the offending tumour, which led to the normalisation of blood pressure and blood glucose levels, indicating a cure post-tumor removal. This case highlights the importance of thorough evaluation and appropriate management in cases of catecholamine-secreting tumours.

Keywords: Catecholamines, diabetes mellitus, hypertension, paraganglioma, tumour

Abstract No: ABS217: Heterogenous tale of two siblings with triple a syndrome in kalyana Karnataka

Swaraj Waddankeri, Hemanth Reddy, Meenakshi Waddankeri

M R Medical College, Gulbarga, Karnataka, India

E-mail: swaraj_amit@yahoo.com

Background: Triple A syndrome (Allgrove syndrome) is an extremely rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia of the esophageal cardia and alacrima. It is caused by mutations in the AAAS gene. We present two cases of Triple A syndrome in siblings of Asian-Indian origin.

Methods: The two siblings, born to consanguineous parents, exhibited typical features of Triple A syndrome, including alacrima, adrenal insufficiency, and achalasia cardia. Case 1 presented with dysphagia, hyperpigmentation, and adrenal insufficiency at the age of 14, while Case 2 exhibited abnormal gait and failure to gain weight since the age of 2. Both cases had Schirmer’s test-positive alacrima, orthostatic hypotension and severe adrenal hypoplasia on radiological imaging. Genetic analysis confirmed a homozygous pathogenic variant (c.43C>A, p.Gln15Lys) in Case 1 but not in Case 2.

Results: Triple A syndrome is exceedingly rare, with only sporadic cases reported worldwide. Clinical manifestations can vary, making diagnosis challenging. Early recognition is crucial to prevent life-threatening consequences. Both cases in this report highlight the importance of considering Triple A syndrome in patients with alacrima and associated symptoms.

Conclusion: Triple A syndrome should be suspected in individuals presenting with alacrima and a combination of symptoms including dysphagia, adrenal insufficiency, and neurological deficits. Genetic analysis is essential for confirming the diagnosis. Timely diagnosis and management are critical to improving the quality of life for affected individuals.

Keywords: Achalasia cardia, Addisons disease, alacrima, Allgrove syndrome

Abstract No: ABS218: Joubert’s syndrome – 2 case reports

Vasamsetti Sai Ramya, G. Arun, K. V. S. Harikumar, Shaikh Naseemuddin Nayeemuddin

ESIC Medical College and Hospital, Hyderabad, Telangana, India

E-mail: vs.ramya93@gmail.com

Background: Joubert syndrome (JS), is an autosomal recessive ciliopathy, is characterized by the presence of molar tooth sign on brain MRI, hypotonia, and other neurodevelopmental features. JS is underreported, with only around 200 cases reported worldwide and its prevalence is less than 1: 1000. The diagnosis of this disorder is usually delayed sometimes up to years because of the nonspecific symptoms even though clinical features present at an early age.

Methods: The 1^st case is 19-year-old female with delayed developmental milestones along with failure during childhood now presented with short stature and primary amenorrhea. On examination, she has round face, squint in right eye, high arched palate and horizontal nystagmus. Magnetic resonance imaging brain done which revealed pituitary aplasia, thickening and elongation of superior cerebral peduncle with midline shift at Ponto-mesencephalic junction, aplasia of inferior cerebellar vermis causing opposition of inferior cerebellar hemisphere. Fourth ventricle shows typical bat wing appearance all features suggestive of Joubert syndromeThe second case is isolated growth hormone deficiency presented with delayed milestones and short stature, who underwent physiotherapy and speech therapy with which she has improvement in milestones. Brain magnetic resonance imaging showed pituitary hypoplasia along with thickened cerebral peduncle, aplasia of inferior cerebellar vermis, bat wing appearance of fourth ventricle and characteristic molar tooth sign of midbrain in both cases.

Results: The 1^st patient was started with growth hormone (GH) for short stature and oestrogen valerate for induction of puberty and the 2 nd patient was already on GH therapy and is on follow up.

Conclusion: Early identification and treatment have better outcomes and awareness of clinical and characteristic radiological features helps in early diagnosis and successful rehabilitation.

Abstract No: ABS219: A case of Xp21 contiguous gene deletion syndrome (Xp21-CGDS)

Santosh Kumar Singh

Private Practice

E-mail: drsksingh61@gmail.com

Introduction: Xp21 Contiguous Gene Deletion Syndrome (Xp21-CGDS) is a rare genetic disorder characterized by the loss of multiple genes located on the short arm of X chromosome. This syndrome encompasses a spectrum of clinical manifestations including Adrenal Hypoplasia Congenita (AHC), Duchenne Muscular Dystrophy (DMD) and Glycerol Kinase Deficiency (GKD). The Index Patient: A 17 year old short-statured boy with delayed puberty [weight age (WA)-11.25, height age (HA)-11.75, SMR-G1P2, BP-94/64 mmHg, prepubertal LH, FSH, Testosterone(T)] was on hydrocortisone since neonatal period with later addition of fludrocortisone. There was hyponatremia, hyperkalemia, increased PRA in the past records. Previous data showed WA-11, HA-9.25, bone age (BA)-8-10 with normal IGF-1at chronological age (CA)-14 when he was prescribed Inj. T-100 mg/month (intramuscular) for 3 months for delayed puberty and later Inj. HCG for hypogondotropic hypogonadism (HH). He had right inguinal hernia repair at the age of 6.5 years. The genetic analysis revealed X-linked recessive AHC (OMIM#300200) and DMD (OMIM#300376) associated with NROB1/DAX1(-) and DMD (-) mutations. There was no evidence of muscle weakness.

Discussion: Xp21-CGDS encompasses AHC and DMD. The severity of the symptoms can vary depending on the size and location of deletion of neighboring genes. The onset of adrenocortical hypofunction is, mostly, early in life but can vary suggesting a role of other epigenetic factors influencing the clinical course of AHC. Most patients with AHC also suffer from HH since NROB1/DAX1 mutations can lead to impaired synthesis and release of gonadotropins characterized by a lack of or delayed puberty. Milder forms of of AHC have been observed in patients with AHC with normal puberty. The clinical association of DMD may be evident in future.

Conclusion: This case provides a comprehensive overview of Xp21-CGDS, highlighting its clinical features, genetic basis, diagnostic methods and therapeutic strategies. Early detection is crucial for timely intervention and management of this genetic disorder encompassing AHC, HH and DMD.

REFERENCES

1. Ferraz-de-Souza B, Lin L, Acherman JC, et al . Molecular analysis of the NROB1 gene in patients with AHC and Xp21 contiguous gene deletion. Horm Res 2004;62:250-7.

2. Rojek A, Obara-Moszynska M, Malecka E, et al . NROB1(DAX1) mutations in patients affected by congenital adrenal hypoplasia with growth hormone deficiency as a new finding. J Appl Genet 2014;54:225-30.

Abstract No: ABS221: Lingual papillary carcinoma thyroid: A case report and literature review

Sidhartha Sankar Bhuyan, Kishore Kumar Behera, Sayantan Ray

AIIMS, Bhubaneswar, Odisha, India

E-mail: sidhartha.bhuyan1990@gmail.com

The Thyroid gland has the special privilege of being the 1^st endocrine gland to develop inside the fetus. It is the anterior most organ to arise from the gut tube as an endodermal outpouching called thyroid anlage. In the course of the development and caudal migration, the thyroid primordium descends to its final anatomic position at around 50^th embryonic day. Defect in migration of embryonic primordium results in ectopic thyroid tissue. Prevalence of ectopic thyroid is about 1 in 100,000 to 300,000. The most common location for an ectopic thyroid is at the base of the tongue. An ectopic lingual thyroid may be an incidental finding or it can sometimes present with symptoms like airway obstruction, dysphagia or dysphonia and more commonly associated with hypothyroidism than hyperthyroidism. Risk of malignancy developing from ectopic thyroid tissues is estimated to be less than 1%. Lingual papillary carcinoma thyroid is a very rare clinical entity with 57 case reports published till date. Here we present a case of 18 year old female with ectopic lingual PTC. She presented with occasional blood tinged saliva while brushing for 2 months. Oral examination revealed a small nodular lesion at base of tongue that bled on manipulation. CECT oral cavity and neck reported absence of thyroid gland in its normal position and a hyperdense 18×19 mm mass at midline tongue base. Biochemically she was found to be hypothyroid and was put on levothyroxine supplimentation. She was subject to thyroid scintigraphy which revealed focal tracer uptake in lingual region. US guided FNA of lingual mass reported features suggestive of PTC. She underwent transoral excision of the same and is kept on follow up with thyroxine suppressive therapy. In this case report we review the incidence of ectopic lingual PTC, its clinical presentation, natural course, diagnostic work up and treatment.

Keywords: Ectopic, lingual, papillary thyroid carcinoma, rare

Abstract No: ABS222: Fibrodysplasia ossificans progressiva: A rare disorder of heterotopic ossification

Shivani

AIIMS, Bathinda, Punjab, India

E-mail: shivani66sidana@gmail.com

Background: Fibrodysplasia ossificans progressiva (FOP), also called Munchmeyer disease or myositis ossificans progressiva, is an extremely rare genetic disorder in which fibrous connective tissue such as muscle, tendons, and ligament gradually ossify into bone tissue. It is a severely disabling genetic condition that can occur due to sporadic mutation or have autosomal dominant inheritance. FOP is caused by a mutation of the gene ACVR1/ALK2 that induces osteoblast activation The mutation affects the body’s repair mechanism, causing fibrous tissue including muscle, tendons, and ligaments to become ossified. Minor injuries can cause joints to become permanently fused as new bone forms, replacing the damaged muscle tissue, brides the joint space. This new bone formation also known as “heterotopic ossification” eventually forms a secondary skeleton and progressively restricts the patient’s ability to move.

Case Summery: 12 yr male child presented with progressive and complete restriction in movements of most of the joints- wrist, ankle, knee, spine, and temporomandibular joint over two years. Classical appearance of great toe helps to differentiate this disorder clinically from other causes of heterotopic ossification like Progressive osseous heteroplasia, aggressive juvenile fibromatosis, and fibrous dysplasia etc. Many drugs failed to show improvements on patients with FOP, hence the disease remains without a cure, However, recently palovarotene has shown some promising results. Still, Palliative management is only treatment available till now. In our patient pain was managed with short course of with non-steroidal anti-inflammatory drugs. Hager mouth opening gag was used to sufficiently open the mouth for feeding assistance. Surgical intervention is contraindicated as it may result in extensive ectopic bone formation.

Conclusion: Clinicians should be aware of this rare entity, as can mimic with other causes of heterotopic ossification and misdiagnosis may results in un-necessary biopsies that often hasten disease progression, which may have catastrophic implications for patient.

Abstract No: ABS224: Pituitary double trouble: To kill two birds with one stone

K. Archana, Subhash Chandra B. Yadav, Awadhesh Kumar Jaiswal

SGPGI, Lucknow, Uttar Pradesh, India

E-mail: justmailarchana@gmail.com

Background: Pluri-hormonal pituitary tumours secreting two or more hormones have been found to occur in 7.8% of the surgical specimens. Most commonly encountered as prolactin co-secretion with growth hormone in acromegaly. But concomitant secretion of prolactin and adrenocorticotropic hormone (ACTH) is very rarely reported.

Case Description: A 42-year-old gentleman, known case of Cushings’ disease with pituitary macroadenoma had undergone transsphenoidal resection at 22 years of age. Patient had documented remission with secondary adrenal insufficiency at time of discharge. However patient was lost to follow up till now when he developed difficulty getting up from lying down, climbing stairs, poorly controlled blood pressure since 1 year. It was associated with undocumented weight gain and rounding of facies. On examination overt cushingoid features (hypertension, abdominal reddish striae, proximal muscle weakness with cervical hump and moon facies) were noted. On evaluation, ACTH dependent hypercortisolemia (8 am cortisol 525nmol/l, low dose dexamethasone suppression test- 571nmol/l, high dose dexamethasone suppression test-531nmol/l, 8am ACTH 24.8pmol/l) along with raised prolactin of 20982miu/l. MRI Sella showed 7.7 x 19mm right sided pituitary adenoma with no optic chiasma involvement. Patient was started on cabergoline 0.5mg/week and post 3 days had biochemical response (Prolactin 9215miu/l 8am cortisol 132nmol/l. Stimulated cortisol 535nmol/l). Follow up prolactin was raised 15737miu/l, cabergoline was increased to 2mg/week gradually, targeting prolactin and at this dose, he developed adrenal insufficiency and had to be started on steroid replacement.

Discussion: Amongst previously described seven cases, dopamine agonist therapy led to remission in 3 cases. Hence, co-secreting ACTH and prolactin tumours are a rare cause of cushings’ disease which may be medically managed successfully, circumventing transsphenoidal surgery.

Abstract No: ABS231: Hurler-Scheie syndrome (Mucopolysaccharidosis Type 1) in a young male patient: A case report of rare disease

Shoiab Mohd Patto, Shahnawaz Ahmed Mir, Mohammad Hayat Bhat, Pooran Sharma

Government Medical College, Srinagar, Jammu and Kashmir, India

E-mail: shoiab_123@yahoo.com

Mucopolysaccharidoses are a family of rare inherited metabolic disorders caused by deficiency of lysosomal enzymes needed to degrade glycosoaminoglycans, or mucopolysaccharides. Mucopolysaccharidosis type I (MPS I) is a clinically progressive disorder caused by the deficiency of the lysosomal enzyme, α-L-iduronidase. The disease is inherited in an autosomal recessive manner. MPS I has been classified into a severe (Hurler syndrome) and an attenuated type (Hurler-Scheie and Scheie syndromes). Attenuated MPS 1 is very rare with an estimated incidence of 1 in 500,000 births. We present a case of 18 years old boy, product of consanguineous marriage, fourth in birth order, with history of sibling death at 4 years of age. Patient presented with main complaints of failure to gain height, progressive stiffness of almost all joints (large and small) with limited mobility and deformities involving hands, knees. On examination patient was found to have severe disproportionate short stature with height SDS of -10 and ratio of upper to lower segment of 0.71. cm. The child had coarse facies with large (macrocephalic) head, protruded eyes, depressed nasal bridge, macroglossia, low set ears with large pinna. Corneal clouding was present bilaterally and both liver and spleen were markedly enlarged. Skeletal system examination revealed gibbus deformity, fixed flexion deformity of knee joints, elbow joints, and interphalangeal joints of hands. Lab investigations revealed elevated urinary glycosoaminoglycans. Radiographic survey revealed mandibular hypoplasia, thoracolumbar kyphosis, flexion deformities of finger joints (claw hand), poorly formed pelvis with coxa valga. MRI Brain showed J shaped sella, prominent Virchow- Robin spaces and vetriculomegaly. The patient was diagnosed as case of MPS 1 (Hurler-scheie variant) based on clinical and imaging findings along with elevated urinary GAGs. Mutation testing was not carried out due to limited availability and financial constraints.

Abstract No: ABS233: Android and gynoid adiposity among males and females with type 2 diabetes and It’s effect on bone mineral density

Surapaneni Lakshmi Sravya, Jayshree Swain, Swayamsidha Mangaraj, Jayabhanu Kanwar, Pooja jadhao

IMS and SUM Hospital, Bhubaneswar, Odisha, India

E-mail: straberryeye@gmail.com

Context: Males tend to have “android” obesity, while females have “gynoid” obesity. Whether this gender difference of fat distribution affects the BMD at various sites had not been well studied.

Objective: To evaluate the association of the bone mineral density at various sites (neck of femur, total hip and lumbar spine) with android and gynoid fat mass and android/gynoid fat ratio, among male and female with type 2 diabetics.

Methods: This cross-sectional study enrolled 97 (57-females & 40 males) type 2 diabetic patients (mean HbA1c-7.7%) aged 45-80 years (mean-58), excluding patients with chronic systemic illness, treatment for osteoporosis, severe arthritis, on weight loss programmes or surgeries. Lumbar spine, total femur and neck of femoral bone mineral densities, android and gynoid fat mass were measured by Dual-Energy X-ray Absorptiometry and android /gynoid (A/G) ratio was calculated. Student t test used to analyse the continuous parametric variables and Karl Pearson’s correlation co-efficient was used to analyse the association between parameters.

Results: Mean age, HbA1c and BMI are similar in both males and females. As expected, males had higher BMD at various sites (P<0.001). Females had higher gynoid fat mass (p<0.001), whereas android fat mass (p- 0.82) was similar in both sexes. Android/Gynoid fat ratio (p<0.001) is higher in males. Males showed a positive correlation between total hip BMD and A/G ratio (r=0.335, p<0.034). No significant association was found in females.

Conclusion: In our study we found positive association between total hip BMD and A/G ratio in males. No correlation between fat distribution and the BMD at various sites among females.

Abstract No: ABS235: Correlation of serum testosterone to androstenedione ratio (TT/A4) and serum testosterone to dihydrotestosterone ratio (TT/DHT) with various inflammatory and metabolic parameters determining health outcomes in women with polycystic ovarian syndrome

Subhendu Kumar Sahoo, Debarchan Jena, Deepak Kumar Dash, Ipsita Mishra, A. K. Baliarsinha, Madan Mohan Majhi

SCB Medical College Cuttack, Odisha, India

E-mail: subhendu241@gmail.com

Background: There is dearth of literatures on the role of different androgens with metabolic and inflammatory parameters. Measurement of serum androstenedione (A4) and dehydrotestosterone (DHT) are very less frequent in clinical practice for patients with suspected polycystic ovarian syndrome (PCOS), because of their uncertain diagnostic values. Considering the need of diagnostic importance of inflammatory & metabolic parameters in chronic disease and also in PCOS the present study is undertaken if TT/A4 ratio and TT/DHT ratiocan predict metabolic risk in Indian women with PCOS.

Objectives: To study correlation of serum testosterone to androstenedione ratio and serum testosterone to dihydrotestosterone ratio with inflammatory (IL6&hsCRP) and metabolic parameters (HOMA IR & Lipid profile) in women with polycystic ovary syndrome women.

Methods: Patients with PCOS diagnosed as per Rotterdam Criteria, presenting to Dept. of Endocrinology, SCBMCH between July 2022 to August 2023 were included. Total 32 women consenting for the study were included following inclusion and exclusion criteria. Relevant sociodemographic, clinical, anthropometric parameters of the patients were obtained. Different biochemical parameters of blood were analysed. USG abdomen and pelvis was done. Data analysed using SPSS (Trial version). A p value of <0.05 was considered for declaring significance difference. Ethical clearance was obtained from Institutional Ethics committee. Results: Among all women with PCOSmajority were overweight. Inflammatory markers IL6 ((r=0.3) and hsCRP (r=0.45); metabolic parameters HOMA-IR (r=0.44) and Triglyceride were positively corelated with TT/A4 ratio. These parameters were also positively correlated with TT/DHT ratio. Though both inflammatory and metabolic parameters were positively correlated with TT/A4 ratio and TT/DHT ratio none of the parameters found to be statistically significant.

Conclusion: This is obvious from this study that the inflammatory and metabolic parameter in the patients with PCOS were positively correlated with TT/A4 ratio and TT/DHT ratio, However, further research is mandated to establish any significant association.

Keywords: Inflammatory markers, metabolic parameters, polycystic ovarian syndrome, testosterone to androstenedione ratio, testosterone to dihydrotestosterone ratio

Abstract No: ABS236: A rare case of acrogigantism due to mixed growth hormone and prolactin secreting adenoma

Neelam Yadav, Sunanda Tirupathae, R. Naga Anil Krishna, N. A Sai Kiran, Kharidehal Durga

Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India

E-mail: ineelamy@gmail.com

Background: Pituitary gigantism is a rare condition that results from excess secretion of Growth hormone from pituitary adenoma or hyperplasia, prior to epiphyseal fusion. Most cases of adult somatotroph adenoma are of sporadic origin, while about 50% of Acrogigantism cases have genetic origin.

Case Presentation: A 6 years 10 months’ girl presented with chief complaints of tall stature since 2 years of age, increased perspiration since 4 years of age and progressive diminution of vision for last 7 months. No significant family history. Her anthropometry - Height SDS (+) 4.8, Weight SDS (+) 6.3, US:LS 1, Arm Span- Height (-) 8. And Tanner stage of B1P1. Having coarse facial features like- broad nose, thickened nasolabial fold, broad fleshy lips and widened gap between teeth, large hands and feet and, sweaty hands. Visual acuity limited to finger count at 1meter distance. Biochemical investigation - elevated GH and prolactin with central hypothyroidism and hypocortisolism. MRI Pituitary Hypothalamic area revealed a large heterogenous sellar and suprasellar mass measuring 4.5 X 3.2X 4.4 cm, T1 heterogenous hyperintense, T2 intermediate hyperintense, compressing optic chiasm and displacing carotid arteries in cavernous sinus. Patient underwent debulking surgery. GH and prolactin levels were high and no remnant was seen on MRI, in immediate post- operative period. HPE- cells with moderate amount eosinophilic cytoplasm, arranged in trabecular pattern, foci of psammoma bodies. IHC - positive for GH. Sparsely granulated somatotroph adenoma. MIB1 labeling 3%. Patient started on dopamine agonist. 3 months’ post -surgery and on dopamine agonist, she is having persistent high levels of IGF-1, GH and prolactin, planned for Somatostatin analogue therapy.

Conclusion: Pituitary gigantism should also be kept in mind when a child presents with very early onset, rapid and excessive acceleration of height and body size. Multimodal therapeutic approach combining medical, surgical and rarely radiotherapy is required. Early diagnosis and effective treatment can prevent devastating complications like visual loss and can lead to normal adult height.

Abstract No: ABS247: A rare pathogenic variant of DHX37 associated with 46 XY sex reversal 11 in a 10-year-old child

Sayyad Aleem, K. V. S. Harikumar, G. Arun, Shaikh Naseemuddin Nayeemuddin

Department of Endocrinology, ESIC Medical College and Hospital, Hyderabad

E-mail: syedmbbs786@gmail.com

DEAH-box helicase 37 (DHX37) gene heterozygous mutation is responsible for Autosomal dominant 46, XY sex reversal 11 (OMIM#273250) with genital ambiguity. We present a case of 10-year-old male child presented with micropenis, penoscrotal hypospadiasis, left side anorchia and identified a rare pathogenic variant of DHX37 c.1346T>G (p. Leu449Arg) through Whole exome sequence.

Abstract No: ABS249: Distal renal tubular acidosis presenting with refractory rickets – A case report

Vishal Agarwal, Dayanidhi Meher, Arun Choudhury, Sambit Das

Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India

E-mail: vishal.agarwal018@gmail.com

Background: Distal renal tubular acidosis (dRTA) is a rare renal tubular disorder characterized by normal anion gap metabolic acidosis, hypokalemia, and high urine pH. It can be inherited or acquired. In untreated paediatric patients with dRTA, rickets and growth retardation are common.

Case Report: A 14 years old girl child presented with chief complaints of poor height and weight gain since birth and skeletal deformity for last 13 years. At the age of 2 years, the parents noticed that the child had spontaneous bowing of bilateral lower limbs. By 5 years of age, the child had history of fracture of right clavicle and right humerus following trivial trauma. Examination revealed height SDS= -4.3, weight SDS= -3.4, frontal bossing, enamel hypoplasia, rachitic rosary, metaphyseal end swelling in bilateral wrist joint, along with genu valgus and short 4th metatarsal bilaterally. Systemic examination was unremarkable. On investigation: ABG revealed acidosis with arterial pH 7.269 with K+- 2.8 mEq/L. Alkaline phosphatase was raised with values 721 U/l, 25-OH vitamin D level was 78.5 ng/ml, serum creatinine 1.98 mg/dl, serum calcium 6.7 mg/dl and serum phosphorus 3.0 mg/dl. Urinary pH was 6.5, along with hypercalciuria documented by urinary calcium creatinine ratio of 0.77. Ultrasonography of abdomen revealed medullary nephrocalcinosis along with grade 3 medical renal disease and nephrolithiasis. A diagnosis of distal RTA with rickets was made and the child was immediately initiated on potassium citrate supplementation, iv calcium gluconate and oral potassium replacement therapy. On follow up, patient was symptomatically better with resolution of acidosis.

Conclusion: Renal tubular acidosis is a cause of refractory rickets which can be a challenging diagnosis for a physician. RTA can have varied presentation in the form of rickets, short stature, failure to thrive, growth retardation, and nephrocalcinosis. Step wise evaluation is necessary for proper diagnosis and management of the patient.

Abstract No: ABS250: Pituitary stalk interruption syndrome – A case report

Binod Prusty, Dayanidhi Meher, Arun Choudhury, Sambit Das

Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India

E-mail: mkcg.binod@gmail.com

Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital endocrine abnormality with a developmental defect of pituitary gland that is responsible for anterior pituitary hormone deficiency. This syndrome is characterised by classical triad of thin, interrupted, attenuated or absent pituitary stalk, hypoplasia or aplasia of the anterior pituitary, and an ectopic posterior pituitary identified on magnetic resonance imaging of pituitary and hypothalamus. Clinically may present with growth hormone or other anterior pituitary hormone deficiencies.

