Endocrine Week - Free Paper Session

. 2020 Sep-Oct;24(5):452–505.

Endocrine Week - Free Paper Session

PMCID: PMC7810050

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

PUBLIC HEALTH ENDOCRINOLOGY: Prevalence and correlates of peripheral neuropathy among type 2 diabetes mellitus patients – A community based epidemiological study in a town of Eastern India

Sumanta Chakraborty ¹, Anirban Mazumdar ¹

Context: Diabetic peripheral neuropathy (DPN) is a microvascular complication of type 2 diabetes mellitus which may be attributed to chronic uncontrolled hyperglycemia. DPN increases the risk of foot ulcers and non-traumatic amputations, leading to disability, morbidity and poor quality of life for the diabetics.

Aims: To find out the prevalence of peripheral neuropathy among type 2 diabetes mellitus patients and ascertain the correlates for the same.

Settings and Design: A cross-sectional study was conducted among 104 diabetic individuals of Bankura city of West Bengal using principles of simple random sampling technique.

Methods and Material: Data on peripheral neuropathy were collected using Michigan Neuropathy Screening Instrument (MNSI) and correlates were assessed by a pre-designed pre-tested schedule consisting of background & socio-demographic characteristics along with Morisky's médication adhérence scale.

Statistical Analysis Used: Data were entered into Excel (Microsoft Inc.) and all calculations were done using IBM Statistical Package for the Social Sciences (SPSS) (Version 20.0, IBM). Data were analysed and presented using principles of descriptive and analytical statistics.

Results: Prevalence of diabetic peripheral neuropathy was 59.1%. Presence of co-morbidities, poor socio-economic status, polypharmacy, food insecurity, catastrophic health expenditure and lack of social insurance were found significantly associated with diabetic peripheral neuropathy.

Conclusions: DPN prevalence was found to be considerably high. Multiple factors was found to culminate it, upon which socio-economic and health care affordability issues were prominent. A multi-disciplinary approach focusing on them using POEM approach, diabetes education and periodic screening of the diabetic population may help in mitigating the morbidity risks.

Keywords: Diabetic peripheral neuropathy, catastrophic health expenditure, food insecurity, POEM, polypharmacy

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Mental disability due to congenital hypothyroidism despite timely diagnosis: Study from Vellore, Tirupattur and Ranipet districts of Tamil Nadu

Parandhaman Arumugam ¹, Srilakshmi R ¹, Sudha Seshayyan ¹, Shriraam Mahadevan ²

Introduction: Congenital hypothyroidism (CH) is the one of the most common preventable causes of mental retardation. The clinical features of Congenital Hypothyroidism are so subtle that many newborn infants remain undiagnosed at birth. Delayed diagnosis leads to the most severe outcome of CH which is intellectual disability.

Aim and Objective: To find out the prevalence of Congenital hypothyroidism among intellectually disabled children in Vellore, Tirupattur and Ranipet district.

Methodology: The survey was conducted in Vellore, Tirupattur and Ranipet District. Total children covering 513670 in the above 3 district, Tamil Nadu state was conducted during the years 2014-2019 using a specially designed questionnaire. Ethical clearance was obtained from Institutional Ethical Committee (IEC), The Tamil Nadu Dr MGR Medical University, Guindy. A door-to-door survey was done in 743 village (Total 22 Blocks). Survey was done over a period of 5 years. Children between the ages of 5 and 14 years were evaluated.

Results: During the study, in the age group of 6 to 14yrs it was observed that out of 6084 disabled children 2901 (47.68%) had intellectually dysfunction. Consanguinity was common in this population. On further probing, 21 children had Congenital Hypothyroidism diagnosed in early infancy but they discontinued treatment. Reasons for discontinuation included socio-economic status, ignorance, financial burden, distance to reach the centre, testing facility, availability of medicine etc. This reveals that inspite of diagnosing hypothyroidism very early significant number of people may end with mental disability. The success of New Born Screening (NBS) program for hypothyroidism thus depends on long term follow up and regular monitoring.

Conclusion: Newborn screening for Congenital Hypothyroidism and its impact would be realized only if long term follow up is also included in the program.

Keywords: Congenital Hypothyroidism, Newborn Screening, Mental Disability

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

INTER-DISCIPLINARY ENDOCRINOLOGY: Intraoperative use of real time continuous glucose monitoring (rt-CGM) to predict complete insulinoma removal

Ravindra Shukla ¹, Vaibhav Varshney ¹, Subhash Chandra Soni ¹

Background: Insulinoma associated with MEN-1 syndrome are multifocal and rarely metastasize. Surgical management involves total or partial pancreatectomy leading to significant post-operative morbidity. Current guidelines are pragmatic, with emphasis on pre-operative localisation. Most insulinomas are small enough to be amiable for enucleation; its difficult for surgeon to predict complete removal of lesion causing symptoms.

Description: Abott Libre Pro was applied to two MEN-1 patients 3-4 days before surgery and continued till 2-3 days after discharge. Pre-operatively and intra-operatively these subjects are kept at fixed DNS infusion. Upward blood glucose spike was used to define dominant lesion enucleation. Once spike in blood glucose is observed, no further exploration was carried out and pancreatectomy avoided.

Impact on current practise: Studies on type 1 DM have shown Abott Libre pro to be inferior in picking up hypoglycemia. However during insulinoma surgery, we looked for spike in blood glucose rather than hypoglycemia, especially the steepness of line. We have >20 months follow-up of two patients without any recurrence. Intra-op rt-CGM should be widely adopted as handy tool by endocrinologists in India, as state of art localizing techniques like arterial calcium stimulation with hepatic venous sampling (ASVS) are not available.

Conclusion: Further studies including long term follow up (>5 years) should be done to delineate perioperative and intraoperative rt-CGM indices which predict clinical remission. This will help in better management of insulinoma especially those associated with MEN-1 syndrome.

Keywords: Insulinoma, MEN-1, real time CGM

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Spectrum of 21-hydroxylase deficiency congenital adrenal hyperplasia from tertiary care Centres in India

Shinjan Patra ¹, Madhukar Mittal ^1,², Ravindra Shukla ¹, Arun K Singh ³, Neeraj Gupta ³, MK Garg ¹

Introduction: Congenital Adrenal Hyperplasia (CAH) has varied clinical presentations ranging from life-threatening adrenal insufficiency to genital ambiguity, precocity, short stature, amenorrhea, hirsutism and infertility.

Case Report: We report cases of 21-hydroxylase deficiency (21-OHD) CAH representative of the full clinical spectrum. Case1: Presentation on day-4 after birth with genital ambiguity; salt-wasting episodes and failure to thrive. Case 2: Presentation at 5-year age with precocious puberty. Case 3: Presentation with hirsutism and virilisation at age of 12-years during puberty. Case 4: Presentation with primary amenorrhea, hyperandrogenism and clitoromegaly. Case5: Presentation with primary Infertility Case6: . Presentation with virilisation at the age of 25 years Case7: Presentation with short stature and male infertility due to Testicular adrenal rest tissue (TART). Baseline and/or Stimulated 17-OH Progesterone (17-OHP) levels were diagnostic. Direct DNA sequencing and multiplex ligation dependent probe amplification analysis were used to characterize genetic mutations in the CYP21A2 gene.

Discussion: 21-Hydroxylase deficiency, the most common form of CAH can thus present to neonatologists, pediatricians, gynecologists, physicians and endocrinologists. Clinical examination is by far the most important tool to pick up these cases early at primary care level. Timely referral for specialist endocrine care is essential. The treatment formulation and choice of steroids varies depending on the CAH type and age of patient. 21OHD CAH in males and NCCAH are usually detected late in young adults.

Conclusion: Late detection of Simple-Virilising CAH can be seen in our country. Timely referral, diagnosis and treatment can help these patients. Besides Endocrine treatment, standard of care should also cover surgical and psychologic management.

Key words: 21-Hydroxylase deficiency, congenital adrenal hyperplasia, simple virilising CAH, virilization

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Auto-immune Hypoglycemia: Double Trouble in Insulin Autoimmune Syndrome or Hirata Disease

Prasoon Rastogi ¹, Shinjan Patra ¹, Madhukar Mittal ¹, Subhash Soni ¹, Vaibhav K Varshney ¹, Ravindra Shukla ¹, MK Garg ¹

Introduction: Elevated levels of insulin in presence of insulin auto-antibodies (IAA), known as insulin autoimmune syndrome (IAS) or Hirata disease (HD), is the third most common cause of spontaneous hypoglycaemia in Japan and rare elsewhere.

Case Report: We report two cases of IAS with recurrent symptomatic hypoglycemia.

Case-1: 56-year non-diabetic female presented with recurrent hypoglycemic episodes fulfilling classic Whipple's triad with RBS 51 mg/dl. Critical sample revealed fasting insulin >600.0 -U/ml, C-peptide-11.33 ng/ml and Insulin antibody-274.12 U/ml.

Case-2: 60-years non-diabetic male presented with recurrent generalized seizures. Critical sample showed plasma glucose 28mg/dl with Insulin 124.89 mIU/L, C-Peptide-5.43 ng/mL and Insulin Antibody >300 U/ml. In both patients, high insulin levels and insulin antibody titres were seen while GH and cortisol were normal. CECT scan pancreas was negative for tumour. The condition resolved in both individuals over next few months with glucocorticoids and withdrawal of suspected offending drug. Acarbose was also given in case-2. No recurrence of symptoms was seen on follow-up and steroids could be withdrawn.

Discussion: Formation of insulin-IAA complexes prevents insulin binding to its receptor leading to hyperglycemia; insulin subsequently released from the complexes leads to unpredictable hypoglycemia. High IAA titre's clinches the diagnosis. Etio-pathogenesis includes genetic predisposition (HLADR4), sulfhydryl-containing medications (Methimazole, α-lipoic acid, others) Graves disease and idiopathic/spontaneous causes. Only Anecdotal case-reports are available from India. Therapy involves dietary measures, somatostatin analogues, diazoxide, glucocorticoids and immunosuppressants.

Conclusion: Diagnosis of IAS is challenging and requires careful workup to exclude other causes of hyperinsulinemic hypoglycemia. IAS should not be missed as it can lead to unnecessary surgery.

Key words: Insulin antibodies, Insulin autoimmune syndrome, Hirata disease, hypoglycemia

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

PITUITARY: Pituitary dysfunction following snakebite envenomation: A case series

Ayan Roy ¹, Varun Suryadevara ¹, Nagarajan K ¹, Sadishkumar Kamalanathan ¹, Jayaprakash Sahoo ¹, Dukhabandhu Naik ¹, Nandhini Lakshmana Perumal ¹, Niya Narayanan ¹, Chandhana Merugu ¹, Deepika Patel ¹, Milind Patil ²

Background: Snakebite envenomation is an important tropical disease in India, causing significant morbidity and mortality among patients with systemic envenomation. The hormonal deficiencies due to the involvement of pituitary in case of snake envenomation can present in either acute or delayed setting. Hypopituitarism (HP) is often an under-recognized and relatively rarely reported complication of this neglected disease.

Methods: We present here retrospective data of 15 patients who were diagnosed to have HP following systemic snake bite envenomation and are currently followed up in the Endocrinology outpatient department.

Results: The mean age of the patients was 43 ± 9 years and 80% of patients were male. Ninety percent of patients belonged to upper-lower socioeconomic status according to the modified Kuppuswamy scale. The commonest snake species reported was Russell's viper. Thirteen patients had delayed HP. The median duration of snakebite to onset of HP symptoms was one year (range 0.33-10 years). However, the median time from snakebite to the diagnosis of HP was 7 years (range 1-13 years). Central hypothyroidism and hypogonadism were present in all subjects. But central hypocortisolism was noted in 93% of patients. Low IGF-1 was noted in all the six patients where data were available. One patient had partial central diabetes insipidus. Thirteen out of 15 patients had MRI abnormalities including a significant reduction in pituitary volume.

Conclusion: Hypopituitarism in patients with snakebite envenomation can appear slowly and the diagnosis is frequently delayed for years. Following snakebite, multiple pituitary hormone deficiencies associated with radiological abnormalities like a significant reduction in the pituitary volume are common. This study strengthens the idea that all snakebite patients with systemic envenomation irrespective of the initial severity should be regularly followed up for timely diagnosis and treatment of HP.

Key words: Hypopituitarism, MRI, Pituitary, Snakebite

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Efficacy of steroid treatment in Primary Hypophysitis: A single centre experience

Yash Chauhan ¹, Jugal Gada ¹, Prema Varthkavi ¹, Nikhil Bhagwat ¹

Introduction: Primary Hypophysitis (PH) is characterised by inflammation of the pituitary gland. Response to steroids is variable (15%-90%).

Objective: To analyse the effect of steroids on imaging and recovery of hormonal functions in PH.

Materials and methods: Retrospective observational study of patients with PH from 2014 to 2020.

Results: 19 patients (14 females; mean age 38.5 years) with PH, with a mean follow up of 27 months were analysed. 13 patients were treated with steroids (Group A) and 6 were observed (Group B). In Group A, 10 patients received intravenous methylprednisolone (1 gm/day for 3 days) followed by oral prednisolone (1 mg/kg for 6 weeks and tapered) and three patients received oral steroids only. 60% (6/10) patients with central hypocortisolism, 33% (2/6) with central hypothyroidism and 33% (1/3) with diabetes insipidus recovered in Group A. However, there was no recovery in gonadal axis (0/3) [Table 1]. 90% (9/10) showed maximum regression in pituitary size in first 6 months of therapy. Two patients later developed empty sella. In Group B, 50% (2/4) patients with central hypocortisolism and 33% (1/3) with diabetes insipidus recovered. Radiological improvement was seen in only one patient and three (50%) developed empty sella. Overall, more axes improved in Group A than Group B, although not statistically significant (p = 0.465). In subgroup analysis, patients with oral steroids had no major recovery in axes or imaging as compared to intravenous steroids.

Table 1.

Number of patients with axis affected at each follow up visit. Group A – Steroids; Group B – Observation

Axis	Baseline	3 months	6 months	1 year	2 years	≥3 years	Group
Central Hypocortisolism	10	10	5	5	5	4	A
	4	4	4	3	2	2	B
Central Hypothyroidism	6	6	4	4	4	4	A
	3	3	3	3	3	3	B
Central Hypogonadism	3	3	3	3	3	3	A
	2	2	2	2	2	2	B
Diabetes Insipidus	3	2	2	2	2	2	A
	3	2	2	2	2	2	B

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Conclusion: Steroids help in radiological resolution of PH within 6 months of therapy, however, effect on hormonal recovery needs further long-term studies with a larger population.

Key words: Hypophysitis, Lymphocytic, Primary, Autoimmune, Steroids

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Outcomes of patients with pituitary apoplexy managed surgically or conservatively: Study from a tertiary care hospital in southern India

Pragya Gupta ¹

Introduction: Patients with pituitary apoplexy (PA) present with headache, neurological and hormonal deficits. There is no consensus on its preferred management strategy.

Objectives: We studied the baseline clinical, hormonal and radiological profile of patients of PA and compared the outcomes among surgically vs medically managed patients.

Methodology: We retrospectively reviewed 241 patients with a documented diagnosis of pituitary apoplexy over a period of 13 years and selected 54 patients, who had a clinical presentation of PA along with radiological and/or histological evidence of pituitary hemorrhage. Result: Among 54 patients, 45 (83.3%) were men, their mean age was 48 years and they had a median follow-up of 8 years. Patients presented with headache (87%), diplopia (55.5%), ptosis (44.4%), visual impairment (44.4%), vomiting (25.9%) and altered sensorium (25.9%). Forty-nine (90.7%) patients had non-functioning pituitary adenoma. Twenty-three (42.6%) underwent surgical intervention and 31 (57.4%) were managed conservatively. Ophthalmoplegia and ptosis resolved in all patients. The mean initial tumor size 27.6 × 24.1 mm2 decreased to 7.2 × 6.1 mm2 in the operated patients and 8.6 × 6.2 mm2 in the conservatively managed group. Among the surgically managed group new onset hypothyroidism and hypogonadism were seen in 4/8 (50%) & 8/11 (72.7)% patients, respectively. Whereas the same in the conservative group was 10/16 (62.5%) and 15/18 (83.3%). The incidence of new onset hypocortisolemia was similar in both groups.

Conclusion: This is the first Indian series to study the clinical, hormonal and radiological outcomes in patients following PA. Clinical and radiological resolution was similar in both treatment groups but a higher incidence of new onset hypothyroidism and hypogonadism were noted in the conservatively managed group.

Key words: Pituitary Apoplexy, Conservative management, Hormone dysfunction, Tumor size

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Clinical characteristics, diagnostic challenges and therapeutic outcomes of thyrotropin-secreting pituitary adenomas: A case series of three patients

Prudwiraj Sanamandra ¹, Jugal Gada ¹, Nikhil Bhagwat ¹, Premlata Varthkavi ¹

Background: TSH-secreting pituitary adenomas (TSHomas) account for about 0.5-3% of all pituitary adenomas. Most of them tend to be misdiagnosed initially because of their unique presentation with thyrotoxicosis and inappropriately normal/high levels of thyrotropin (TSH).

Case Report: We describe the clinical characteristics and surgical outcomes of three cases of TSHomas. All the three patients presented with thyrotoxic symptoms with inappropriately high TSH. Mean TSH was 18 mIU/ml (range 2-50 mIU/ml). One patient had concomitant autoimmune thyroiditis. Short acting Octreotide suppression test suppressed TSH in two out of three cases. All the three had macroadenomas with one being giant adenoma invading into parietal lobe. Two patients were surgically cured without recurrence till 5 years of follow up. The uncured patient had GH co-secreting TSHoma, underwent surgical resection followed by radiotherapy and is presently on somatostatin analogue from last 2 years.

Discussion: Diagnosing an isolated TSHoma can be a challenge. Short Octreotide suppression test can be used effectively to differentiate from RTH in 60-80% of cases. TSHoma can coexist with autoimmune thyroiditis and they can have extremely high TSH. 20-25% of TSHomas are mixed adenomas, characterized by concomitant hypersecretion of other anterior pituitary hormones, mainly GH or PRL. Surgical resection is the first-line therapy, which can cure 45% of macroadenomas and 80% of microadenomas.

Conclusions: High index of suspicion for TSHoma is warranted when patient presents with high total or free T4 and inappropriately normal or high TSH.