Case Report: A 11-years 6 months old girl presented to the endocrine department with chief complaints of poor height gain and weight gain since last 6 years. The child was born out of non-consanguineous marriage and was delivered at term by normal vaginal breech delivery without any complications. Her birth weight was 3.4 Kg with her family history was unremarkable. There was no history of delayed achievement of developmental milestones and she has good scholastic performance. She has one sibling with normal history of growth and development. On examination her blood pressure was 90/60 mmHg with Height SDS= -4.86 (height age- 5 years 3 months), Upper and lower segment ratio 0.89, Weight SDS= -3.89 (weight age- 5years). She had cherubic face with depressed nasal bridge, midfacial hypoplasia and no goiter. Tanner staging of A - P1 B1. Systemic examination was unremarkable. On investigation her complete blood count, Renal and liver function tests, electrolytes, calcium profile, and IgA tTG were normal. Hormonal profile showed serum free thyroid hormone FT4 0.58 ng/dl (N 0.8-2.0), thyroid stimulating hormone TSH 2.915 IU/ml (N 0.27-4.2), 0800h baseline cortisol 23.98 ug/dl (6.7-22.6), LH 1.56 mIU/ml, FSH 6.06 mIU/ml, Prolactin 24.2 ng/ml (3.6-12) and IGF1 19.10 ng/ml (N 96-554). Her bone age was 6 years according to the Greulich and Pyle method, as shown by X-rays, contrast enhanced magnetic resonance imaging (CEMRI) sella showed: ectopic anterior pituitary with hypoplastic anterior and absent/thin pituitary infundibulum. With this profile, a diagnosis of PSIS with multiple pituitary hormone deficiency (GH and TSH) with Short Stature was made and treated with replacement of deficient hormones particularly thyroxine and growth hormone.

Conclusion: Although, pituitary stalk interruption syndrome (PSIS) is a rare disorder which leads to pituitary dwarfism it should be kept in the differential diagnosis of a patient presenting with short stature. The prognosis is good if there is timely diagnosis and treatment.

Abstract No: ABS251: Celiac disease: The great masquerader celiac disease: The great masquerader

Kashish Gupta, Deepti Sharma, Anamika Gora, Himanshi Soni, Esha Naik, Naincy Purwar, Sanjay Saran, Balram Sharma, Sandeep Kumar Mathur

SMS Medical College, Jaipur, Rajasthan, India

E-mail: kashishgupta8@yahoo.com

Background: Celiac disease (CD) is an autoimmune disease, triggered by ingestion of gluten in genetically predisposed individuals. Classically characterized by malabsorption, diarrhea, and weight loss; it can also cause a wide range of extra-intestinal complications. We present 5 unusual manifestations where the CD hides in plain sight, to highlight this issue.

Case: A 62-year-old man K/c/o Graves’ disease, presented with a 3 year history of fatigue and loss of libido. Laboratory evaluation revealed elevated total testosterone, LH and FSH levels leading to a diagnosis of Celiac associated androgen resistance. A 20 yr-old-girl with bilateral genu valgum deformity and bone pain for 15 yrs, despite having received replacement for vitamin D deficiency, showed minimal improvements. Her Ttg-IgA test was negative but biopsy proved celiac disease. A 23 year old short female presented to us with c/o difficulty in walking for 20 days and a h/o trivial trauma 2 months back. She had received intermittent vitamin D replacement following a repeatedly negative metabolic bone panel. Her X-ray revealed b/l neck of femur fracture; she was diagnosed to have osteomalacia secondary to celiac. A 9yr old type 1 diabetic girl with excessive glycemic variability and a consistently negative celiac serology tested positive for HLA-DQ2 alleles; subsequently celiac was proven by biopsy. A 24yr old lady presented with anasarca, refractory anemia and diarrhea for 2 weeks, lab-reports revealed severe dyselectrolemia. She was diagnosed as a case of celiac crises and treated with steroids and gluten free diet with her symptoms resolving over 2 weeks.

Discussion: This case series highlights the multiple unusual manifestations of a common entity like celiac disease. A high index of suspicion and prompt diagnosis can help in preventing serious complications as withdrawal of gluten from the diet leads to resolution of most symptoms.

Abstract No: ABS255: Postpartum presentation of metastatic insulinoma

Deepali, Subramanian Kannan, K. S. Shivaprasad, Kranti Shreesh Khadilkar, G. S. Basavaraj, Anirudh J. Shetty, Nidhi Tandon, J. A. Karthik, Hetashvi Gondaliya, Narmada Nangadda

Narayana Hospitals Bommasandra, Bengaluru, Karnataka, India

E-mail: deepskaje@yahoo.in

Introduction: Insulinomas are mostly benign pancreatic neuroendocrine tumours characterized by fasting hyperinsulinemia hypoglycaemia. The presence of Whipple’s triad: symptoms and signs of hypoglycaemia with low plasma glucose levels, which are reversed by the administration of carbohydrate, are characteristic diagnostic features. The most common cause of hyperinsulinemic hypoglycaemia in adults is insulinoma.

Case: A 28/F, Para 2 Living 2, postpartum 1 month presented to us with episodes of sweating, shivering and slurring of speech, predominantly in the early mornings, on most of the days since past 20-25 days. Patient has documented hypoglycaemia, capillary blood glucose readings being 30-40mg/dl. She used to recover symptomatically following oral intake of sugar water. She was diagnosed with gestational diabetes mellitus in her second pregnancy and was treated with metformin. She delivered a 3.7 kg female child through caesarean section 21 days before presentation. Neonate had an episode of hypoglycaemia following birth. During postpartal period she underwent evaluation for transient weakness and paraesthesia of her right hand, which revealed B/L MOYA MOYA. On examination, her pulse - 68 BPM and her BP -110/80mmhg. There were a few skin tags and acanthosis around nape of neck. She was subjected to observed Prolonged Fast Test, when she developed hypoglycemia (Blood Glucose 34 mg/dl) at 1 hour postprandial with inappropriately elevated insulin levels of 19.4 micro IU/ml (N: undetectable) and c peptide levels of 2.29 ng/ml. CECT Abdomen demonstrated ill defined soft tissue density in the pancreatic tail showing heterogeneous enhancement post-contrast. There was hepatomegaly with multiple metastasis. She underwent ultrasonographic guided biopsy of one of the liver lesions which was reported as well differentiated NET Grade 3 with Ki 67 proliferative index of 25%. She was being treated symptomatically with daily multiple doses of octreotide subcutaneously. Later she was administered intramuscular 20 mg octreotide depot once a month and 100mg of Diazoxide daily. Her symptoms subsided. She was reassessed 8 weeks later on follow up and was found to have increase in size of liver metastasis despite good control symptomatically. With bilateral MOYA-MOYA and hepatic lesions that were unresectable, she was started on chemotherapy- capecitabine and temozolomide and doses were increased on follow up. After a month of chemotherapy her diazoxide requirement reduced. Fasting insulin (9/6/23) was 26.8micro IU/ml with C peptide levels of 2.21ng/ml when RBS was 142mg/dl. She is maintaining off diazoxide since past few weeks.

Discussion: Case reports on association of insulinoma and diabetes mellitus is extremely limited but its important not to miss it when iatrogenic causes of hypoglycemia has been ruled out. In a pregnant mother, insulinomas get manifested mostly during first trimester or postpartum period. In the post partum period, insulin sensitivity quickly recovers, which, in addition to breastfeeding, can lead to hypoglycemia shortly after delivery. In her case, pregnancy- an insulin resistant state must have prevented the manifestations of hypoglycemia and thereby causing some delay in seeking medical attention. It was a dedifferentiated tumor which had progressed to become Metastatic in a short period of time. She started experiencing symptomatic hypoglycemias in immediate postpartum period. Though islet cell tumors have higher propensity for metastasis, metastatic insulinoma is a rare entity. Association of 2 rare diseases- insulinoma and MOYA MOYA is even rarer. MEN1 may be associated with multicentric insulinomas. Malignant insulinoma carries a poor prognosis. A multimodal approach will help in better management of such patients.

Abstract No: ABS257: Rathke’s cleft cyst with adrenal insufficiency

Raveen Titus Thomas

Osmania Medical College, Hyderabad, Telangana, India

E-mail: raveenthomas@hotmail.com

Background: Rathke’s cleft cyst is a benign cystic pituitary mass which is usually asymptomatic and detected incidentally on MRI of the brain. However, it can cause headache, visual disturbance and endocrine disturbances when it enlarges – due to its compression on normal pituitary gland. Rathke’s cleft cyst associated inflammatory change in the pituitary gland can also cause pituitary dysfunction. Here we report a rare case of adrenal insufficiency due to Rathkes cleft cyst hemorrhage.

Aims and Objectives: To present a case of adrenal insufficiency secondary to Rathkes cleft cyst hemorrhage.

Case Details: A 21 year old male presented with severe headache, not subsiding with analgesics. MRI brain with contrast a suprasellar mass measuring 1.2 x 1.4 x 1.3 cm with features of hemorrhage within provisionally diagnosed as pituitary macroadenoma. Hormonal evaluation showed features of secondary adrenal insufficiency with all other axis within normal limits and he was started on Hydrocortisone. A repeat MRI done after 3 months was suggestive of a Rathke’s cleft cyst of 1.2 x 1.1 x 1 cm, and 8 am cortisol was within normal limits – suggesting that the initial episode was probably hemorrhage within Rathke’s cleft cyst with adrenal insufficiency, now resolved.

Conclusion: Rathke’s cleft cyst hemorrhage is a rare clinical entity that can present with acute adrenal insufficiency – treatment with corticosteroid showed shrinkage of cyst size in our case.

Abstract No: ABS258: Fatal post-operative hepatotoxcity in patient with ectopic Cushings syndrome: Time to strategize peri-operative use of ketoconazole?

Nangadda Narmada, Subramanian Kannan, K. S. Shivaprasad, Kranti Kadhilkar, G. S. Basavaraj, Anirudh J. Shetty, George Varghese, Hetashvi Gondaliya, Deepali

Narayana Hospitals, Bengaluru, Karnataka, India

E-mail: narmada.nangadda@yahoo.com

47 year male with ectopic Cushings syndrome related a neuro-endocrine tumour of the lung presented with a 6-8 month history of uncontrolled hypertension and severe hypokalemia (K 2.0 mEq/L) with S cortisol 30.1ug/dL and elevated ACTH (130.8 pg/ml (Normal: 9-20)). Gallium DOTATOC PET CT showed a 1.4 x 1.3 cm lesion (SUV max 9.6) in superior lingular region of left lung suggestive of bronchial carcinoid [Figure 1]. So, he was started on oral potassium replacement, Ketoconazole and Spironolactone. Dose of Ketoconazole was titrated to 1200 mg/day and spironolactone to 200 mg/day which normalized his blood pressure and potassium (4.5mEq/L) and his serial liver function testing (ALT: 30 IU/ml, AST: 27 IU/ml) was normal before the surgery [Table 1]. He successfully underwent robotic left lung segmentectomy under general anaesthesia with isoflurane and post operative period was uneventful and his ACTH dropped to 27.2 pg/mL and cortisol dropped to 34.4 ug/mL. His last dose of Ketoconazole was the night before surgery. He was discharged on 3^rd post operative day with hydrocortisone (50mg/day). He developed severe epigastric and right hypochondrial pain on 4^th post operative day and presented to emergency department. Biochemistry showed elevated liver enzymes (ALT 433 U/L, AST 370U/L, GGT 233 U/L). A CT scan of the abdomen was normal. During ICU stay (5^th post operative day), he developed bleeding diathesis and altered sensorium. Repeat Labs suggested fulminant hepatic failure (ALT 5053 U/L, AST 7844/L, GGT 207 U/L, PT>120 sec, aPTT >180 sec, INR:> 11) and patient succumbed within a span of 12 hours.

Discussion: Ketoconazole, which is CYPA 3A inhibitor administered in a dose range of 200-1200mg inhibits several steps in steroidogenesis (side chain cleavage complex, 17, 20 lyase, 17 a hydroxylase, 11 beta hydroxylase). However the CYPA 3A inhibition property of Ketoconazole makes it also a potent inhibitor of the metabolism of other drugs making it prone to drug interactions. Isoflurane, a commonly used inhaled anaesthetic, was administered intraoperatively. Isoflurane metabolises to Tri-fluro-acetyl acid which binds covalently to proteins is postulated mediator of centrilobular necrosis of liver. We suspect the enzyme inhibitory effect of Ketoconazole resulted in this fatal complication. Isolated Ketoconazole hepatoxicity seemed rather unlikely given the normal liver function tests pre-operatively and the hepatotoxicity occurring post-operatively after 4 days of cessation of Ketoconazole. We suggest that in patients with Cushings syndrome undergoing surgery, to withhold Ketoconazole 24-48 hours prior to surgery to avoid drug interactions with inhaled anaesthetic agents and other potentially hepatotoxic agents. One could also avoid the use of inhaled anaesthetics and use total intravenous anaesthetic agents in these cases thus minimizing the hepatotoxicity.

Abstract No: ABS260: Case series on hypoglycemia in children

Hamlipur Anusha

Osmania Medical College, Hyderabad, Telangana, India

E-mail: anushahamlipur21@gmail.com

Background: Congenital hyperinsulinemia (CHI) is hereditary disorder of insulin secretion and is the main cause of persistent and refractory hypoglycemia in infants. Inactivating mutations in KATP-related genes, including ABCC8 and KCNJ11, are the most common cause of CHI, accounting for approximately 45–50% of cases. The treatment of CHI depends on the specific gene mutations involved.

Case Details: C1: 4 year old male, born out of third degree consanguinity brought in status epilepticus due to hypoglycaemia, he had h/o neonatal seizure at 2^nd day of life, recurrent episodes of hypoglycaemia. Critical sample revealed high insulin, absent ketones. Genetic analysis revealed ABCC8 Polymorphism, homozygous mutant. C2: 3 year old girl product of second degree consanguinity presented with 1 episode of seizure following missing of her feed. On post natal day 3 child had history of seizures history of excessive crying, RBS was 33 mg/dl. Critical sample revealed high insulin, absent ketones. In view of persistant low sugars injection octrotide was added Genetic analysis revealed Homozygous non sense mutation in ABCC8 gene. C3: 15 month old male, product of non consanguinity. At day 3 of life child had seizure episode, RBS was 37 mg/dl, Critical sample revealed high Insulin Genetic analysis showed KCNJ11 - Homozygous type, ABCC8 polymorphism – Homozygous type.

Conclusion: Hperinsulinemia can arise from multiple causes. Genetic causes such as ABCC8 mutations should be considered when a persistent hypoglycemic state cannot be explained by perinatal stress alone. In such cases, genetic testing is recommended. Genetic testing may help in developing individual treatment plans and predicting outcomes and future impacts for children and their families.

Abstract No: ABS261: Pediatric Graves’ disease a case series of 4 patients

Anand C. Sonwane, Srinivas Kandula, Bipin Kumar Sethi

Care Hospital, Hyderabad, Telangana, India

E-mail: annd358@gmail.com

Introduction: Graves’s disease is rare but have serious complications in childhood. The relapse rate is high. We are presenting a series of 4 children who presented to our hospital with graves’ disease.

Objective: To study the clinical profile and management strategies in childhood Graves’ disease.

Methods: In this observational study we are describing the 4 patients with Pediatric Graves’ disease. Of these 1 was girl and 3 were boys. The girl child 10 years, presented with unilateral outward protrusion of left eye, which on evaluation found to have suppressed TSH and normal T4 value. Further evaluation reveals elevated TRAb antibody levels and started on Antithyroid medication. The second boy 11 years old presented with characteristics features of Hyperthyroidism. Laboratory evaluation reveals thyrotoxic profile with TSH< 0.008 uIU/ml and T4= 30 ug/dl. TRAb levels were found to be markedly elevated. Child was started on ATD on the clinical and biochemical profile improved with treatment and the patient is on continuation phase of ATD. last and 4th child present at age 16 years received ATD but didn’t go into remission, hence was given Radioactive iodine therapy. Pt develops hypothyroidism after this but soon there was relapse of Hyperthyroidism while without LT4 supplement. So this patient is planned for second dose of radioiodine.

Conclusion: The presentation is varied in our small case series and treatment strategies also differ individually. Overall graves’ disease in male child is difficult to treat.

Abstract No: ABS262: Monogenic autoimmune diabetes gene variants in young onset diabetes mellitus

J. Jabasteen, Anna Simon, Sarah Mathai, Praveen George Paul, H. S. Asha, Nihal Thomas, Aaron Chapla

Christian Medical College, Vellore, Tamil Nadu, India

E-mail: jabasteenjabasteen93@gmail.com

Background: Currently, there are at least 40 genes reported to be implicated in monogenic forms of autoimmune diabetes. In these cases, diabetes manifests as a part of autoimmune syndrome. Importantly there is limited data available regarding these monogenic forms of autoimmune diabetes. A genetic diagnosis can be invaluable for effective management, offering insight into prognosis, and communicating the genetic risk to affected families.

Methods: We performed targeted next-generation sequencing on 221 subjects diagnosed with young-onset diabetes mellitus below 25 years, showing clinical indications of monogenic diabetes. This study was approved by the Institutional Ethics Committee at Christian Medical College, Vellore (IRB MIN NO/10813 dated 23/08/2017). The case series comprises 16 subjects with variants in autoimmune monogenic diabetes genes.

Results: Fourteen subjects were positive for heterozygous variants, and two were positive for compound heterozygous variants: 4 (25%) had FOXP3, 7 (43.75%) had LRBA, 2 (12.5%) had STAT3, 2 (12.5%) had AIRE, and 1 (6.25%) had IL2RA gene variants. To gain further insight, we compared the clinical profiles of these subjects with those of individuals with confirmed MODY and those who are negative for MODY mutations. The average age at diagnosis was: 17.25 years vs. 20.6 years vs. 21.1 years, respectively. The mean BMI values were: 23.8 kg/m² vs. 23.5 kg/m² vs. 22.2 kg/m², respectively. Additionally, the mean HbA1C levels were: 9.1% vs. 7.5% vs. 8.6%, respectively. Interestingly, even with small number of patients, there is a notable trend towards significance in the age of diagnosis and HbA1C levels.

Conclusion: This study underscores the importance of genetic testing to differentiate monogenic autoimmune diabetes from polygenic type 1 diabetes. These results suggest the need for further investigations in this group. However, a larger cohort studies are required to confirm the role of heterozygous variants in monogenic autoimmune diabetes genes in India.

Abstract No: ABS268: Primary hyperparathyroidism beyond the usual: A case series exploring various clinical presentations

Deepti Sharma, Kashish Gupta, Esha Naik, Himanshi Soni, Naincy Purwar, Sanjay Saran, Balram Sharma, S. K. Mathur

SMS Medical College, Jaipur, Rajasthan, India

E-mail: sharmadeepti1992@gmail.com

Introduction: Primary Hyperparathyroidism (PHPT), a metabolic bone disease most commonly presents as asymptomatic hypercalcemia, however, the classical clinical presentation includes “bones, stones, abdominal moans and psychiatric groans”. Unusual presentations include rickets, distal renal tubular acidosis, acute psychosis, recurrent pancreatitis, proptosis, facial asymmetry.

Case Series: A 6 year old male presented with progressively increasing functionally limiting genu varus, with no clinical improvement on vitamin D supplementation. A 47 year old non alcoholic male with no history of gall stones presented with recurrent bouts of pancreatitis with normal lipid profile. 21 year old female presented with acute onset psychosis with delusions and hallucinations with proximal myopathy. 18 year old female presented to emergency with quadriparesis with electrolyte and metabolic imbalance. All the cases mentioned above had hypercalcemia and hypophosphatemia with raised parathyroid hormone levels.

Discussion: Excessive parathyroid hormone secretion in PHPT can lead to increased bone resorption, leading to rickets. The relationship between PHPT and pancreatitis is likely due to elevated calcium levels that precipitate within the pancreas. Psychosis is a rare but severe neuropsychiatric manifestation resulting from hypercalcemia affecting central nervous system. PHPT can impair renal tubular function and can contribute to the development of RTA. Collectively, these cases illustrate the diagnostic challenges associated with atypical presentation of PHPT.

Conclusion: The cases above underscore the importance of considering PHPT as a potential diagnosis in patients with atypical clinical presentations. PHPT is known for its varied and often subtle symptoms, making it a diagnostic challenge. There is a need for a high index of suspicion among healthcare providers for timely recognition and appropriate management to prevent long term complications associated with untreated PHPT.

Abstract No: ABS269: Case of maignant insulinoma

Y. M. Shilpa anand

M S Ramaiah Medical College, Bengaluru, Karnataka, India

E-mail: shilpaym28@gmail.com

Background: Insulinomas functional neuroendocrine tumors of pancreas are the leading cause of tumor related hypoglycemia with estimated incidence of 1-3 per million per year.4-15% of insulinomas are characterised malignant d/t locoregional extension/metastatic spread. Presence of liver metastasis worsens the prognosis. Despite the different treatment modalities available malignant insulinoma still has a poor prognosis/.

Case: 61 years/male. K/C/OHypertension. Presented with recurrent episodes of dizziness, sweating followed by loss of consciousness since 3 years. He was evaluated in an outside hospital &mri brain was done which showed chronic ischemic periventricular changes. He was also found to have episodes of hypoglycemia. Upon further evaluation during the episode of hypoglycemia critical sample serum cortisol was 18 ug/dl /insulin was 24 milu/ml &c-peptide was 2.96 ng/ml. In v/o hyperinsulinemic hypoglycemia whole body gallium 68 dotanoc was done done -2.1*1.6cm hyperrvascular somatostatin receptor avid lesion in proximalbody of pancreas. Distal pancreatic duct dilatation &parenchymal atrophy, somatostatin receptor avid focus in anterior subcapsular segment of IV-A segment s/o liver metastasis. Distal pancreatectomy was done (spleen sparing) with excision of metastatic deposits. Hpe confirmed pancreatic neuroendocrine tumor with uninvolvement of pancreatic tail with liver biopsy s/o tumor deposits. Ihc of pancreatic cells was positive for synaptophysin and weakly positive for chromogranin A. POST OP -CT showed hypodense nodules in segments of III, IV, VIII&VI of liver. He was started on capecitabine +TMZ-follow up pet ct showed regression of nodules in segments III, IV, VIII &VI of liver. It was changed to injectable sandostatin in v/o toxicity. currently he is on sandostatin and is being managed with premix insulin.

Conclusion: We report a case of metastatic insulinoma with severe &refractory hypoglycemia, The combination of temozolamide +capecitabine resulted in good response but stopped because of liver toxicity. Currently changed to injectable sandostatin which is showing a good response.

Abstract No: ABS271: Immune check point inhibitor induced endocrine dysfunction

Buddharaju P. Varma

Dr. Padmanabha Varma’s Hormone Clinic, Hyderabad, Telangana, India

E-mail: bpadmanabhavarma@gmail.com

Background: The incidence of autoimmune complications caused by immune check point inhibitors (CPIs) are increasingly reported. These autoimmune complications, called immune-related adverse events (irAEs), often involve the endocrine organs and can cause hypophysitis, thyroiditis and adrenalitis and autoimmune diabetes (CPI-DM).

Case report: A 56-year-old woman was a non-diabetic and known case of primary hypothyroidism on thyroxine 100 mcg for 10 years. She is a known case of carcinoma of esophagus, status post surgery and chemotherapy. She took immunotherapy 6 months ago with inj. NIVOLUMAB 240 mg (PD-1 inhibitors) fortnightly. Before starting immunotherapy her blood sugars were normal. After completion of 10 cycles of inj. Nivolumab, patient admitted with very high sugars and diabetic ketoacidosis. She was treated with insulin and discharged. Three months later she presented to our clinic with nausea and giddiness. Blood sugars were normal with insulin. Workup showed low ACTH (2.96 pg/ml) and borderline 8am cortisol (8.49 mcg/dl). Stimulated cortisol was 12 mcg/dl, indicating central adrenal insufficiency. Thyroid profile was normal with thyroxine 100 mcg replacement. MRI pituitary was normal without any evidence of stalk thickening. Fasting c peptide levels checked when the fasting blood glucose was 142 mg/dl were found to be very low (< 0.01 ng/ml). GAD antibodies were negative. So she was diagnosed to have a checkpoint inhibitor induced diabetes mellitus (CPI-DM) and central adrenal insufficiency. She was treated with replacement dose of prednisolone and advised not to stop insulin in the future.

Conclusion: Endocrine dysfunction after immunotherapy though rare but increasingly seen these days with the growing use of CPIs. Here we have presented a case who developed insulin dependent diabetes mellitus and secondary adrenal insufficiency 5 months after initiation of immunotherapy. One should be vigilant about development of endocrine dysfunction among patients who receives immunotherapy and actively screen for the same.

Abstract No: ABS276: Pediatric Dyslipidemia – A single centre experience

C. Sindhuja Reddy, Rakesh Kumar Sahay, K. Neelaveni

Osmania Medical College, Hyderabad, Telangana, India

E-mail: sindhu.chada@gmail.com

Background and Aims: NAFLD is common in PCOS women. Insulin resistance causes NAFLD and it is related to various comorbidities. The hyperinsulinemic euglycemic clamp is technically challenging so markers like Homeostasis model assessment for insulin resistance (HOMA-IR) emerged. But due to limitations like absence of standardization of the insulin assay technique, triglyceride glucose (TyG) index, has emerged as a marker of IR. In this study we aim to compare effectiveness of TyG index and HOMA-IR in identifying NAFLD in PCOS women and to calculate the prevalence of NAFLD in PCOS women.

Materials and Methods: It is a single centered, hospital based, cross-sectional study at our department of Osmania general hospital. After ethical committee approval and consent, people satisfying Rotterdam criteria of PCOS were recruited. In these patients TyG index and HOMA IR was calculated and USG abdomen or fibro scan for fatty liver was done.

Results: This study is still ongoing. The prevalence of NAFLD in PCOS patients is 55.13% (n=111). The prevalence of NAFLD (n= 79) increased with increase in TyG index and HOMA IR. An unadjusted regression analysis was performed. When highest quartile was taken as reference category (odds ratio = 1) lowest quartile of HOMA IR and TyG index had Odds ratio of prevalence of NAFLD of 0.137 (p=0.007) and 0.153 (p=0.009) respectively. According to ROC analysis, HOMA IR is superior to TyG index in predicting NAFLD [0.74 (p=0.00) vs 0.68 (p=0.004)].

Conclusion: Both HOMA IR and TyG index can be used for predicting the prevalence of NAFLD.

Abstract No: ABS277: A rare case of hypomagnesemia presenting with refractory seizures due to novel mutation in the Mg-channel TRPM6

EdigaKornapalli Sumana, K. Neelaveni, Rakesh Kumar Sahay

Osmania Medical College, Hyderabad, Telangana, India

E-mail: sumanambbs@gmail.com

Background: Hypomagnesaemia can cause hypocalcaemia by inhibiting parathyroid hormone release and inducing resistance at its receptor sites. Primary hypomagnesaemia with secondary hypocalcaemia (HSH) is a rare metabolic disorder of intestinal magnesium absorption. Affected individuals have a defect in the transient receptor potential melastatin6 (TRPM6) gene on chromosome 9q22. The condition typically presents in the neonatal period with seizures refractory to antiepileptic therapy. To avoid mortality or long-term neurodevelopmental effects, timely diagnosis and magnesium replenishment are crucial.

Case Details: 4months male child brought by parents with history of 1episode of seizure. Initial investigations showed hypocalcemia, hyperphosphatemia and low PTH. Initial diagnosis of hypoparathyroidism was considered. IV calcium supplementation was given. The child continued to have multiple episodes of seizures and hypocalcemia. In view of refractory hypocalcemia, hypomagnesemia as a cause of low calcium and low PTH was considered. Seum Mg levels were 0.4mg/dl.FeMg was low. After correction with IV MgSO4 calcium levels improved. Child was discharged on oral magnesium and calcium supplementation. Due to noncompliance with magnesium supplementation, the child presented with seizures after one month. Child was started on IV MgSo4 and subsequently changed to Tab. MgO 200mg BD. Genetic analysis (WES) S/o TRPM6 homozygous deletion of exon 24 on chr.9 of TRPM6 gene. Child is now 10months old on Tab. MgO 200mg TID, with Serum Magnesium of 1.2mg/dl, calcium of 9.2mg/dl. He experienced no further seizure episodes and met developmental milestones as expected for his age.

Conclusion: A diagnosis of HSH should be considered in all paediatric patients presenting with seizures or tetany as it is a treatable disease. Magnesium replacement is key to managing this condition and the aim should be to normalise serum calcium.

Abstract No: ABS278: Prevalence of non-thyroidal malignancies in DTC – A single centre experience

Karun Mammen Philip

Amrita Institute

E-mail: drkarunmammen@gmail.com

Background: Differentiated Thyroid carcinoma (DTC) patients can present with Non thyroidal malignancies (NTM) during follow-up; which can be incidental or can be associated with Radioiodine therapy or genetic factors. Prevalence of other malignancies is higher in Thyroid malignancy in multiple studies regardless of Radioiodine exposure. This study examined the prevalence of NTM in thyroid carcinoma cohort (including malignancies before Thyroid carcinoma onset and second malignancies after DTC diagnosis).

Methods: This was a Cross-sectional Observational study of a cohort of 944 patients who attended Thyroid cancer clinic between 8 years with minimum 5-year follow-up.

Results: In this Cohort 29 cases had NTM (6 of which had other NTM prior to DTCs, and 23 cases had NTM after DTC diagnosis). Average Age was 43.7years.17 subjects were females. DTCs included 5 cases of micropapillary carcinoma;14 cases of classical PTC;15 cases of follicular variant of PTC;3 cases of tall cell variant PTC and 2 cases of Follicular Thyroid carcinoma. Of the cases 3 cases were intermediate risk; 6 high risk cases ;14 -low risk cases and rest of the cases initial status is not known.50% cases were NED status ;15.4% were indeterminate and 19.2%; persistent structural disease and 7.7% were Persistent biochemical disease. RAI therapy was used in 17 Out of 23 patients with second NTMs. The average sessions of radioiodine were 2.47. The cumulative dose of radioiodine was 112.5mCi in the second NTM group. Among the patients who received RAI the average years before presentation of secondary malignancy was 6.8years. 2 patients had strong family history of other malignancies at presentation.

Conclusion: Prevalence of NTM in DTC cohort was 3.07%. and the prevalence of some solid tumors (Eg-RCC) were higher than in general Indian population.

Abstract No: ABS283: Autoimmune poly glandular syndrome-1 in siblings – A case report

Prathyusha Segu, Srinivas Kandula, Anand C. Sonwane, Pritesh Nagar, Bipin Kumar Sethi

Care Hospital, Hyderabad, Telangana, India

E-mail: prathyusha.30.3@gmail.com

Background: Autoimmune polyglandular syndrome 1 (APS-1) is rare autosomal recessive syndrome with female preponderance. It’s characterised by developing at least 2 of 3 main components, chronic muco-cutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. However clinical manifestations are widely variable. Here we are presenting a case report of APS-1 in two sisters.

Sibling 1: 7-year girl 2nd born child of non-consanguineous marriage had an index presentation at the age of 3 years with jaundice, autoimmune workup was positive for anti LKM antibody and thus was diagnosed to have autoimmune hepatitis, started on azathioprine and prednisolone. Later at the age of 4, she developed an episode of generalised tonic clinic seizure due to hypocalcaemia and was diagnosed to have hypoparathyroidism. Genetic analysis done was positive for AIRE gene transcript. At the age of 6 years, she had an episode of vomiting and altered sensorium due to hyponatremia, also had hyperkalaemia and was diagnosed to have primary adrenal insufficiency, currently being treated with hydrocortisone and fludrocortisone.

Sibling 2: The elder sibling presented with tetany at the age of 12 year due to hypocalcaemia and was diagnosed to have hypoparathyroidism, hence screening for other components was done. However, patient did not have adrenal insufficiency or muco-cutaneous candidiasis. Genetic analysis was done in view of positive family history. Whole genome exon sequencing was positive for AIRE gene transcript, variant c 179A.

Conclusion: In this case report, we are presenting a case report of APS1 who presented with hypoparathyroidism and adrenal insufficiency (in one of the siblings) with no evidence of muco-cutaneous candidiasis till date representing the varied spectrum of clinical manifestations and role of genetic testing for early diagnosis.

Abstract No: ABS285: Acrodysostosis with coexisting Celiac disease: A novel D151E variant in PRKAR1A gene

P. Pradakshna, Ravindra Shukla, Mahendra Kumar Garg, Kuldeep Singh, Nayankumar G. Tada, Eram Nahid, Madhukar Mittal

AIIMS, Jodhpur, Rajasthan, India

E-mail: pradakshnaporche@gmail.com

Background: Acrodysostosis, also known as Maroteaux-Malamut syndrome, is a rare skeletal dysplastic syndrome due to mutations in the parathyroid hormone receptor pathway. We present a case of acrodysostosis in a teenage girl presenting with AHO phenotype and celiac disease wherein genetics revealed a novel D151E variant in the PRKAR1A gene.

Description: A 14-year-old girl born out of a non-consanguineous marriage presented with weight gain and inadequate height gain since four years of age. Evaluation revealed anemia, high titres of celiac serology and was initiated on gluten-free diet since childhood. She was on levothyroxine in view of subclinical hypothyroidism. Anemia improved with no change in growth. On presentation to our institute at 14 years of age, she was 138cm tall (-3.37Z), weighed 52.3Kg (0.18Z) with BMI of 27.5kg/m². She was short, obese had round facies with brachydactyly bearing a resemblance to Albright’s Hereditary Osteodystrophy (AHO) phenotype. Severe acanthosis nigricans was evident and tanner staging was A+ P5 B5.

Investigations: Complete blood count, renal and liver function tests were unremarkable, whereas intact PTH was elevated (>5 times upper limit of normal) with normal calcium, elevated phosphorus and vitamin D deficiency. Biochemistry revealed elevated TSH and normal T3, T4. She was initiated on cholecalciferol & levothyroxine dose titrated. CT scan head showed punctate basal ganglia calcifications bilaterally. With AHO features, associated insulin resistance, TSH resistance, and uncertain PTH resistance, probable iPPSDs were considered. Genetic testing revealed a heterozygous pathogenic variant of c.453T>A (p.Asp151Glu) in the exon 5 of PRKAR1A gene.

Conclusion: Acrodysostosis, an extremely rare skeletal dysplasia, should not be an overlooked differential for the obesity. AHO phenotype, although classically described in pseudohypoparathyroidism (PHP), is not exclusive to PHP. We report a case of acrodysostosis who had a coexistent autoimmune disorder which has not been previously reported to the best of our knowledge.

Abstract No: ABS286: Follicular thyroid cancer with bone metastasis presenting as autonomously functioning thyroid nodule

Akshay Narayan Ambekar

Care Hospital, Hyderabad, Telangana, India

E-mail: aambekar238@gmail.com

Objective: Follicular carcinomas are relatively rare thyroid malignancy and accounts for 10 to 15% of all thyroid cancers. About 7-23% have distant bone metastasis. AFTNs harboring an intranodular thyroid cancer are seen in about 3.1% (0-12.5%). We are presenting an interesting case of follicular thyroid carcinoma presenting as autonomously functioning thyroid nodule with skull metastasis.

Results: 53 yr old female presented with swelling over occipital area of size 4*5cm, which is progressive in size for 3 years. On further evaluation found to have lytic lesions in occipital area of the skull with swelling over right side of neck. Baseline investigation s/o thyrotoxicosis. Patient undergoneTc99m thyroid scintigraphy which reveals hot nodule in right lobe of thyroid gland. Further work up for primary lesion detected thyroid nodule in right lobe of thyroid on USG neck which reveals features suspicious of malignancy TIRADS 4. FNAC was done it showed Bethesda category 4 (follicular neoplasm). PET scan done to rule out metastasis which showed increased uptake in posterior aspect of skull. Diagnosis of follicular thyroid carcinoma with autonomously functioning thyroid nodule (AFTNs) with bone metastases was made. Patient is treated with antithyroid medications cleared for surgery.

Conclusion: Thyroid cancer can possibly masquerade as an AFTN, thus delaying its diagnosis and treatment in absence of visible metastasis. Usually, cold nodules are malignant but hot nodules can also be malignant in rare occasions. Ultrasonography with FNAC findings are confirmatory for diagnosis of thyroid malignancy.

Abstract No: ABS287: Pagets disease a rare disease of bone still exist

Said Jabir, Neelaveni, Rakesh sahay

Osmania Medical College, Hyderabad, Telangana, India

E-mail: Sjabir2@gmail.com

Background: Paget’s disease of bone (PDB) is not commonly reported from India. Prevalence of Paget’s disease has been reported to be high in individuals predominantly of a European descent in contrast to, Asians, and especially people of the Indian subcontinent. Pagets disease is a disease with abnormal bone remodelling with exaggerated osteoclastic bone resorption followed by increased osteoblastic activity, leading to new bone formation.

Case Details: Case 1: A 70 -year-old female was referred to the department of endocrinology and metabolism due to elevated blood alkaline phosphatase (ALP) levels (440 IU/L) with h/o lower back pain and left hip pain. There was no reported family history of bone diseases. The serum level of calcium, phosphorus, intact parathyroid hormone, and 25-hydroxyvitamin D were normal. We performed clinical evaluation with a plain radio graphic skeletal survey, MRI and whole-body bone scan in addition to bone densitometry. Diagnosed as a case of monoosteotic Pagets disease. Case 2: A 74 -year-old male was referred to the department of endocrinology and metabolism with Right thigh pain. The serum level of alkaline phosphatase (ALP) levels (130 IU/L) calcium, phosphorus, intact parathyroid hormone, and 25-hydroxyvitamin D were normal. We performed clinical evaluation with a plain radio graphic skeletal survey, MRI and whole-body bone scan in addition to bone densitometry. Diagnosed as a case of monoosteotic Pagets disease.

Conclusion: A normal or elevated level of ALP level may be seen in patients with monoostotic disease and in some patients with polyostotic disease. Awareness and early recognition in these cases is necessary for optimal management of the patient.

Abstract No: ABS288: Giant prolactinomas: A case series from St. John’s Medical College Hospital, Bengaluru

Shah Smit Tushar

St. John’s Medical College Hospital, Bengaluru, Karnataka, India

E-mail: smittusharshah@gmail.com

Giant prolactinomas are large lactotroph adenomas, defined as those with maximum dimension of >4cm or serum prolactin value >1000 ng/ml. They constitute <5% of all prolactin secreting tumors and are more frequently seen in men. They present with features of hyperprolactinemia like infertility, galactorrhea, menstrual disturbances and hypopituitarism and are responsive to dopamine agonist therapies. In the current study we have shared our experience on management of giant prolactinomas over the last 18 years. We collected clinical data retrospectively from medical records of patients with giant prolactinoma managed at our institute. This study describes symptomatology, tumor characteristics and response to therapy. Our study included 43 patients with 30 males and 13 females. The mean age of presentation was 38.06 +- 12.35 years, ranging between 10 to 66 years. Vision defect was the predominant complaint (27 patients), followed by headache (25 patients). Erectile dysfunction was a presenting feature in 10% of men (3 patients) and amenorrhea/galactorrhea in 38.46% of women (5 patients). Infertility was complaint in 4 patients. Polyuria with polydipsia, altered sensorium, gynaecomastia were present in 1 patient each. The mean maximum tumor dimension was 41.76 mm with mean basal PRL of 13, 400 ng/ml. Tumor associated pituitary dysfunction manifested as hypogonadism in 23 patients, central hypothyroidism in 20 patients, hypocortisolism in 9 patients and diabetes insipidus in 1 patient. Ten patients underwent debulking surgery (23.25% of the patients) for indications such as apoplexy/raised intracranial tension. All patients received cabergoline at a mean dose of 1.70 ± 1.33 mg/week (range, 0.5-7 mg/week). After a mean follow up of 11.78 +- 14.89 months, nadir median PRL of 47.22 ng/ml was seen. The follow-up MRI data was analyzed for 17 patients. Tumor shrinkage of >50% from the baseline was seen in 13 patients (76.47%), <50% in 2 patients (11.76%) and 2 patients (11.76%) had disappearance of radiologically detectable tumor. Although giant prolactinomas have a greater tumor burden than the more common macroprolactinomas, the responsiveness to dopamine agonist therapy is excellent and surgical therapy is reserved for any exceedingly large tumors to relieve compression on vital structures.

Abstract No: ABS290: Diazoxide: A tale of two cities

Santosh Kumar Singh

Private Practice

E-mail: drsksingh61@gmail.com

Introduction: Diazoxide is a medication that is used to treat hypertension and hyperinsulinism. It is a potent activator of ATP sensitive potassium (KATP) channel and is capable of crossing the blood-brain barrier whereby it contributes to reduction of hyperphagia by reducing the secretion of NPY and AgRP by activating the KATP channel in NPY/AgRP neurons in the hypothalamus. These actions of the drug are complemented by activating the KATP channel in the dorsal nucleus of the vagus, pancreatic B cells and adipocytes to reduce hyperinsulinemia and excess body fat and improve insulin and leptin resistance as well as satiety. These effects of Diazoxide are utilized in the management of Prader-Willi Syndrome (PWS) and Congenital Hyperinsulinism (CHI). Diazoxide is a well- tolerated drug with some adverse events viz. hypertrichosis, hyperglycemia and peripheral edema.

Materials and Methods: A 6 year old boy with PWS due to uniparental disomy/imprinting centre mutation on chromosome 15 [weight age (WA)-13.75, height age (HA)-7.0] was initiated on diazoxide at a dose of 3 mg/kg/d in two divided doses. It was well tolerated with perceptible reduction in hyperphagia after 3 weeks of recall. Another 9.5 year old boy with CHI due to ABCC8 mutation [WA-9.5, HA-9.25] was doing well on 5 mg/kg/d (three divided doses) diazoxide along with 0.1 mg/kg/d hydrochlorothiazide. He was diagnosed at 2.5 years age on evaluation of epilepsy.

Discussion: Diazoxide inhibits insulin secretion from pancreas and modulates insulin-sensitive enzymes leading to supressed lipogenesis and enhanced lipolysis thereby benefiting patients with CHI. It reduces hyperphagia which occurs due to hypothalamic dysregulaion involving NPY/AgRP as a consequence of deletion of SNORD116 in the PWS critical region. The dosage of Diazoxide in PWS and CHI is based on body weight and response to treatment. The usual starting dose in PWS is 3-8 mg/kg/d divided in two or three doses and in CHI is 5-15 mg/kg/d divided in three or four doses.

Conclusion: Diazoxide can be utilized for proper growth and development of patients with PWS and CHI.

Abstract No: ABS296: Diverse clinical presentations of McCune-Albright syndrome: A case series

Bangaru Sai Kiran

Osmania Medical College, Hyderabad, Telangana, India

E-mail: saikiranbangaru@gmail.com

Background: McCune-Albright syndrome is a rare, complex disorder with a prevalence of 1 in 100,000, characterized by somatic, gain-of-function mutations in GNAS. This case series highlights the diverse manifestations of McCune-Albright syndrome.

Case Details: C1: 3-year-old boy presented with multiple fragility fractures, heat intolerance, decreased sleep, and diarrhea. Examination revealed café-au-lait macules, wrist widening, anterior bowing of tibia, and rachitic rosary. Polyostotic fibrous dysplasia, hyperthyroidism, and hypophosphatemic rickets. C2: 6-year-old girl presented with inability to walk, bony pains, limping gait, multiple fractures, and vaginal bleeding. Examination showed multiple café-au-lait macules, anterior bowing of both tibia, and kyphosis, Breast B2 Polyostotic fibrous dysplasia, Warm thyroid nodule with subclinical hyperthyroidism, and peripheral precocity. C3: 7-year-old girl with cyclical vaginal bleeding, breast enlargement-waxing and waning type, and hip pain. Examination revealed café-au-lait macules and genu valgum. USG-Rt ovarian cyst. Xray-Shepherd crook deformity. Peripheral precocity with ovarian cyst and Polyostotic fibrous dysplasia. C4: 8-year-old girl with gradually progressive leg bowing, delayed dentition, dental caries, vaginal bleeding & breast enlargement. Examination showed enamel hypoplasia, pectus carinatum, lumbar lordosis, genu varum & café-au-lait macules, Hypophosphatemic rickets and peripheral precocity. C5: 16-year-old boy presented with fingers and toes enlargement, coarsening of facial features, accelerated height gain. Examination revealed gynecomastia, expressive galactorrhea, and café-au-lait macules. MRI: Enlarged pituitary gland. This case presented with ACROMEGALY and Polyostotic fibrous dysplasia. Clinical examination revealed multiple café au lait macules in all cases; hypophosphatemia with low TmP-GFR in C1, C4; subclinical hyperthyroidism in C2, clinical hyperthyroidism in C1. Except in C1, hormonal profile was suggestive of GIPP in all cases. Acromegaly in C5; Bone scan showed polyostotic fibrous dysplasia in all.

Conclusion: The broad phenotypic spectrum can make MAS a challenging disorder. Comprehensive evaluation and management of associated endocrinopathies are essential.

Abstract No: ABS297: Novel PHEX mutation in a patient with sporadic hypophosphatemic rickets – A case report

Kishore Kumar Behera, Jagganatha Sahu

AIIMS, Bhubaneswar, Odisha, India

E-mail: drkishorebehera@gmail.com

Objective: X-linked dominant hypophosphatemia (XLH) is the most prevalent form of inherited rickets/osteomalacia in children. This study aimed to identify PHEX gene mutations and describe the clinical features observed in a case of hypophosphatemic rickets

Methods: Targeted next-generation sequencing of the PHEX gene was perfumed at CMC Vellore Endocrine Lab. Case-1-A 14-year-old girl presented with short stature with bowing of both legs and pain in the lower extremities while walking. Laboratory evaluation confirmed hypophosphatemia rickets.

Results: Targeted next-generation sequencing of the PHEX gene revealed positive for likely pathologic heterozygous novel (NM_000444.6:c.1356_1361delAAAGA (p.Glu453Ter) gene nonsense mutation in exon 12 resulting frameshift and change in amino acid glutamic acid to a premature stop codon at 453 instead of 751. This mutation is expected to cause a loss of protein function through premature function or nonsense-mediated mRNA decay.

Conclusions: The molecular diagnosis of a PHEX genetic mutation is of great importance for confirming the clinical diagnosis of XLH, conducting genetic counseling, and facilitating prenatal intervention, especially in the case of sporadic patients.

Abstract No: ABS299: Massive splenomegaly with myelofibrosis in primary hyperparathyroidism

Rini Yadav, Simran Thakkar, C. M. Batra, Shishir Seth, Pankaj Baweja

Indraprastha Apollo Hospital, New Delhi, India

E-mail: riniy.gmc@gmail.com

Background: Primary Hyperparathyroidism (PHPT) has diverse clinical manifestations. Hematologic manifestations include anemia or pancytopenia. We report a patient with PHPT who presented with anemia, thrombocytopenia and massive splenomegaly due to myelofibrosis.

Methods: Bone marrow biopsy at presentation is included. Other causes of myelofibrosis were ruled out with appropriate investigations.

Results: A 55-year-old male presented with complains of easy fatigability, bony pains and loss of weight for 2 years. He was pale and had massive splenomegaly on examination. Full blood count revealed bicytopenia (hemoglobin-6.1 gm/dL; platelet count-72000 cells/mm³) with reticulocyte proliferation index of 1.99; suggestive of hypoproliferative marrow. Bone marrow biopsy showed hypocellular marrow with predominant fibrosis in marrow spaces. Biochemical evaluation showed renal dysfunction (serum creatinine-2.7 mg/dL), hypercalcemia (12.4 mg/dL) and elevated alkaline phosphatase (1890 U/L). Ultrasound abdomen showed borderline hepatomegaly, massive splenomegaly with dilated splenic vein and few splenic collaterals, medullary nephrocalcinosis. Further investigations confirmed the diagnosis of PHPT (serum parathyroid hormone-3787 pg/mL; ultrasound neck- presence of 19x20 mm hypoechoic lesion inferior to left thyroid lobe and another lesion of 17x9mm inferior to right thyroid lobe; sestamibi scan-avid nodular lesions in relation to both lobes of thyroid likely parathyroid adenoma). Following curative parathyroidectomy, he developed hungry bone syndrome. At 2 months’ follow up, his parathyroid hormone levels and calcium normalized with some improvement in hematologic parameters (hemoglobin-7.6 gm/dL; platelets-120000 cells/mm³). Renal dysfunction has persisted which may have compromised the improvement in hematologic parameters.

Conclusion: Severe hyperparathyroidism may lead to bone marrow fibrosis with consequent anemia, thrombocytopenia or pancytopenia in a patient. This is likely to improve following parathyroidectomy, however complete resolution may take time (from 3 months to 1 year). In presence of renal disease, the recovery might be further delayed as was seen in our patient.

Abstract No: ABS309: Congenital generalised lipodystrophy – When fat seeped from skin to serum

T. R. Lakshmi Priya, C. Jayakrishnan

SGPGI, Lucknow, Uttar Pradesh, India

E-mail: trlakshmipriya@gmail.com

Introduction: The commonly considered diagnoses for young onset diabetes include type 1 diabetes, pancreatogenic diabetes, MODY, mitochondrial diabetes and Wolfram syndrome. Rarely, one may stumble upon a patient with a constellation of features that do not fit into these diagnoses. Here, we report a patient with a rare cause of young onset diabetes mellitus with management implications.

Case Presentation: 21-year-old lady, born out of a consanguineous marriage and known to have primary hypothyroidism, presented with diabetes mellitus that was diagnosed two years earlier. She was on oral antidiabetic agents and had poor glycemic control. On examination, she had a BMI of 20. Her head-to-toe examination revealed acanthosis, low-set ears, triangular facies, muscular hypertrophy and prominent veins. GAD antibody was negative. Lipid profile was abnormal with elevated triglycerides (402 mg/dL). Her liver enzymes were deranged as well (AST-96 U/L, ALT -97 U/L). Ultrasonography of abdomen revealed gross hepatomegaly, dilated portal veins and bulky ovaries. She underwent percutaneous liver biopsy and the histopathological examination revealed features of non-alcoholic steatohepatitis. Owing to the clinical presentation that evoked the suspicion of lipodystrophy, next generation sequencing was done. There was homozygous mutation in the intron 4 of AGPAT2 gene [homozygous c.588+1G>A(5’splice site)] and it was reported to be likely pathogenic for congenital generalised lipodystrophy type 1. She was manged with insulin, fibrates and statins and is under close follow-up.