Key words: TSHoma, pituitary adenoma, hyperthyroidism

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Post-operative hyponatremia: Prevalence, predictors and prognosis – A study from a tertiary care center in southern India

Remya Rajan ¹, Shivendra Verma ¹, Nitin Kapoor ¹, Ari G Chacko ¹, Thomas V Paul ¹, Nihal Thomas ¹, Felix Jebasingh ¹, Kripa Elizabeth Cherian ¹, Shalini Sahu ¹, HS Asha ¹

Background: Delayed hyponatremia(DH) is a common complicationfollowing trans-sphenoidal surgery(TSS) for pituitary tumor. Identifying factors that predict DH may reduce the associated morbidity as well avoid prolonged hospitalization. Objectives: We evaluated the prevalence of DH following TSS, and also assessed the factors associated with DH, including early post-operative diabetes insipidus (EPDI).

Methodology: This was a retrospective study that involved 100 TSS for pituitary adenoma in 98 patients, over a period of 26 months. Subjects were divided into two groups- those who developed hyponatremia and those who did not during post-operative days 4-14. Clinical characteristics andperi-operative parameters were compared between the two groups, to identify factors predicting DH.

Results: The mean age of the patients was 42 ± 13.6 years, 59 (59%) were females, and 61 (61%) had functional tumors.Thirty-six (36%) patientsdeveloped DH following TSS of which majority (58%) were diagnosed on post-operative days 7 and 8;8/36 (22%) were symptomatic. Syndrome of inappropriate antidiuretic hormone(SIADH) was found to be the most common etiology of DH. On comparing the various factors predicting DH, by logistic regression, intra-operative CSF leak (OR 5.0; 95% CI 1.8-13.8; p 0.002), EPDI (OR 3.4; 95%CI 1.3-9.2; p 0.015) andperi-operative steroid use (OR 3.5;95%CI 1.3-9.8; p 0.014) were found to be significantly associated with DH.

Conclusion: EPDI, intra-operative CSF leak and peri-operative steroid use were significant predictors of DH. As most patients have asymptomatic hyponatremia, serum sodium measurement on post-operativedays 7 to 8 would be helpful to identify DH in patients at increased risk.

Key words: Hyponatremia, post-operative diabetes insipidus, syndrome of inappropriate antidiuretic hormone, trans-sphenoidal surgery

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Sheehan syndrome; experience from a tertiary care center from Central India

Jaideep Khare ¹, Sushil Jindal ¹, Saifali Bansal ¹

Introduction: Sheehan Syndrome (SS) though not uncommon is identified as a consequence of ischemic pituitary necrosis due to severe postpartum hemorrhage leading to various manifestations due to varying degree of anterior pituitary hormone deficiency.

Aim: The aim of our study was to determine the clinical and biochemical characteristics of Sheehan's syndrome in our patients. Material and Methods: It was the retrospective cohort study in which we identified the patients who visited our endocrine department and were diagnosed with SS. The various clinical, biochemical and radiological findings of these patients were recorded and analyzed.

Results: Mean age of our patients was 36.65 years. 16 patients had history of blood transfusion during peri- partum period but only 11 patients had history of massive bleeding at delivery. 19 patients reported lactation failure and 12 patients reported loss of menstruation following delivery while rest all reported amenorrhea within 2 – 3 years following delivery. On anterior pituitary hormonal analysis 19 patients had secondary hypothyroidism, 13 had adrenal insufficiency, 21 had low gonadotropin levels, 9 had low prolactin levels. Biochemical character of our patients is described in table 1. On radiological examination by magnetic resonance imaging (MRI) complete or partial empty Sella was recorded in 23 patients.

Table 1.

Biochemical Characteristics of our patients

Parameter (Normal range)	Mean ± SD	Range	Low Levels recorded	High Level recorded
Hemoglobin (12 – 14 g/dl)	9.8 ± 1.91	6- 16	17	4
Serum Sodium (135 - 145meq/L)	131.3 ± 4.14	114 - 142	9	2
Serum Potassium (3.5 – 5.5meq/L)	4.1 ± 0.46	3.5 – 5.8	4	3
Random Blood Sugar (70 – 200 mg/dl)	121.3 ± 34.33	59 - 231	2	1
TSH (0.45 – 4.5 UIU/mL)	3.7 ± 1.61	0.01 – 8.8	12	3
T4 (6.5 – 12.5 mcg/dl)	6.7 ± 2.14	0.5 – 14.1	19	2
T3 (0.6 – 1.8 ng/ml)	0.8 ± 0.21	0.1 – 1.7	21	1
LH (mIUI/ml)	5.1 ± 1.13	0.01 – 4.1	20	1
FSH ( mIUI/ml)	6.8 ± 1.96	0.01 - 13	21	2
Prolactin (1.5 – 24 ng/ml)	14.3 ± 8.13	0.5 – 41.2	9	2
Cortisol (8 am) (5.5 – 18.6 mcg/dl)	8.5 ± 2.34	0.1 – 16.5	16	1
Cortisol (Post Acton Prolongatum Stimulation) (> 18.6 mcg/dl) ( N =16)	11.8 ± 7.76	0.8 – 36.4	13	3

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Conclusion: The SS is not an uncommon condition and increases the risk of morbidity and mortality if not diagnosed and managed early. In our cases early menopause and lactational failure were the most common clinical findings and early clue to suspect for SS and do necessary work up for further management.

Key words: Amenorrhea, empty Sella, lactation failure, pituitary necrosis, Sheehan syndrome, postpartum hemorrhage

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Snake bite related panhypopituitarism, addisons disease (multiple endocrine apoplexy)

Ayan Roy ¹, S Jayaram ¹

Introduction: Snake bite envenomation is a major concern in tropical countries resulting in multiple effects like renal failure, capillary leak syndrome, ARDS, DIC due to pro and anticoagulant enzymes mostly in acute phase. Late sequalae such as renal failure seen in vasculotoxic snake bite like vipers. There are very few case reports describing endocrine dysfunction as a late complication of viper bites resulting in significant morbidity and mortality in such patients. Chatterji et al in their study of profile of 86 hypopituitarism patients found that snake bite as an important etiological factor. Involvement of multiple endocrine glands post snake bite can occur during acute or after several months or years. Hereby we report a patient who presented with panhypopituitarism after 1 ½ years of snake bite. Early suspicion, active hormonal replacement and supportive management will improve the outcome of the patient.

Case Report: A 49 year old male, farmer by occupation, residing at Villupuram, presented with complaints of syncopal episodes for 1 months. He was doing well one and half years back. Then he had H/O snake bite followed by cellulitis and AKI progressed to CKD secondary to snake bite in Jan 2019 had H/O prolonged hospital stay, intubation and ICU stay in Jan 2019. He was evaluated for endocrinopathy and discharged that time. He was on regular medication and no drug default was there. Now presented with multiple episodes of syncope for 1 month started in June 2020. Pre-syncope and followed by sycope, multiple episodes over 20 days, spontaneous recovery in 4 to 5 minutes. No chest pain, palipitations, No headache, seizures. Syncope associated with nausea, sweating. H/O vomiting immediately after food consumption for the past 2 weeks. Multiple episodes of fall due to syncope and trauma to head and foot present. No H/O altered speech or behaviour or FND. No H/O drop attacks previously. No H/O fear of heights or abnormal sensitivity to sound. H/O giddiness on getting up from bed postural giddiness. H/O loss of appetite for 2 weeks, weight loss present and constipation for 2 days. No H/O dysphagia, difficulty in swallowing. No H/O B/L leg swelling, facial puffiness, SOB or burning micturition. Normal urine output. No H/O fever. O/E, patient was conscious, oriented and was in depressed mood. He was pale, dehydrated. . Skin of peripheries were coarse, cool, dry and pigmented. Haematological tests were normal. RFT revealed creatinine derangement of 2.6 and hyponatremia and hyperkalemia present. Hormonal panel analysis was sent. Endocrinology opinion soughted. Patient was diagnosed to have panhypopituitarism with hypothyroidism and adrenal insufficiency and AKI on CKD secondary to Viper snake bite. He was treated with steroid replacement (hydrocortisone), thyroxine and sodabicarb for CKD and treated with IVF and electrolyte abnormalities were corrected. The patient symptomatically improved and creatinine trend improved and static.

8 AM serum cortisol	3.6 (less than normal)
Free T3	2.76
Free T4	1.02
TSH	0.01 (0.35-5.5) (TSH is low)

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Discussion: Vasculotoxic ophitoxemia can cause coagulation activating enzymes to activate and direct endothelial damage, abnormal platelet function and microthrombi formation leading to shock and pituitary apoplexy and adrenal insufficiency. Follow up of the patient of snake bite and anticipation of this complications in tropical countries is necessary. Our patient had syncopal attacks, loss of appetite, weight loss, vomiting, giddiness, recurrent syncope refractory to medications, fatigue, depression, etc… detailed past history and hormonal assay helped in supporting the diagnosis. Hence, good clinical suspicion, timely hormonal replacement with steroids can help in improvement of symptoms.

Conclusion: Along with vascular, renal and local complications, endocrine complications must also be suspected eventhough it may occur in days, months or years. Significant past history and hormonal panel and good clinical suscipion and timely hormonal intervention will help to save the life of the patient. Hence pituitary and adrenal gland dysfunction to be considered in patients who had viper bite in the past.

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Avascular osteonecrosis of femoral head in a patient cured of pituitary Cushing's disease

Raj Mohan Lekshmi Narayanan ¹, Thushant Thomas ¹

We describe a rare case of operated and cured Cushing's disease caused by pituitary microadenoma now presenting with bilateral avascular osteonecrosis (AVN) of the femoral head. AVN is a well-recognized complication of patients on long term steroids. A 24-year-old man was diagnosed with Cushing's disease in 2017 when he presented with typical signs and symptoms of Cushing’ syndrome and biochemical investigations revealed hypercorticolism. MRI brain showed 4.5 mm nodule on the right side of anterior pituitary lobe. IPSS confirmed the source of hypercortisolism and he underwent surgery for the same in 2017. Postoperative imaging as well as biochemical tests confirmed cure from Cushings disease. However 3 years later he developed bilateral hip pain and MRI of hip showed bilateral AVN of both femoral heads. Repeat tests for hypercortisolism including overnight dexamethasone suppression tests and 24 hour urine free cortisol were negative. He denied any ethanol abuse and was non smoker. Investigations for other causes of AVN including SLE, hyperparathyroidism were negative. Exogenous hypercortisolism is well known cause of AVN but secondary to endogenous hypercortisolism is rare and very few case reports are available. Even fewer literature is available on AVN presenting post-pituitary surgery for Cushing's disease. Here we present a young man who presented with AVN of both hips 3 years after surgery for Cushing's disease which had resulted in complete remission. This case illustrates that AVN, an orthopedic emergency, can be an alarming manifestation of Cushing's disease which can occur even after biochemical cure from disease.

Key words: Avascular Necrosis, Cushings Disease, Steroids

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Thyroid Stimulating Hormone (TSH) secreting pituitary adenoma. A diagnostic and therapeutic challenge – A series of 4 cases

Kumar Thulasidass ¹, Muthukumaran Jayapaul ¹, Velayudham P ², Shriraam Mahadevan ¹

Introduction: TSH secreting pituitary adenoma is a rare entity. Less than 1% of all diagnosed pituitary adenomas are TSHomas. We present a case series of 4 TSHomas with varied presentations and underwent different courses of management.

Materials and methods: We had amongst us 4 patients with TSHoma presenting in a 3 year period 2017-2020.

A 26 year old lady, had increased tiredness and sleep disturbance. She had no typical thyrotoxic symptoms. She had a one cm pituitary adenoma. Normal other pituitary functions.

A 56 year old gentleman, had eye examination for broken spectacles;had increased ocular pressure and MRI showed pituitary tumour. Blood tests revealed central hyperthyroidism. His only symptom was migraineous headache.

A 43 year old gentleman, had gradual weight loss. Normal appetite. No thyrotoxic symptoms. Inappropriate TSH elevation was found incidentally. Imaging revealed a large sellar tumour.

35 year old lady, was investigated for weight loss of 3-4 kgs. She had mild palpitation and sometimes increased bowel movements. Sleep and appetite normal. This patient had a large pituitary tumour pressing on optic chiasma but had normal visual fields by perimetry.

Results: First patient underwent surgery. She had immunopositivity for TSH, GH, Prolactin but did not have manifestations of those hormonal excess. She was cured.

Second patient had biochemical evidence of hypersecretion of TSH and prolactin but asymptomatic. He was treated with Octreotide and cabergoline. He responded to treatment.

The third patient had asymptomatic partial adrenocorticotroph insufficiency. He was treated with carbimazole and hydrocortisone.

Fourth patient was treated with Octreotide and surgery was planned. Her thyroid hormones normalised but she did not agree for surgery. She also was lost to follow up.

Conclusion: From above patients, we could see that all had different presentation features and they underwent different course of treatment.

One had surgery for 1 cm adenoma and cured. One patient was treated with Octreotide and cabergoline; one patient treated with carbimazole and hydrocortisone and one had medical treatment, declined surgery, but was lost to follow up.

Common factor in their presentations is that they all were having subtle or no symptoms.

Key words: TSH, Adenoma

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Gonadotropinoma presenting as Spontaneous ovarian hyperstimulation syndrome

Amulya Yalamanchi ¹, Asirvatham Adlyne R ¹, Balachandran Karthik ¹, Mori Krishna S ¹, Visvanathan Krishnaswamy ¹, Mahadevan Shriraam ¹

Introduction: Spontaneous ovarian hyperstimulation due to Gonadotropinoma is extremely rare and is usually secondary to HCG administration as a part of assisted reproductive techniques.

Case Report: A 32 year old female, with history of subfertility, polycystic ovaries, previously on oral contraceptive pills (OCPs), had underwent controlled ovarian stimulation (HCG + Gnrh agonist + Gnrh antagonist), for pregnancy during which there is no increase in the size of the ovarian follicles. Three years after child birth she had presented with features of acute abdomen and was found to have unilateral ovarian torsion with bilateral multiple voluminous cysts and underwent right salpingo-oophorectomy. She was referred to our clinic for Endocrine opinion. In view of elevated estradiol, unsuppressed gonadotropins, hyperprolactinemia, secondary hypothyroidism and hypocortisolism she was evaluated for a pituitary cause and imaging revealed a pituitary macroadenoma. She was started on OCPs and Cabergoline following which her cysts have significantly regressed and later she underwent transphenoidal resection of the tumour because of her visual field deficits.

Discussion: Gonadotroph adenomas presenting as a clinical syndrome is very uncommon and Spontaneous ovarian hyperstimulation due to Gonadotropinoma have been reported. In our case we have an overlapping history of exogenous gonadotropin therapy but the presentation of ovarian hyperstimulation was seen three years after cessation of the treatment which prompted us to look for a pituitary cause.

Conclusion: This clinical case describes Spontaneous ovarian hyperstimulation syndrome, which is an uncommon presentation of a rare disease.

Keywords: Gonadotropinoma, oral contraceptive pills, pituitary macroadenoma, spontaneous ovarian hyperstimulation

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

GONADS : Clinical and hormonal profile of Turner syndrome with relation to karyotype in a tertiary care Center in eastern India

Mounam Chattopadhyay ¹, Pranab Kumar Sahana ¹, Nilanjan Sengupta ¹, Soumik Goswami ¹, Arjun Baidya ¹

Introduction: Turner syndrome (TS) is associated with characteristic clinical features mainly short stature and gonadal dysgenesis affecting 1 in 2500 live births. There is underlying anomaly of one X chromosome e.g. monosomy, mosaicism or structural defect. Yet there are paucity of Indian studieson TS commenting on the phenotype and karyotype associations.

Aims and Objectives: To study the clinical and hormonal profile of TS patients in this part of the country and their relation with different karyotypes.

Materials and methods: 10 consecutive patients visiting our endocrine clinic with clinical stigmata of TS were evaluated with karyotyping (G banding) and hormonal profile.

Results: We have followed up 10 TS subjects. Their karyotypes are e.g. 6 monosomy, 2 mosaic and 2 structural defects. Height is more compromised in monosomy patients i.e. -5 SD below mean for age and mean FSH (96) was found to be higher than mosaic (38) or structural (46) group. Mean age of presentation was lowest (7y) in monosomy and highest in mosaic group. Among the 6 in the monosomy group 2 had bicuspid aortic valves, 1 had coarctation of aorta and 2 had elongated transverse aortic arches. One of the girls in the mosaic group attained spontaneous menarche at 14 years. One of the girls in isochromosome group had autoimmune hypothyroidism.

Discussions and Conclusions: In line with the existing literature, clinical manifestations in TS are found to be more pronounced in patients with monosomy rather than other karyotypes. High index of suspicion must be exercised for the diagnosis and treatment of TS.

Keywords: Turner syndrome, karyotype, monosomy, mosaic

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

46, XX testicular disorder of sexual development: A two rare cases of 46XX male

P Ganesh ¹, Jayanthy Ramesh ¹, KAV Subramanyam ¹, A Mythili ¹, B Vivekananda ¹

46, XX testicular disorder of sex development is a rare genetic syndrome, with a reported incidence of 1:20,000 in new born males and characterized by a complete or partial mismatch between genetic sex and phenotypic sex. Testicular tissue differentiation may be due to the translocation of SRY to the X chromosome or an autosome. In the absence of SRY, overexpression of other pro-testis genes, e.g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue.

We hereby report an interesting rare cases of two 46XX males. First case, 24-year-old phenotypic male carrying a 46 XX presented with poor development of secondary sexual characters, small testicular volume and micropenis. SRY negative on FISH. Second case a 16 year old male came with poor secondary sexual characters and found to have 46 XX on karyotyping.

Keywords: 46 XX male, 46 XX testicular DSD, sex reversal, SRY negative

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Genetic analysis of 46 XY disorders of sex development (DSD) patients in South Indian population

Chandhana Merugu ¹, Lavanya Ravichandran ¹, Rajan Palui ², Niya Narayanan ³, Sadishkumar Kamalanathan ⁴, Jayaprakash Sahoo ⁵, Dukhabandhu Naik ⁶, Nandhini Lakshmana Perumal ⁷, Nihal Thomas ⁸, Aaron Chapla ⁹, Ayan Roy ¹⁰, Deepika Patel ¹¹

Introduction: There are multiple causes of 46 XY disorders of sex development (DSD) and their phenotypical manifestations overlap. Genetic analysis is required for definitive diagnosis.