Discussion: AGPAT2 is one of the four genes implicated in congenital generalised lipodystrophy or Berardinelli-Seip syndrome. The history of consanguinity and morphological features in this case raised the suspicion of lipodystrophy syndrome that was confirmed on genetic study. Though a rare cause of diabetes, identification of the right diagnosis in such cases would help initiate appropriate treatment and prevent complications.

Abstract No: ABS311: Feminizing adrenal tumor – A case series report

Prashant Hubballi, Preeti Dabadghao

SGPGI, Lucknow, Uttar Pradesh, India

E-mail: prashhubli17@gmail.com

Background: Adrenocortical carcinoma (ACC) is rare and highly malignant, with a poor prognosis. Despite aggressive surgical and adjunctive therapy, the 5-year survival rate ranges from 16%-38%. Most ACCs secrete cortisol, rarely secrete androgens and aldosterone and rarely, estrogens. Studies showed high aromatase cytochrome P450 (CYP19A1) and aromatase activity in feminizing ACCs, which may contribute to the ectopic estrogen production in ACC. High CYP19A1 expression may be caused by dedifferentiation of ACCs. The Wnt/b-catenin pathway is known to be important in adrenal cortex development. Activating mutations in CTNNB1 were identified in 16% of ACCs whereas abnormal b-catenin expression was demonstrated in 85% of ACC, Wnt/b-catenin activation is an independent factor associated with shorter disease-free survival.

Methods: Study design- Observational study. A case series of 4 patients of feminising adrenal tumour (FAT) presenting to our institute from 2012-2022. Data recorded- Clinical, biochemical and radiological characteristics of the patients.

Results: All 4 of them had raised estradiol levels (110-1217 pg/ml) and there was post operative decrease in estradiol. The main manifestation in men is gynaecomastia as is in our 3/4 patients. As most of feminizing adrenal tumors are malignant, but one of our patient had benign adrenal mass with estradiol secretion and other three had ACC. Subclinical Cushings can be a part of FAT because of increase in CBG, one patient had ONDST cortisol 87nmol/L and LDDST cortisol of 67nmol/L.

Conclusion: Estrogen secreting ACCs are exceedingly rare in adults and account for 1−2% of ACCs, where as 90% of all feminizing tumors are from adrenal origin. Treatment includes surgery, mitotane and chemotherapy including niclosamide, a wnt inhibitor. Prognosis is very poor, so high index of suspicion is required for diagnosis.

Abstract No: ABS312: Avascular necrosis of talus in type 1 diabetes with pregnancy and lactation related osteoporosis

Azher Rizvi, Madhukar Mittal, Suvinay Saxena, Prasoon Rastogi

All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

E-mail: rizvi.azher@gmail.com

Background: Patients with Type 1 diabetes (T1D) have a distinct fracture pattern. In addition to fractures at the major osteoporotic sites, T1D patients are at risk for fractures at unusual distal sites as well. Pregnancy and lactation related associated osteoporosis (PLO) is a rare condition which can lead to fractures in the third trimester or in the early postpartum period. Avascular necrosis (AVN) of talus is quite rare and not reported previously in T1D.

Case Presentation: Here we present a unique case of a 24-year primiparous female, known case of T1D, who presented to us 3 months after delivery with swelling and pain in her right ankle. She had an innocuous history of trivial trauma to her right ankle in the third trimester of her pregnancy. She also sustained fragility fractures in her left foot (2^nd to 4^th metatarsal heads) 1 month postpartum. Subsequent workup revealed low bone mass on DXA scan. Magnetic resonance imaging revealed avascular necrosis of right talus. Follow up DXA a year later showed significant increase in BMD at hip, although she continued to have low bone mass. A diagnosis of right talar AVN with PLO in the background of low bone mass secondary to T1D was made.

Conclusion: Low bone mineral density is known to be associated with T1D. Pregnancy and lactation are additional vulnerable periods for the maternal skeleton. This case emphasizes the precarious bone health seen in T1D patients especially so during pregnancy and lactation. There may be a case for greater surveillance of deteriorating bone health in patients of T1D during pregnancy and lactation.

Abstract No: ABS315: Chiari frommel syndrome

Saksham Pandey, Supreeth, S. K. Singh, N. K. Agrawal, Ritesh Kumar, Avina, Subhash, Taru, Reshma, Yogesh

Department of Endocrinology and Metabolism, IMS, BHU, Varanasi, Uttar Pradesh, India

E-mail: sakshampandey94@gmail.com

An endocrinal disorder, characterized by the galactorrhea, anovulation and amenorrhea due to uterine atrophy seen in post natal period. It is one of the rare cause of secondary amenorrhoea suspecting underlying prolactinoma. It has a prevalence of 0.6-0.8%.

Case: A 24 years female presented with secondary infertility. She complained of postpartum amenorrhea and spontaneous galactorrhea for 2 years duration since parturition. She is on thyroxine supplementation since pregnancy. There was no systemic abnormality seen. On examination normal visual field and fundoscopic examination was there and Bilateral breast appear normal. Prolactin was done in dilution (1:100) two times which had values-93ng/mL and 104ng/mL. All other hormones were in normal range. MRI brain is suggestive of Empty sella syndrome. For these complains she was started on bromocriptine 2.5mg. Milk secretion was slowed down after bromocriptine (2.5mg) medication for one month. Progesterone withdrawal bleed was not seen. Menstrual bleed was not seen after cyclic oral contraceptive pills. No other significant past medical history or drug history.

Conclusion: Chiari Frommel syndrome is an endocrine disorder affecting the women’s of 17-35 ages who have recently delivered a baby. It is a rare disorder which occurs due to absence of normal hormonal cycles and is mainly due to increased production of prolactin. But still its physiopathology remains unclear. Some cases of Chiari-Frommel Syndrome resolve completely without treatment (spontaneously), hormone levels and reproductive functions return to normal, whereas others require a complete treatment. The prognosis after treatment is excellent.

Abstract No: ABS316: Hyperparathyroidism in Seckel syndrome: A case report

Md Ejaz Alam, Shoiab Mohd Patto, Mohammad Hayat Ahmad Bhat

Government Medical College, Srinagar, Jammu and Kashmir, India

E-mail: ejazpmch@gmail.com

This case report discusses a 32-year-old female with Seckel syndrome, normotensive, non-diabetic, eumenorrheic, born of fourth-degree consanguinity, presented with a history of small head at birth, smaller body size than normal, and a lack of height/weight gain throughout life. Menarche occurred at 15 years, with regular periods since. Recently diagnosed with cholelithiasis following right hypochondrium pain, referred to endocrinology for PAC clearance. On examination: Weight 26.5kg (<3rd percentile), Height 135.5cm (SDS -4.6), Head Circumference 44cm (-8 SDS), Upper Segment 70cm, Lower Segment 66cm, Arm Span 136cm, with physical features including a large beaked nose, receding forehead, retrognathia (bird head appearance), malocclusion of teeth, high-arched palate, and nail hypoplasia. Further evaluation revealed PTH-dependent hypercalcemia, with a neck ultrasound indicating a right inferior parathyroid adenoma. The 99Tc MIBI scan was negative, but the 4DCT neck suggested an atypical parathyroid adenoma (lacking arterial phase enhancement and delayed phase washout). Collaborative decision-making with an ENT surgeon led to the decision for a scheduled right parathyroidectomy. This case emphasises the complexity of hyperparathyroidism in the context of rare syndromes, shedding light on diagnostic challenges and optimising patient care.

Keywords: Hyperparathyroidism, PTH-dependent hypercalcemia, seckel syndrome

Abstract No: ABS320: An atypical silent hypertensive crisis in a child: A case report

Sunkari Venkata Sai Yashwant, Safa Mahek

Niloufer Hospital, Hyderabad, Telangana, India

E-mail: svsyashwant@gmail.com

A 9 year old boy with Unilateral Pheochromocytoma who presented with abdominal pain, vomitings and hypertension. After careful preparation and preoperative optimisation, surgical excision was done.

Background: Pheochromocytoma and Paragangliomas are neuroendocrine tumours arising from the chromaffin cells. The incidence of Paediatric Pheochromocytoma is 1 in 50,000. Most frequently associated syndromes with pheochromocytoma are VHL (Von Hippel Lindau), MEN (Multiple Endocrine Neoplasia) 2A, 2B and neurofibromatosis (NF) Type 1.

Case Report: A 9 year old male child, second in birth order born out of non consanguineous marriage presented with chief complaints of Pain abdomen since 1 week and 3 episodes of vomitings prior to admission. History of urticaria like raised lesions which developed 6 months ago. The child presented with sustained Hypertension with recordings between 180/100 to 130/80 mm of Hg.

Investigations: Urinary VMA (Vanillyl mandelic acid) was positive. CECT Abdomen - revealed 2 well circumscribed heterogeneously enhanced soft tissue density, oval mass lesions measuring 47*40 mm and 26* 23 mm with areas of necrosis seen within Right supra renal Region. Parathormone – Normal, Plasma metanephrines - 232.7 pg/ml, USG Neck – Normal, Carotid Artery Doppler – Normal, 2D Echo - Normal

Fundus - Initially Grade 4 Papilledema, reduced to Grade 2 Papilledema, PET CT - Metabolically active Soft Tissue Density Lesion in the Right Suprarenal Region. No other lesions noted. Biopsy and genetic analysis done.

Treatment Given: Anti hypertensives like Prazosin and Phenoxybenzamine, Nifidipine were used. After careful preparation and preoperative optimisation, surgical excision was done

Post surgery the child is normotensive and doing well.

Message: A rare presentation of cutaneous lesions and hypertension leading to an abdominal mass.

REFERENCE

1. Nelson. Sperling Pediatric Endocrinology. 5^th-21^st ed.

Abstract No: ABS322: Disfiguring brown tumors in primary hyperparathyroidism with temporal relationship to pregnancy and lactation

K. Anupriya, Madhukar Mittal, Vidhu Sharma, Charmi Gandhi, Kanav Khanna, M. K. Garg, Ravindra Shukla

All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

E-mail: anu26791@gmail.com

Androgen secreting tumors of the ovary are a rare cause of androgen excess in females. They usually belong to the category of sex-cord stromal tumors and the most implicated tumors are Sertoli–Leydig cell tumors, Leydig cell tumors, steroid cell tumors, fibrothecomas and granulosa cell tumors. Ovarian fibroma is a variant of sex cord stromal tumor, composed of fibroblastic cells producing collagen. These are usually hormonally inactive. Here we report a patient with ovarian cellular fibroma who presented with symptoms of hyperandrogenism.

Case: A 26-year-old, nulliparous, female patient presented with 6 months history of amenorrhea, facial hirsutism, acne, scalp hair loss and weight gain. Abdominal palpation revealed a 24 weeks sized mass in the midline. Genital examination was normal. The results of biochemical evaluation are in Table 1. Ultrasonography and MRI of the pelvis showed a large rounded heterogeneous lesion measuring 8 x 11 x 13 cm in the pelvis. The left ovary was not separately imaged suggesting a left ovarian origin. The patient underwent left salpingo oophorectomy. Frozen section examination was reported as sex cord stromal tumor. Histopathological examination showed a neoplasm composed of fascicles and bundles of spindle cells. Immunohistochemistry was suggestive of cellular fibroma. 2 months after surgery, the serum testosterone levels reduced to 4.98 ng/dl and there was improvement in hirsutism.

Conclusion: Ovarian cellular fibromas are rarely linked to endocrine activity. To our knowledge there has only been one other instance of ovarian cellular fibroma presenting as hyperandrogenism and might be a good alternative to diagnose IAS. Selective arterial this was in a post-menopausal lady. With this case, we want to emphasize that the hormonal activity of these tumors needs further exploration exploration.

Abstract No: ABS323: Heretidary form of rickets

Sunkari Venkata Sai Yashwant, Safa Mahek

Niloufer Hospital, Hyderabad, Telangana, India

E-mail: svsyashwant@gmail.com

Introduction: A 2 years 6 month old female child resident of Hyderabad was brought by her mother with chief complaints of Not gaining weight and height since 1 year, Bony deformities since 1 year.

Case Report: A 2 years 6 month old female child resident of Hyderabad was brought by her mother with chief complaints of Not gaining weight and height since 1 year, Bony deformities since 1 year. The child was apparently asymptomatic till 1 and a half years of age when the mother observed that the child is not gaining weight nor growing tall. History of swelling of wrists and bowing of legs present. History of similar complaints in his brother, mother and maternal aunt. On examination: Frontal bossing present, Bilateral parietal prominences present, Rachitic rosary present, Wrist widening present, Pot belly present, Genu Varum present, Double malleoli present. Lab investigations revealed the diagnosis. Message: A detailed work up on rickets

Abstract No: ABS325: A rare pituitary tumor

Nikhil Shankar

M S Ramaiah Medical College Hospital, Bengaluru, Karnataka, India

E-mail: drnikhilshankar@gmail.com

Sella – suprasellar masses are a common presentation in the Endocrinology outpatient department. There are a wide range of causes for Sellar masses which could range from infiltrative, inflammatory to neoplastic causes. Sellar masses have to be investigated and evaluated with a detailed history, a thorough hormonal evaluation, imaging of the hypothalamic pituitary region and in some cases which are not straight forward, histopathological assessment by Biopsy. There are wide range of differentials which must be assessed before coming to a final diagnosis. Some of these can be pituitary macroadenoma, optic pathway glioma, pituitary infiltration, and pituitary metastasis. The case described in this paper is of an elderly lady who presented with headache and vomiting. MRI Brain done revealed an enlarged Sella with a 16 X 17 X 19 mm nodule with solid and cystic components suggestive of a pituitary macroadenoma. A Hormonal evaluation done revealed hypogonadotropic hypogonadism and hyperprolactinemia. Endoscopic Trans- nasal and Trans- sphenoidal resection of the tumor was done and a biopsy was taken, which revealed Pituicytoma. Pituicytoma is a rare entity with only 78 cases reported in the literature so far. We report a case of a rare disease presenting as headache and vomiting with pituitary dysfunction.

Abstract No: ABS326: The emerging role of Gallium-68 Dotanoc PET/CT guided radiofrequency ablation in the treatment of tumor-induced osteomalacia

Jyoti Sharma, Puneet Shivnani

Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India

E-mail: drjyotisharmapediatrics@gmail.com

Background: Tumor-induced osteomalacia (TIO) is a rare acquired form of hypophosphatemia that can be cured when the tumor is completely removed. However, these tumors can be small and deeply located, posing difficulties for surgery. CT-guided or Ultrasound (USG) guided Radiofrequency ablation (RFA) has been tried in the past as an effective treatment option. We describe a case here of TIO whose culprit lesion was inconspicuous on plain CT but visible on MRI and Ga-68 Dotanoc PET-CT.

Methods: A 35-year-old male presented with a 6 years history of widespread body pains and severe proximal muscle weakness confining him to bed for the past 4 months. Investigations revealed hypophosphatemia (1.8mg/dl) and elevated FGF 23 (561 RU/ml) levels indicative of TIO. The lesion was inconspicuous on plain CT. MRI showed 3.5 x 1.2 mm lesion involving the posterior column of left acetabulum. Ga-68 Dotanoc PET-CT revealed tracer uptake at the site confirming culprit tumor. Surgery was ruled out due to high probability of surgical failure and significant morbidity. CT guided RFA was tried using corresponding DOTANOC PET CT-guided images. Patient’s biochemical and clinical condition remained unchanged during follow up. Second session of ablation guided by DOTANOC PET CT was contemplated. Under real-time Ga-68 DOTATOC PET CT guidance, an insulated cannula was inserted into the target area with needle tip positioned precisely at the level of tracer uptake. 4 cycles of ablation were performed with overlapping zones.

Results: Patient achieved complete clinical and biochemical remission post RFA alongwith absence of tracer uptake in follow-up imaging.

Conclusion: DOTANOC PET/CT-guided RFA can serve as a safe and effective treatment modality for patients with TIO not detectable on conventional radiographic imaging when surgical resection is not a viable option.

Abstract No: ABS327: Unmasking the uncommon: Acromegaly in a 41 year old female – A case report

Puneet shivnani, Jyoti Sharma

Mahatma Gandhi Medical College, Jaipur, Rajasthan, India

E-mail: puneetshivnani.ps@gmail.com

Background: Acromegaly is a rare disease. It is usually due to hypersecretion of growth hormone from a benign pituitary adenoma. In less than 1% of cases acromegaly may develop because of ectopic secretion of growth hormone releasing hormone (GHRH) or more rarely GH, from a nonpituitary origin, mostly from a neuroendocrine tumor. Distinction between pituitary and ectopic acromegaly is essential as pituitary hyperplasia secondary to GHRH production in ectopic acromegaly may be misdiagnosed as pituitary tumor leading to unnecessary pituitary surgery. We describe here a case of ectopic acromegaly due to GHRH secreting bronchial carcinoid.

Methods: A 41 year old female presented with bilateral loss of vision, headache, coarsening of facial features since 4 years, secondary amenorrhea since 10 years and exertional dyspnoea since 2 months. Examination revealed bitemporal hemianopia. Investigations revealed pituitary hyperplasia on MRI sella and large mass on chest xray and CECT chest. Hormonal profile revealed increased IGF-1, PGGH, serum prolactin, Hba1c and decreased FT4, serum cortisol, LH FSH Estradiol suggesting acromegaly, secondary diabetes mellitus, panhypopituitarism and a opacified left hemithorax. FDG whole body PET CT showed mitotic pathology of left lung and pituitary gland. During ward stay, she developed pituitary apoplexy with right total ophthalmoplegia which was medically managed. Left lung mass biopsy was suggestive of well differentiated NET. Multidisciplinary team meeting decided for Left pneumonectomy. NGS for MEN-1 negative. Preop and postop GHRH level samples sent to France.

Results: Patient achieved complete clinical and biochemical remission post left pneumonectomy. Post op GH, Prolactin, IGF-1 got normal. MRI sella improved.

Conclusion: Acromegaly due to ectopic GHRH release is a very rare disease. No case of ectopic acromegaly reported from India yet. Signs, symptoms and common hormonal evaluation do not differentiate clearly between eutopic and ectopic acromegaly.

Abstract No: ABS332: Ovarian cellular fibroma presenting as hyperandrogenism – A case report

G. Gayathri, V. P. Vipin, Jem Kalathil, Shamema Anvar Sadath, Minnu Prasannan, R. V. Jayakumar, Nibu Dominic, Sarath Chandran

Aster Medcity, Kochi, Kerala, India

E-mail: gayathrigirijathmajan@gmail.com

Background: Androgen secreting tumors of the ovary are a rare cause of androgen excess in females. They usually belong to the category of sex-cord stromal tumors and the most implicated tumors are Sertoli–Leydig cell tumors, Leydig cell tumors, steroid cell tumors, fibrothecomas and granulosa cell tumors. Ovarian fibroma is a variant of sex cord stromal tumor, composed of fibroblastic cells producing collagen. These are usually hormonally inactive. Here we report a patient with ovarian cellular fibroma who presented with symptoms of hyperandrogenism.

Case: A 26-year-old, nulliparous, female patient presented with 6 months history of amenorrhea, facial hirsutism, acne, scalp hair loss and weight gain. Abdominal palpation revealed a 24 weeks sized mass in the midline. Genital examination was normal. The results of biochemical evaluation are in Table 1. Ultrasonography and MRI of the pelvis showed a large rounded heterogeneous lesion measuring 8 x 11 x 13 cm in the pelvis. The left ovary was not separately imaged suggesting a left ovarian origin. The patient underwent left salpingo oophorectomy. Frozen section examination was reported as sex cord stromal tumor. Histopathological examination showed a neoplasm composed of fascicles and bundles of spindle cells. Immunohistochemistry was suggestive of cellular fibroma. 2 months after surgery, the serum testosterone levels reduced to 4.98 ng/dl and there was improvement in hirsutism.

Conclusion: Ovarian cellular fibromas are rarely linked to endocrine activity. To our knowledge there has only been one other instance of ovarian cellular fibroma presenting as hyperandrogenism and this was in a post-menopausal lady. With this case, we want to emphasize that the hormonal activity of these tumors needs further exploration.

Abstract No: ABS334: Enigma of pituitary: Two rare pituitary tumor

Sarath Chandran, V. P. Vipin, R. V. Jayakumar, Nibu Dominic

Aster Medcity, Kochi, Kerala, India

E-mail: drsarath5232@gmail.com

Background: Pituitary tumors are a heterogenous group of tumors with varying etiology, clinical presentation and endocrine abnormalities. A careful evaluation is of great importance for accurate diagnosis. Here are 2 rare cases of pituitary lesions.

Case Details: Case 1: 19-year-old male presented with headache, tiredness, polyuria and polydipsia of 2 months duration. He had papilledema on examination. There were no clinical features of any pituitary hormone excess. Biochemical evaluation showed mildly elevated prolactin, secondary hypothyroidism, secondary hypocortisolism, elevated testosterone with suppressed LH and FSH. On further evaluation he was found to have high beta hCG and MRI brain showed space occupying lesion in supra sellar region and pineal region with obstructive hydrocephalus. CSF beta hCG was also found to be high. Hence a diagnosis of CNS germ cell neoplasm was made and patient was treated with chemotherapy followed by radiation along with pituitary hormone replacement. He had complete resolution of the lesion following the treatment. Case 2: 72 year old female known case of diabetes mellitus and carcinoma breast treated with surgery and adjuvant chemotherapy 20 year back, now presented with features of atypical parkinsonism and tiredness. Routine evaluation showed mild hyponatremia, further evaluation of which revealed secondary hypothyroidism, hypocortisolism and panhypopituitarism. MRI pituitary revealed infiltrative pituitary mass with heterogenous contrast enhancement. PET scan was negative. She was advised tumour decompression and biopsy which she underwent only 1 year later. Histopathology revealed metastasis from carcinoma breast. A repeat PET was still negative for any active lesion outside pituitary and thus a diagnosis of isolated pituitary metastasis from carcinoma breast was made which presented 20 years after initial treatment of carcinoma breast. She is currently being treated with radiotherapy for the residual lesion.

Conclusion: Systematic and judicious evaluation is pivotal in diagnosis and management pituitary lesions.

Abstract No: ABS335: Case series of syndromic childhood obesity with genetic studies

Sudeep Gandra

Andhra Medical College, Visakhapatnam, Andhra Pradesh, India

E-mail: gandrasudeepreddy@gmail.com

Background: Obesity is a complex condition that interweaves biological, developmental, environmental, behavioral, and genetic factors; it is a significant public health problem especially in children. The most common cause of obesity throughout childhood and adolescence is an inequity in energy balance; that is, excess caloric intake without appropriate caloric expenditure, but genetic causes of obesity are an important cause as well. With recent approval of various drugs in syndromic obesity and also with upcoming drugs, it is crucial that we diagnose genetic causes of obesity and treat them appropriately.

Results: After appropriate clinical examination and baseline investigations for patients presenting with obesity, appropriate genetic studies were sent after counselling.

Conclusion: Above are the 9 patients presenting to our institute with childhood onset obesity in the last 6 months. Prader willi syndrome was the most common cause of obesity followed by bardet-biedl syndrome. With improved treatment options, it is important that genetic studies should be done if appropriate for targeted therapy in childhood obesity.

Abstract No: ABS336: A rare cause of monogenic obesity

Ravichand Kalidindi

Andhra Medical College, Visakhapatnam, Andhra Pradesh, India

E-mail: ravichand.varma@gmail.com

Background: Monogenic obesity can be caused by a mutation in one of the single genes involved in hunger and satiety. The most common mutations affect melanocortin 4 (MC4) followed by the leptin gene and its receptor. Leptin receptor (LEPR) gene mutation is an extremely rare endocrine disease characterized by early-onset obesity, hyperphagia in addition to pituitary hormone deficiency, and metabolic abnormalities. Only a handful of cases reported in India with LEPR gene mutation.

Results: We report the case of a 1 year 10months old female born of a consanguineous marriage. she presented to us with rapid weight gain from 2 months of age along with hyperphagia. Birth weight was 2.75kg (–0.70 standard deviations score [SDS]). She was born of normal vaginal delivery. There was no history of gestational diabetes, hypertension, hypothyroidism, or more than recommended weight gain in the mother during pregnancy. No family history of obesity. From 2 months of age, the child exhibited intense hyperphagia and impaired satiety, demanding feeding every half an hour. Now reaching 21.4 kg (+4.6 SDS).

Physical examination revealed a generalized distribution of fat along with deep skin folds, predominant in the neck, abdomen, back, and upper and lower limbs. Biochemistry revealed a deranged lipid profile. On genetic analysis, a novel mutation was detected, which was a homozygous nonsense variant in exon 9 of the LEPR gene (chr1:g.65601601C>T; Depth: 131x).