Aim: The aim of this study was to analyse mutations in SRD5A2 (5 alpha reductase type 2), AR (Androgen receptor) and HSD17B3 (17β-hydroxysteroid dehydrogenase type 3) genes in 46 XYDSD patients.

Materials and methods: Clinical, hormonal and radiological evaluation of patients of the 46 XY karyotype with atypical genitalia (EMS score =10) and suspected to have either a SRD5A2 deficiency, partial androgen insensitivity syndrome (PAIS) or HSD17B3 deficiency presenting to the Department of Endocrinology in JIPMER was done. Genetic analysis was carried out for SRD5A2, AR and HSD17B3 genes using a Next Generation Sequencing (NGS) strategy developed and performed at the Molecular Endocrinology Laboratory, Christian Medical College, Vellore.

Results: This cross-sectional study included 37 patients of 46 XYDSD with a median age of 4 years (Interquartile range-5). Of these, 12 were born of consanguineous parenthood. Based on clinical evaluation and HCG stimulation, 21 (56%) patients were diagnosed to have SRD5A2 deficiency, 6 (16%)- HSD17B3 deficiency, and 10 (27%)- PAIS. A genetic analysis revealed positive results in 9 patients- 6 in the AR gene, 2 in SRD5A2 gene and 1 in the HSD17B3 gene. The clinical and genetic diagnosis correlated in only the patient with the HSD17B3 gene mutation and another with a SRD5A2 gene mutation.

Discussion and Conclusion: These genetic mutations were found in 24% of our patients of 46 XYDSD. The genetic and clinical diagnosis did not correlate in 77% of the patients. Further studies involving a genetic analysis in a larger population of 46 XYDSD patients is required.

Keywords: HSD17B3, PAIS, SRD5A2

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Myotonic dystrophy presenting as primary infertility-a case report

Madhusmita Sahu ¹

Introduction: Myotonic dystrophy (DM1) is defined as a hereditary, autosomal dominant multi-system disorder caused by an expansion of an unstable CTG trinucleotide repeat in the gene DMPK (myotonic dystrophy protein kinase).[1] Reproductive anomalies are well recognized finding in myotonic dystrophy. Testicular atrophy, with the disappearance of the seminiferous tubules, leads to infertility. We report a case of a patient with aspermia associated with DM1.

Case Report: A 38-year-old man married since 7 years came to us with primary infertility and erectile dysfunction since 5 years. He also complained of progressive proximal extremity weakness for the past 3 years. The physical examination revealed soft testicle, measuring 8 ml, bilaterally. The size of the penis and pubic hair growth were unremarkable. Neurologic examination demonstrated facial weakness, ptosis with 4/5 strength at the proximal extremities. Semen analysis performed 2 times, demonstrated a low ejaculate volume (< 1.5 ml) with aspermia. Endocrine evaluation revealed a plasma LH of 20 mIU/ml, FSH of 27 mIU/ml and testosterone of 278 ng/ml. Electromyography demonstrated myotonic discharges. Fertlity prospect was explained.

Discussion: DM1 is the most common cause of an inherited, adult-onset, muscular dystrophy and primary hypogonadism occurs in approximately 80% of men with DM1. Infertility due to myotonic dystrophy is not reversible with medical therapy.

Conclusion: Though Klinefelter is the most common cause of primary hypogonadism, other rare causes like myotonic dystrophy should be kept as differential diagnosis.

Keywords: Myotonic dystrophy, primary hypogonadism, primary infertility, testicular atrophy.

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Serum Anti-Müllerian hormone (AMH) as a biomarker for PCOS diagnosis

Hemant Kumar ¹, Amanpreet K Kalsi ¹, Manish Jain ¹, Ashutosh Halder ¹

Background: PCOS is characterized by hyperandrogenism, chronic oligo-anovulation and polycystic ovary. Although hyperandrogenemia is one of the major features of PCOS, it is rarely observed, hence need for a better marker. In the recent years there is growing evidence about associations of AMH with PCOS.

Objective: To investigate the diagnostic potentials of AMH in PCOS.

Methods: A total of 131 women with PCOS and 49 control women were enrolled prospectively after exclusion of secondary causes of PCOS. Serum AMH was measured using ultra-sensitive AMH ELISA Kit. Statistical analysis was carried out using Mann-Whitney U test and ROC curve.

Results: Mean AMH value was 10.049 ng/ml in the study group whereas in control was 2.59 ng/ml (p < 0.00001). Normal cut off value of 5.54 ng/ml was derived from control mean plus 2SD. With 5.54 ng/ml cut off value we could detect high value only in 6% controls but in 75.57% (total), 80.45% (phenotype A), 65.22% (phenotype B), 50% (phenotype C) and 76.92% (phenotype D) of PCOS cases. The area under ROC curve was 0.9332 (lower & upper bound 95% Conf. Interval 0.88644 & 0.96508) for total cases. The area under the ROC curve yielded highly satisfactory result (diagnostic range) in phenotype A (0.9602) and phenotype D (0.9498) but not with phenotype B & C. We did not find significant differences between pubertal (<20 years) and post pubertal groups (=20 years) as well as with normal or high BMI groups.

Conclusion: AMH can be considered as diagnostic biomarker in PCOS women, in particular with phenotype A and phenotype D.

Keywords: AMH, biomarker, PCOS

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Clinical profile of 46XY males with mullerian structures: A case series

Roshan Nazirudeen ¹, Sangumani Jayaraman ¹, Subbiah Sridhar ¹

Introduction: Persistent Mullerian Duct Syndrome (PMDS) is a rare disorder of sex development, characterized by the presence of Mullerian structures in otherwise normally virilized males, due to autosomal recessive inactivating mutations in AMH or its receptor AMHR2. PMDS has three main clinical presentations: bilateral cryptorchidism (86%), unilateral cryptorchidism and transverse testicular ectopia.[2] There has only been a single case series of PMDS from India to our knowledge.[3] Here we present the clinical profile of four patients with PMDS.

Materials and methods: All cases of cryptorchidism were evaluated in the Pediatric Endocrinology clinic of Madurai Medical College, Madurai. After a detailed history and clinical examination, all patients were evaluated with serum LH, FSH, cortisol, TSH, FT4, 17 hydroxyprogesterone and serum AMH. Imaging by ultrasound, followed by MRI confirmed the presence of uterus and karyotyping revealed 46, XY pattern in all four cases being reported in this series. Laproscopy and histopathology confirmed the imaging finding in 2 patients. The details are summarized in Table 1.

Table 1.

Clinical profile of PMDS patients

	CASE 1	CASE 2	CASE 3	CASE 4
Age at presentation	3 years	25 days	2.5 years	2 days
Consanguinity	Yes	No	Yes	Yes
Cryptorchidism	Bilateral	Unilateral-right undescended testes	Bilateral	Unilateral-Left undescended testes
Hernia	No	Yes	No	No
Hypospadias	No	No	No	Perineal
Other LE findings	SPL- 4.5 cm	Phallus- 0.5 cm	SPL – 3 cm	Phallus 3 cm, bifid scrotum, right testes palpable in Rt labioscrotal fold
	Bilaterally scrotal folds empty	Poorly developed scrotal sac, no rugosity;	Left testes about 2 ml size (post orchidopexy).
		Left testes palpable peanut sized	Rt testes not palpable
		1 × 1 cm
		Bilateral inguinal hernia-reducible
AMH (normal: 0.6- 13.7)	<0.02 ng/ml	17.59 ng/ml	0.03 ng/ml	>24.5 ng/ml
IMAGING (MRI)	Hypoplastic uterus 0.7 0.5 cm, rudimentary gonad like structure 0.6 × 0.5 cm in left inguinal region	Testes-like structure in left inguinal region 0.6 × 0.4 cm, small uterus like structure1.2 × 0.6 × 0.8 on the right side and bilateral congenital hernia with omentum	Uterus 2.5 × 1.6 × 1.2 cm	Uterus 2.8 × 0.7 cm in rectovescical pouch. Rt testes 1.8 × 1 cm in right hemiscrotum, surrounded by fluid collection. Lt testes 7.5 × 5.3 mm in left inguinal canal
			Ovoid gonadal tissue without follicles noted in left iliac fossa region 1.4 × 0.7 cm
			No evidence of gonadal tissue in right inguinal region/ scrotal sac/RIF
Laproscopy findings	Uterus and 2 gonads visualized	Planned	Uterus, cervix and 2 gonads visualized in the expected position of the ovaries	Planned
HPE	uterine tissue showing sheets of myometrium, sections from gonadsinfantile atrophic testicular tissue, no features of malignancy	NA	Sections from both right and left gonadal tissues revealed seminiferous tubules with focal atrophy	NA
Treatment	Removal of Mullerian structures+ bilateral orchidectomy. HCG 2000 IU IM weekly for 5 weeks. Planned for hormonal therapy at puberty	Hysterectomy and left orchidopexy planned	Removal of Mullerian structures+ Lt orchidopexy + Rt orchidectomy	Hysterectomy and left orchidopexy planned

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Discussion: A total of 200 cases of PMDS have been published between 1964 to 2012[4] and 34 new cases published worldwide between 2012 to 2016,[4,5] indicating an increase in prevalence. The detection of 4 cases from single centre with 3 of the cases being detected in the past 1 year supports the increasing prevalence of PMDS. The youngest one presented at age of 2 days and oldest at 5 years, majorities are being diagnosed earlier than previous Indian series.[2] Consanguinity was present in most cases, similar to series from Middle East.[6,7,8,9] All the patients appeared phenotypically as males and presented with cryptorchidism, 50% being bilateral while hernia was present in one patient. These are similar to findings of previous studies[2,3,6,7,9,10] which also showed cryptorchidism to be the most common presentation, but hernia is less common than in most Asian series[3,6,10] but similar to series by Mazen et al.[7] Two patients had very low AMH levels which are expected. However, two patients had elevated AMH levels, possibly due to AMHR2 mutation and this is in contrast to previous reports of normal AMH levels in patients with AMHR2 mutation.[5,11,12]

Conclusion: PMDS should be kept in mind while evaluating male with otherwise normal phenotype, presenting with cryptorchidism.

Keywords: Anti-Mullerian Hormone (AMH), cryptorchidism, disorders of sex development, Persistent Mullerian Duct Syndrome (PMDS)

REFERENCES

1.Schteingart HF, Picard J-Y, Valeri C, Marshall I, Treton D, Di Clemente N, et al. A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome. Hum Mol Genet. 2019;28:3211–8. doi: 10.1093/hmg/ddz147. [DOI] [PubMed] [Google Scholar]
2.Picard J-Y, Cate RL, Racine C, Josso N. The persistent Müllerian duct syndrome: An update based upon a personal experience of 157 cases. Sex Dev. 2017;11:109–25. doi: 10.1159/000475516. [DOI] [PubMed] [Google Scholar]
3.Natarajan S, Periasamy M, Saminathan Rangasamy SM, Sundararajan P. Persistent mullerian duct syndrome: A single-center experience. J Indian Assoc Pediatr Surg. 2018;23:203–5. doi: 10.4103/jiaps.JIAPS_61_17. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Farikullah J, Ehtisham S, Nappo S, Patel L, Hennayake S. Persistent Müllerian duct syndrome: lessons learned from managing a series of eight patients over a 10-year period and review of literature regarding malignant risk from the Müllerian remnants. BJU Int. 2012;110:E1084–9. doi: 10.1111/j.1464-410X.2012.11184.x. [DOI] [PubMed] [Google Scholar]
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9.Naguib KK, Teebi AS, Farag TI, Al-Awadi SA, El-Khalifa MY, Mahfouz ES. Familial uterine hernia syndrome: Report of an Arab family with four affected males. Am J Med Genet. 1989;33:180–1. doi: 10.1002/ajmg.1320330208. [DOI] [PubMed] [Google Scholar]
10.Saleem M, Ather U, Mirza B, Iqbal S, Sheikh A, Shaukat M, et al. Persistent mullerian duct syndrome: A 24-year experience. J Pediatr Surg. 2016;51:1721–4. doi: 10.1016/j.jpedsurg.2016.06.005. [DOI] [PubMed] [Google Scholar]
11.Tosca L, Giltay J, Bouvattier C, Klijn A, Bouligand J, Lambert A, et al. Persistent Müllerian duct syndrome due to anti-Müllerian hormone receptor 2 microdeletions: A diagnostic challenge. Hum Reprod. 2020;35:999–1003. doi: 10.1093/humrep/deaa014. [DOI] [PubMed] [Google Scholar]
12.Unal E, Yildirim R, Tekin S, Demir V, Onay H, Haspolat YK. A novel mutation of AMHR2 in two siblings with persistent Müllerian duct syndrome. J Clin Res Pediatr Endocrinol. 2018;10:387–90. doi: 10.4274/jcrpe.0013. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Prevalence of depression among adolescent Indian girls with PCOD

Vipan Talwar ¹, Gourav Talwar ¹

Background: Women with PCOS often suffer from psychiatric comorbidities including depression. Six out of ten females diagnosed with PCOS are teenage girls. Data regarding the prevalence of depression in adolescent Indian girls with PCOS are scarce.

Aim: To find out the prevalence of depression and its associations among adolescent PCOS. Methods: This cross-sectional study evaluated 135 newly diagnosed PCOS girls (Revised Rotterdam criteria) aged between 13-19 years and 65 healthy non-PCOS controls. Anthropometrics and hormonal evaluation were done. Depression was assessed by administering Patient Health Questionnaire- Adolescents (PHQ-A). PHQ-A score >10 was considered as the threshold for significant depression. Statistical evaluation was with SPSS and p < 0.05 was significant.

Result: The frequencies of significant depression in PCOS and control groups were 38.5% and 12.3% respectively. PCOS adolescents having higher HOMA-IR value, higher hirsutism score, higher BMI had a higher risk of significant depression. Menstrual irregularity, acne, dyslipidaemia, serum testosterone, 17-OHP, prolactin and serum TSH levels had no significant correlation with depression.

Discussion: PCOS commonly prevails during adolescence, a phase when girls are more concerned about their physiology and physical health. Our study has found higher prevalence of depression (almost 3 times) in adolescent PCOS girls as compared to controls. PCOS is characterized by heterogeneous complications especially in adolescents and is an urgent health problem that needs careful assessment, timely intervention and appropriate treatment of all aspects including mental health.n

Conclusion: The initial evaluation of PCOS in adolescent girls should also include the assessment of mental health disorders.

Keywords: PCOD, adolescents, Indian, depression

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

A rare case of idiopathic gonadal dysgenesis with primary adrenal insufficiency

O Raghupathi ¹, B Vivekanand ¹, A Mythili ¹, K A V Subrahmanyam ¹, Jayanthy Ramesh ¹

Introduction: 46,XY partial gonadal dysgenesis can be defined by multiple characteristics, including varying degrees of testicular dysgenesis, ambiguous genitalia and often absence or regression of Mullerian structures. The prevalence is unknown. Here we report case of 46XY DSD, partial gonadal dysgenesis with primary adrenal insufficiency brought by with ambiguous genitalia.

Case Report: A 2 months old child reared as male, product of 3rd degree consanguineous couple 1st in birth order was brought with ambiguous genitalia. no h/o maternal exposure to androgens or androgenic progestins and no maternal virilization during pregnancy. born at term with LSCS. Birth weight-3.75 kgs. birth history uneventful. There is no dysmorphic features, hyperpigmentation, skeletal deformities and salt wasting crisis. Microphallus (10 mm) present with single urethral opening at tip of meatus without chordee. gonads were not palpable with labia like bifid scrotal folds with absence of rugae and hyperpigmentation. Karyotype was 46XY. Ultrasonography shows uterine like structure behind the bladder with non visualization of gonads. MRI shows non visualized both mullerian and wolffian structures. Biochemical work up showed stimulated 17OHP -2.89 ng/ml with persistent hyperkalemia. Baseline 8am cortisol 1.15 ug/dl, total testosterone-<7 ng/dl, serum FSH-13 mIU/ml, serum AMH-0.13 ng/ml, serum androstenodione-<0.3 ng/ml.

Discussion: In view of clinical, laboratory and imaging findings, presumptive diagnosis of 46XY DSD due to gonadal dysgenesis with primary adrenal insufficiency was made. However genetic testing for SF1, DAX1 and CAH genes came negative. So in this case gonadal dysgenesis with primary adrenal insufficiency may be due to some unknown gene mutation. I think this is the 1st case report of gonadal dysgenesis with primary adrenal insufficiency with negative SF1/DAX 1 mutation in India.

Conclusion: Partial gonadal dysgenesis is a very rare cause of ambiguous genitalia with variable phenotypic spectrum. It associated with primary adrenal insufficiency or renal abnormalities. Known genetic mutation is identified in only 20-40% of individuals with 46 XY testicular dysgenesis.

Keywords: Gonadal dysgenesis, adrenal insufficiency

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

An Interesting Case of Hypokalemic Periodic Palsy with Hypertension and Primary Amenorrhea

Yogesh Kumar ¹, Amit Nachankar ¹

Introduction: Congenital adrenal hyperplasia (CAH) due to 17alfa hydroxylase deficiency is a rare cause of hypertension in young with very few cases published from Indian literature. It is an autosomal recessive disorder with incidence of 1 in 70000.

Case Report: 24 year old phenotypic female, born out of non-consanguineous marriage having primary amenorrhea and received estrogen therapy at 15 years of age, presented with 02 episodes of flaccid quadriparesis, detected to have stage II hypertension and hypokalemia (serum potassium 2.1mEq/L). Hormonal analysis showed elevated LH and FSH levels, low 17 OHP levels and low plasma aldosterone and renin activity. USG abdomen / MRI abdomen showed blind vagina with absence of uterus and ovaries; karyotyping showed 46XY. Patient has been reared as female after due counselling and being managed with oral hydrocortisone, spironolactone and conjugated equine estrogen.

Discussion: Initial step in diagnostic workup of a case of hypertension with hypokalemia requires plasma aldosterone and renin activity estimation. In our case both aldosterone and renin activity were low and differential diagnosis to be considered are CAH, Cushing's syndrome and rarely DOC tumor. This XY genotype patient with female phenotype and absence of wolffian/ mullerian structures presenting as hypertension with hypokalemia, was diagnosed as CAH due to 17alfa hydroxylase/lyase deficiency.