Conclusion: LepR deficiency is quite rare, It is inherited in an autosomal recessive manner. Most of the cases are reported in families with a high degree of consanguinity. Individuals affected by LepR deficiency exhibit normal birth weight with rapid weight gain in infancy leading to early-onset obesity, hyperphagia, and impaired satiety. SETMELANOTIDE has recently been approved. Identification of LepR mutation is important because setmelanotide can offer substantial benefits in these patients.

Abstract No: ABS339: A rare case report of thyrotoxicosis with overlapping disorder? NF1-Noonan syndrome

Nishank Kashyap, Nishank Kashyap

MGM Institute of Health Sciences, Navi Mumbai, Maharashtra, India

E-mail: nishank.kashyap23@gmail.com

Background: 14 /Female presented with history of protrusion of eyeballs since last 2 months. She underwent Thyroid Function Test and Ultrasonography Neck in view of swelling on the anterior aspect of the neck. Thyroid profile concluded to be a case of primary Hyperthyroidism (elevated T3 and T4 with TSH<0.005 microIU/L and sonographic finding suggested homogeneous enlargement of thyroid with increased vascularity Mother also gave history of non attainment of menarche and her concern was also about short stature. On examination it was found that patient had exopthalamos, joffroy’s sign and stellwag sign, palmar freckling, webbing of neck, increased carrying angle and short stature. Patient also had tachycardia and hypertension. ultrasonography abdomen-pelvis suggested hypoplastic uterus and ovaries. XRay elbow was done to look for ossification and epiphyseal closure. Karyotyping for suspected Turner Syndrome came 46XX. Neurofibromatosis type I and Noonan syndrome were also under consideration. Hormonal workup (Sr. LH, Sr FSH, Sr Cortisol, Sr Estradiol and Sr IGF-1) of which Serum IGF-1came significantly low. Patient was then started on Tab Carbimazole and Tab Propranolol. Gynaecologist advised to induce menstruation through breakthrough bleeding post progesterone pills consumption. Furthur plan of action is to give Inj Somatotropin in view of short stature. Molecular genetic testing including Hybridisation is also being taken under consideration.

Results, Discussion and Conclusion: This overlapping Syndromes are not very common to be seen in day-to-day practice and hence should be studied with interest so that early intervention, diagnosis and treatment can be given. Appropriate intervention like Growth Hormone Suppression Test, genomic sequencing and testing and treating Thyrotoxicosis should give a better outcome.

Abstract No: ABS338: Short stature and pain abdomen

G. Naveen Kumar

Magna Centre for Diabetes

E-mail: drnaveen.magnacode@gmail.com

Background: In children with short stature, where there are no apparent indicators of inflammatory bowel disease (IBD), diagnosis is often delayed, and final height is compromised.

Case Report: A 11 year 7-month-old male child was brought for not growing in height. His birth and developmental history were uneventful. In the last four years, his peers outgrew him, including his 8-year-old sister. On examination he was -3SDS short with 125cm height (MPH-172.5cm) and 25.6 kgs (<3^rd centile) weight. His baseline investigations were normal. Bone age was 5.6years (TWIII). Coeliac testing with total IgA and IgATTG was negative, and his IGF-1 was low. His Peak GH was 7.36 (Clonidine). Pituitary height was normal for his age (5.1mm). He was initiated on injrHGH @0.18mg/kg/week and had a catchup growth of 7cm in 6 months. Thereafter his height remained static even with higher doses of rHGH (0.3mg/kg/week). On reevaluation child gives a vague history of nonspecific chronic intermittent pain abdomen relieving on its own in 1-2 hours and not associated with vomiting, constipation, or diarrhea. Colonoscopy revealed a transmural inflammatory ulcerative lesion in the distal colon and HPE was suggestive of Crohn’s disease. He underwent right hemicolectomy and received steroids transiently and was kept on InjAdalimumab (Anti-TNF) monthly.

Discussion: The diagnosis of IBD and Growth Hormone Deficiency (GHD) is rare and represents a minority of cases where children with GHD exhibit an inadequate response to Growth Hormone (GH) therapy. Many IBD symptoms can be seen in other gastrointestinal conditions or in healthy children, but some “red flag” signs may indicate IBD. These red flag signs include: 1) Persistent diarrhea 2) Abdominal pain 3) Rectal bleeding 4) Unexplained weight loss or poor growth, 5) Fatigue or malaise, 6) Extraintestinal manifestations like joint pain, skin rashes, mouth ulcers, and eye inflammation, 7) Family history of IBD.

Conclusion: Children with IBD can present themselvesas short stature without any notable warning signs. It needs to be considered in GHD children who falters on growth even with GH therapy.

Abstract No: ABS337: From XY to female: Clinicoetiological exploration of 46XY DSD individuals rearing as females

Velugu Pradeep Kumar

Andhra Medical College, Visakhapatnam, Andhra Pradesh, India

E-mail: pradipidarp@gmail.com

Introduction: 46XY DSD (Disorder of sex development) is a group of rare and challenging conditions that can be caused by abnormalities of Karyotype, gonadal formation, androgen synthesis and androgen action. They can present with Delayed puberty with female external genitalia or Ambiguous genitalia. Some of them can be reared as females.

Objective: To explore the clinical and etiological profile of patients with 46XY DSD, being reared as females, presenting to a tertiary care center in South India. Methods: Retrospective analysis. 9 patients with 46XY DSD females were included. We analysed clinical data, hormonal profile, Karyotype, other relevant information including Chromosomal or Genetic tests and gonadal biopsy.

Results: Among 9 cases, 4 cases presented with Ambiguous genitalia with EMS score 1-4, age at diagnosis ranged from 4 months to 4 yrs, among these 2 cases were diagnosed as 5alpha reductase2 deficiency, 1 case as 17beta HSD2 deficiency, 1 case as Yp deletion. Other 5 cases presented with female external genitalia with Primary Amenorrhea, age at diagnosis ranged from 16 yrs to 30 yrs, among these 2 were diagnosed as complete gonadal dysgenesis, 1 as mixed gonadal dysgenesis, 2 were diagnosed as Complete Androgen Insensitivity Syndrome (CAIS). All of them underwent bilateral gonadectomy. None of them had gender dysphoria.

Conclusion: 55% of individuals presented after 16 yrs age with primary amenorrhea. 45% of individuals presented before 4yrs of age with ambiguous genitalia. Majority of the cases were due to Gonadal dysgenesis, CAIS and 5Alpha reductase2 deficiency which contribute to almost 80% of cases.

Abstract No: ABS225: A syndrome of pentad symptoms: When symptoms are more concerned than disease

Syed Azmal Mahmood

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

E-mail: azmaldmc@gmail.com

Background: Bardet Biedl syndrome (BBS), is a clinically and genetically heterogenous disorder that manifests as a result of primary cilia impairment, characterized by retinitis pigmentosa, obesity, mentalretardation, hypogonadismandpolydactyly. The five findings together are called “thepentad”and are found in most of the cases.

Methods: We present the clinical findings, laboratory tests, imaging findings and management.

Results: A 14-year-old boy, 2nd issue of consanguineous marriage of his parents, having positive family history, presented with progressive dimness of vision, learning disability, increased hunger and obesity since childhood. Initially, there were impaired night vision and peripheral vision problem and later loss of color vision. He had no hearing problem, anosmia, cold intolerance or steroid taking history. His intranatal and postnatal history were uneventful except low IQ and slightly delayed developmental milestone. His BMI was 32.7 kg/m2, waist hip ratio: 1.08, height was in 50th centile on growth chart. He had polydactyly, high arched plate, acanthosis nigricans, buried penis, testicular volume was prepubertal. Laboratory findings revealed high Triglyceride, impaired glucose tolerance, Hypogonadotropic hypogonadism and grade-III fatty liver. He had bony spicule like pigmentation in periphery of both eyes suggestive of retinitis pigmentosa. Based on these data Bardet Biedl syndrome was diagnosed. Dietary supplement with high dose vitamin E, metformin and liraglutide were prescribed. Currently the patient is under regular follow up.

Conclusion: BBS is a rare clinical syndrome that may go unnoticed by many clinicians. Renal failure is the leading cause of morbidity and mortality in patients with BBS. Therefore, early detection of BBS is vital to halt the progression of renal impairment.

Abstract No: ABS156: Addition of resveratrol to orlistat improves outcomes in overweight/obese subjects: A real world evidence study

Hardik Gandhi, Tint Swe Latt, Khin Maung Aye, Khin Maung Win, Kyaw Soe Tun

Zydus Lifesciences Ltd

E-mail: hardikp.gandhi@zyduslife.com

Background: Orlistat is approved for weight loss and weight maintenance in overweight /obese subjects. However, some patients do not achieve desired weight loss with orlistat which can be attributed GI adverse events like steatorrhea but more importantly to lack of physical activity which is recommended in addition to drug therapy. Resveratrol is an anti-oxidant with multiple benefits on cardiovascular and metabolic health supported small & large clinical trials. Studies suggest that low doses of resveratrol (150-500 mg/d) might contribute to weight loss through by SIRT-1 mediated increase in energy expenditure.

Methods: 298 subjects aged 18 years or older (67% female) with obesity/overweight (BMI more than or equal to 25kg/m²) were randomized in two groups: The control arm (O) received orlistat 120 mg hard capsules thrice daily, and the test arm (O-R) received orlistat 120 mg + resveratrol 100 mg hard capsules thrice daily for 12 weeks. Patients were followed up for 12 weeks.

Results: 247 subjects with a mean body weight ~80 kg completed the study with more than 80% patients achieving greater than 5% weight loss in 12 weeks. As compared to baseline, the O-R group exhibited a higher weight loss of -3.31 kg (p<0.001) compared to -2.92 kg (p=0.001) in the O group as compared to baseline. Weight loss was accompanied by reduction in total body fat assessed by anthropometry as well as a concomitant reduction of diastolic blood pressure. Among sub-group of patients with diabetes, O-R demonstrated significant loss as compared to O – particularly those with a BMI ≥30 (-2.79 kg vs -1.04 kg, p=0.045) and those with steatosis (-2.17 kg vs -0.44 kg, p=0.048). Overall, the incidence of adverse events was low in this study. The number of cases for steatorrhea were similar in both the group whereas diarrhoea was only observed in O group (7 patients). Large sample size is a strength of this study while short duration of treatment is a limitation of this study.

Conclusion: Addition of resveratrol to orlistat provides synergistic benefits to weight loss with additional benefit in terms of reducing total body fat and diastolic BP. These benefits were apparent in subgroup of patients with diabetes suffering from obesity or steatosis.

Abstract No: ABS153: Adherence and persistence to basal insulin therapy is associated with decreased health care utilization in adults with Type 2 Diabetes

D. Shabeer

Novo Nordisk India Pvt Ltd

E-mail: seqd@novonordisk.com

Objectives: Lack of adherence and persistence to prescribed therapy impact achievement of glycemic goals. This study aimed to assess the association between adherence and persistence to basal insulin therapy with healthcare resource utilization (HCRU) among adults with type 2 diabetes (T2D).

Methods: This was an observational, retrospective cohort study of commercially insured US patients using IQVIA PharMetrics® Plus claims data. We identified adults with T2D initiating basal insulin therapy between January 1, 2016 and December 31, 2018. Adherence/non-adherence and persistence/non-persistence were assessed per established definitions. Demographic and clinical characteristics were assessed over the one-year baseline period (prior to initiation). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding by adherence and persistence status. Post-IPTW, all-cause medical HCRU and costs in the one-year follow-up period were compared across cohorts.

Results: The final sample consisted of 64,953 patients: 42% and 58% met criteria for adherence and non-adherence, respectively; 57% and 43% met criteria for persistence and non-persistence, respectively. The proportion of patients with ≥1 hospitalization was lower for the adherence and persistence cohorts compared to their reference groups (adherence: 12.2% vs. 13.8%; persistence: 12.5% vs. 14.2%, both P<0.0001); for these patients, mean hospitalization days were lower among adherence and persistence cohorts (adherence: 10.1 vs. 13.2; persistence: 10.4 vs. 13.8, both P<0.0001). Total mean medical costs were also lower (adherence: $16,118 vs. $17,991; persistence: $16,459 vs. $18,399, both P<0.0001), driven by lower acute care costs (adherence: $6,210 vs. $7,775; persistence: $6,385 vs. $8,171, both P<0.0001).

Conclusions: In this study, adherence and persistence to basal insulin therapy was associated with lower HCRU and costs, particularly for acute care.

Abstract No: ABS100: Predictors of Adherence and Persistence to Basal Insulin Therapy in Adults with Type 2 Diabetes

Aparna Manjunath

Novo Nordisk India Private Ltd. (0088)

E-mail: apmh@novonordisk.com

Objectives: Treatment adherence and persistence lead to gaps in achieving glycemic control in type 2 diabetes (T2D). We sought to identify predictors of adherence and persistence to basal insulin therapy among adults with T2D initiating therapy.

Methods: Commercially insured US adults with T2D initiating basal insulin treatment between January 1, 2016 and December 31, 2018 were identified using IQVIA PharMetrics® Plus claims data. Adherence and persistence were quantified based on basal insulin claims in the one-year follow-up period and established definitions. Logistic regression models were developed to identify predictors of adherence and persistence based on baseline clinical and demographic information.

Results: Among the 64,953 patients sampled, medication adherence and nonadherence (42% and 58%) and medication persistence and non-persistence (57% and 43%) were identified. Older age at baseline, oral and injectable antidiabetic medicine use, and physician office visits were associated with increased persistence and adherence; baseline hospitalization and emergency room visits were associated with decreased levels.

Conclusions: Multiple predictors of adherence and persistence with basal insulin therapy were identified. These findings may help guide therapeutic choices and research priorities to bridge the gap between achievable efficacy of insulin therapy and real-world effectiveness.

Abstract No: ABS206: A 4 year old boy with progressive penile enlargement and accelerated growth

Md Ashiqur Rahman

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

E-mail: ashiqur149dmc@gmail.com

Background: Though Adrenocortical tumour is rare in children, it should be considered when evaluating peripheral precocious puberty.

Methods: We present the clinical findings, laboratory tests, imaging findings, histopathological study, post-operative follow-up, and management.

Results: A 4-year-old boy presented with progressive penile enlargement, pubic hair, acne, and aggressive behaviour for two years. Physical examination revealed; height 120 cm, Tanner stages for pubic hair was IV, stretched penile length was 14 cm, testicular volume 3 ml. His bone age was 11 years. Laboratory findings showed gonadotropins were low, testosterone was high. So precocious puberty was gonadotropins independent (peripheral). Abdominal ultrasonography showed a hypoechoic mass in the right adrenal gland (22×17) mm, and abdominal CT scan demonstrated a mass in the right adrenal gland measuring (2.2×1.8×1.7) cm. Based on the above data the interpretation was adrenal androgen-secreting tumor either adenoma or carcinoma. The patient underwent a right open adrenalectomy. The histopathology study was consistent with an adrenocortical tumour. It was confirmed to be an adenoma by immunohistochemistry. Postoperative serum cortisol was normal and testosterone was in the prepubertal range. Subsequent follow-up at 6 months showed testicular volume was 5 ml, pubic hair IV, stretched penile length 15 cm, and height 125 cm. His LH was 1.99 miu/L, testosterone 440 ng/dl and GnRH stimulation showed pubertal response. It suggests secondary activation of the hypothalamic-pituitary-gonadal axis. The patient was started on monthly leuprolide.

Conclusion: Even after successful treatment of precocious puberty due to a virilizing tumour, the patient should be followed up to detect the appearance of secondary central precocious puberty.

Abstract No: ABS067: Title: Pharmacokinetic properties of once-weekly insulin icodec in individuals with renal impairment vs normal renal function

Sushil Kiran Kunder, Hanne Haahr, Niels R. Kristensen, Jonas H. Larsen, Frank-Dietrich H. Wagner, Stanislav Ignatenko

Novo Nordisk India Pvt Ltd

E-mail: SKKQ@novonordisk.com

Background: Insulin icodec is a once-weekly basal insulin in development. This trial investigated if renal impairment affects pharmacokinetics (PK) of icodec.

Methods: In an open-label, parallel-group trial, 58 individuals (39 males; mean±SD age 50±13 yrs, BMI 26.5±3.1 kg/m²) were allocated to five groups according to renal function based on measured glomerular filtration rate (GFR): normal renal function (NRF; ≥90 mL/min; N=12), mild (60 to <90 ml/min; N=12), moderate (30 to <60 mL/min; N=12), severe (<30 mL/min; N=12) renal impairment and end-stage renal disease (N=10). A single s.c. icodec dose (1.5U/kg) was administered and blood was sampled for PK until 840 h (35 days) post-dose.

Results: A minor increase was observed in total exposure (AUC _0-840,SD) with decreasing GFR, but the estimated effect of GFR on AUC _0-840h,SD did not differ significantly from zero (-0.069; 95%CI [-0.150;0.013]; p=0.099). Pairwise group comparisons showed numerically slightly higher AUC _0-840h,SD and C_max,ss for renal impairment vs NRF. AUC _0-840h,SD was statistically significantly higher for moderate renal impairment vs NRF.

Conclusion: icodec exposure tended to be slightly higher for renal impairment vs NRF. The clinical relevance is however limited as icodec should be dosed according to individual need. Thus, no specific dose adjustment of icodec is required in individuals with renal impairment.

Abstract No: ABS023: First presentation of growth hormone excess as generalized tonic clonic seizures in a young girl

Beminahennadige Minuri Sanika Fernando, B. M. S. Fernando, S. W. Gnanathayalan, H. K. G. A. M. Kariyawasam, U. Bulugahapitiya

National Hospital of Sri Lanka, Colombo, Sri Lanka

E-mail: minuri30@gmail.com

Background: Growth hormone excess in adolescence is rare. Growth hormone excess presenting as a seizure is also rare. This describes an adolescent with growth hormone excess presenting with a generalized tonic clonic seizure (GTCS).

Methods: A 17 year old girl presented with headache followed by a GTCS. She had intermittent headache followed by vomiting and visual blurring of left eye over the last one year. Over the past two years she experienced increased weight gain and height with frequent change in shoe size. Also had primary amenorrhoea. On admission she was newly diagnosed with diabetes mellitus. Her height was 163 cm, weight 59kg, had prognathism, facial swelling, large hands and feet, pubic hair - Tanner 1, breast development - Tanner 3 and visual fields showed bitemporal hemianopia.

Results: MRI brain revealed a very large extra axial predominantly cystic mass, (8.2 cm x 3 cm x 4.7 cm) in the sellar and suprasellar region, with extensive invasion and optic chiasma compression. On hormonal assessment her IGF 1 was elevated [797.6ng/ml (168 – 367)] and remaining pituitary axis was suppressed. Transcranial surgery was done and histology revealed a somatotroph adenoma with positive growth hormone staining, Ki 67- 2%. Post operatively she had both biochemical and radiological uncured disease, with residual tumour in left parafalcine region, sellar and bilateral suprasellar region (1 x 0.8 cm). Currently she is awaiting trans -sphenoidal surgery for residual tumour and genetic screening.

Conclusion: Growth hormone excess in adolescents and somatotroph adenoma presenting with GTCS is rare. Seizure occurrence is mainly due to suprasellar extension of tumour. It is important to identify the features of growth hormone excess during initial clinical assessment of patients presenting with generalized tonic clonic seizure.

Abstract No: ABS038: Expert opinion for the early screening, diagnosis, and management of hyperthyroidism in India

Shashwat Verma, Tejal Lathia, Piya Ballani Thakkar

Abbott Healthcare Pvt. Ltd.

E-mail: shashwat.verma@abbott.com

Background: Hyperthyroidism prevalence in India ranges from 0.9% to 1.3%. Grave’s disease, toxic multinodular goitre, and toxic adenoma are commonest causes of hyperthyroidism. Due to lack of awareness among primary care practitioners, diagnosis of hyperthyroidism is commonly missed and delayed. The objective of this consensus was to develop an expert opinion for early identification of hyperthyroidism by identifying common clinical features in patients.

Methods: Seven advisory board meetings with 70 endocrinology experts were held. These meetings were dedicated to thorough review of available evidence, in-depth discussions of clinical experiences, and development of a consensus among experts.

Results: Experts agreed that hyperthyroidism symptoms commonly mimic cardiovascular, gynaecological, or psychiatric disorders. Because of diverse symptoms, patients visit different specialities with resultant delay in diagnosis and management. Therefore, a screening tool for hyperthyroidism was proposed by expert group. The expert committee unanimously identified that palpitations and weight loss were most common symptoms and tachycardia with/without irregular rhythm, tremors, goitre, and eye signs were most common signs of hyperthyroidism presenting at the time of diagnosis. Experts also shared uncommon signs and symptoms of hyperthyroidism. Based on overall suspicion, experts opined that serum TSH, free T4 and total triiodothyronine (T3) is evaluated simultaneously compared to initial TSH sequentially followed by T4 and T3 evaluation. Antithyroid drugs are preferred first-line treatment option for management of hyperthyroidism followed by Radioactive Iodine and surgery. Carbimazole is the preferred antithyroid drug in Indian clinical practice and is usually advised for 12-18 months. Once euthyroid state is achieved, long term maintenance with low dose can result in lower relapse rate.

Conclusions: Varied clinical presentation of hyperthyroidism may lead to delay in diagnosis which can be prevented by early screening through clinical assessment and appropriate thyroid function testing. Appropriate management with antithyroid drugs titrated for right dose and duration is important.

Keywords: Carbimazole, goitre, hyperthyroid, screening, symptoms

Conflicts of interest: Tejal Lathia and Piya Ballani Thakkar received grant from Abbott for participation in the development of this consensus.

Abstract No: ABS021: Co-occurrence of composite pheochromocytoma with mild autonomous cortisol secretion

Beminahennadige Minuri Sanika Fernando, S. W. Gnanathayalan, H. K. G. A. M. Kariyawasam, S. A. I. U. Jayawardana, U. Bulugahapitiya

National Hospital of Sri Lanka, Colombo, Sri Lanka

E-mail: minuri30@gmail.com

Background: Composite pheochromocytoma is a rare histological variant of pheochromocytoma, composed of pheochromocytoma and neurogenic tumour. Mild autonomous cortisol secretion (MACS) is a condition where overt Cushings syndrome is absent, with failure to suppress cortisol sufficiently after administration of dexamethasone. Co-occurrence of MACS with pheochromocytoma is reported, but co-occurrence with composite pheochromocytoma is not reported. This case report describes the management of this co-occurrence.

Methods: A 54 year old woman with hypertension, diabetes mellitus, dyslipidaemia and recent left sided stroke, presented with intermittent abdominal pain, dyspeptic symptoms, episodic headache, palpitations and sweating for 8 months.

Results: Imaging revealed a right suprarenal mass, 8 x 8.6 x 10.8 cm characteristic of phaeochromocytoma. Left adrenal gland was normal. Her 24 hour urinary metanephrine 2895mcg/d (<350 mcg/d), overnight dexamethasone suppression test (ODST) revealed non-suppressed cortisol 152nmol/l, with suppressed ACTH [<10pg/ml (10 – 60pg/ml)]) suggestive of MACS. ODST was repeated and confirmed. She had low DHEAS [0.57 umol/l (0.8 – 7)] level further supporting MACS. She underwent right sided adrenalectomy under perioperative steroid cover, followed by oral steroid replacement postoperatively for 2 months, following which short synacthen test was normal and steroid replacement was stopped. Histology revealed a composite pheochromocytoma, composed of pheochromocytoma (Chromogranin positive) and ganglioneuroma (S100 positive). ACTH staining was negative. Post-operative 1 month, 24 hour urinary metanephrine was 30.34 mcg/day (<350mcg/day). Post-operative 2 months, FDG PET CT scan was negative for metastatic deposits. Currently awaiting repeat ODST to confirm resolution of MACS.

Conclusion: Behaviour and prognosis of composite pheochromocytoma is similar to the classical form. Co-occurrence of composite pheochromocytoma with MACS needs perioperative hydrocortisone cover followed by oral steroid replacement. Patient benefits by screening for MACS in pheochromocytoma as it is important in the perioperative management. Further, suppressed DHEAS guides towards the diagnosis of MACS.

Abstract No: ABS019: Breaking new ground: A crucial role of endocrine complexity in Coffin-Lowry syndrome. What have we learned from the case studies?

Sabyasachi Maity, Stephan Bandelow

St. George’s University School of Medicine, True Blue, Grenada

E-mail: maity.sachi82@gmail.com

Background: Coffin-Lowry Syndrome (CLS) is a rare X-linked syndrome with features of low IQ, delayed developmental milestones, and neuromusculoskeletal and cardiac defects. It is previously demonstrated that the ribosomal S6 kinase RSK2 mutation leads to the dysregulation of a critical component of the MAP kinase signaling pathway, resulting neurodevelopmental symptoms in patients. Despite significant progress in elucidating the molecular basis of CLS, individuals with CLS can also experience various endocrinological abnormalities. These abnormalities can have a significant impact on the overall health and well-being of affected individuals.

Objective: This abstract explores the current state of research on CLS case studies and the prevalence of endocrine and metabolic complications to investigate the effects of RSK2 mutations on brain development, behavior, and physiology. We aimed to characterize the endocrinological abnormalities associated with CLS, their clinical manifestations, and potential management strategies. Materials and methods: In this study, the reviewers conducted systematic review of case studies from the medical databases and found relevant articles. The articles published in English were selected till 2022. The relevant articles were read thoroughly to extract the information on endocrinological complexities of CLS patients.

Results: This systematic review provides an analysis of endocrinological features associated with RSK2 gene mutation amongst the CLS patients worldwide, emphasizing the urgent need for diagnostic and therapeutical approaches. The authors found common endocrine abnormalities such as Growth Hormone Deficiency (GHD), Thyroid dysfunction, Obesity, and diabetes mellitus among the included case studies of almost 200 patients. Although not apparent at the birth sometimes, GHD-mediated stunted growth and short stature becomes more noticeable as the affected individual grows older. Hypothyroidism and associated symptoms such as fatigue, weight gain, and cold intolerance were also present in some patients of CLS. Metabolic abnormalities and related complications such as diabetes mellitus and Obesity were also prevalent among the CLS affected individuals. Targeted therapy such as grown hormone replacement, exogenous thyroid administration can be considered to promote the skeletal growth and in the management of hypothyroidism in CLS. Adherence to a proper diabetic management plan such as a balanced, physical exercise, and regular monitoring of blood glucose is essential in managing weight-related issues in CLS.

Conclusion: Recognizing and managing the endocrine abnormalities is essential to improve the quality of life for affected individuals with CLS. By working closely with healthcare providers and specialists, parents of affected individuals with CLS can develop comprehensive management plans tailored to their specific needs, ultimately enhancing their overall well-being and quality of life. Future research should explore the pathophysiology of CLS to better understand the underlying mechanisms of these endocrinological abnormalities and improve the management options available to affected individuals. As research in this field continues to evolve, the collaboration between clinical observations and animal models will undoubtedly advance our knowledge on endocrine abnormalities and ultimately improve the lives of those affected by CLS.

Abstract No: ABS013: Pregnancy and lactation associated osteoporosis – A rare bone breaker

Shahini Winson Gnanathayalan

Endocrinology and Diabetes Unit, The National Hospital of Sri Lanka, Colombo, Sri Lanka

E-mail: winsgshahini@gmail.com

Background: Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition affecting women during the late pregnancy and early postpartum period. PLO is manifested with multiple fragility fractures mainly involving the spine with the height loss. Fractures of the hip also have been reported.

Methods: We report a 31-year-old lady presenting with severe lower back pain during early postpartum period after her second pregnancy. She reported history of similar back pain after delivery of first baby 2 years back. Vertebral imaging revealed multiple compressive fractures (Th9, L1 and L2). There was evident height loss of 7cm compared to her pre-pregnancy height. Bone mineral density assessment with the DXA scan revealed severe osteoporosis with L1-L4 Z-score of -3.3 with the minimum Z-score of -4.3 at L3. She denied family history of osteoporosis.

Results: Biochemical assessment showed normal level of calcium, phosphorus, vitamin D and alkaline phosphatase. Secondary causes of osteoporosis such as primary hyperparathyroidism, Cushing syndrome and hyperthyroidism were excluded. She was explained about the diagnosis and advised on cessation of breastfeeding, proper contraception and lifestyle modifications. Calcium carbonate and vitamin D supplements were started with adequate pain relief. On 6 months follow-up, she had significant improvement in back pain, and she didn’t have new fractures on repeat imaging. Repeat DXA scan showed 20% improvement in the lumbar spine BMD. She is awaiting her reassessment in 1 year, in August 2024. During the postpartum period after her first pregnancy also she had severe osteoporosis with L1-L4 Z-score of -4.7 and she was treated with calcium, vitamin D supplements and alendronate therapy for 1 year. But she lost to follow-up after that due to improvement in symptoms.

Conclusion: Early diagnosis and treatment of PLO improves the outcome. It can recur in the subsequent pregnancies. More evidence is needed regarding antiosteoporotic treatment in PLO.

Abstract No: ABS011: A case of non-islet cell tumor hypoglycemia due to gastrointestinal stromal tumor in a patient with neurofibromatosis

Shahini Winson Gnanathayalan, Beminihennedige Minuri S. Fernando, Chandrika Subasinghe, Uditha Bulugahapitiya

Endocrinology and Diabetes Unit, The National Hospital of Sri Lanka, Colombo, Sri Lanka

E-mail: winsgshahini@gmail.com

Introduction: Non-Islet Cell Tumor Hypoglycemia (NICTH) is a rare but serious complication of malignancy leading to recurrent episodes of severe hypoglycemia and impaired quality of life. It is commonly due to mesenchymal and epithelial tumors. The underlying mechanism is overproduction of insulin-like growth factor-2 (IGF-2) and its precursors that activate the insulin receptor. Patients with Neurofibromatosis type 1 (NF-1) have high incidence of GISTs. GISTs are rare mesenchymal tumors. This case describes a case of NICTH due to GIST with hypoglycemia as the first presentation.

Methods: A 57-year-old man with NF-1 was evaluated for frequent major hypoglycemic episodes including seizures and loss of consciousness. He also reported reduced appetite, weight loss and melena. He denied history of diabetes mellitus, alcohol abuse or illegal drug abuse. Initial biochemical assessment showed anemia with normal liver, renal, thyroid profile, and cortisol level.

Results: Further laboratory assessment during an episode of hypoglycemia with plasma glucose of 35 mg/dL revealed very low insulin, C-peptide and beta-hydroxybutyrate. IGF-1 was suppressed. Unfortunately, IGF-2 level could not be done due to unavailability in Sri Lankan settings. He had a dramatic rise in blood glucose level with glucagon administration, suggesting the presence of insulin like substance. Computed Tomography (CT) of the chest, abdomen and pelvis showed multiple large liver lesions and a large enhancing paraaortic lesion. Histology from the liver lesion with immune staining confirmed metastatic GIST. He was started on imatinib. He is treated with prednisolone for NICTH with good response in hypoglycemia.

Conclusion: In patients with known malignancy, if clinical and biochemical findings are compelling for NICTH, additional assessment with IGF levels is not usually necessary. Glucagon challenge test is a supportive investigation for the diagnosis. Steroids may be effective to control hypoglycemia and to improve quality of life, if tumor can’t be surgically treated.

Abstract No: ABS012: A case severe hypoglycemic coma in a young woman due to insulin autoimmune syndrome

Shahini Winson Gnanathayalan, Beminihennedige Minuri S. Fernando, Chandrika Subasinghe, Uditha Bulugahapitiya

Endocrinology and Diabetes Unit, The National Hospital of Sri Lanka, Colombo, Sri Lanka

E-mail: winsgshahini@gmail.com

Background: Insulin Autoimmune Syndrome (IAS) is a rare cause of recurrent hypoglycemic episodes due to the presence of high titers of insulin autoantibodies. It may be triggered by exposure to some drugs and viruses but may manifest spontaneously as well. Although symptoms are usually transient and mild, severe hypoglycemia with life threatening outcomes also have been reported. Here we describe a young lady presenting with recurrent major hypoglycemia due to IAS.

Methods: A 25-year-old Asian woman was evaluated for recurrent episodes of early morning seizures with loss of consciousness associated with severe hypoglycemia. When she was brought once with prolonged loss of consciousness, her blood sugar was 15 mg/dl. She was treated with intravenous dextrose with recovery of consciousness. Vital signs and physical examination were unremarkable. She was previously healthy, denied taking alcohol or any medications and had no access to insulin or oral hypoglycemic medications. She had 3 prior hospital admissions with major hypoglycemia.

Results: During the hospital stay, fasting insulin level was 15260 IU/ml with elevated C-peptide level of 7.6 ng/ml. HbA1C was 7.3% suggesting alternating hypoglycemia and hyperglycemia in IAS. Insulin autoantibodies was detected with the titer of >300 U/ml. Other labs including renal and liver function test, cortisol and TSH were normal. Computed Tomography of abdomen was normal. Diagnosis of IAS was made and started on prednisone considering the severity of the disease. She was advised to have frequent small meals. Symptoms gradually reduced with steroids and further major hypoglycemic events didn’t occur. Steroids are being tapered off.

Conclusion: IAS should be considered in endogenous hyperinsulinemic hypoglycemia especially when the insulin level is disproportionately very high in compared to C-peptide level with insulin/C-peptide ratio of more than 1. Pharmacotherapy with immunosuppressants may be helpful in severe cases, though most cases recover spontaneously over time.

Abstract No: ABS05: Efficacy of topical capsaicin in alleviation of painful diabetic peripheral neuropathy – A systematic review

Ameet Kumar Jha

Saint Matthews University, Grand Cayman, Cayman Islands

E-mail: ameetjha197@gmail.com

Background and Aims: Painful diabetic neuropathy (PDN) is a serious, polymorphic, and prevalent complication of diabetes mellitus occurring in approximately 25-30% of patients which significantly impairs quality of life and can be difficult to treat. Capsaicin is FDA approved for the temporary relief of minor aches and pains associated with backache, strains, and arthritis and is used for off-label treatment of postherpetic neuralgia and painful diabetic neuropathy. Topical capsaicin creams are considered to be second-line therapy used to treat pain from a wide range of chronic conditions including neuropathic pain. Capsaicin causes enhanced sensitivity to noxious stimuli followed by reduced sensitivity over a period of time and finally persistent desensitization due to repeated cutaneous application. The current study discusses the recent trends in management and alleviation of pain in Diabetic Neuropathy by using the topical capsaicin and reviews the results from controlled trials supporting the effectivity of topical capsaicin. This study aims to examine the evidence for the efficacy and reliability profile of topical capsaicin in the management of neuropathic pain caused by diabetes mellitus.

Methods: Systematic review of the literature discussing the management of painful diabetic peripheral neuropathy through low dose topical capsaicin and high dose capsaicin skin patches were done. Existing treatment guidelines were studied and compared. PubMed Central, MEDLINE, Scopus, Google Scholar, HINARI and EBSCO databases were searched.

Results: Treatment with capsaicin 0.075% cream applied to the painful area resulted in significant pain relief but local skin irritation, which is often mild and transient, may lead to withdrawal from the study. However, combining capsaicin 0.025% with doxepin 3.3% led to decreased skin irritation compared with capsaicin alone. The significant improvement has been found in pain relief with a decrease in pain intensity through a double-blind placebo-controlled trial by topical capsaicin. A topical application of capsaicin 0.025% for four to six weeks has been shown to provide either complete or significant relief whereas initial results of a multicenter controlled trial with topical capsaicin cream 0.075% suggest that this preparation produced more relief of the pain associated with diabetic neuropathy than placebo. However, an analysis on treatment intention showed insignificant improvement in pain control with capsaicin lotion compared with placebo for all pain measures and the proportion of patients who had 30% or 50% pain relief, respectively.

Conclusions: Capsaicin plays a significant role in neuropathic pain reduction. The alleviation of pain in painful peripheral diabetic neuropathy has been challenging, but effective management has proven enhanced patient’s quality of life. Capsaicin is an alkaloid derived from red chili peppers and a topical application has been found to be effective in PDN. The studies have found significant improvements in pain relief and a decrease in pain intensity in a double-blind placebo-controlled trial. However, the demonstration of epidermal denervation in patients treated with capsaicin with impaired subsequent nerve regeneration in subjects with diabetes cautions the use of this therapy, especially in patients with established neuropathy. Capsaicin in both ways either a low dose (0.075%) topical cream or high dose (8%) dermal patch has been found alleviating the pain in the patients suffering from painful neuropathic conditions.

Keywords: Capsaicin, diabetes, diabetic peripheral neuropathy, review

Abstract No: ABS16: New-onset diabetes in children during the COVID-19 Pandemic in Mississippi: An assessment of biomarkers and psychosocial risk factors

Naznin Dixit

University of Mississipi Medical Centre, Jackson, MS, USA

E-mail: ndixit@umc.edu

Background: Increased incidence of pediatric diabetes has been reported during the SARS-CoV-2 pandemic. However, there remains a paucity of data regarding possible factors affecting the pediatric population, such as weight, inflammatory markers, vitamin D level, etc., and behavioral changes due to lockdowns and virtual learning.

Objectives: To investigate associations between the COVID-19 pandemic and new-onset diabetes in children.

Methods: Children aged 1-18 years admitted with new-onset-diabetes between March 2020 and December 2021 were eligible. Leptin, CRP, cytokines IL-1b, IL-6, and TNF-α, SARS-Co-2 IgM and IgG Ab assays completed for enrolled patients. Demographic and laboratory data were gathered from the electronic medical record. Families completed a behavioral questionnaire at the time of enrollment.

Results: Of enrolled children 19 (33%) had positive SARS-CoV-2 IgG antibodies (Ab) while 39 (67%) were IgG Ab negative, 18 (31%) had type 1 diabetes (T1D), while 36 (62%) had type 2 diabetes (T2D). 4 patients could not be classified at the time of diagnosis. Those with T2D were older (median age 14.0 vs 10.5 years, p=0.004), majority African American (94.4 vs 44.4%, p< 0.001) and had a higher median BMI percentile (99.2 vs 67.6% ile, p< 0.001), lower Vitamin D (median 12.8 vs 24.5 ng/mL, p< 0.001), and higher Leptin (median 19.9 vs 3.45 ng/mL, p< 0.001) and CRP (median 4.9 vs 0.40 mg/L, p< 0.001). For every percentile increase in BMI, the odds of having T2D were 1.07 times greater (adjusted odds ratio 1.07 [95% CI 1.02-1.17], p=0.047).

Conclusions: Few markers among COVID-19 Ab positive vs Ab negative patients were highlighted. Differences in predictors of T1DM vs T2DM were observed, however, all except BMI% ile lost significance on multivariate analysis. Further work with greater statistical power is needed to elaborate correlations between psychosocial factors & SARS-CoV-2 infection-related biomarkers with incident diabetes in children.

Abstract No: ABS88: Hypoglycaemia in people with Type 2 diabetes mellitus in outpatient clinics in Sri Lanka

M. M. P. T Jayasekera, U. T. N. Senaratne¹, D. A. Lamabadusuriya, A. T. Mattiyas², H. M. M. Herath³, P. D. W. D. De Zoysa³, M. Pathirage⁴, V. Sujanitha⁵, M. Umakanth⁶, H. Sathischandra⁷, W. M. P. R. Jayasekera⁷, W. G. G. Senaratne⁷, K. Jayasinghe⁷, W. G. S. G. Karunaratne⁷, P. Sudarshan⁷, N. Rajaratnam⁷, W. M. D. D. Wickramaratne⁷, B. Ratnayake⁷, L. Rasnayake⁷, R. Liyanage⁷, J. Pushpakumara⁷, T. Wanigarathne⁷, P. D. P. Siriwardhane⁷, K. G. Y. U. Kumara⁷, K. S. C. Kuruppu, R. A. N. K. Wijesinghe

Faculty of Medicine, General Sir John Kotelawala Defence University, ¹Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, ⁷Ministry of Health Sri Lanka, Colombo, ²Faculty of Medicine, University of Sri Jayawardhanpura, Nugegoda, ³Faculty of Medicine, University of Ruhuna, Matara, ⁴Faculty of Medicine, University of Peradeniya, Peradeniya, ⁵Faculty of Medicine, University of Jaffna, Jaffna, ⁶Faculty of Medicine, Eastern University of Sri Lanka, Chenkalady, Sri Lanka

E-mail: priyamja@kdu.ac.lk

Background: Hypoglycaemia has been an often neglected complication of diabetes therapy. Mild hypoglycaemia reduces QoL, while severe hypoglycaemia is life-threatening and can precipitate major cardiovascular and cerebrovascular events.

Methods: A multicenter cross-sectional study was conducted on hypoglycaemia among adults with diabetes attending to medical clinics in government hospitals in Sri Lanka using an interviewer administered questionnaire.

Results: Among 2005 participants in 18 centres, mean age was 62.12 ±11.94 years (58.1% female). Median duration of diabetes was 8 (IQR11) years. Only 491 (24.5%) had glucometers at home. Among them, 808 (43%), 757 (37.8%) and 376 (18.8%) had neuropathy, retinopathy, and nephropathy respectively. While 415 (20.7%), 50 (2.5%), 22 (1%) had ischemic heart disease, strokes and peripheral vascular disease respectively. A 1349 (67.3%) experienced hypoglycaemia and 462 (34.2%) had hospital admissions (9 (0.7%) intensive care admissions). Only 665 recall the capillary blood sugar (CBS) at hypoglycaemic episode. Their mean CBS during hypoglycaemic episodes was 57.04 ±18.15 mg/dL. 1552 (77.4%) were on oral hypoglycaemic {1327 sulphonyl urea (1306 (66.2%) gliclazide), 1468 (73.2%) metformin, 556 (27.7%) DPP4I and 55 (2.7%) SGLT2I} medications, 453 (22.6%) on insulins and 126 (6.3%) on both insulin and oral hypoglycaemic medications. Skipped meal 511 (37.9%), strong medication 391 (29%), consumption of the sugar reducing native food items 203 (15%), taken high dose insulin 112 (8.3%) and oral medication 74 (5.5%) than prescribed, intercurrent illness 61 (3%) and alcohol 10 (0.5%) were the recognised causes. Commonest hypoglycaemic symptoms were cold sweat 1013 (75.1%), dizziness 911 (67.5%) and excessive tiredness 899 (66.6%). To alleviate symptoms, 985 (73%) taken sugary drink, 350 (26%) consumed sweets, 223 (16.5%) take glucose, 226 (16.7%) omit the next drug dose. But 339 (25.1%) have taken the next drug dose and 191 (14.1%) did nothing.

Conclusion: Hypoglycaemia is a significant issue which needs to be addressed. Patients need advice on prevention and treatment.

Abstract No: ABS133: Endogenous hyperinsulinemic hypoglycemia: Experience from a tertiary care center in Sri Lanka

Shahini Winson Gnanathayalan, Isuru Udayanga Jayawardana, Dilini Abeyratne, Beminahennedige Minuri S. Fernando, Vinitharan Varunanatharajah, Rafiuldeen Ahamed Raiyees, Nethrani Sameera Wijesekara Pathirana, Dhulashiha Jegavanthan, Umesha Wijenayake, B. M. C. M. Balasooriya, Prasad Katulanda, Manilka Sumanatilleke, Uditha Bulugahapitiya

National Hospital of Srilanka, Colombo, Sri Lanka

E-mail: winsgshahini@gmail.com

Background: Endogenous hyperinsulinemic hypoglycemia (EHH) is a rare entity in Endocrinology characterized by inappropriately elevated insulin levels despite hypoglycemia. Most cases of EHH are due to insulinoma while the relatively rare causes are insulin autoimmune syndrome (IAS) and nesidioblastosis.

Methods: We retrospectively analyzed 7 patients who were diagnosed with EHH in 2023, from January to September, in a tertiary hospital.

Results: Among the 7 patients, four patients, two and one were diagnosed with insulinoma, IAS and nesidioblastosis respectively. One patient had multifocal insulinoma with MEN 1 syndrome. Among cases of IAS, one was idiopathic and the other one was carbimazole-induced. The patient with nesidioblastosis didn’t have a history of gastric surgeries. Most patients had recurrent level 111 hypoglycemia. All cases of insulinoma and nesidioblastosis had an insulin /c-peptide ratio of less than one while both patients with IAS had very high insulin levels with a ratio of more than one with very low percent of insulin recovery after PEG precipitation. The details of symptoms, laboratory investigations, localization studies, treatment and outcome have been summarized in the Table 1 below.

Conclusion: An accurate diagnosis of aetiology is necessary for EHH to institute appropriate treatment. This series highlights the challenges in differentiation. Neither fasting nor postprandial hypoglycemia is a good indicator to differentiate the etiologies. In resource-poor settings where insulin autoantibodies cannot be done freely, the insulin/c-peptide ratio with insulin recovery after PEG precipitation might be a good alternative to diagnose IAS. Selective arterial calcium stimulation test is useful in the diagnosis of nesidioblastosis and insulinomas in settings with a lack of availability of functional imaging.

Abstract No: ABS158: Young onset diabetes in Sri Lanka: A preliminary analysis of the multicentre database for patients with young-onset diabetes in Sri Lanka (DYOD-SL)

M. H. Arambewela, A. W. Wickramarachchi, U. N. Wijenayake, M. D. S. A. Dilrukshi, C. J. Subasinghe, G. M. Ratnayake, S. Seneviratne, N. L. de Silva, G. Samarasinghe, M. Amarawardena, D. Karupaiah, T. Samarasekara, K. D. Liyanarachchi, M. Ahmad, S. Pathmanathan, D. T. Muthukuda, C. Antonypillai, U. Bulugahapitiya, M. Sumanatilleke, S. Cooray, N. P. Somasundarum, P. Katulanda, C. Garusinghe, A. Wijesinghe, S. Jayakody, S. Abhayaratne, D. Kottahachchi, S. Gunatilake

National Hospital, Colombo, Sri Lanka

Introduction: There is an increasing prevalence of young onset diabetes (YOD) globally as well as locally.

Methods: Database for the patients with YOD in Sri Lanka (DYOD-SL) is a multi-centre hospital based database established in 2021 for patients diagnosed with diabetes <25 years. A retrospective analysis was conducted to determine disease characteristics and state of care.

Results: 29 centers (2/27 peadiatric/adult) participated. Of the 2393 patients, (female 57.5% / male 42.5%) median age was 20 (IQR 6) years, median age at diagnosis was15 (IQR 6) years and median BMI was 20.47 (IQR6.195) kg/m2. Type 1 diabetes (T1D), type 2 diabetes (T2D), type 3c diabetes (T3cD) and MODY accounted for 57%, 33.4%, 2.9% and 2.4% respectively. Thalassemia caused 81.3% of T3cD. There was no difference in male and female proportions between T1D and T2D (x² (1)=2.094;p=0.148). Among 76 patients with T1D undergoing early GAD antibody testing 26% were negative. Median BMI [19 (SD3.13) vs 24 (SD4.92) kg/m², p=0.000] Age-at-diagnosis [13.47 (SD5.31) vs 16.39 (SD4.36) years, p=0.000] positive family history [42.9% vs 74.2%, p=0.000] were significantly lower in T1D vs T2D. Prevalence of complications were nephropathy 8.03% (104/1294), retinopathy 6.66% (80/1199), neuropathy 4.25% (55/1293), foot disease 1.32% (27/2031) macrovascular complications 0.52% (9/1702) DKA 29.1% (535/1842) and major hypoglycaemia 9.9% (141/1424). Prevalence of hypertension and dyslipidaemia were 2.5% and 14.2% respectively. DKA (p=0.000), major hypoglycaemia (p=0.000) and retinopathy (p=0.000) were significantly higher in T1D. AmongT1D, 62% were on premixed insulin, 20% were on basal bolus regimen and 14.9% were on basal bolus regimen with self titration of insulin. Notably 39.09% among T2D was on insulin. HbA1c of entire cohort was 10.05 with significantly poorer control in T1D [10.49 (SD 3.05) vs 9.39 (SD 3.15), p=0.000]. Better HbA1c noted with increasing age. Performance of SMBG was 79% in T1D and 57.7% in T2D.

Conclusion: T1D was the commonest subtype of YOD in this cohort and complications were relatively higher in them compared to T2D. Poor disease control with unsatisfactory glucose monitoring and suboptimal therapeutic regimens requires urgent measures to step-up care.

Abstract No: ABS190: Proportion, risk factors, and autoimmunity in hypothyroidism among the pregnant ladies attending a tertiary care hospital

Mita Dutta, Faria Afsana, Md. Feroz Amin, Md. Faruque Pathan

Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh

E-mail: mitadutta42@gmail.com

Background: Subclinical hypothyroidism in pregnancy is one of the most frequently encountered issues in daily clinical practice. However, there is continuing debate regarding universal screening, the use of a TSH cut-off value, and levothyroxine replacement.

Objectives: The aim of the study was to find out the proportion of newly detected hypothyroidism in pregnancy.

Methodology: This cross-sectional, observational study enrolled 175 pregnant women recruited by convenient sampling from the Department of Obstetrics and Gynecology, BIRDEM General Hospital, with or without diabetes. FT4 and thyroid autoantibodies were advised to those patients who had elevated TSH above the ATA 2011-defined trimester-specific reference ranges. TSH, FT4, and anti-thyroid antibodies were tested using the chemiluminescent technique by the ADVIA centaur, Siemens. Data were analysed by SPSS version 25. Non-parametric tests were chosen for statistical analysis.

Results: The majority (53%) of the participants, were 30 years of age or younger, and 39.4%, were in their third trimester of pregnancy. Using the ATA 2011-defined trimester-specific reference ranges of TSH, 26.3% had subclinical hypothyroidism and 5.7% had overt hypothyroidism. While using the conventional criteria (TSH 0.4 - 4 mIU/L), hypothyroidism was diagnosed in 20.6% of cases. Statistically significant discordance (p =.001) was found in thyroid function status as defined by the ATA 2011 and conventional cut values of TSH. History of subfertility and a family history of thyroid disease and thyromegaly were significantly (p =.036, p <.001, p <.001) associated with hypothyroidism. TPO antibodies were positive in 69.6% of hypothyroid subjects. Sixty percent of hypothyroid pregnant ladies had dysglycemia (GDM, DIP, Pre-existing diabetes).