Conclusion: Secondary causes must be excluded in young patient with hypertension and hypokalemia and if any genital ambiguity present, CAH should be considered. Always consider CAH due to 17a hydroxylase deficiency with a triad of primary amenorrhea, hypertension and hypokalemia.

Keywords: Congenital Adrenal Hyperplasia (CAH), 17 Alfa Hydroxylase Deficiency, Hypokalemic Periodic Palsy

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

'H Syndrome’ – A rare Endodermatosis!

Krishna Mori ¹, Karthik Balachandran ¹, Adlyne Reena Asirvatham ¹, Shriraam Mahadevan ¹

Introduction: H Syndrome is a rare Autosomal recessive Genodermatosis with myriad presentations like hyperpigmentation, hypertrichosis, sensorineural hearing deficit, hypogonadism, short stature, heart anomalies, Insulin dependent diabetes mellitus, hepatosplenomegaly, flexion contracture of fingers and toes and hypertriglyceridemia. Around 100 cases of this syndrome are reported in the literature-majority of them being from Arab origin and only 10 cases reported from India.

Case Report: A 24 old year male born out of non-consanguineous marriage presented to the endocrine OPD with short stature. He was 138 cm (<3 centile for age) with mid –parental height being 170 cm. Patien had sensorineural hearing loss from the age of 5 years and autoimmune haemolytic anaemia from the age of 15 years. He had hyperpigmentation with hypertrichosis on the medial aspect of thighs, scrotum, shin and foot [Figure 1]. He was found to have Hypergonadotropic hypogonadism on laboratory evaluation. Clinical phenotype favoured H Syndrome following which targeted Gene Sequencing was performed which confirmed a homozygous nonsense variation in exon 6 of the SLC29A3 gene, thereby confirming the diagnosis.

Discussion: The management of H-Syndrome involves treatment of individual manifestations like growth hormone therapy in childhood, testosterone supplementation and artificial hearing aids. Though there is evidence of underlying inflammatory pathogenesis of the disease, there is lack of consensus on the treatment of primary pathology of the disease.

Conclusion: The pathognomonic features of H-syndrome are the skin manifestations; it does manifest a constellation of endocrine abnormalities like insulin dependent diabetes mellitus, short stature, hypogonadism, amenorrhoea, microphallus, infertility, hypothyroidism and hypertriglyceridemia. Here, we report this case focussing on the endocrine aspects of H syndrome.

Keywords: H-Syndrome, Hypergonadotropic Hypogonadism, Short stature.

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

DIABETES: A predictive model to foretell onset of Type-2 Diabetes and analyse different contributing factors

Prasidha Prabhu ¹

Introduction: Type-2 Diabetes is one of the common ailments that affects a vast population of the world. To effectively study and analyze the different causative factors, it is recommended to conduct a thorough research on a small subsect of people belonging to the same race and falling within a particular age group. This helps us to narrow down our findings, and these findings can later be applied to study larger groups of people. Using multiple machine learning algorithms, the data from over 700 patients was studied to build an effective model with a high accuracy of predicting the risk of being diagnosed with the disease.

Description: The features of the dataset included No. of Pregnancies, Weight, BMI, Insulin levels, etc. Logistic Regression proved to be the best model since it yielded a higher accuracy than the rest. Impact: Predictive models can be used as a supportive system whilst diagnosing patients, or even to foretell the imminent risk of developing Type 2 Diabetes. The various factors that impact Diabetes can also be analyzed, and the weightage of each feature can be figured out. This can help doctors to zero in on the factors that carry more weightage, and aim to correct/rectify those features in particular.

Conclusion: The accurate prediction and forewarning of the risk of diabetes can largely help suppress the growing prevalence of Type-2 Diabetes in our nation.

Key words: Analysis, diabetes, diagnosis, endocrinology, health, logistic regression, machine learning, prediction, risk, statistics

Tabulated Model Findings (values in percentage)

Model	Precision	Recall	F1-Score	Average	Accuracy
Decision Trees	78	76	77	77	71
K-Nearest	77	89	82	82.66	75
Numbers
Logistic	83	87	85	85	81
Regression
Naive Bayes	82	81	81	81.33	75
Random Forests	80	80	80	80	75
Support Vector	78	93	84	85	78
Machines
XGBoost	82	78	80	80	75

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REFERENCE

1. The dataset: Available from: https://www.kaggle.com/uciml/pima-indians-diabetes-database .

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Insulin resistance and inflammatory markers in patients with pancreatic diabetes

Mohd Abdul Mujeeb Afzal ¹, Apsia Ruhi ¹, Thaduri Krishna Reddy ¹, Piyush Lodha ¹, P Srinivas Rao ¹, Vijay Sheker Reddy Danda ¹

Introduction: Pancreatic diabetes is a form of secondary diabetes with prevalence of microvascular complications[1] similar in pancreatic diabetes patients when compared to that of type 2 diabetes mellitus, but macrovascular complications[2] are less frequent. Insulin resistance and Inflammation play a major role in etiopathogenesis of macrovascular disease.

Aim: To assess the Insulin Resistance and Inflammatory markers in patients with pancreatic and compare to those of Type 2 Diabetes mellitus.

Methodology: It is a Cross sectional Observational study. Among Individuals attending OP and IP of department of Endocrinology, Gandhi Hospital, 50 pancreatic diabetes subjects and 50 type 2 diabetes were assessed clinically and biochemically for Insulin resistance and inflammatory markers.

Results: In the present study, the mean age of the study participants in pancreatic DM group was 35.44 +/- 5.26, type 2 diabetes mellitus patients were 58.6 +/- 9.67 years. Among pancreatic diabetes patients 13 subjects had diabetic retinopathy changes in their fundoscopy whereas 32 subjects of the type 2 diabetes mellitus patient showed retinopathy. The serum insulin among the pancreatic DM group was 4.15 +/- 1.14, Type 2 DM group was 7.57 +/-2.67 and The Homa index among the pancreatic DM group was 2.84 +/- 1.17, Type 2 DM group was 4.51+/- 1.57 with significant p value (<0.05). A statistically significant difference (p < 0.0001) was observed between the pancreatic and type 2 DM in HsCRP (0.76 vs +/- 0.14 vs 3.81+/- 8.8)

Conclusion: Insulin resistance as measured by HOMA IR and inflammatory markers measured by HsCRP were found to be low in pancreatic patients to that of type 2 DM.

Key words: Insulin Resistance, pancreatic diabetes, Type 2 Diabetes

REFERENCES

1.Mohan R, Rajendran B, Mohan V, Ramachandran A, Viswanathan M, Kohner EM. Retinopathy in tropical pancreatic diabetes. Arch Ophthalmol. 1985;103:1487–9. doi: 10.1001/archopht.1985.01050100063020. [DOI] [PubMed] [Google Scholar]
2.Mohan V, Ramachandran A, Viswanathan M. Two case reports of macrovascular complications in fibrocalculous pancreatic diabetes. Acta Diabetol Lat. 1989;26:345–9. doi: 10.1007/BF02624647. [DOI] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

High prevalence of cardiovascular risk factors in Eastern-Indian type 2 diabetes mellitus adults younger than 40 years

Ramdas Barure ¹, Vijaya Sarathi H A ¹, Sridevi Atluri ¹, Kollla Gautham ¹

Introduction: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). ADA recommends considering statin therapy in T2DM patients younger than 40 years only if one additional cardiovascular (CV) risk factor is present. However, early CV disease (CVD) has an increasing trend in Asian Indians.

Aim: To estimate the prevalence of CV risk factors in T2DM adults younger than 40 years from Eastern- India.

Materials and methods: This study conducted at a tertiary care centre from Bengaluru, included young adults (age: 18-40 years) from Eastern India. The data from diabetic medical health check-up records from March 2018 to January 2019 was retrospectively analysed. A total of 506 patients with T2DM who were free of CVD at baseline were included. We analysed data for presence of atherosclerotic CVD risk factors.

Results: Of 506 study participants 382 (66.1%) were males whereas 233 (46%) were overweight and 172 (34%) were obese. The prevalence rates of serum LDL-cholesterol >100 mg/dl, hypertension, albuminuria, chronic kidney disease, and history of smoking were 75.3%, 17.9%, 21.1%, 2.8%, and 17.9% respectively. At least one CV risk factor was present in 75.3% while two, three, and four risk factors were present in 23.7%, 5.1%, and 0.79% of patients respectively.

Conclusions: The study demonstrates three-fourth of T2DM adults younger than 40 years from Eastern India have an additional CV risk factors which indicates to consider statin therapy in them. Hence, all such patients should be evaluated for additional CV risk factors.

Keywords: Cardiovascular disease, hypertension, prevalence, type 2 diabetes mellitus

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Prevalence and determinants of sudomotor dysfunction in patients with fibrocalculous pancreatic diabetes

Kolla Gautham ¹, Shivaprasad C ¹, Vijaya Sarathi H A ¹, Sridevi Atluri ¹, Ramdas Barure ¹

Background: The prevalence of neuropathy in patients with fibrocalculous pancreatic diabetes (FCPD) is higher than that in patients with type 2 diabetes mellitus (T2DM). A few studies have demonstrated the utility of sudomotor dysfunction in the diagnosis of neuropathy in patients with T2DM. However, the data on sudomotor dysfunction in patients with FCPD is sparse.

Aim: To determine the prevalence of sudomotor dysfunction and its determinants in patients with FCPD.

Methodology: We recruited 90 consecutive adult patients with FCPD. Sudomotor dysfunction, a mean (right and left foot) electrochemical skin conductance (ESC) <60 μS, and an abnormal vibration perception threshold (VPT) >15 v, were used to define peripheral neuropathy. Binary logistic regression was performed to determine the predictors of sudomotor dysfunction in patients with FCPD.

Results: The prevalence rates of neuropathy by sudomotor dysfunction and VPT were 30% and 17.8% respectively. A moderate agreement (k = 0.49) was observed between diagnosis of neuropathy by sudomotor dysfunction and VPT. Duration of diabetes (DDD) (7.03 ± 4.17 vs 3.85 ± 3.54 years, p = <0.0001) and fasting plasma glucose (FPG) (234.41 ± 56.12 vs 196.13 ± 55.19, p = 0.004) were found to be significantly associated with sudomotor dysfunction on univariate as well as on multivariate analysis (Odd's ratio: 1.198, p = 0.006 for FPG and Odd's ratio: 1.011, p = 0.033 for FPG).

Conclusion: The prevalence of neuropathy by sudomotor dysfunction was significantly higher than that by VPT with a moderate agreement between them. However, further studies are required to verify whether sudomotor dysfunction is an early marker of neuropathy in patients with FCPD.

Keywords: Sudomotor dysfunction, Peripheral neuropathy, FCPD

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Study on insulin storage and administration techniques in patients with type 2 diabetes mellitus

Shyam Sundar C M ¹, Vivekananda B ¹, Mythili A ¹, Subrahmanyam KAV ¹, Jayanthy Ramesh ¹

Introduction: The use of Insulin in Type 2 Diabetes Mellitus is increasing, with 15.5% using it for glycemic management. Optimal glycemic control is not achieved despite increasing dose of insulin. Proper storage and use of insulin is of prime importance.

Aims and Objectives: To Study Insulin storage and use practices.

Material and Method: Cross sectional study included consecutive 160 patients attending Endocrinology OPD in our Institute.

Results: 53% were male with mean age 51 years and mean diabetes duration of 10 years. 50% were illiterate. Only 21% had FBS/PPBS in target range. 93.8% were using premix insulin and 84.4% using two doses per day. 81.3% stored Insulin in refrigerator, 70% administered insulin immediately after it taking out. 81.3% practised rolling of insulin before administration. Only 28.3% individuals waited for 15-30 mins after injection for food intake. 46% used only single site, periumbilical being the commonest, 54% used multiple sites and among them 90% practised site rotation. 53.1% practiced proper injection technique and commonest improper method was acute angle of insulin syringe (80%). 25% used a syringe more than 10 times. 81.3% individuals administered insulin by themselves. 62.5% were able to properly identify insulin markings in syringe. In 53.1% the prescription matched the actual dose used.

Conclusion: Despite advice on insulin storage and use techniques, many improper methods are followed by patients, which can affect efficacy of prescribed Insulin. Periodic reinforcement and education preferably by educator or video demonstration in OPD will aid in obtaining maximum benefit from insulin therapy.

Keywords: Administration technique, insulin, storage, type 2 diabetes mellitus

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Oxidative stress and beta cell function improves with early insulin treatment

M Madhu Babu ¹, Ashok Makineni ¹, Srivalli Madhira ¹, Jayanthy Ramesh ¹

Introduction: T2DM is a metabolic disorder with long term complications. Oxidative stress plays a significant role in the pathophysiology of T2DM. Clinical Data regarding oxidative stress in diabetes is sparse and is limited to those with long duration. We planned this study inorder to understand the role of oxidative stress in the newly diagnosed diabetics and the effect of insulin treatment.

Aims and Objectives: To study the effect of early insulin therapy in newly diagnosed T2DM on oxidative stress and beta cell function.

Materials and methods: 21 newly diagnosed T2DM patients, attending the endocrinology OPD of a tertiary care hospital were enrolled in this study conducted between May 2019 – February 2020. Patients with HbA1C > 8.5% to <12.5% were included. Conventional pre-mix insulin therapy was started with 0.5 U/kg/day and the dose was titrated according to FPG and 2 hr PPG, HbA1c which were assessed with periodic followup. Homa beta and Total antioxidant capacity (TAOC) were assessed at baseline and at 9 months of insulin treatment.

Results: Baseline mean FPG, 2 hour PPG, HbA1C, were 213.70 ± 43.64 mg/dl, 305.19 ± 78.23 mg/dl, 10.21 ± 1.73%, At baseline Homa beta and TAOC were low (21.71 ± 8.59, 0.371 0.09 mM/L respectively). At the end of 9 months, a significant reduction in the mean FPG (113.3 ± 25.7 mg/dl), PPG (145.2 ± 24.23 mg/dl), HbA1C (6.74 ± 0.42%) was observed and a significant increase in mean TAOC and Homa beta was evident (2.646 ± 0.36 mM/L and 212.92 ± 79.47) indicating an improvement in oxidative stress and beta cell function. There was a significant positive correlation between change in HOMA beta and change in TOAC from 0 to 9 months.

Conclusion: Oxidative stress and beta cell dysfunction correlates with metabolic control and improves with early insulin treatment in new onset T2DM.

Keywords: Early insulin therapy, oxidative stress, type 2 diabetes

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Training primary care physicians in management of diabetic retinopathy: The impact of intensive education program in India

Manoj Joshim ¹, Sandeep Bhalla ¹, Tanu Soni ¹, Rajesh K Mishra ¹, Pushkar Kumar ¹, G V S Murthy ¹, Ranjit Unnikrishnan ², Viswanathan Mohan ², Ramachandran Rajalakshmi ², Ramasamy Kim ³

Background: The spiraling burden of diabetes and the associated visual impairment, and shortage of specialists in the periphery necessitates the training of Primary Care Physicians (PCPs) to combat the increasing Diabetic Retinopathy (DR) burden in India.

Aims and Objectives: To improve PCPs knowledge and skills about DR management and to identify the impact of an educational program about DR.

Materials and methods: The Certificate Course in Evidence Based Management of Diabetic Retinopathy (CCDR) is a four modular program with a judicious mix of case studies, pre-post-tests, assignments, group activities, direct teaching and hands-on-training. Improvement in knowledge of physicians was assessed by pre and post test scores and a pretested baseline and end line questionnaires before and after completion of program.

Results: Total 578 PCPs from 114 districts trained in DR management over four years. Pre-post-test scores showed significant improvement {two-tailed Anova (p value< 0.05 t-test)} in knowledge regarding systemic management and prevention of DR. Baseline/end line survey showed improvement of 23% in scores. As per feedback, 92% percent PCPs agreed that the course learnings were adequate for initiating discussions for replicating real life case scenarios in DR management. More than 95% agreed that the training facilitated them to manage patients with DR and refer people with sight threatening DR to the retina specialist. Almost all PCPs rated the course and teaching methodology with an overall score of 9/10 (excellent). Few of the PCPs have already included fundus photography as a part of their investigation for people with diabetes, and are referring to ophthalmologist as necessary.

Discussion & Conclusion: CCDR is an effort to tackle shortage of trained work force and will positively set a trend in the field of DR education and help improve diabetes indices in India. To ensure scalability and sustainability of the model the course is also available in an e-learning mode.

Keywords: Diabetic retinopathy, education, impact, primary care physicians (PCPs)

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Diagnostic dilemma in diabetes: Autoimmune or coexistent MODY with Autoimmune diabetes

D Sandeep Reddy ¹, Krishna Reddy Thaduri ¹, Apsia Ruhi ¹, Piyush Lodha ¹, Vijay Sheker Reddy Danda ¹, Srinivas Rao Paidipally ¹

Introduction: Maturity onset diabetes of the young (MODY) refers to a group of monogenic form of diabetes in young adults.[1] KLF11 gene mutations are pathogenic for MODY Type 7.[2] Diagnosis of the etiology of young onset diabetes is sometimes a puzzle and are often misdiagnosed.

Case Report: A 27year old female presented with osmotic symptoms for 3 months. Both father and paternal grand mother were diagnosed diabetes at about 35 years of age and are well controlled with oral anti diabetic drugs. BMI was 23.5 kg/m², signs of insulin resistance were absent. Investigations revealed FBS 226, PPBS 420, Hba1c 10.2%, urine for ketones was negative, Anti GAD antibodies-strong positive, IA 2A and IAA antibodies were negative. Good glycemic control was achieved with insulin of 0.4IU/kg. There was poor response to trial of glibenclamide. Post prandial C-peptide was 0.9ng/ml after 6 months. With a suspicion of MODY, Next Generation Sequencing (NGS) was done which revealed heterozygous mutation at Exon 3 (p.Val374Met) of KLF 11 gene, which was reported as variant of unknown significance. The mutation was not described earlier in genome databases. NGS of father and grandmother revealed the same mutation in KLF11. NGS of other family members couldn't be done. Various mutations of KLF 11 gene were earlier reported as pathogenic for MODY 7. Whether the patient has autoimmune diabetes or coexistent MODY with autoimmune diabetes couldn't be concluded. Population studies are needed for this mutation to be labelled as either pathogenic or benign variant.