Conclusions: The adamant criteria of the ATA 2011 encompassed nearly one-third of the studied subjects designated as having subclinical hypothyroidism who were considered euthyroid by conventional criteria. Incorporating universal screening for all pregnant women can provide timely, holistic management of hypothyroidism and improve pregnancy outcomes.

Abstract No: ABS223: TCF7L2 rs12255372 mutation among Bangladeshi adult type 2 diabetes patients

Syed Azmal Mahmood, Shehjada Selim

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

E-mail: azmaldmc@gmail.com

Introduction: While the etiology of T2DM is complex, genetic markers for T2DM are surfacing fast and amidst such markers, the transcription factor 7-like 2 (TCF7L2) gene has been emerged as the most promising T2DM causing gene. The intronic variant rs12255372 of the TCF7L2 gene has been found to be strongly associated with T2DM in different ethnic populations.

Objectives: To determine frequency of rs12255372 polymorphism in the TCF7L2 gene in Bangladeshi adult population with T2DM and without diabetes.

Materials and Methods: This cross-sectional study was conducted in department of Endocrinology, BSMMU. Eighty T2DM patients and 80 age and sex matched controls were recruited consecutively by non-random sampling, history and clinical examination findings were recorded. Blood samples were collected. Genomic DNA was extracted and single nucleotide polymorphisms rs12255372 were determined by restriction fragment length polymorphism (RFLP) method. P values ≤ 0.05 was considered as statistically significant.

Results: The minor (T) allele frequencies for rs12255372 (G>T) among T2DM and NGT were 28% and 11% respectively. The observed genotype frequencies of rs12255372 were different than those expected from the Hardy-Weinberg equation. There was significant association of TCF7L2 SNP rs12255372 with T2DM in all four genetic models. GT heterozygous and TT homozygous variants were found to cause approximately 3-fold and 5.2-fold increase in T2DM risk respectively. Univariate logistic regression analysis also predicted that there is about 3.5 times higher likelihood of developing T2DM for those having at least one “T” allele in rs12255372 position in this subgroup but when adjusted for age, family history of diabetes, BMI and central obesity the odds for developing T2DM equalizes.

Conclusion: The minor T allele frequency of rs12255372 (G>T) among T2DM and NGT participants were about one-fourth and one-tenth respectively indicating the rs12255372 polymorphism of the TCF7L2 may be associated with risk of T2DM in the studied Bangladeshi population.

Abstract No: ABS317: Hypoglycaemia in people with type 2 diabetes mellitus in outpatient clinics in Sri Lanka: comparative study in young and older adults

M. M. P. T. Jayasekera, U. T. N. Senaratne, D. A. Lamabadusuriya, A. T. Mattiyas, H. M. M. Herath, P. D. W. D. De Zoysa, M. Pathirage, V. Sujanitha, M. Umakanth, H. Sathischandra, W. M. P. R. Jayasekera, W. G. G. Senaratne, I. K. Jayasinghe, W. G. S. G. Karunaratne, P. Sudarshan, N. Rajaratnam, W. M. D. D. Wickramaratne, R. P. Bandusiri, L. Rasnayake, R. Liyanage, W. M. J. Pushpakumara, T. Wanigarathne, P. D. P. Siriwardhane, K. G. Y. U. Kumara, K. S. C. Kuruppu, R. A. N. K. Wijesinghe

General Sir John Kotelawala Defence Univesity, Colombo, Sri Lanka

E-mail: priyamja@kdu.ac.lk

Introduction: Hypoglycaemia is a condition of reduced blood glucose levels below the normal range. Hypoglycemic symptoms change with age and those symptoms are often atypical expression in elderly individuals and they are more likely to develop iatrogenic hypoglycaemia than young.

Objectives: We evaluated the hypoglycaemia in diabetic patients undergoing outpatient treatment in Sri Lanka, with a special emphasis on the patient’s demographics, risk factors, clinical presentation, treatment in two main groups (young (<65 years of age) and old (>65 years of age).

Methods: A cross-sectional study was conducted in diabetic patients attending medical clinics in 18 Sri Lankan hospitals from November 2022 to April 2023. Hypoglycemia was diagnosed by symptoms and capillary blood sugar <70 mg/dL or symptoms alone.

Results: There were 2005 participant (young, 60.2% (females 58.4%) and old, 39.8% (females 57.6%). From young, 63.2% {median FBS 125mg/dL (IQR 60)}and from old 73.5% {median FBS 124 (IQR54)} were experienced at least a single episode of hypoglycemia during the last year. Both groups experienced common hypoglycemic symptoms except sweating (p=0.022) lethargy (p< 0.001) and cognitive dysfunction (<0.001) which are significantly more in older adults. Only 23.5% young and 26.1% old had a glucometer at home. Most of the old were suffering from postural giddiness (p=0.002), numb feet (p<0.001), leg cramps (p<0.001) and bilateral leg oedema (p<0.001) than young. About 330/796 (41.5%) old are frail. Among old, 76.3% are on metformin and 24.2% on insulin. Hypoglycemia is secondary to skip meals in 37.2% and strong drugs in 38.8% in most of both categories. Elders were better than young in taking remedies for alleviating the hypoglycemia. They always carry sweets (p.0.044), take sugary food (p=0.025).

Conclusion: Fasting blood sugars is reasonable in both categories despite the high percentage of hypoglycaemic episodes. Older adults are affected than young. Further details of hypoglycemia and its relationship with frailty need to be explored.

Abstract No: ABS331: Association between obesity indices and glycemic control in type 2 diabetes mellitus patients: A tertiary care hospital experience

Nazma Akter

MARKS Medical College and Hospital, Dhaka, Bangladesh

E-mail: nazma_aktar_endo@yahoo.com

Background: Obesity is a major risk factor for Type 2 diabetes (T2DM) and studies have shown that obesity indices such as Body Mass Index (BMI), weight, neck circumference (NC), hip circumference (HC), waist circumference (WC) and waist to hip ratio (WHR) are predictors of diabetes. Studies have also shown that weight loss causes a reduction in the progression from impaired glucose tolerance to frank Type 2 diabetes, and reduces mortality in persons with diabetes.

Aims: The objectives of this study were to determine the obesity indices and their relationship with glycemic control in Type 2 diabetes mellitus patients attending a tertiary care hospital in Dhaka, Bangladesh.

Methods: A cross-sectional, observational study was done among 435 type 2 diabetes mellitus (T2DM) patients attending Hormone and Diabetes clinic in a tertiary care hospital, Dhaka, Bangladesh during February 2022 to December 2022. Various anthropometric measurements were used as obesity indices according to standard World Health Organization (WHO) protocols. Data were gathered on clinical and anthropometric characteristics: fasting blood glucose (FBG), post prandial blood glucose (PPBG), glycosylated haemoglobin (HbA1c), blood pressure (BP), weight, height, body mass index (BMI), hip circumference (HC), waist circumference (WC), neck circumference (NC), and waist to hip ratio (WHR).

Results: The proportion of BMI ≥ 25 kg/m² was 25.3% and 42.5% in male and female subjects respectively [p < 0.05]. The proportion of female subjects with high WC cut-offs (>80cm) was 90.4% and male subjects (cut-off >90cm) was 48.1% [p < 0.001]. However, with regard to WHR, 25.9% of the males and only 0.4% of females were at the ideal cut-off points of 0.90 and 0.80 respectively [p < 0.001]. The mean HbA1c of the participants was 8.60% (± 1.49). Only 8.0% of participants (male vs. female: 4.1% vs. 3.9%) achieved good glycemic control (HbA1c: <7.0%); [p<0.05] The correlation between HbA1c level and various obesity indices showed that HbA1c levels were positively correlated with NC and WHR [p < 0.001] but not correlated with WC, HC or BMI [p > 0.05].

Conclusion: Glycemic control was poor among our study participants. Increased HbA1c was significantly positively correlated with increased NC and WHR but not correlated with increased WC, HC or BMI. An aggressive approach should be adopted in managing Type 2 diabetes with particular reference to tight control of blood glucose and obesity indices.

Abstract No: ABS050: Combination therapy with dapagliflozin and vildagliptin in Indian T2DM patients in a real world setting: DAVIL Study

Sanskruti Jayesh Patel

Intas Pharmaceuticals Limited

E-mail: sanskrutipatelmd@gmail.com

Background: Real – world data are required to support the use of combination therapy with SGLT2i and DPP4i in type 2 diabetes (T2D). DAVIL study assessed the efficacy and safety of dapagliflozin and vildagliptin combination therapy in adults with T2D in real – world clinical practice.

Methods: This was a multi-centre, observational, retrospective, non - interventional study of 3567 T2D patients who initiated with combination of dapagliflozin plus vildagliptin. The data was collected between April 2022 and March 2023 from centers across India. Primary outcome was change in glycemic parameters at 3 months from baseline. Other outcomes included socio – demographic details, clinical characteristics, and global tolerability assessment.

Results: Mean age of patients was 55.4 years, and majority were males (66.1%). Majority of patients (65%) were aged 40 to 60 years. Baseline HbA1c, FBG, PPBG and BW, were 8.8%, 188.6 mg/dL, 273.0 mg/dL and 76.8 kg respectively. Around 75.3% of the patients were either overweight (41.9%) or obese (33.4%). Hypertension was the most common comorbidity (64.1%) followed by dyslipidemia (11.3%). Mean HbA1c decreased significantly by 1.2% from 8.8 ± 1.7% at baseline to 7.6 ± 2.9% after 3 months (p value <0.001). About 24.8% of patients on the combination therapy achieved an HbA1c level less than 7% (53 mmol/mol) after 3 months of treatment. Metformin (88.4%) and SU (73%) were most commonly prescribed on-going antidiabetic medications. Commonly reported adverse effects were UTI (2.6%), genital mycotic infections (1.8%), GI disturbances (1.6%) and hypoglycemic episodes (1.5%) and all were mild in nature.

Conclusion: These findings support the benefits of combination therapy of Dapagliflozin and Vildagliptin in a real – world setting in T2D adults (with or without cardio – renal comorbidities), showing a significant reduction across all glycemic parameters. Additionally, it demonstrated a well-tolerated safety profile.

Abstract No: ABS047: Long-term remission rates with intensive lifestyle therapy in young adults with type 2 diabetes mellitus

Satish Kumar Samal

Vydehi Institute of Medical Sciences and Research Hospital, Bengaluru, Karnataka, India

Objective: We have previously reported the rates of diabetes remission (reversal) at two years in a cohort of young adults with newly diagnosed type 2 diabetes mellitus (n=30) following intensive lifestyle therapy (ILT). Here, we report the remission rates at 5 and 10 years in the same cohort with continued ILT.

Methods: This retrospective study was conducted at a tertiary health care center in south India. The young adults (18-30 years of age at diagnosis) with newly diagnosed T2DM registered between November 2012 and October 2013 were advised ILT (calorie: ≤ 1500 kCal/day, physical activity: brisk walking for 1 hour daily) ± pharmacotherapy. Diabetes remission was defined as glycated hemoglobin (HbA1c) of < 6.5% at least 3 months after cessation of glucose-lowering medications. Patients with relapse of diabetes (HbA1c of > 6.5%) were offered more intensification of the lifestyle (further reduction of calorie intake up to 800 kCal/day or increase in physical activity up to 2 hours daily) whereas those with HbA1c of > 7% were also (re)started on pharmacotherapy (metformin ± DPP4 inhibitors). Patients achieving HbA1c < 6.5% of pharmacotherapy were offered reduction/cessation of pharmacotherapy and assessed for re-remission after 3 months.

Results: At 5-year follow-up, ten patients were in remission off pharmacotherapy whereas 10, six, and two patients had HbA1c of < 7% on mono, dual, and triple oral hypoglycemic agents, respectively whereas one patient each had HbA1c >7% on mono and dual therapy. At 10-year follow-up, three patients were in remission off pharmacotherapy whereas five, eight, and 10 patients had HbA1c of < 7% on mono, dual, and triple oral hypoglycemic agents, respectively whereas one, two, and one patient had HbA1c >7% on mono, dual and triple therapy, respectively.

Conclusions: Diabetes remission can be maintained in one-third and one-tenth of newly diagnosed young adults with T2DM at 5 and 10 years, respectively. Hence, diabetes remission with ILT should be offered to all newly diagnosed young adults with T2DM.

Abstract No: ABS300: Hypokalemic paralysis associated with thyrotoxicosis and distal renal tubular acidosis in a young female: A cause or a co-occurrence? – A case report

Shahini Winson Gnanathayalan

National Hospital Sri Lanka, Colombo, Sri Lanka

E-mail: winsgshahini@gmail.com

Background: Thyrotoxic paralysis occurs mainly due to over-sensitization of sodium-potassium ATPase activity in the skeletal muscle membrane, driving potassium into cells. Over 95 percent of thyrotoxic paralysis cases occur in males. Here, arterial blood-gas analysis and urinary potassium excretion are usually normal. Though thyrotoxicosis and distal renal tubular acidosis (RTA) are two well-known causes of hypokalemic paralysis, thyrotoxicosis leading to distal RTA has rarely been reported. It is rare to have co-existence of these conditions to cause hypokalemic paralysis too.

Methods: Here, we describe a case of a female presenting with hypokalemic paralysis having active Graves’ disease and distal RTA concurrently.

Results: This previously healthy, 27-year-old lady presented with hypokalemic paralysis at 5 months postpartum. On admission, potassium was 1.8mmol/L. She had no personal or family history of hypokalemic paralysis. She was clinically thyrotoxic and investigations confirmed active Graves’ disease with FT4 of 2.9ng/dl, TSH <0.008mIU/L and positive Anti-TSH Receptor Antibodies. Unexpectedly, further evaluation confirmed the co-existence of distal RTA (blood pH 7.2, bicarbonate 8mmol/L and urinary pH 8) and increased urinary potassium excretion. Ultrasonically, she had bilateral nephrocalcinosis. She denied features of Sjogren syndrome or other rheumatological conditions. ANA, rheumatoid factor and both anti-Ro and anti-La antibodies were negative. In addition, she had mild PTH-independent hypercalcemia with PTH of <3pg/ml. She was started on propylthiouracil, oral potassium chloride, sodium bicarbonate and potassium citrate. One month after treatment initiation, FT4 and calcium became normal but acidosis with hypokalemia persists requiring the supplements. She is awaiting radio-active iodine ablation therapy. She needs continuous follow-up to define the association between thyrotoxicosis and distal RTA.

Conclusion: This rare case highlights the need for extensive workup for secondary causes and continuous follow-up of female patients presenting with thyrotoxic paralysis in view of strong male predominance of thyrotoxic paralysis, particularly when there are atypical metabolic features.

Abstract No: 340: Weight loss outcome associated with orlistat for patients with overweight or obesity who were prediabetic, diabetic and non-diabetic

Sachin Chittawar, Naima Parveen

Harmony-Dr Sachin’s 360-Degree Diabetes Care, Bhopal, Madhya Pradesh, India

Background: Obesity is a chronic, complex, relapsing condition with a growing prevalence that is expected to reach 49% by 2030. Multiple comorbidities, including type 2 diabetes, dyslipidemia, hypertension, stroke, coronary heart disease, and various malignancies, are part of its medical burden. Therefore, effective weight control is crucial to reduce the morbidity and mortality brought on by obesity, especially in light of the economic and medical costs involved.

Methodology: The study conducted at Harmony- Dr Sachin’s 360 Degree Diabetes Care for weight management, retrospectively collected data on the use of orlistat for adults with overweight or obesity (non-diabetic/prediabetic/diabetic) between June 2021 and August 2023, with a follow- up of 6 months. A total of 2211 patients with a body mass index of 27 kg/m² or more were prescribed orlistat (120 mg thrice daily) for two months or more. Patients who have discontinued orlistat before 2 months were excluded from the study. The population was divided into three groups, in which the first group consisted of patients without diabetes, the second with diabetes, the third comprised of patients who were in the prediabetic phase. The study was approved by the ethical committee of Sir Aurobindo Institute of Medical Sciences, Indore. One way ANOVA and unpaired t- test were used for the statistical analysis.

Results: Out of 2211 patients, only 1391 patients (285 [20.4%] males; 1106 [79.51%] females; mean [SD] age, 36.8 [13.2]; BMI, 33.1 [5.4]) continue orlistat for 2 months. Number of patients taken orlistat in group 1, 2, and 3 were 760 (54.63%), 384 (27.60%), and 247 (17.75%) respectively. The mean weight loss in group 1, 2, and 3 after 2 months was 7.1 [6.1] %, 6.3 [4.9] %, 6 [2.6] % respectively (p<0.05), mean weight loss after 4 months was 14.6 [12.9] %, 8.7 [4.7] %, 15.5 [15.4] % (p<0.05) and the mean weight loss after 6 months was 16.1 [6.7] %, 12.9 [2.4] %, 15.8 [6.2] % (p<0.05). We observed that the patients without diabetes had higher mean weight loss at 2, 4 and 6 months followed by the pre diabetic patients and then the patients with diabetes.

Conclusion: Orlistat was found effective in weight reduction for patients with overweight or obesity who were either diabetic or non-diabetic.

Keywords: Diabetes, harmony, obesity, orlistat, overweight

Abstract No: 342: Gut-thyroid axis and emerging role of probiotics in thyroid disorders

Sachin Chittawar, Naima Parveen

Harmony-Dr Sachin’s 360-Degree Diabetes Care, Bhopal, Madhya Pradesh, India

Background: A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Preliminary studies suggest that the intestinal microbiota and its metabolites may affect the thyroid either directly or indirectly by affecting the conversion and storage of iodothyronine, the absorption of thyroid related microelements such as iron, iodine, zinc, selenium etc, and the metabolism and storage of thyroid hormones by immune regulation. These findings may offer new insights into the pathogenesis of thyroid disorders and their clinical management.

Methodology: A literature research was performed to examine the interplay between gut microbiota and thyroid disorders. For this, we searched PubMed, Web of Science, and Embase databases without language restrictions and conducted a thorough review of literature.

Results: The literature sheds light on the differences in the composition of the intestinal microbiota including Bifidobacterium, Lactobacillus, etc in patients suffering from thyroid diseases compared to healthy individuals. The microbiome affects the proper functioning of the thyroid gland, and the existence of the gut–thyroid axis is discussed in the context of both thyroid diseases and intestinal dysbiosis. Additionally, the composition of the gut microbiota has an influence on the availability of micronutrients essential for the metabolism of thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. But, evidence as of now from the literature for probiotic supplementation to prevent or treat any thyroid disease is limited and not clearly proven. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.

Conclusion: The study provides an updated view on the the current scientific evidence related to an association between thyroid dysfunction and alteration of gut microbiota composition and pave the way for precise research on the gut-thyroid axis in the future.

Keywords: Gut microbiota, gut-thyroid axis, micronutrients, pathogenesis, thyroid

Abstract No: 343: Beneficial role of imeglimin as add on drug with other oral hypoglycemic agents among patients with type 2 diabetes: A single centre observational study

Sachin Chittawar, Naima Parveen

Harmony-Dr Sachin’s 360-Degree Diabetes Care, Bhopal, Madhya Pradesh, India

Background: Imeglimin is a brand-new oral antidiabetic medication and the pioneer in a group of tetrahydro triazine-containing substances that prove effective for glycemic management. However, the actual alterations brought about by imeglimin treatment in real-world contexts are not much explored. Therefore, Imeglimin’s short-term effects and safety on glycemic control in patients with type 2 diabetes were the focus of the present investigation.

Methodology: The subjects (n=167) of this observational study were recruited from among diabetic outpatients who visited at Harmony 360-Degree Diabetes Care, Bhopal from January 2023 to June 2023. Patients were taking two or three oral hypoglycemic agents (OHAs) but their HbA1c (haemoglobin A1c), FPG (fasting plasma glucose), and PPG (post-prandial glucose) levels were not under control and they were not ready to start insulin. So, imeglimin as the third or fourth drug was prescribed to those patients to improve their glycemic control. Demographic profile, physical, and haematological parameters of the patients have been collected and/or analyzed. The study was approved by the ethical committee of Sir Aurobindo Institute of Medical Sciences, Indore. One-way ANOVA was used for the statistical analysis.

Results: The mean age of the population was 55.2±9.9 years and the duration of diabetes was from 6 months to 25 years. There was male dominancy, 92 (55.1%) observed as compared to females, 75 (44.9%). Professionally, working patients, 77 (46.10%) were more than the homemaker or unemployed, 65 (38.9%) and retired patients, 25 (14.97%). 19.16% population was found to have a family history of diabetes. Before commencing imeglimin, patients were prescribed other OHAs of class biguinide, sulfonylurea, DPP4 inhibitors, SGLT2 inhibitors, AG inhibitors, etc as first and second drugs. However, the glycemic level of those patients was not under control therefore imeglimin was prescribed in addition to these combination drugs and after administration of imeglimin, there was a significant decrease in their FPG, PPG, and HbA1c observed. The mean baseline FPG, PPG and HbA1c before imeglimin dose was 176.61±45.75, 247.86±68.17 and 9.1±1.8 which was then significantly decreased to 108.05±24.79 (p=0.013), 156.49±38.53 (p=0.020) and 7.2±1.2 (p=0.004) respectively after imeglimin was added to their dose. The most common adverse effect with imeglimin was gastrointestinal issues and the incidence of hypoglycemia was also observed in some patients.

Conclusion: Imeglimin was found to be effective additional drug works along with other OHAs in order to manage glycemic control.

Keywords: Diabetes, harmony, hypoglycemia, imeglimin, insulin

Abstract No: ABS344: Improved patient-reported outcomes with once-weekly insulin icodec with a dosing guide app versus once-daily basal insulin analogues in type 2 diabetes (ONWARDS 5)

Manu Chandrappa, Ronald Goldenberg¹, Malik Benamar², Lisbeth Carstensen², Melanie Davies³, Anders M. Donatsky², Edward Franek⁴, Monika Kellerer⁵, William Polonsky⁶

Novo Nordisk, India, ¹LMC Diabetes and Endocrinology, Concord, Ontario, Canada, ²Novo Nordisk A/S, Søborg, Denmark, ³Diabetes Research Centre, University of Leicester, Leicester, UK, ⁴Central Clinical Hospital of the Ministry of Interior, Warsaw, Poland, ⁵Clinic for Internal Medicine, Marienhospital Stuttgart, Germany, ⁶Behavioral Diabetes Institute, San Diego, CA, USA

Background and Aims: Effectiveness and safety of once-weekly insulin icodec with dosing guide app vs once-daily basal analogues used as per standard clinical practice in insulin-naive adults with T2D were evaluated in ONWARDS 5, a 52-week, randomised, open-label trial with real-world elements. At week 52, patient-reported outcomes (PROs; change from baseline in DTSQs and TRIM-D compliance domain) were significantly greater with icodec and dosing guide app vs OD analogues (DTSQs change: 4.68 vs 3.90, ETD: 0.78 [95% CI: 0.10; 1.47], p=0.025; TRIM-D: 90.42 vs 87.37, ETD: 3.04 [95% CI: 1.28; 4.81], p=0.0007). Here, we report the items impacting the change in DTSQs total treatment score.

Materials and Methods: Participants (n=1085) were randomised 1:1 to icodec with dosing guide app (n=542) or OD analogues (degludec, glargine U100 or glargine U300; n=543). PROs were evaluated through the completion of the DTSQs (baseline and week 52).

Results: Greater improvement in DTSQs total treatment score seen with icodec and dosing guide app was mostly driven by the items related to participants’ willingness to continue the trial treatment (p=0.0022) and willingness to recommend treatment to others (p=0.0190). Participants randomised to icodec with dosing guide app also reported numerically larger positive changes in three additional DTSQs items, participant satisfaction, treatment convenience and flexibility, though these differences were not statistically significant. After 52 weeks, the odds of achieving a clinically meaningful change in DTSQs total treatment satisfaction score (defined as a change from baseline >0.5 SD) were numerically but not statistically significantly higher with icodec and dosing guide app than OD analogues.

Conclusion: The larger improvement in DTSQs score with icodec with dosing guide app vs OD analogues used as per standard clinical practice appeared to be driven by participants’ willingness to continue and recommend the trial treatment; participant satisfaction, treatment convenience and flexibility also contributed positively.

Abstract No: ABS345: Improved treatment satisfaction with once-weekly insulin icodec versus once-daily insulin degludec in basal insulin-treated type 2 diabetes (ONWARDS 2)

A. Kulhari, W. Polonsky¹, M. Benamar², L. Carstensen², M. Davies³, A. M. Donatsky², E. Franek⁴, M. Kellerer⁵, R. Goldenberg⁶

Novo Nordisk, India, ¹Behavioural Diabetes Institute, San Diego, CA, USA, ²Novo Nordisk A/S, Søborg, Denmark, ³Diabetes Research Centre, University of Leicester, Leicester, UK, ⁴Central Clinical Hospital of the Ministry of Interior, Warsaw, Poland, ⁵Clinic for Internal Medicine, Marienhospital, Stuttgart, Germany, ⁶LMC Diabetes and Endocrinology, Concord, ON, Canada

Background and Aims: ONWARDS 2 assessed the efficacy and safety of once-weekly (OW) icodec compared with once-daily (OD) degludec in daily basal insulin-treated T2D. Participants randomised to icodec reported a significantly greater increase from baseline in the DTSQs total treatment satisfaction score at week 26 (4.22 vs 2.96; ETD: 1.25 [95% CI: 0.41, 2.10]; p=0.0036). Here, we explore individual DTSQ items and report results from the Insulin Preference Questionnaire (IPQ).

Materials and Methods: ONWARDS 2 was a 26-week, randomised, open-label phase 3a trial in 526 participants receiving OW icodec (n=263) or OD degludec (n=263). Patient-reported outcomes were measured using the DTSQs (completed at baseline and 26 weeks) and the IPQ, which assessed participants’ preferences for OW icodec compared with their previous basal insulin.

Results: At week 26, significantly greater increases from baseline were reported with icodec on the following DTSQs items: convenience (p=0.0059), flexibility (p=0.0025), willingness to recommend treatment to others (p=0.0043) and willingness to continue the trial treatment (p=0.0148). The odds of achieving a clinically meaningful improvement in DTSQs total treatment satisfaction score (p=0.0018), as well as two individual DTSQs items, flexibility (p=0.0178) and willingness to continue the trial treatment (p=0.0358), were all significantly greater with icodec compared with degludec. As measured by the IPQ, almost all participants preferred using icodec vs their previous daily basal insulin (93.7%), with most reporting a ‘very strong’ preference (74.1%). The main reasons for this preference were the frequency of injections (69.5%), ease of use (52.3%), better control of blood sugar (36.0%) and fitting well with daily activities (24.7%).

Conclusion: Clinically meaningful improvements in treatment satisfaction scores with icodec vs degludec were driven by differences favouring convenience, flexibility, willingness to recommend treatment to others and willingness to continue treatment. Most participants had a strong preference for icodec over their previous daily basal insulin.

Abstract No: ABS346: Once-weekly insulin icodec and hospitalisation: Insights from the ONWARDS 1–6 trials

U. Sanat, A. Philis-Tsimikas¹, J. K. Bache², T. J. Bari², K. Salvesen-Sykes³, M. Kellerer⁴

Novo Nordisk, India, ¹Scripps Whittier Diabetes Institute, San Diego, CA, USA, ²Novo Nordisk A/S, Søborg, Denmark, ³Novo Nordisk Inc., Plainsboro, NJ, USA, ⁴Center for Internal Medicine, Marienhospital, Stuttgart, Germany

Background and Aims: ONWARDS programme comprises six phase 3a trials (ONWARDS 1–6) assessing the efficacy and safety of once-weekly insulin icodec in T1D & T2D vs once-daily basal insulin comparators. Here, we assess the impact of icodec use during hospitalization.

Materials and Methods: In the ONWARDS trials, hospitalisation data were only recorded based on reports of SAEs as part of safety monitoring procedures. Upon trial completion, available data were assessed according to diabetes type and assessed for: treatment discontinuation; observed individual changes in basal insulin dose, HbA1c, SMBG levels, and participant-reported hypoglycaemic episodes before, during and after hospitalisation.

Results: ONWARDS 1–5 randomised 3765 participants (icodec, n=1882; OD comparators, n=1883); ONWARDS 6 randomised 582 participants (icodec, n=290; OD comparators, n=292). Across trials, 135 participants (mean [SD] age, 62.5 [10.7] years; 127 T2D, 8 T1D) receiving icodec were hospitalised 160 times. Mean (SD) durations of hospitalisation for icodec were 6.64 (4.65) days for medical and 9.27 (11.36) days for surgical reasons. Most participants with hospitalisations (85.9%) completed end-of-trial visits without discontinuing icodec. For participants with T2D, mean (SD) HbA1c for medical and surgical cases was 8.5% (1.1%) and 8.7% (1.3%) at trial baseline, 7.3% (0.9%) and 7.1% (0.8%) at hospitalisation, 7.5% (1.1%) and 7.1% (1.1%) after discharge, and 7.1% (1.0%) and 7.0% (1.0%) at end of trial. For participants with T1D, mean (SD) HbA1c for medical and surgical cases was 8.1% (0.9%) and 6.9% (0.5%) at trial baseline, 8.8% (2.3%) and 7.0% (2.1%) at hospitalisation, 8.6% (1.5%) and 7.0% (2.1%) after discharge, and 8.1% (1.4%) and 7.0% (2.1%) at end of trial. Reported hypoglycaemia rates were low, with minimal differences before, during or after hospitalization.

Conclusion: Most participants continued once-weekly insulin icodec treatment despite hospitalization. HbA1c, SMBG and hypoglycaemia did not change substantially before, during or after hospitalisation.

Abstract No: ABS347: Once-weekly insulin icodec: Pharmacokinetic and pharmacodynamic properties in type 1 diabetes

E. Karthik, U. Hovelmann¹, S. Engberg², T. Heise¹, N. R. Kristensen², L. Norgreen³, R. Ribel-Madsen², E. Zijlstra¹, H. Haahr²

Novo Nordisk, India, ¹Profil, Neuss, Germany, ²Novo Nordisk, Soborg, Denmark, ³Novo Nordisk, Aalborg, Denmark

Background and Aims: Insulin icodec is a once-weekly basal insulin currently in clinical development. This trial investigated the pharmacokinetic and pharmacodynamic properties of icodec at steady state in type 1 diabetes individuals.

Materials and Methods: In a randomised, open-label, two-period crossover trial, 66 individuals with T1D (56 males/10 females, mean±SD age 43±13 years, BMI 26.1±2.1 kg/m2, HbA1c 7.2±0.7%) were allocated to receive icodec for 8 weeks and glargine U100 for 2 weeks. During a run-in period, the dose level of glargine U100 was individually titrated to a pre-breakfast SMPG target of 4.4-7.2 mmol/L. Icodec and glargine were administered at equimolar total weekly doses. Aspart was used as bolus insulin. Blood samples for assessment of pharmacokinetic properties were drawn from first icodec dose until 35 days after last dose. Partial glucose-lowering effect of icodec at steady state was assessed with two automated glucose clamps at 16-52 h and 138-168 h after last dose. The glucose-lowering effect of icodec during a full one-week dosing interval was predicted by pharmacokinetic-pharmacodynamic modelling.

Results: Clinical steady state for icodec was reached within 2-3 weeks. Geometric mean half-life of icodec at steady state was 175 hours. Results suggested dose-proportionality for icodec exposure at steady state. Glucose-lowering effect of icodec at steady state was shown to cover the dosing interval of one week. Rates of level 2 hypoglycaemia were 32.8 vs. 23.9 episodes per PYE for icodec vs. glargine overall and 5.4 vs. 4.4 episodes per PYE for nocturnal episodes. The mean±SD duration of level 2 hypoglycaemic episodes was 33±25 vs. 30±18 min for icodec vs. glargine U100.

Conclusion: The PK PD properties show that icodec can provide basal insulin coverage with once-weekly dosing in individuals with T1D on basal-bolus insulin treatment.

Abstract No: 348: Efficacy of semaglutide for the management of type 2 diabetes: A population based cross sectional study

Sachin Chittawar, Naima Parveen

Harmony-Dr Sachin’s 360-Degree Diabetes Care, Bhopal, Madhya Pradesh, India

Background: Diabetes is confirmed as a substantial concern to the health and wellness of people and families in India. Therefore, to manage diabetes, the search for the efficacy of such drug which has an ability to treat diabetes as well as to reduce body weight gets expanded. Additionally, it can minimize the risk of cardiovascular events and also safe and well tolerated by the patient of chronic kidney disease. One such drug is semaglutide and thus the present study aims to find out the efficacy of semaglutide in diabetic patients.

Methodology: A cross sectional study was performed on 106 diabetic (type II diabetes mellitus) patients presented at Harmony- Dr. Sachin’s 360-Degree Diabetes Care, Bhopal. Demographic profile, physical and haematological parameters have been collected and/or analyzed. Moreover, patients were asked to provide an assessment for tolerability of semaglutide in terms of adverse effects on a Likert 5-point scale from ‘strongly agree’ to ‘strongly disagree’. Cost satisfaction on a same scale was also asked from the patients. The study was approved by ethical committee of Sir Aurobindo Institute of Medical Sciences, Indore. One way ANOVA was used for the statistical analysis.

Results: Out of 106 patients, only 26 (24.5%) continued using semaglutide, rest were discontinued. Mean age of the patients was 50.41 ±1.02 years and there was male dominancy (58.49%). About 51.88% of population have family history of diabetes. The baseline mean HbA1c, weight and BMI was 8.05±0.2, 96.19±3.9, 35.07 ±1.08 which was then reduced to 7.3 ±0.2 (p= 0.018), 92.88 ± 3.8 (p= 0.047), 33.69 ±1.06 (p= 0.029) by using semaglutide. 93.5%, 91.3% and 87.4% patients rated strongly agree or agree for some adverse events including nausea, diarrhoea, loss of appetite respectively. High cost was rated as strongly agree or agree by 71% patients.

Conclusion: Semaglutide was found to be effective for T2DM management as well as for the reduction of body weight. However, some adverse effects including nausea, diarrhoea, loss of appetite were observed using semaglutide.

Keywords: BMI, diabetes, Harmony- Dr Sachin’s 360 Degree Diabetes Care, HbA1c, Semaglutide

Abstract No ABS349: Primary aldosteronism-the commonest cause of secondary HTN: To screen or not?

Sharmin Jahan

Department of Endocrinology, BSMMU, Dhaka, Bangladesh

Primary aldosteronism (PA), first described by Jerome W. Conn in 1955, is the disorder that results from renin-independent aldosterone secretion by the adrenals. It is classically characterized by the triad of hypokalemic hypertension (HTN), suppressed plasma renin activity, and increased aldosterone excretion. Primary aldosteronism (PA) is one of the most common causes of treatment-resistant hypertension (TRH) that is referred to tertiary hypertension centers comprising 4.6% to 13.0% of uncomplicated HTN and up to 20%-30% of patients with treatment-resistant HTN. It is associated with a higher risk of stroke, nonfatal myocardial infarction, coronary artery disease, heart failure, and atrial fibrillation compared to blood pressure (BP) matched essential hypertension. Moreover, first-line medications for hypertension have not been shown to effectively treat the excess mineralocorticoid receptor (MR) activation characteristic of PA. When PA goes undetected, patients may not receive effective treatment for excess MR activation and will not be offered surgery, which can cure PA (and sometimes hypertension) in patients with aldosterone-producing adenomas (APA). However, it remains an underdiagnosed condition. The misconception of the rarity of the disease and the obligatory presence of hypokalemia as a screening prerequisite, the absence of a typical clinical phenotype, and the seemingly complicated diagnostic procedures are all responsible for this phenomenon. In a recent study over 180 hypertensive patients screened at BSMMU, Dhaka only 17.2% fulfilled the classic diagnostic triad of primary aldosteronism but eventually 46% of them were proved to have the disorder following confirmatory testing with saline infusion. The Endocrine Society has referred to PA as a “major public health issue” that needs adequate appraisal. It is indeed a wake-up call for the physicians to screen for this silent killer in hypertensive patients and revisit the historic guidelines.

Abstract No: ABS350: An unusual case of isolated pituitary sarcoidosis presenting as panhypopitutarism due to empty sella syndrome

Paulami Deshmukh¹, Salomi Shaikh², Vaishali Deshmukh³

¹Final MBBS Student SKNMC, Pune, Member: SPHERE, Pune, ²MBBS, KGN Diabetes and Endocrine Centre, Mumbai, ³Consultant Endocrinologist: Deshmukh Clinic and Research Centre; Secretary, SPHERE, Pune, India

41 year lady presented to us in December 2022 with gradual progressive severe weight loss, loss of appetite, severe weakness and premature menopause since 6 years. Occasional fainting episodes. She had weight loss around 40 kg. Had received multiple treatments for 6 years.

On examination: Cachectic, frail female with sunken eyes, apathic and lethargic. No lymphadenopathy, systemic examination was normal.Weight: 38kg (was 78kg 9 years ago) Height: 150 cm BMI =16.88 kg/m² Bp: 90/64 mmHg, no postural drop P:104/min Laboratory investigations revealed Hb 11.9 gm/dl Tlc 13200 leucocytosis with eosinophilia reduced to 9800 after 6 months of therapy. Neutrophil 7748 reduced to 6321/mm³ after 6 months of therapy. Lymphocyte 4039 reduced to 3001/mm³ after 6 months of therapy. Eosinophil 1294 reduced to 98 /mm³ after 6 months of therapy. Anti thyroid antibody: 8.73 borderline positive. Esr 61 mm reduced to 17 mm after 6 months of therapy. Crp 21.6 mg/l reduced to 0.3 mg/l after 6 months of therapy. S FSH 1.2 U/L, LH 0.5 U/L Estradiol <10 pg/ml, S. 8 am cortisol 0.3 mg/ml; S.ACTH: 1.3 u/l, ACE level: 96 u /l reduced to 10.56 u/l after 6 months of therapyF T3 3.44 pmol/l, FT4 12.78 pmol/l, TSH:0.06 iu/ml, S Na /K/Cl: 141/4.0/103 meq/lit Sosmolality: 278 mosm /l, XRC-PA view: normal; TT was negative. MRI brain showed partial empty sella syndrome pituitary height 0f 3mm. Final Diagnosis was: Panhypopitutarism with Secondary hypogonadism, Secondary hypocortisolemia and secondary hypothyroidism due to Partial empty sella syndrome probably due to pituitary sarcoidosis. Treatment was started with Tab Prednisolone 5 mg 1-1/2-1/2; Ethinyl estradiol 0.03 mg and levonorgestrol 0.15 mg; L Thyroxine 25 microgram daily; Calcium 500mg daily. After 6 months of therapy lab parameters and ESR CRP and ACE levels had normalized. Patient was asymptomatic and had regained appetite, menses and weight increased to 56 kg (18 kg).

Pituitary involvement in neurosarcoidosis is a rare with prevalence of around 5% in systemic sarcoidosis. Our case is an unusual case of pituitary sarcoid without the multi-organ involvement typically observed in systemic sarcoidosis and presented as Isolated pituitary involvement which still rare in neurosarcoidosis.

Abstract No: 351: An Uncommon Presentation of Metastatic Pheochromocytoma: A Case Report

Paulami Deshmukh¹, Salomi Shaikh², Vaishali Deshmukh³

¹FINAL MBBS Student SKNMC, Pune; Member: SPHERE, Pune, ²MBBS,KGN Diabetes and Endocrine Centre, Mumbai, ³Consultant Endocrinologist: Deshmukh Clinic and Research Centre; Secretary, SPHERE, Pune, India

33-year old male presented to a medical oncologist with c/o pain in neck , left upper limb and both lower limb thighs ,generalized body ache,tingling in both hands.H/o COVID-19 in July 2021 with mucormycosis underwent Left maxillectomy with mucor debridement. No historyof weight or appetite loss, headache, palpitations, sweating and hypertension. No family history suggestive of MEN syndrome or any neoplastic disorder. On Examination : GC –good Weight –58 kg; Pulse:86/min;BP – supine 120/80 mm Hg, standing 124/80 mm Hg; No focal neural defect.

Neurological examination: Sharp shooting pain on movement of Left upper limb, sensory and motor examination was normal.Bone examination: generalized tenderness over neck and all 4 limbs.Systemic examination was normal.

Lab investigations: Hb:9.4 gm/dl;24 hours urinary metanephrines: 473 mcg/24 hoursSerum calcium-8.8 mg/dl, Serum Phosphorous-4.1 mg/dl, Serum Alkaline phosphatase 94 IU/L, Serum Parathyroid hormone (PTH) 57 pg/ml, Tsh : 1.3 mIU/ml S chromogranin A :2100 ng/ml Ca 19-9:2 u/ml, S calcitonin:4.576, S cortisol :14.4mg/dl, PSA 0.26 ng/ml,ECG :normal ;USG abdomen and pelvis showed a large left suprarenal mass MRI spine done for neck pain showed : Altered signal intensity in vertebral column ,skull base and vault, sternum, lung parenchyma, epidural, paravertebral soft tissue at C3,5,6 and S3,4 levels suggestive of multifocal metastasis.DOTA-PET CT Scan showed.

Large hypodense heterogeneously enhancing left suprarenal lesion measuring 11x 8.8x11 cm SUV 12.74 with abnormal somatostatin expression and few necrotic and calcific areas within, displacing pancreas anteriorly with indistinct fat planes with tail region, inferiorly displacing left kidney with no cortical involvement. Partial encasement of splenic vessel and splenic flexure with indistinct fat planes at places.

Multiple lytic sclerotic skeletal with increased uptake in skull vault ,multiple dorso-lumbar vertebrae, bilateral humerus and proximal ends of both femur, entire pelvis, multiple bilateral ribs ,clavicle and scapulae and sternum

Multiple bilateral lung parenchymal lesions and few deposits involving intercostal muscles of right hemithorax with increased somatostatin expression

Histopathology: Poorly differentiated tumor cells composed of round to ovoid cells with hyperchromatic nuclei and scanty cytoplasm. At places cells appear spindle shaped. Abnormal mitoses seen. IHC: positive for Vimentin ,synaptophysin and chromogranin suggestive of Pheochromocytoma .Trucut biopsyof the L4 vertebral lesion

Marrow involvement by metastatic deposits of pheochromocytoma consistent with suprarenal primary The large atypical cells express chromogranin (moderate) and synaptophysin (strong) Proliferative indices are not uniform and the lesion comprises approximately 40-50% of tumor cells .Final Diagnosis : L malignant Pheochromocytoma with metastasis in bones lungs and muscles.

Treatment: Pain management with Gabapentin and Nortryptilline- one tab for 10 daysPatient was explained option and risk of debulking surgery pheochromocytoma versus radioactive peptide receptor link radionuclide therapy versus targeted chemotherapy. In view of the adrenal mass being extensive, cytoreduction was planned initially.High dose (200 mci) Lutetium 177 PRRT- DOTA therapy first cycle was administered .BP rose during therapy when tab Prazosin was given for a week and then eventually discontinued.Patient is currently receiving further cycles at Tata memorial hospital due to financial constraints.Currently patient is asymptomatic and has plan for adrenal mass resection after cytoreductive PRRT.Genetic evaluation was suggested but not done by patient due to financial concerns.Pheochromocytoma is a rare endocrine tumors (0.05-0.2% hypertension cases) and uncommon in non hypertensive patients . Out of these only 10 percent are malignant with 20 % presenting without any symptoms and variable presentation .Our patient was one such rare case with the relatively uncommon asymptomatic presentation and the disease detected accidentally. He lacked hypertension in spite of florid disease and very high metanephrine levels. Response to PRRT was significantly good and the patient is currently asymptomatic and reported an improvement in quality of life.

Abstract No: 352: A rare case report of thyrotoxicosis with overlapping disorder? NF1-Noonan syndrome

Nishank Kashyap

MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India

Objective: To review a rare case report of Thyrotoxicosis with overlapping disorder? NF-1-Noonan Syndrome.

Background: 14 /Female presented with history of protrusion of eyeballs since last 2 months. She underwent Thyroid Function Test and Ultrasonography Neck in view of swelling on the anterior aspect of the neck. Thyroid profile concluded to be a case of primary Hyperthyroidism (elevated T3 and T4 with TSH<0.005 microIU/L and sonographic finding suggested homogeneous enlargement of thyroid with increased vascularity Mother also gave history of non attainment of menarche and her concern was also about short stature. On examination it was found that patient had exopthalamos, joffroy’s sign and stellwag sign, palmar freckling, webbing of neck, increased carrying angle and short stature. Patient also had tachycardia and hypertension. Ultrasonography abdomen-pelvis suggested hypoplastic uterus and ovaries. XRay elbow was done to look for ossification and epiphyseal closure. Karyotyping for suspected Turner Syndrome came 46XX. Neurofibromatosis type I and Noonan syndrome were also under consideration. Hormonal workup (Sr. LH, Sr FSH, Sr Cortisol, Sr Estradiol and Sr IGF-1) of which Serum IGF-1came significantly low. Patient was then started on Tab Carbimazole and Tab Propranolol. Gynaecologist advised to induce menstruation through breakthrough bleeding post progesterone pills consumption. Furthur plan of action is to give Inj Somatotropin in view of short stature. Molecular genetic testing including Hybridisation is also being taken under consideration

Results, Discussion and Conclusion: This overlapping Syndromes are not very common to be seen in day-to-day practice and hence should be studied with interest so that early intervention, diagnosis and treatment can be given. Appropriate intervention like Growth Hormone Suppression Test, genomic sequencing and testing and treating Thyrotoxicosis should give a better outcome.

Abstract No: 353: A study of cortisol reserve and adrenal gland size in patient’s with Graves’ disease’

Pooran Sharma, Shoaib Mohd Patto, Shahnawaz Ahmed Mir, Basharat Qayoom Dar

Department of Endocrinology, Government Medical College, Srinagar, Jammu and Kashmir, India

Introduction: Clinical thyrotoxicosis states have been reported to be associated with increased rate of cortisol metabolism. Increase in cortisol metabolism can deplete functional reserve of adrenal cortex and lead to adrenocortical insufficiency even when there is no pre-existing Addison disease. In developing countries patients with graves’ disease present themselves in advanced state of thyrotoxicosis. Besides they are also exposed to a variety of environmental stress such as recurrent febrile illness, salt, and Water loss due to manual labour in hot and humid climates. Which can precipitate adrenal; crisis in the presence of compromised adrenal reserve. The present study therefor, was undertaken to assess cortisol reserve in patients with active treatment naïve graves’ disease.

Abstract for oral paper presentation: Basal and 60 min post adrenocorticotrophic hormone (ACTH) (Synacthen 250ug IV) adrenal cortisol response were assessed in 34 graves disease patients with no coexisting illness [M:F 1:1.3, median age 34 years, range 22-48 years during hyperthyroid state in treatment naïve patients. A 60 min post ACTH cortisol value < 500nmol/l was considered abnormal. Estimations of serum T3, T4, TSH and cortisol were done by in house -RIA. Adrenal gland was measured by 4mm thick CT scan 28/34 patients. Mean basal cortisol of graves disease patients in treatment naïve condition were significantly lower compared with their value in euthyroid state [ 206+/- 103nmol/l v/s 421+/- 136nmol/l, respectively p < 0.05. In 8/34 patients (22%) cortisol response to ACTH in hyperthyroid state was subnormal compared with their euthyroid stat. Patient with serum T4 >18ug/dl and T3 > 4ng/ml had lower one hour post ACTH cortisol response (560+/- 133nmol/l compared with T4< 16ug/dl, and T3< 4ng/ml (724+/- 294nmol/l) and significantly lower delta cortisol response 213+/- 73nmol/l v/s 428+/- 265nmol/l. in 6 of them normalization of cortisol response was observed at 6 months of treatment in euthyroid stat. In 20 out of the 28 patients studied by CT scan, adrenal gland showed diffuse enlargement of either thickness or AP width. This observation support to the widely prevalent clinical practice of steroid supplementation in impending thyroid crisis. Presence of diffuse enlargement of adrenal gland on CT- imaging is an original observation.

Abstract No: ABS 354: Glycaemic Control in Adult Patients with Diabetes Mellitus Type-II, Receiving Care Through Nurse–led Diabetic Follow-up Clinic versus Conventional Care: A Randomized Controlled Trial

Thakur K, Sharma SK, Kant R, Kalyani V

AIIMS, Jodhpur

Background: Diabetes affects close to 80 million Indians, and is expected to reach 135 million in 2045. Nurses working in collaboration with doctors can provide a more effective way to treat diabetic patients, especially in rural regions of our country. In these areas, most diabetic complications are not addressed due to the lack of endocrinologists and resources.

Methods: A total of 106 patient were randomly assigned either to follow-up in a nurse-led clinic for dosage titration or to receive usual care. The diabetic nurse-led clinic was managed by a specially trained diabetic nurse researcher managed all protocol-driven changes in insulin dosage and training of patients in self-monitoring of blood glucose. Further, follow-up was scheduled within 3-6 months of duration to monitor changes in HbA1c levels, coping mechanism and satisfaction of patients. She also provided education on diabetic complications, and offered social support to both the patient and family.

Results: The clinical parameters (systolic pressure and postprandial glucose levels) were significantly lower in the intervention group than in the control group [diff=-7.09, 95 % CI (-13.74, -.037) and [diff= -54.21 (-93.91, -14.50). Patients in intervention group showed a decrease in HbA1c [diff = 1.75 %, 95% CI (-2.39, -1.12), P = 0.00] but, this difference was not statistically significant in comparison to control group. Patients attending nurse-led follow-up diabetic clinic reported higher satisfaction and improved coping strategies compared with patients seeking treatment at routine diabetic OPD and the difference was significant [diff= 3.77, 95% CI (1.57, 5.97), p=0.000] and [diff=5.37, 95% CI (3.59, 7.16), p=0.000] respectively.

Conclusion: A well-specified nurse-led diabetes follow-up clinic will be an effective way to treat chronic diseases like diabetes. These findings support a definitive study of this approach for improving nursing adherence, over a long period of time. The clinical and cost-effectiveness results will strengthen clinical practice.

Keywords: Nurse-led clinic, insulin titration, Diabetes, Randomized trial~