Conclusion: Diagnosis of young diabetes might be difficult even with genetics and overlap of different types of diabetes in a single individual is a possibility.

Keywords: Autoimmune diabetes, KLF11, MODY

REFERENCES

1.Mohan V, Radha V, Nguyen T, Stawiski E, Pahuja K, Goldstein L, et al. Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India. BMC Med Genet. 2018;19:22. doi: 10.1186/s12881-018-0528-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, et al. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci U S A. 2005;102:4807–12. doi: 10.1073/pnas.0409177102. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Continuous glucose monitoring for the detection of hypoglycemia in patients with pancreatogenic diabetes

Kolla Gautham ¹, Channabasappa Shivaprasad ¹, Kejal Shah ¹, Soumya Gupta ¹, Preethika Palani ¹

Background: Detailed evaluations of hypoglycemia and associated indices based on continuous glucose monitoring (CGM) are limited in patients with pancreatogenic diabetes. Our study sought to evaluate the frequency and pattern of hypoglycemic events and to investigate hypoglycemia-specific indices in this population.

Methods: This was a cross-sectional study comprising 88 participants with pancreatogenic diabetes. CGM and self-monitoring of blood glucose (SMBG) were performed on all participants for a minimum period of 72 hours. The frequency and pattern of hypoglycemic events as well as hypoglycemia-related indices was evaluated.

Results: Hypoglycemia was detected in 90.9% of patients using CGM and 38.6% of patients using SMBG. Nocturnal hypoglycemic events were more frequent (1.9 episodes/patient) and prolonged (141.9 min) compared to day-time events (1.1 episodes/patient; 84.5 min, p <0.05). The mean low blood glucose index (LBGI) was 2.2 and glycemic risk assessment diabetes equation (GRADE) hypoglycemia was 9.4%. The mean time spent below (TSB) <70 mg/dL was 9.5%, and TSB <54 mg/dL was 3.9%. The mean area under curve (AUC) <70 mg/dL was 1.7 ± 2.5 mg/dL/hour and AUC <54 mg/dL was 0.7 ± 1.4 mg/dL/hour. All of the CGM-derived hypoglycemic indices were significantly more deranged at night compared to during the day (p <0.05).

Conclusion: Patients with pancreatogenic diabetes have a high frequency of hypoglycemic episodes that are predominantly nocturnal. CGM is superior to SMBG in the detection of nocturnal and asymptomatic hypoglycemic episodes. CGM-derived hypoglycemic indices are beneficial in estimating the risk of hypoglycemia.

Keywords: Continuous glucose monitoring, hypoglycemia, hypoglycemic indices, pancreatogenic diabetes

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Diabetic muscle infarction: Experience from a tertiary care centre in Southern India over two decades

Mathews E Kurian ¹, Felix K Jebasingh ¹, Jyoti Panwar ¹, Grace Rebekah ², Kripa E Cherian ¹, Nitin Kapoor ¹, Asha H S ¹, Thomas V Paul ¹, Nihal Thomas ¹

Background: Diabetes-related muscle infarction (DMI) is an uncommon complication occurring in patients having long-standing diabetes mellitus, entailing the spontaneous ischemic necrosis of skeletal muscle. The presentation involves a non-traumatic, tender swelling of the limb, commonly involving the thigh. The most appropriate diagnostic imaging modality is T2-weighted magnetic resonance imaging (MRI), albeit being non-specific.

Objective: We aimed to represent our experience with DMI between 2002 and 2020, with respect to the symptomatic profile at presentation, findings from clinical examination and imaging, biochemistry, treatment profile as well as prognosis.

Methodology: Retrospective data of patients having DMI was retrieved. Statistical analyses were performed to look for associations with respect to the aforementioned variables and outcomes.

Results: A total of 21 patients diagnosed with DMI were included. At presentation, the mean age was 52.7 ± 10.5 years while the median (IQR) duration of diabetes was 14 (7.5) years with a male preponderance. Poor glycaemic control was generally observed with a mean HbA1c of 8.8 ± 1.9% and 76.2% (n = 16) of subjects were found to have both nephropathy and retinopathy. While the biochemistry appeared to be relatively non-conducive in eliciting a diagnosis, the MRI showed T2-weighted hypo-intense heterogeneous lesions in 95.2% (n = 20) of patients. Although most of the subjects improved with conservative management, a recurrence rate of 23.8% and mortality of 19% were recorded within a median (IQR) duration of 37 (33) weeks and 43.5 (60.5) weeks, respectively.

Conclusion: In this group of Asian Indian patients with DMI, findings from MRI were found to be the linchpin of diagnosis despite moderately varying clinical presentations and unremarkable biochemistry.

Keywords: Diabetic, magnetic resonance imaging, muscle infarction, myonecrosis, nephropathy

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

The effect of renal impairment on insulin resistance in subjects with and without diabetes

Radhika Govil ¹, Sushil Jindal ¹, Shaifali Bansal ¹

Introduction: Patients with T2DM or hypertension developing nephropathy are at increased risk of hypoglycemia, suggesting that they have probably become insulin sensitive or their insulin resistance seems to have declined. Hence, this study was undertaken to determine the status of insulin resistance/sensitivity in persons with diabetic and non-diabetic nephropathy and compare it to that found in similar persons without nephropathy

Aims and Objectives: To study the effect of renal impairment on insulin resistance in subjects with and without diabetes.

Materials and methods: Subjects with renal impairment (with eGFR< 60), both diabetic and non diabetic attending OPD in Peoples Hospital, Bhopal (MP) were included in this study. Age and BMI matched controls with normal renal functions were selected. The insulin resistance of each subject was calculated by HOMA-IR.

Results: We found a significantly less prevalence of insulin resistance in subjects with CKD with eGFR <60 (diabetic and non diabetic) compared to those with normal renal function. Fifty five percent of cases with normal renal function (with and without diabetes) were insulin resistant, as compared to 14.4% in subjects of CKD (with and without diabetes). The result was statistically very highly significant with a p value of <0.001. This difference was more pronounced in persons with diabetes.

Conclusion: In our study we found a significantly less prevalence of insulin resistance in subjects with CKD when compared with similar subjects having normal renal function. The difference in insulin resistance was more pronounced in persons with diabetes.

Keywords: Insulin Resistance, HOMA-IR, CKD, T2DM

Table 1.

Percentage of insulin resistant patients by HOMA-IR in all 4 groups

	HOMA-IR					Chi square	Pvalue

	<2.5	%	>2.5	%	Total
DIAB WITH CKD	35	81.4	8	18.6	43
DIAB WITH NO	7	33.3	14	66.7	21
CKD
NON DIAB	42	89.3	5	10.7	47
WITH CKD
NON DIAB	11	57.9	8	42.1	19	26.93	0.00001
WITH NO CKD

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Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Monitoring and evaluation mechanism of a diabetes training program for primary care physicians in India – An effective pathway to quality assurance

Anuradha A Monga ¹, Santosh Kumar ¹, Amit K Singh ¹, Sandeep Bhalla ¹, Pushkar Kumar ¹, Ranjit Unnikrishnan ¹, V Mohan ¹

Background: Certificate Course in Evidence based Diabetes Management (CCEBDM), implemented by PHFI was envisioned in 2010 with the academic support from Dr Mohan's Diabetes Education Academy (DMDEA). Till date, the program has enrolled 14000 PCPs across 450 districts in 290 training centres. CCEBDM was also adopted by 7 Govt. bodies (MP, Odisha, Kerala, Haryana, Kolkata Municipal Corporation, Manipur, Mizoram) and Reliance India Limited for their PCPs. Internationally course has been adopted by Bangladesh, Myanmar, East Africa Diabetes Study Group, Kabul University, Afghanistan, Ministry of health Rwanda and Nepal.

Objectives: To describe the Monitoring and Evaluation (M&E) mechanism of CCEBDM for PCPs and identify factors impacting its success.

Research design and methods: The M&E system of CCEBDM constituted of onsite monitoring of randomly selected 13% sessions, by observers, offsite monitoring of 10% participants from unobserved centres, online feedback, end line evaluation of 10% of eligible participants and baseline and end line knowledge assessment, to assess knowledge improvement attributable to the course.

Results: Of the 7487 sessions conducted in 5 cycles, 999 sessions were randomly monitored on-site by observers. Observers are public health specialists or hospital administrators (faculty of community medicine or hospital administration) as well as representatives from PHFI. During monitoring, results demonstrated 89% adherence to protocols like session adherence to timings, discussion of pre- and post- test and case studies. End line evaluation covered 991 participants, who rated 92% satisfaction with course curriculum and faculty teaching. 98% felt that the course added value to their knowledge and skills. The difference in the baseline and end line assessment demonstrated knowledge improvement by 3 units.

Conclusion: While training programs require enormous resources for implementation, they can be strengthened and standardized by robust M&E mechanisms. This study demonstrated that M & E mechanism of CCEBDM has been quintessential towards its colossal success in India.

Keywords: Capacity building, diabetes, evaluation, monitoring

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Nation wide capacity building model in gestational diabetes management for primary care physicians in India

Haresh Chandwani ¹, Pushkar Kumar ¹, Sandeep Bhalla ¹, Ranjit Unnikrishnan ¹, V Mohan ¹

Background: Pregnancies complicated by GDM have fourfold increased risk of perinatal mortality and has a long-term health impact, with more than 50% of women with GDM going on to develop type 2 diabetes within 5-10 years of delivery. In India an estimated 4 million women have GDM.

Aim: The aim is to highlight the components of PAN India training model designed to enhance the knowledge, skills and core competencies of PCPs in management of GDM.

Methodology: Addressing the issue of dearth of trained professionals in specialised area like GDM by building the capacity of PCPs is an important strategy towards improving GDM management. A four modular course was developed jointly by Public Health Foundation of India and Dr. Mohan's Diabetes Education Academy in 2013 to train PCPs with strong course curriculum, vetted and approved by the national experts constituting of eminent endocrinologists and gynaecologists.

Result: CCGDM has trained over 3600 participants and covered 26 states & 2 UTs, 49 cities and 257 districts in the last six cycles spanning over a period of seven years. It has been adopted by five state governments- Gujarat, Madhya Pradesh, Meghalaya, Tripura and Uttarakhand for training their medical officers. The robust monitoring mechanism and precise certification method led to 90% pass percentage.

Conclusion: Focusing on GDM by training PCPs is a low-cost intervention both to improve maternal and child health as well as to prevent future diabetes. CCGDM is a well- defined training model and has the potential to be adopted by low income countries.

Keywords: Capacity building, Gestational Diabetes Mellitus, Primary Care Physicians

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Waist hip ratio is a poor marker of insulin resistance and hyperglycemia in Indian youth. Do we have better markers?

Shameer Basheer ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Background: Prevalence of Diabetes in adult Indians is 7.3%.[1] South Asians develop insulin resistance and type 2 diabetes at younger ages and lower BMI.[2,3] Community studies on prevalence of diabetes and prediabetes in children and youth is lacking from India.

Objective: To find the prevalence of diabetes and prediabetes among individuals less than 30 years and to identify the clinical risk factors of diabetes in such population.

Materials and methods: Subjects of age less than 30 years from rural, urban and coastal areas of Trivandrum district were enrolled using stratified cluster sampling. Socio-demographics and Clinical assessment including food habits, family history, anthropometry and features of insulin resistance (IR) were recorded. Fasting or random capillary blood glucose measurement was done for all subjects. Subjects with random glucose =130 mg% underwent oral glucose tolerance test or HbA1c estimation for diagnosing or ruling out diabetes and prediabetes.

Results: The study enrolled 1601 participants 550 males and 1051 females. The prevalence of diabetes and prediabetes study was 0.31% and 2.4% respectively. In the age group of 18- 30 years of age 47% were overweight or obese (BMI > 23 kg/m²) and 25% showed clinical features of IR. Although hip circumference correlated with hyperglycemia and IR Waist-Hip Ratio surprisingly, didn't show any association with either. The product of BMI with the sum of abdominal circumference and hip circumference showed the best correlation with hyperglycemia as well as IR. This index could become a useful marker of IR in youth.

Conclusion: Modifiable risk factors of diabetes are present in a very high proportion of community dwelling South Indian youth, though the prevalence of diabetes and prediabetes is low. The findings indicate a strong need for community interventions to control the epidemic of diabetes in India.

Keywords: Diabetes Mellitus, Insulin Resistance

Table 1.

Table showing Anthropometric indices and relation to Hyperglycemia and IR

	Normo glycemic N = 865		Hyperglycemic N = 28		P Value

	Mean	Std. Deviation	Mean	Std. Deviation
BMI X AC	1800.7	599.5	2226.3	1006.4	0.034
Weight	59.9	13.0	67.8	17.3	0.002
BMI	23.5	7.7	26.2	7.0	0.070
AC	75.6	13.1	82.5	14.5	0.006
Waist Circum	85.6	13.6	92.0	20.1	0.022
Neck Circum	31.7	3.6	33.7	4.6	0.005
Mid Arm circ	29.0	4.5	31.6	5.5	0.002
Calf Circum	31.2	3.7	33.4	5.0	0.035
HC	94.4	12.8	103.1	16.6	0.000
WHR	0.9	0.1	0.9	0.1	0.419

	Subjects without CFIR (n = 616)		Subjects with CFIR (n = 217)		P Value

	Mean	Std. Deviation	Mean	Std. Deviation

Weight	58.74	12.31	64.69	14.80	<0.05
BMI	23.07	8.24	25.35	5.05	>0.05
AC	74.48	12.76	79.95	13.54	<0.05
Waist Circum	84.69	13.10	89.15	15.55	<0.05
Neck Circum	31.49	3.53	32.76	3.79	<0.05
Mid Arm cir	28.69	4.34	30.27	4.97	<0.05
Calf Circum	30.81	3.45	32.87	4.07	<0.05
HC	93.55	12.54	98.15	13.68	<0.05
WHR	0.91	0.09	0.91	0.07	0.583
AC/Height	0.47	0.08	0.50	0.08	<0.05
BMI X AC	1729.54	544.89	2074.34	753.17	<0.05
(AC + HC) X BMI	3876.50	1160.00	4617.06	1555.79	<0.001

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AC = abdominal circumference, HC = Hip circumference, WHR = waist hip ratio, BMI = Body Mass Index

REFERENCES

1.Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK, et al. Prevalence of diabetes and prediabetes in 15 states of India: results from the ICMR–INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol. 2017;5:585–96. doi: 10.1016/S2213-8587(17)30174-2. [DOI] [PubMed] [Google Scholar]
2.Ramachandran A, Snehalatha C, Viswanathan V, Viswanathan M, Haffner SM. Risk of noninsulin dependent diabetes mellitus conferred by obesity and central adiposity in different ethnic groups: A comparative analysis between Asian Indians, Mexican Americans and Whites. Diabetes Res Clin Pract. 1997;36:121–5. doi: 10.1016/s0168-8227(97)00040-5. [DOI] [PubMed] [Google Scholar]
3.Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM. Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab. 1999;84:2329–35. doi: 10.1210/jcem.84.7.5817. [DOI] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Normoalbuminuric chronic kidney disease in diabetes – Substantive or serendipity?

Karthik V ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Background: There is paucity of studies regarding normoalbuminuric form of renal dysfunction in diabetes patients in India.

Objective: To find the prevalence of normo-albuminuric renal dysfunction and its clinical associations in a diabetic Indian population.

Methods: A cross sectional study among patients with type 2 diabetes mellitus getting enrolled at a tertiary care centre in Trivandrum Kerala, was done. Based on urinary albumin creatinine ratio and e-GFR, patients were classified as having no kidney disease (NKD), albuminuria alone (ALB), normoalbuminuric low e-GFR (NACKD) (after ruling out other causes of renal dysfunction) and albuminuria with low e-GFR (ACKD). Clinical and biochemical data of these groups were compared.

Results: Data from 3534 diabetes patients with a mean age and duration of diabetes of 53.8 ± 10.9 years and 10.3 ± 7.5 years respectively was analysed. ACKD and NACKD was found in 3.4% and 2.1% among diabetic subjects and thus ACKD constituted 39.1% of all subjects with reduced GFR. Compared to NKD subjects, NACKD was found to have an independent association with higher age, male sex, lower body weight and with statin intake. None of the glycaemic parameters like HbA1c, FPG, PPPG showed an association with NACKD. When compared to ACKD subjects, only a higher age was found to have an association with NACKD. Retinopathy was more prevalent in the ACKD patients, whereas the rates of macrovascular complications were similar between the ACKD and NACKD groups. When considering more severe chronic kidney disease (CKD, stage 3b or worse) the prevalence of normoalbuminuric CKD decreased compared to that of albuminuric CKD.

Conclusion: Normoalbuminuric CKD constitutes more than one third of Indian patients with diabetes and decreased e-GFR, is strongly related to age but lacks association with duration or severity of hyperglycemia or the presence of retinopathy whereas it has a similar association with macrovascular disease as Albuminuric CKD. Hence, its pathogenesis may be related to aging and renal macrovascular disease.

Key words: Normoalbuminuric, Diabetic kidney disease, Diabetic nephropathy, e-GFR, CKD

Table 1.

Comparison of clinical characteristics of patients with NACKD with those of NKD and ACKD

	NKD [Mean >± SD/Median (IQR) or N (%)]	p Value (NACKD vs NKD)	NACKD [Mean ± SD/Median(IQR) or N (%)]	p Value (NACKD vs ACKD)	ACKD [Mean ± SD/Median (IQR) or N (%)]
Number of subjects (N)	2379	NA	75	NA	121
Age(years)	52.7 ± 10.5	<0.001*	70.7 ± 10.0	<0.001*	64.9 ± 9.0
Duration of diabetes (years)	6.2 (2.1-11.6)	<0.01	14.9(5.7-21.3)	0.17	16.8 (11.0-24.7)
Male N(%)	1409(59.2%)	0.04*	53(70.6%)	0.16	96(79.3%)
Hypertension N(%)	741 (31.2%)	<0.01	37(49.3%)	<0.01	92(76%)
Dyslipidemia N(%)	510 (21.5%)	<0.01	30(40.0%)	0.01	60(50.4%)
Fasting Blood Glucose (mg/dl)	179.6 ± 69.2	0.09	158.6 ± 64.6	0.02	189.4 ± 95.0
Post prandial Blood Glucose (mg/dl)	267.0 ± 109.8	0.99	253 ± 96	<0.01	305.9 124.0
Glycated hemoglobin (% or mmol/mol)	8.5 ± 2.3	0.99	8.2 ± 2.3	0.21	9.0 ± 2.2
Urine Albumin to creatinine ratio (mg/g%)	11.1(7.3-16.2)	0.61	11.1(7.8-16.4)	<0.01	153.8(97.3-198.2)
Statin Intake (N%)	819 (34.5%)	<0.01*	38(50.6%)	0.67	65(53.7%)
ACEI/ ARB Intake (N%)	475(20%)	<0.01	34(45.3%)	0.20	66(54.5%)
Past history of coronary artery disease (N%)	Details NA	-	20/66 (30.0%)	0.70	34/98 (34.6)
Previous cerebrovascular accident (N%)	Details NA	-	3/66 (4.5%)	0.95	8/98 (8.2%)

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Variables showing independent association with NACKD on binary logistic regression have been marked with asterix (*)

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Comparison of islet cell function, insulin sensitivity, and incretin axis in Asian-Indians with impaired fasting glucose, impaired glucose tolerance, and normal healthy controls

Ayan Roy ¹, Jayaprakash Sahoo ¹, Sadishkumar Kamalanathan ¹, Dukhabandhu Naik ¹, Nandhini Lakshmana Perumal ¹, Sitanshu Sekhar Kar ¹, Niya Narayanan ¹, Chandhana Merugu ¹, Deepika Patel ¹

Background and Aims: Prediabetes is the intermediates state of hyperglycemia that progresses to diabetes. But the underlying pathophysiology of prediabetes is not clear. The objective of this study was to compare islet cell function, insulin sensitivity, and incretin axis between subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT).

Materials and methods: Prediabetes patients underwent a mixed meal tolerance test after overnight fasting. Samples for glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) were collected at 0, 30, 60, and 120 minutes. Insulin secretion sensitivity index-2 (ISSI-2) for beta-cell function and Matsuda index for insulin sensitivity were assessed. Alpha cell function was assessed by measuring the area under the curve AUC0-120 glucagon/AUC_0-120 glucose.

Results: A total of sixty subjects were recruited with twenty in each group. The beta-cell function was impaired in both isolated IFG and isolated IGT subjects as compared to NGT group (2.09 ± 0.44 vs. 3.04 ± 0.80, p < 0.0001, and 2.33 ± 0.59 vs. 3.04 ± 0.80, p = 0.002 respectively). Similarly, AUC0-120 glucagon/AUC0-120 glucose was also lower in both IFG and IGT subjects as compared to NGT group [0.41 (0.54) vs. 1.07 (0.39), p = 0.003 and 0.57 (0.38) vs. 1.07 (0.39), p = 0.001, respectively]. But there was no difference in insulin sensitivity and plasma GLP-1 level between the groups.

Conclusion: Indian prediabetes patients have reduced both beta-cell and alpha cell function as compared to normal healthy controls.

Key words: Alpha cell, Beta-cell, Prediabetes, Glucagon, Glucagon-like peptide-1

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Prevalence of NAFLD in T1DM and its correlation with various parameters

Vaibhav Pathak ¹, AK Baliarshinha ¹, AK Choudhury ¹, I Mishra ¹

Introduction: Prevalence of non-alcoholic fatty liver disease (NAFLD) is high, especially in patients with obesity and type 2 diabetes (T2DM), and is projected to rise further in future. In contrast to the knowledge about NAFLD and T2DM, there are limited and inconsistent data on NAFLD prevalence in patients with type 1 diabetes mellitus (T1DM). The aim of the current study was to estimate the prevalence of NAFLD in patients with T1DM and its correlation with various metabolic parameters and complications.

Material and Methods: Total 95 patients of T1DM presenting to OPD were recruited. They were screened for complications and metabolic parameters were done for them. Using Fibroscan and USG they were screened for presence of NAFLD.

Results: Of total patients 56.8% were <18 years and 43.2 % were >18 years. 54.7% were male and 45.3% were females. Mean age was 18.09 ± 7.305 and Mean duration of diabetes was 7.15 ± 3.898. 74.7% had normal BMI while 22.1 were overweight or obese. Mean HbA1c was 9.35 ±2.18. Median LSM (liver stiffness measurement) on fibroscan was 5.2KPa. 13.7% of T1DM and 18.7% of control had LSM >7 KPa. On USG 12.6% of T1DM and 14.3% of control had raised echogenecity of liver. 31.8% of patients had microvascular complications. Using Spearman's correlation fibroscan values correlated significantly with age, weight, waist circumference, BMI, ALT triglycerides, total cholesterol, VLDL.

Conclusion: NAFLD prevalence in patients with T1DM is considerable and is highly dependent on the specific diagnostic modality and NAFLD definition used. These data suggest that clinical and metabolic parameters may give a clue about NAFLD and its early diagnosis.

Key words: FIBROSCAN, NAFLD, T1DM

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Mauriac syndrome: A rare complication of uncontrolled type 1 diabetes mellitus

Banerjee Abhirup ¹, Goswami Soumik ¹, Baidya Arjun ¹, Sahana Pranab K ¹, Sengupta Nilanjan ¹

Introduction: Mauriac Syndrome(MS), a rare complication of poorly controlled Type 1 diabetes mellitus(T1DM), is characterized by hepatomegaly, growth failure, delayed puberty, cushingoid features.

Case Report: A 17-year-old girl, diagnosed with T1DM 3 years back, presented with nausea, abdominal distension, secondary amenorrhea. Examination revealed hepatomegaly(liver span 22cm), Height SDS -0.58, SMR P4B4A+, bone age – 14 years. Moon facies, dorsocervial pad of fat were present. HbA1c was 13.3. Her SGOT and SGPT were slightly high. Serum albumin, bilirubin, coagulation profile were normal. Hypertriglyceridemia was present. Ultrasonogram showed hepatomegaly with grade2 fatty changes. Wilson disease, hemochromatosis, hepatitis B and C infection, autoimmune hepatitis, biliary tract obstruction, celiac disease were ruled out. LH, FSH, estradiol were 1.6 mIU/ml, 0.9 mIU/ml, 13 pg/ml respectively. Endometrial thickness (EMT) was not visualized. Microvascular and macrovascular complications were absent. IGF1 was low, ONDST was normal. A diagnosis of MS in T1DM was made. Intensified multiple insulin injection therapy was instituted. After 3 weeks, liver size decreased (Liver span 17 cm), EMT was 3.5 mm.

Discussion: Pathophysiology of MS in T1DM is poorly understood, probably due to fluctuating glycemic status. Other causes of glycogenic hepatopathy are anorexia nervosa, dumping syndrome, insulin overdose and steroid therapy. NAFLD is the most important differential diagnosis. Our patient had normal stature and normal onset of puberty with incomplete progression that can be explained by age of onset of the disease. MS is a reversible condition, hepatomegaly is usually resolved within 2-14 weeks after stabilization of the glycemic control.

Conclusion: Good glycemic control causes rapid reversal of symptoms in patients with MS.

Key words: Mauriac syndrome, Type 1 diabetes mellitus

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

When insulin hits too hard; though with a different hammer

Mounam Chattopadhyay ¹, Soumik Goswami ¹, Pranab Kumar Sahana ¹, Arjun Baidya ¹, Nilanjan Sengupta ¹, Abhirup Banerjee ¹, Yashaswi ¹

Introduction: Insulin and its analogues, mainstay of treatment for diabetes for a century, can cause hypoglycemia by its pharmacodynamic and other mechanisms.

Case Report: Our case a 14 year old girl with type 1A diabetes on basal bolus regimen developed recurrent hypoglycaemic episodes which were mainly nocturnal and postabsorptive while admitted in our institution. They continued to recur even after bolus insulin was withheld and only glargine was continued 3 units/day only. After excluding factitious, drug-induced causes, systemic diseases and hormonal deficiencies, a critical sample was drawn at the time of hypoglycaemia and analysed which showed an exogenous hyperinsulinemic hypoglycemia. An assay for anti insulin antibody was sent and it came out to be high normal in chemiluminescent method. Estimation of antibody specific to glargine was not possible due to resource constraints. Considering a diagnosis of exogenous insulin antibody syndrome (EIAS) mediated by anti-glargine antibodies, hypoglycemic episodes in CGMS profile were improved after replacing insulin glargine with degludec.

Discussion: Increased Insulin Antibody (IA) formation is seen with certain histocompatibility leukocyte antigen (HLA)s e.g.-HLA-B15, HLA-DR4 and HLA-DR7. The most common symptom of EIAS is wide fluctuations in blood glucose with diurnal hyperglycemia and nocturnal hypoglycaemia. Recent studies revealed that insulin glargine and aspart to be more immunogenic compared to insulin lispro which reduces antibody formation.

Conclusion: There are a handful of case reports especially in Asian descents developing antibodies against insulin or its analogues. Therefore such patients who have unexplained high or low plasma glucose must be investigated to exclude EIAS.

Key words: Insulin, hypoglycaemia, antibody, glargine, degludec

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Prevalence of metabolic risk factors for long term complications in south Indian children with type 1 diabetes mellitus

Sridevi A Naaraayan ¹, Raghavan V Dhakshayani ¹, Rema Chandramohan ¹

Background: The risk factors for long term complications of type 1 diabetes mellitus include dyslipidemia, hypertension and increased body mass index (BMI). Universally there is wide variation in prevalence of these risk factors and limited Indian data is available.

Materials and methods: This cross-sectional study was done at diabetes clinic of a Government pediatric tertiary care center from April 2016 to May 2018 and included 85 children more than 8 years of age with diabetes for more than 2 years duration who came to the hospital in fasting state. Clinical data was captured in structured proforma. Anthropometry and blood pressure were measured by standard methods and lipid profile was estimated by enzymatic methods. Triglycerides more than 150 mg/dl, total cholesterol more than 200 mg/dl, LDL cholesterol more than 130 mg/dl and HDL cholesterol less than 35 mg/dl were the defining criteria for dyslipidemia.

Results: The prevalence (95% confidence interval) of dyslipidemia in the study was 30.6% (21.1% - 41.5%). The duration of diabetes and dose of insulin were significantly higher in children with dyslipidemia (p < 0.05). The prevalence (95% confidence interval) of prehypertension and hypertension were 2.4% (0.3%-8.3%) each and the prevalence (95% confidence interval) of increased BMI was 7.1% (2.6%-14.7%). All participants with increased BMI had LDL levels above 100 mg/dl.

Conclusion: As much as one third of South Indian children and adolescents with type 1 diabetes mellitus had dyslipidemia though a small number required drug therapy. HDL levels are considerably lower in this population. The prevalence of hypertension and increased BMI were minimal.

Keywords: Adolescents, dyslipidemia, hypertension, increased BMI, type 1 diabetes mellitus

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Utility of a local language version of DDS-17 scale in assessment of diabetic distress in T2DM subjects

Vipan Talwar ¹, Gourav Talwar ¹

Background: Diabetes distress (DD) is an emotional response characterized by extreme apprehension, discomfort or dejection, due to perceived inability in coping with the challenges and demands of living with diabetes.

Aim: To assess DD and its association with various parameters in subjects with T2DM.

Methods: In 550 OPD patients with T2DM, DD was measured using Punjabi version of Diabetes Distress Scale-17 (DDS-17), a self-reported scale with subscales in 4 domains- Emotional burden (EB), Physician related, Regimen related and Interpersonal distress. Overall score < 2.0 - little or no distress, 2.0 - 2.9-moderate distress, and = 3.0 - high distress. Data analysis used SPSS.

Results: Mean age of participants was 52.5 ± 8.7 years. Prevalence of DD was 28.4%, with moderate distress in 21.3% and high distress in 7.1%. Mean total DD score was 1.98 ± 0.67. Mean score was higher in women (2.29 ± 1.14) than in men (1.59 ± 0.83). Mean for EB, physician related, regimen related and interpersonal distress were (2.1 ± 0.92), (1.41 ± 0.68), (1.872 ± 0.96), (1.61 ± 0.71) respectively. Total DD had significant association with BMI, diabetes duration, Hba1c, neuropathy, nephropathy and insulin use.

Discussion/Conclusion: Our study, first of its kind, using Punjabi version of DDS 17, identifies high prevalence of DD in T2DM. The women have higher levels of distress in managing diabetes. Local language versions of DDS-17 can be conveniently used in clinical practice, for timely detection of DD and plan its appropriate management, which is purely based on patient–provider conversation and communication.

Keywords: Distress, diabetes, DDS 17

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Observational study on effect of lock down due to COVID 19 on HBA1c levels in patients with diabetes: Experience from Central India

Jaideep Khare ¹, Sushil Jindal ¹

Introduction: Diabetes is a chronic metabolic condition characterized by hyperglycemia and is associated with several complications. Glycemic control is an important factor in preventing the complications associated with diabetes. HBA1c is the indicator of long-term glycemic control and slight variation in it significantly alters the risk of diabetic complications. Pillars for good glycemic control are good life style modification with proper medication under medical guidance.

Aim: The aim of this study was to study the change in HBA1c levels due to lock down in diabetic patients.

Material and Methods: 307 diabetic patients who had attended our endocrine OPD in last 3 months before lockdown, and had HBA1c report in past, and willing to participate were included in the study after informed consent, to identify the change in HBA1c levels during the lockdown period in our diabetic patients.

Results: The patients were aged between 25 to 69 years and male to female ratio was 181:126 (1.44: 1). The mean age and mean duration of Diabetes in our patients was 55.68 years and 7.95 years respectively. Increment of 0.51% was seen in mean HBA1c levels in our patient from 7.92% mean pre-lockdown HBA1c to mean of 8.43% after release of lock down [Table 1].

Table 1.

Blood sugar and HBA1c pre and post Lock down due to COVID 19 in male patients

		Pre- Lock Down		Post Lock Down		P Value

		Mean	Range	Mean	Range
Male (N = 181)	FBS	123.3±10.7	90-146	129.2±11.7	97-164	0.04
	PLBS	139.7±7.3	93-227	159.5±49.3	112-355	0.01
	HBA1c	7.85±1.32	6.1-13.0	8.37±1.52	6.0-15.0	0.03
Female (N= 126)	FBS	127.3+17.1	94-181	135.6±21.3	102-203	0.03
	PLBS	143.1+31.3	107-254	168.2±44.7	121-340	0.02
	HBA1c	8.03±1.93	6.3-15.0	8.52±1.47	6.6-15.0	0.02
Overall (N = 307)	FBS	124.9+14.6	90-181	131.8±23.3	97-203	0.04
	PLBS	141.1+30.3	93-254	163.1±49.5	112-355	0.01
	HBA1c	7.92±1.71	6.1-15.0	8.43±1.83	6.0-15	0.02

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Conclusion: Our study showed that overall glycemic control got deranged during lockdown period with significant increase of mean HBA1c by 0.51%, which may significantly increase the annual incidence of complications related to diabetes. But through early identification and multidisciplinary approach which is patient centric, good glycemic control can be achieved back and reduce the predicted annual percentage increase in complication rate.

Key words: COVID 19, diabetes, glycemic control, HBA1c, lockdown

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Can previous antidiabetic treatment influence outcome in hospitalized COVID-19 patients - A retrospective study

M Rajesh ¹, S L Sagar Reddy ¹, O Raghupathi ¹, P Ganesh ¹, Jayanthy Ramesh ¹

Introduction: The pandemic, COVID-19 continues to take its toll on the world. The death toll is linked to various comorbidities including diabetes. Recent studies show conflicting data regarding prior antidiabetic medication and prognosis. Hence we assessed the association between prior antidiabetic treatment and outcomes in hospitalized COVID-19 diabetic patients.

Study Design: This retrospective study included 41 consecutive COVID-19 positive patients with diabetes admitted to KGH, Visakhapatnam in month of September 2020. Data was collected on the day of admission and regularly followed up till discharge or death and tabulated in Excel sheet. Statistical analysis was done using SPSS 25.0.

Results: Out of 41 patients, 32 patients were on metformin therapy while 9 patients were on insulin prior to admission. Out of 41 patients, 16 expired. Admission Random blood glucose levels was 296.6 mg/dl and had positive correlation with mortality (p = 0.003). Metformin usage prior to admission had negative correlation with mortality, R value is -0.362 (p = 0.02). However, metformin dose at admission had no statistical correlation with mortality. Insulin usage prior to admission had no statistical correlation with mortality, while increased insulin requirement in hospital was associated with poor outcomes, R value is 0.327 (p = 0.002).

Conclusion: The result of the study shows that although diabetes is an independent risk factor for the COVID-19 mortality rate, the risk is reduced significantly in patients who were on metformin before exposure to COVID-19 and significantly increased in patients who required higher insulin doses for in hospital management.

Keywords: Admission RBS, Covid-19, coronavirus, diabetes, insulin, metformin, mortality

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Portable refrigeration system for insulin storage

Varsha Seshadri ¹, B Harsha ¹, S Pravin Kumar ¹, A Kavitha ¹, Shriraam Mahadevan ¹

Introduction: Diabetes is a serious and a common disease. Though different methods have been developed for insulin delivery, storage and transport of insulin is still a challenge. Current cooling systems and insulation bags to store insulin are of high cost which is not feasible to people living in rural areas and for travellers. Moreover, there is a lack of refrigeration unit in such places. Hence there is a need to develop a robust methodology. So our proposal focuses on the development of a refrigeration unit for insulin storage such that it is cost effective, portable and compact compared to other existing cooling systems.

Description: The proposed cooling system consists of 2 chambers, one for storing used vials or cartridges and other one for the unused ones. These thermally insulated chambers are maintained in the required temperature using peltier modules (Thermoelectric cooling). The modules work based on Peltier effect which is used to deliver the required temperature by supplying a known amount of current. The temperature can be regulated and maintained at a preferred range using a microcontroller through a trigger circuit automatically. User is alerted if any failure occurs in the system, through proper indication. Impact on current endocrine/medical/health practice: This system does not require the use of compressors or other components as seen in conventional cooling systems. Moreover, these portable cooling systems are cost effective, can be transported everywhere and does not cause pollution, and consumes less power unlike the conventional cooling systems. Also, the temperature of the system can be regulated automatically.

Conclusion: Overall, we conclude that the proposed cooling system can be beneficial and can be used extensively over a long run.

graphic file with name IJEM-24-452-g001.jpg — Block diagram of the proposed system

Keywords: Peltier, refrigeration, insulin, microcontroller, temperature sensor

REFERENCES

1.Pungaiya S, Raj RA, Kannan TTM. Study and development of new portable refrigerator kit for medical application. Int J Mech Eng Rob Res. 2013:2. [Google Scholar]
2.Güler NF, Ahiska R. Design and testing of a microprocessor-controlled portable thermoelectric medical cooling kit. Appl Therm Eng. 2002;22:1271–6. [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Does consumption of A2 milk affect prevalence of diabetes or hypertension? A population based cross-sectional study

Vanishree Shriraam ¹, Shriraam Mahadevan ¹, Parandhaman Arumugam ¹, AnithaRani Muthuthandavan ²

Introduction: There are few studies from abroad analysing the effect of A2 (a type of beta casein) milk on the incidence on type 1 diabetes, autism and some digestive disorders. This is the first of its kind, population based study to evaluate if consumption of A2 milk has any effect on prevalence of type 2 diabetes or hypertension.

Methods: Through extensive travel and search, an area in Thiruvallur district of Tamil Nadu (northern part), where the prime occupation was dairy farming and people have been predominantly consuming A2 milk was identified. The investigator was trained in identification of different types of cows visually. Also a random sample of milk from the cows in the area was tested in a dairy lab and confirmed to be predominantly A2 variant. The consumer's history on the type of milk consumed was also taken. In that area, the team contacted houses with cows – whatever be the variety and collected data. A different district (in Thirupattur) where again the prime occupation was agriculture or cottage industry but people predominantly consumed A1A2 variant milk was selected. A minimum sample size of 312 in each area was arrived at and data on all known risk factors was collected using a pretested questionnaire, blood pressure and random glucose was measured.

Results: There were 310 and 385 participants from each area of whom, 203 (65.5%) and 12 (3.1%) were A2 consumers. The A2 and other consumers were similar in background characteristics except for family history of DM, hypertension and salt intake. The prevalence of diabetes among A2 consumers and A1A2 consumers was 17 (7.9%) and 58 (12.1%) p value (0.101) and that of hypertension was 33(15.3%) and 124 (25.8%) p value (0.002). Upon logistic regression for hypertension including the factors which were significant by univariate analysis (BMI, area, DM, age, type of milk), the significant predictors were study area, age above 50 years, BMI in overweight and obese range (p<0.05). A2 milk consumption was not associated with diabetes or hypertension in this study.

Conclusion: A2 milk consumption was not associated with prevalence of diabetes or hypertension in this population based study.

Keywords: A2 milk, A1A2 milk, Diabetes, hypertension

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

An unique partnership model for diabetes education for primary care physicians (PCPs) in India

Pushkar Kumar ¹, Amit Kumar Singh ¹, Haresh Chandwani ¹, Sandeep Bhalla ¹, Ranjit Unnikrishnan1 ¹, V Mohan ¹

India is home to over 77 million individuals with diabetes which is expected to rise to 134.2 million by 2045. Given the low doctor population ratio of 1:1456, unequal distribution of specialists with an urban preference and initial diagnosis being made by non-specialists, strengthening primary health care is the key in effectively addressing this challenge.

Considering the burden, Public Health Foundation of India in 2010 launched a pan-India capacity building programs for PCPs. The aim of the Certificate Course in Evidence Based Diabetes Management (CCEBDM) is to enhance knowledge, skills and core competencies of PCPs in managing diabetes and its comorbidities. The program is conceptualized by PHFI in collaboration with an academic partner DMDEA and involving national experts, faculty, observers and PCPs. Every stakeholder has unique role and responsibilities with a robust monitoring and evaluation programme to ensure standardized delivery and implementation. A total 13363 PCPs have been trained under these programs in 102 cities across 25 states/UTs. Passing percentages ranged from 88 to 92 with average score of 39 out of 50. PCPs reported significant increase in knowledge (p < 0.05) and confidence in managing diabetes in end line evaluation and establishing a referral linkage in organic manner. The program has been adopted by seven States (Kerala, Haryana, KMC, Manipur, MP, Mizoram, and Odisha) of India to build capacities of its Medical Officers. The learning from the model is now adopted by other LMICs including Bangladesh, Nepal, Myanmar, Afghanistan and East African countries that are in throes of an alarming burden of diabetes and shortage of trained physicians.

Keywords: Primary care Physicians (PCPs), Diabetes management, capacity building

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Statistical model analysis and prediction of PIMA Indians type 2 diabetes

Prasidha Prabhu ¹, S Pravin Kumar ¹, A Kavitha ¹, Shriraam Mahadevan ¹

Introduction: Type-2 Diabetes is one of the common ailments that affects a vast population of the world. To effectively study and analyze the different causative factors, it is recommended to conduct a thorough research on a small subsect of people belonging to the same race and falling within a particular age group. This helps us to narrow down our findings, and these findings can later be applied to study larger groups of people. Using multiple machine learning algorithms, the data from over 700 patients was studied to build an effective model with a high accuracy of predicting the risk of being diagnosed with the disease.

Description: The features of the dataset included No. of Pregnancies, Weight, BMI, Insulin levels, etc. Logistic Regression proved to be the best model since it yielded a higher accuracy than the rest.

Impact: Predictive models can be used as a supportive system whilst diagnosing patients, or even to foretell the imminent risk of developing Type 2 Diabetes. The various factors that impact Diabetes can also be analyzed, and the weightage of each feature can be figured out. This can help doctors to zero in on the factors that carry more weightage, and aim to correct/rectify those features in particular.

Conclusion: The accurate prediction and forewarning of the risk of diabetes can largely help suppress the growing prevalence of Type-2 Diabetes in our nation.

Tabulated Model Findings (values in percentage)

Model	Precision	Recall	F1-Score	Average	Accuracy
Decision Trees	78	76	77	77	71
K-Nearest	77	89	82	82.66	75
Numbers
Logistic	83	87	85	85	81
Regression
Naive Bayes	82	81	81	81.33	75
Random Forests	80	80	80	80	75
Support Vector	78	93	84	85	78
Machines
XGBoost	82	78	80	80	75

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Keywords: Analysis, diabetes, diagnosis, endocrinology, health, logistic regression, machine learning, prediction, risk, statistics

REFERENCES

1. https ://www.kaggle.com/uciml/pima-indians-diabetes-database .
2.Smith JW, Everhart JE, Dickson WC, Knowler WC, Johannes RS. Proceedings of the Symposium on Computer Applications and Medical Care. IEEE Computer Society Press; 1988. Using the ADAP learning algorithm to forecast the onset of diabetes mellitus; pp. 261–5. [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

HYPERGLYCAEMIA AND COVID-19: Observational study in tertiary COVID centre

Srinivas S Gumpina ¹, Uma K Saikia ¹, Bipul K Choudhury ¹

Background: The ongoing pandemic COVID19 is causing significant morbidity and mortality among those with premorbid medical conditions like diabetes mellitus, hypertension, cardiac or respiratory disorders. There is a two-way complex relationship between diabetes and Covid-19. Diabetes is associated with an increased risk of severe Covid-19. Coronavirus disease itself is leading to New-onset diabetes and severe metabolic complications of pre-existing diabetes.

Aim: To study severity and outcome of COVID-19 patients with hyperglycemia vs normoglycemia.

Methodology: An prospective cohort study of patients with COVID-19 admitted between 1st to 7th September, 2020 and followed up till outcome (discharge or death). Subjects were divided into 2 groups- normoglycemia and hyperglycemia (random plasma glucose >200 mg/dl at admission) or a known case of diabetes mellitus. Outcome measures including severity of COVID-19, mortality, duration of hospital stay, need for ICU care/mechanical ventilation were compared between the two groups.

Results: There were 263 cases of COVID-19 of which 66 (27.9%) were known diabetics and 8 (3.04%) were found to have newly detected hyperglycemia. 32 (19.7%) patients in the normoglycemia group vs 19 (25.7%) patients in hyperglycemia group had severe disease.

Mortality: normoglycemia-19 (11.7%); diabetes-9 (12.2%)

Normoglycemia	Diabetes mellitus	Newly detected Diabetes
19 (11.7%)	Controlled uncontrolled	1 (12.5%)
	2 (3%) 6 (9.1%)

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Conclusion: People with diabetes with COVID-19 are at a greater risk of poor prognosis and mortality. Given the high worldwide prevalence of diabetes, these individuals represent a large vulnerable segment of the COVID-19 population.

Keywords: COVID-19, diabetes mellitus, hyperglycaemia

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Duodenal expression of GLP-1 and GIP in healthy individuals and Type 2 diabetes

Adlyne Reena Asirvatham ¹, Vadivukkarasi ¹, Archana B ², Leena Dennis Joseph ³, Karthik Balachandran ⁴, Ganesh P ⁵, Shriraam Mahadevan ⁶

Background: Enteroendocrine cells and their secretory products Glucagon like peptide 1(GLP1) and Glucose-dependent Insulinotrophic Polypeptide (GIP) play a major role in glucose homeostasis. They exert incretin effect, the deficiency of which contributes to Type 2 Diabetes (T2D) and is assumed to be the predominant pathophysiological abnormality among Indians. However, limited data is available on expression of K and L cells in the gut in Indian population.

Aims and Objectives: We aimed to study and compare the expression of K and L cells secreting GIP and GLP1 in proximal duodenum of healthy individuals and in those with T2D.

Materials and methods: We included 10 healthy volunteers and 10 with T2D who underwent upper GI endoscopy with mucosal biopsy taken from D2 and D3. Subjects who were on incretin based therapy were excluded.

Results: Mean age of participants was 50.1 ± 8.8 in T2D and 42 ± 9.6 in controls. Median Q score of GIP in T2D and controls were 6 and 3 respectively. Statistically significant increase in Q scores of GIP was observed in T2D (p = 0.007) by Wilcoxon Rank sum test. Q scores of GLP1 were numerically high in T2D, but was statistically insignificant (p = 0.29). Within T2D group, there was no statistically significant difference between GLP-1 and GIP expression.

Discussion and Conclusion: In our study, greater GIP expression observed in T2D appears to be a compensatory result of GIP resistance as shown in previous studies. The clinical significance of enhanced GLP1 expression in T2D is unclear owing to limited biopsy sites. Larger studies are required to prove and link our findings to the pathophysiology of T2D.

Keywords: Enteroendocrine cells, glucagon like peptide 1, glucose-dependent insulinotrophic polypeptide

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Obesity & Metabolism: Three rare cases of homozygous familial hypercholesterolemia and review of literature

Patti Ganesh ¹, KAV Subramanyam ¹, Jayanthi Ramesh ¹, A Mythili ¹, B Vivekananda ¹

Familial Hypercholesterolemia (FH) is an autosomal dominant hereditary disorder of lipid metabolism, characterized by strikingly elevated levels of low density lipoprotein (LDL) cholesterol, cutaneous xanthomas, and family history of premature atherosclerosis. FH causes lifelong exposure to increased LDL. Cholesterol, resulting in premature coronary disease and cardiovascular mortality. It occurs in 1 in 1.6-10 lack people. Here we report 3 cases of homozygous familial hypercholesterolemia presenting with cutaneous xanthomas.

Keywords: familial hypercholesterolemia, homozygous FH, cutaneous xanthoma, LDL. Cholesterol

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Hyperandrogenism, Insulin Resistance and Acanthosis nigricans (HAIR-AN) syndrome reflects Adipose tissue dysfunction ('Adiposopathy’ or ‘Sick fat') in Asian Indian girls

Kritika Agrawal ¹, Rachita Mathur ¹, Naincy Purwar ¹, Sandeep K Mathur ¹, Deepak K Mathur ¹

Background: HAIR-AN syndrome and Polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of same syndrome is still in doubts. HAIR-AN syndrome is characterized by high insulin resistance, obesity and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of ‘adiposopathy'.

Materials & Methods: A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6 and TNF alpha levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlation between adipocytokines, inflammatory markers, serum testosterone and serum insulin were determined. Data analysis was done using SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, Illinois, USA) software program.

Results: Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF alpha and IL-6) were similar in both the groups (p > 0.05). Serum Adiponectin showed negative correlation with HOMA IR and Testosterone levels while Leptin showed positive correlation with both in HAIR-AN patients while no such correlation was found in PCOS group.

Conclusion: The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients, indicates the primary role of adipose tissue dysfunction ('adiposopathy') in pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with overlapping phenotype.

Keywords: HAIR-AN syndrome, Adipocytokine, Hyperandrogenism, Insulin resistance, Adiposopathy

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

A unique learning model for primary : care physicians (PCPs) in the : prevention and management : of obesity

Deepak Monga, Sandeep Bhalla ¹, Pushkar Kumar ¹, Arshit Koundal ¹, AG Unnikrishnan ¹, Shailesh Deshpande ¹, Vedavati Purandare ¹

Background: Obesity, an established public health problem in the developed world, is fast becoming an important issue in the developing countries as well, as confirmed by numerous studies. From a public health perspective, obesity is a major risk factor for a range of chronic diseases including diabetes, cardiovascular diseases and cancer. Physicians and other health professionals often lack training in the behavioural counselling and interdisciplinary team work that is necessary for a comprehensive lifestyle intervention.

Methods: Considering the crucial role of PCPs in the prevention and management of obesity, CDI and PHFI have developed a new online course – “Certificate Course in Obesity Prevention and Management (CCOPM)”. CCOPM is a six-modular course presented in video format and aimed to develop the knowledge and skills of primary care physicians and to play a crucial role in helping patients achieve sustainable weight loss.

Results: Good response has been received from PCPs for the course. The course has received endorsement from the World Obesity Federation (WOF). WOF has also decided that the further learning value, quality, and structure of CCOPM comply with Strategic Centre for Obesity Professional Education (SCOPE) principles and has provided accreditation with 4.0 SCOPE Points, which count towards SCOPE Certification.

Conclusion: This unique course promises to engage both national and international participants since it provides flexibility to learn at their own convenient pace. SCOPE Certification is the internationally recognised standard of excellence in obesity management and participants are bound to greatly benefit with learnings from this course.

Key words: Capacity building, obesity, training

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Clinical and molecular characteristics of Prader - Willi syndrome – A case series

Subbiah Sridhar ¹, Roshan Nazirudeen ¹, Sangumani Jayaraman ¹

Background: The prevalence of childhood and adolescent obesity has been increasing world-wide as well as in India. Syndromic causes of obesity are recognized in less than 5% of obesity population due to their very low prevalence and lack of awareness among treating physician. Prader-Willi syndrome (PWS) is one of the most common causes of syndromic obesity with varied clinical manifestations across different lifespan. Herewith, we describe clinical and molecular characteristics of six PWS who were diagnosed in an obesity clinic of a tertiary care centre in Southern Tamil Nadu.

Materials and methods: Clinically suspected cases of PWS who attended the obesity clinic of Department of Endocrinology, Madurai Medical College, Madurai, were screened between January 2014 and January 2020. Detailed history and clinical examination were done to look for typical features of PWS like characteristic facial appearance, short stature, obesity, hyperphagia, delayed puberty or hypogonadism, diabetes mellitus, developmental delay, cognitive dysfunction, learning disabilities or abnormal behaviour. All were evaluated with 75g oral glucose tolerance tests (GTT), HbA1c, Free T4, TSH, LH, FSH, testosterone and growth hormone level. Intelligent quotient (IQ) of each patient was assessed by psychiatrist using Binet-Kamat test. Molecular confirmation of clinically suspected PWS was done by either Methylation specific polymerase chain reaction (MS-PCR) or Fluorescence in situ Hybridization (FISH) methods.

Results: Based on clinical and molecular characteristics, six were diagnosed as PWS. Except one, all were male with characteristic facies, mean age of study cohort was12 years and mean BMI of 44.58. Obesity, short stature, hyperphagia, hypotonia and mild to moderate mental retardation noted in entire (100%) PWS study population. All male PWS patients had cryptorchidism, which was bilateral in four patients and unilateral (right undescended testes) in the remaining. Apart from obesity, short stature, other endocrine associations noted were diabetes mellitus in 50% and subclinical hypothyroidism in 33% of PWS. Molecular characteristics of PWS were confirmed by Methylation Specific PCR in five and by FISH method in one.

Conclusion: Prader-Willi syndrome should be kept in mind in case of childhood or adolescent obesity with short stature, hypotonia, cryptorchidism and developmental delay or cognitive dysfunction. Judicious use of molecular diagnostic testing should be made in all clinically suspected cases. Early diagnosis and appropriate management of this complex disorder by a multidisciplinary team will improve the quality of life and treatment outcome.

Key words: Cryptorchidism, hyperphagia, hypogonadism, hypotonia, obesity, Prader Willi syndrome

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

THYROID: Liquid biopsy in differentiated thyroid cancer

Soham Tarafdar ¹, Susmita Dutta ¹, Nitai P Bhattacharyya ¹, Pradip Mukhopadhyay ¹, Sujoy Ghosh ¹

Background: Evaluation of thyroid nodules encompasses ultrasonographic evaluation and fine needle aspiration cytology and surgical biopsy is considered gold standard for diagnosis. Indeterminate nodules pose a diagnostic dilemma and molecular diagnostics like detection of driver mutation in FNA samples is often used to guide therapy. Liquid biopsy a novel diagnostic technique may help in identifying known driver mutations from plasma of patients presenting with indeterminate nodules.

Objectives: To detect known driver mutations from plasma samples and FNA materials of patients with thyroid nodule and its role as marker for predicting thyroid malignancy in indeterminate thyroid nodules.

Methodology: Patients presenting with thyroid nodules underwent ultrasonography (as per TIRADS) and cytological examination (Bethesda classification). The DNA/RNA from plasma and FNA samples were isolated by using commercially available kits and mutations were detected by ARMS PCR. Histopathology of surgical samples was taken as gold standard of diagnosis.

Results: We had recruited 153 patients of which 48 patients were in the indeterminate category (Bethesda 3,4) underwent surgery as per current treatment protocol. Of them 37 were malignant and 11 were benign. Using a panel of driver mutations containing BRAF, PAX8-PPARg, HRAS, KRAS, NRAS, RET-PTC1, RET-PTC 3 we could identify differentiated thyroid cancer with 91.9% sensitivity and 90.9% specificity from plasma and 94.6% and 90.9% respectively from FNAC.

Discussion and Conclusions: Our study suggests that by using liquid biopsy from plasma we were able to detect known driver mutations with a high degree of sensitivity and specificity which could serve as a useful non-invasive marker for diagnosis of indeterminate thyroid nodules and aid in decision making for further management.

Key words: Liquid biopsy, indeterminate nodules, driver mutation, differentiated thyroid cancer

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

A case of congenital athyreosis with PAX 8 gene mutation

Anil Kumar Behera ¹, Nithin Reddy ¹, Chetan Reddy ²

Introduction: Congenital hypothyroidism (ch) characterised by elevated thyroid stimulating hormone (tsh) resulting from reduced thyroid function at birth is the most common congenital endocrine disease with incidence of1 in 2000 to 4000 newborns. Ch is now a highly identifiable and treatable condition at any early stage. Thyroid dysgenesis characterised by devlopmental defects of thyroid gland accounts for 85 percent of ch cases and presenting with various clinical types. Thyroid agenesis consist of 30 to 45 percent of cases of thyroid dysgenesis. Thyroid dysgenesis is mainly sporadical while 2 percent is familial. Mutation in genes for tsh receptor, nkx2-1 (thyroid transcription factor 1), thyroid transcription factor 2, paired box transcription factor 8 have been identified in some patients with various forms of thyroid dysgenesis. Pax 8 is a major specific regulator of thyroid gland, is encoded by single gene on chromosome 2q12-q14, essential for thyroid devlopment when thyroid bud envaginates from floor of pharynx and maintenance of thyrocyte cell type.

Case Report: Patient aged 48 day old infant came with the chief complain of jaundice, macroglossia and incidental finding of high tsh on evaluation. Patient had normal birth weight, cried immediately after birth. Baby is product of non consangieous marriage, full term with lscs delivery on regular vaccination. There was no significant family history of thyroid disorder. On evaluation, haemogram and renal parameters are normal. Liver function test showed hyperbilirubinemia (direct), prothrombin time and inr are normal. Tsh on evaluation found to be high and t3 and t4 levels are diminshed. X ray showed no epiphysis at lower end of femur and tibia. Tchenctium thyroid scintigraphy was performed and no significant tracer activity noted in thyroid bed. Mutation analysis showed pax 8 mutation (missense mutation). Patient was started with thyroid hormone supplementation and followed up on regular basis. Clinical

Discussion: Defective mutation of the pax8 gene have been considered to mainly cause thyroid hypoplasia. Pax8 gene mutationsmay have varaiable penetrance or expressivity. In our case, patient had high tsh and macroglossia. Thyroid scinitigraphy showed no significant tracer uptake in thyroid bed. To evaluate congenital athyreosis, pax 8 gene mutation was found.

Conclusion: Congenital athyreosis is one of the most common cause of thyroid dysgenesis. Many mutation of genes are linked to congenital athyreosis like ttf1, ttf2 and pax 8 here we present a case of congenital athyreosis case of 45 day old infact concluding pax 8 being major contributor for thyroid devlopment.

Keywords: Atheyrosis, congenital hypothyroidism, pax 8 gene mutation, thyroid gene

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Effect of thyroxine replacement on depression in subjects with primary hypothyroidism

Karan Saran Kapur ^1,², Sushil Jindal ³, Shaifali Bansal ⁴

Introduction: It is known that impaired thyroid function has effect on mood and there is overlap of symptoms among hypothyroidism and depression. In this study we looked at the phenomenon of depressive symptoms in subjects with overt and subclinical hypothyroidism and the effect of thyroxine replacement on them.

Aims and Objective: To find the prevalence of depression in subjects of overt and subclinical hypothyroidism and in a prospective study to assess the effect of thyroxine replacement on depression in them.

Materials and methods: A total of 109 subjects with hypothyroidism were screened for depression using Hamilton Depression scale (HAM-D) score. These subjects were put on thyroxine replacement. No anti depressant drugs were added. After achieving euthyroidism, they were reassessed for depression by using the same score.

Results: There was a significant improvement in depression score after achieving euthyroidism. Out of the 109 subjects, 80 had depression according to HAM-D score. Amongst them 45% were overt and 55% were subclinical hypothyroidism. On achieving euthyroidism, 87% subjects showed complete recovery and 13% showed partial recovery in depression according to HAM-D score. The mean HAM-D scores declined from 11.18 ± 5.74 to 5.66 ± 3.96 (p value < 0.001).

Conclusion: Majority of subjects suffering from subclinical and overt hypothyroidism have concomitant depression. There is a significant decline in depression scores after thyroxine replacement in these subjects.

Keywords: Depression, HAM-D, primary hypothyroidism

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Diagnostic utility of thyroid doppler in differential diagnosis of thyrotoxicosis

Sandeep Kumar ¹, Naresh Bansal ¹

Introduction: Differentiation of the etiology of thyrotoxicosis is important in planning the appropriate line of management. Although Graves’ disease (GD) is the most common cause of hyperthyroidism, the absence of pathognomonic features of Graves’ disease may make it challenging to distinguish it from Destructive Thyroiditis (DT), especially when the disease is mild or subclinical.

Aims Objective: To identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake.

Material and Method: We analysed a total of 85 treatment naÏve patients of presenting with thyrotoxicosis. Based on clinical findings, thyroid function tests and thyroid scintigraphy, the patients were divided into two groups: 63 as GD and 22 as DT. Peak systolic velocity (cm/sec) in the inferior thyroid artery was measured using CDFU.

Result: Thyroid blood flow as assessed by systolic velocity was significantly higher in GD as compared to DT (50.00 ± 25.74 versus 20.34 ± 5.40, respectively, p < 0.001). At a mean PSV-ITA cutoff value of 26 cm/sec, PSV-ITA differentiated GD from DT with a sensitivity of 90.2% and specificity of 90.9%.

Discussion and Conclusion: Measurement of PSV-ITA by CFDU is a good diagnostic approach in the differential diagnosis of thyrotoxicosis. High correlation with thyroid scintigraphy findings suggests it may be used as a simple and more cost efficient alternative.

Keywords: Thyroid doppler, thyrotoxicosis, peak systolic velocity, inferior thyroid artery

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

A rare entity of dual ectopic thyroid: Importance of multidisciplinary approach

Yashaswi Pathak ¹, Sajal Kamat ¹, Soumik Goswami ¹, Arjun Baidya ¹, Pranab Kumar Sahana ¹, Nilanjan Sengupta ¹

Background: Dual ectopic thyroid is rare with only 34 cases reported in world literature. Ectopic thyroid can present with obstructive symptoms. However, all patients with obstructive symptoms do not mandate surgical excision. Thyroxine supplementation should be the initial therapy, to induce glandular shrinkage.

Case Presentation: A 6 year old female was referred to endocrinology OPD for hypothyroidism post operatively. She presented to surgery with a midline neck swelling and mild obstructive symptoms. Examination revealed a midline swelling in the upper neck and no thyroid gland in its normal site. Pre-operatively, the thyroid function tests revealed subclinical hypothyroidism. USG neck showed a mixed solid cystic swelling in the supra hyoid region without normally located thyroid gland. FNAC revealed hyperplastic nodule with cystic degeneration. Radionuclide scan revealed a dual ectopic thyroid (sublingual and submental). In view of obstructive symptoms, she underwent surgical excision of the dual ectopic thyroid. Histopathologically, the resected tissue showed heterotopic thyroid tissue in the thyroglossal cyst and sublingual region without evidence of malignancy. USG neck showed absence of thyroid tissue in eutopic or ectopic locations. Her TFTs showed overt hypothyroidism. She was started on 75mcg of levothyroxine.

Discussion: Surgery is seldom necessary for ectopic thyroid in the absence of life threatening obstructive symptoms or malignant transformation. Even in the presence of obstruction, suppressive dose of levothyroxine is the initial line of management to cause shrinkage of the ectopic thyroid tissue.

Conclusion: A multidisciplinary approach including endocrinology, endocrine surgery and nuclear medicine is needed for the correct diagnosis and treatment of ectopic thyroid in order to prevent unnecessary surgery.

Keywords: Ectopic thyroid, thyroglossal cyst, multidisciplinary

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Utility of MRI in graves ophthalmopathy to increase the detection of active disease

Vivek Kyatham ¹, Krishna Reddy Thaduri ¹, Apsia Ruhi ¹, Srinivas Rao P ¹, Vijay Sheker R Danda ¹

Background: Clinical activity score is commonly used to measure disease activity. It is subjective and highly dependent on the examiner. It is not useful for monitoring change of clinical manifestations. Evidence for cut-off of CAS =3 is lacking in Asian population, who have a different orbital structure.

Aims and Objectives: To determine the ability of MRI to improve the detection of active GO in those with clinically inactive disease.

Materials and methods: Study design: observational study of 40 GD patients. Subjects: 27 were women, 13 being men. Mean age was 34 years (15-52years). 62.5% (n = 25) had ocular symptoms excluding CAS. Iodised salt consumption was 85% (n = 24). 3 subjects were active male smokers. 20% (n = 8) were treated with ATD. Grade 3 goitre was present in 50% (n = 20), grade 2 goitre in 45% (n = 18), grade 1 goitre in 5%.

Methods: CAS, Severity of GO and orbital MRI imaging: Activity was graded using CAS score by Mourits et al. Severity was graded according to EUGOGO criteria. Orbital MRI was done in all patients after evaluation with CAS. Patients were diagnosed with active GO independently of CAS if they presented with enlarged EOMs.

Results: All patients had CAS score 0. Mild GO was present in 90% (n = 36), moderate GO in 10% (n = 4). Overall 12.5% subjects (n = 5) had active disease on MRI even though none had clinically active disease. 11% of subjects (n = 4) with mild GO and 25% with moderate GO (n = 1) had evidence of active disease on MRI.

Conclusion: Along with CAS score, MRI is a useful adjunct to increase detection of active disease with management implications.

Keywords: Magnetic resonance imaging, Cas score, graves orbitopathy

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Spectrum of cardiac disease in long standing Graves’ disease: Experience from a tertiary care centre

Jeeban Pradhan ¹, Ipsita Mishra ¹, Arun K Choudhury ¹, Anoj K Baliarsinha ¹

Introduction: There is significant impact of thyroid hormones on cardiac function and structure. Thyrotoxicosis affects cardiovascular hemodynamics which causes various clinical manifestations and may lead to various complications like atrial fibrillation and heart failure.

Case Report: A total of 21 patients (13 male/ 8 female) of Graves’ disease presented with different cardiac diseases. Atrial fibrillation was found in 7 patients, 3 had exclusive AF others were associated with heart failure and/or valvular heart disease. Heart failure without structural heart disease was found in 4 patients and heart failure with structural heart disease was found in 4 patients. Valvular heart disease was present in 7 patients, most had mild to moderate Mitral regurgitation. Mild to moderate Pulmonary arterial hypertension was present in 6 patients. On follow up evaluation there was significant improvement in 16 patients, 4 patients with moderate to severe valvular heart disease had symptoms controlled and 1 patient with 12 years of poorly treated graves with AF had persistent AF.

Discussion: Heart disease increases the morbidity and mortality in patients with graves’ disease. Findings at our centre was consistent with previous reports with the exceptions of a greater number of patients with MR. Effective treatment lead to significant improvements in majority of patients.

Conclusion: Early and effective treatment of Graves’ disease can prevent development of consequent heart disease and related complications.

Keywords: Atrial fibrillation, Graves’ disease, heart failure, mitral regurgitation, PAH.

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Thyrotoxic periodic paralysis- 15 years ex1perience from a tertiary care centre in southern India

Jinson Paul ¹, Felix Jebasingh K ¹, More Atul Ramchandra ¹, Kripa E Cherian ¹, Nitin Kapoor ¹, H S Asha ¹, Thomas V Paul ¹, Nihal Thomas ¹

Introduction: Thyrotoxic periodic paralysis (TPP) is an uncommon presentation of thyrotoxicosis characterised by transient and recurrent episodes of flaccid muscle paralysis.

Objective: To describe the clinical and biochemical profile and treatment outcome of subjects with TPP.

Methodology: Retrospective study from a tertiary care centre in southern India (2005-19). Demographic, clinical, laboratory details and the treatment received were obtained from the medical records.

Results: Forty-one subjects (93% males), mean age 33.1 ± 7.7 years were included in the study, with 1 year follow up of 63.4%. Around 60% were from north eastern states of the country. 65.8% had more than one attack. One patient had respiratory muscle paralysis requiring mechanical ventilation. Overt thyrotoxic features were seen in 80.4%. The mean serum potassium was 3.4 ± 0.9 mmol/L and 60% had normal serum potassium. All except 3 had Graves’ disease. 41.4% were managed with antithyroid drugs alone, 31.7% by radioiodine ablation alone and 14.6% received both therapies. Two subjects underwent total thyroidectomy. Two subjects had persistent hypokalaemia even after normalisation of thyroid function, and they were having additional aetiology (renal tubular acidosis and Gitelman syndrome).

Conclusion: This is the largest series of TPP from India. Around three fourth presented in third and fourth decades of life. Graves’ disease was the most common cause. More than three fourth were overtly thyrotoxic at the time of presentation and hypokalaemia was not seen in majority of them.

Keywords: Graves’ disease, hypokalaemia, thyrotoxic periodic paralysis

REFERENCES

1.Lin S-H. Thyrotoxic periodic paralysis. Mayo Clin Proc. 2005;80:99–105. doi: 10.1016/S0025-6196(11)62965-0. [DOI] [PubMed] [Google Scholar]
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Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Predictive accuracy of American College of Radiologists Thyroid Imaging Reporting And Data System (ACR-TIRADS) in diagnosing carcinoma in Thyroid nodule in Indian population

Soumya S ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Introduction: In India, incidence of differentiated thyroid cancer (DTC) has increased over decade by 55%.[1] Selection of nodules for FNAC is aided by ultrasound-based risk-stratification systems, of which 2017 ACR TIRADS is considered to be objective with lesser inter-observer variability.[2,3]

Aims and objectives: 1) To assess predictive accuracy of ACR-TIRADS in diagnosing thyroid malignancy, considering FNAC as gold standard. 2) To estimate efficacy of size cut off criteria for FNAC put forward by ACR-TIRADS.

Materials and methods: Subjects 10 years old, with palpable or ultrasound-revealed thyroid nodule were included in the cross-sectional study over 1.5 years. Ultrasonography (2017ACR-TIRADS) will be done on all. Nodules of size =1 cm in maximum diameter and nodules of TIRADS score 4 or 5 with maximum diameter >5 mm underwent ultrasound-guided FNAC by a single investigator. Bethesda 4, 5 and 6 nodules and selected (patient preference) Bethesda 3 nodules underwent thyroidectomy.

Results: Two-hundred-and forty nodules from 161 patients were studied. Proportion of euthyroid, hypothyroid, hyperthyroid (FNA done after achieving euthyroid state) nodules were 64.2%, 24.2% and 11.6%. Nodules which turned out Bethesda 3 and 4 were considered as indeterminate for the gold standard and excluded from primary analysis. There were 18 malignant nodules (Bethesda 5 and 6) out of 213 nodules included. ACR TIRADS 4 and 5 were considered as test positive (malignant). The sensitivity and specificity of ACR TIRADS was 100% and 61.5%. The sensitivity and specificity of size cut off criteria was 88.8% and 63.5%. Among 27 indeterminate nodules 13 underwent surgery; 8 were malignant (61.5%). Prevalence of DTC was 11.5% (26 out of 226 nodules).

Discussion and Conclusion: ACR-TIRADS is a sensitive tool in selecting nodules for malignancy evaluation agreeing with the previous studies. It should be considered as a good tool to rule out malignancy but not to predict the same. Size, TIRADS and Bethesda may be put together for risk prediction by a risk calculator which may revolutionise the diagnostic evaluation of DTC.

Keywords: ACR-TIRADS, differentiated thyroid carcinoma, fine needle aspiration thyroid, thyroid nodule

Table 1.

Comparison between characteristics of benign and malignant nodules

	Malignant	Benign	P value
SIZE (mm)	22.27 ± 11.12	22.49 ± 12.2	0.93
BMI (kg/m2)	23.79 ± 3.6	24.9 ± 3.0	0.103
TSH	2.42+ 1.3	1.62 +1.02	0.036
Thyroid status
Euthyroid	15 (68.18%)	114 (60.22%)
Hypothyroid	5 (22.7%)	52 (25.7%)
Hyperthyroid	2 (9.09%)	25 (17.07%)

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REFERENCES

3.Sekkath Veedu J, Wang K, Lei F, Chen Q, Huang B, Mathew A. Trends in thyroid cancer incidence in India. J Clin Oncol. 2018;36:e18095. [Google Scholar]
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Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Management of Graves disease: Looking beyond thionamides in a catch-22 situation

Vanishri Ganakumar ¹, Madhukar Mittal ¹, Himanshu Pandey ¹, MK Garg ¹

Introduction: Antithyroid drugs are the first line management in Graves disease(GD) patients. Comorbidities and adverse effects of anti-thyroid drugs, though infrequent, can present challenge to the treating physician.

Case Report: We report a case of 30-year female, presenting with significant unintentional weight loss, palpitations, increased sweating, tremors and polymenorrhea for 4-months. Laboratory evaluation was suggestive of thyrotoxicosis and Tc-99m thyroid scan revealed diffusely enlarged gland with increased uptake(4.5%). Methimazole and propranolol were started considering GD. 2-weeks later, she developed itching and jaundice, with elevated bilirubin and transaminases. Methimazole was stopped with repeat liver function tests. The patient was lost to follow-up and presented 3-months later with right-sided loin pain and frank thyrotoxicosis. Imaging revealed left-sided gross hydroureteronephrosis and poorly functioning right kidney. Early definitive treatment was offered and patient chose radioiodine ablation(RAIA) over thyroidectomy. She was started on lithium (well-tolerated) and given RAI. DJ-stenting was done and planned for pyeloplasty in view of solitary functioning kidney. She became hypothyroid 10-weeks post-RAIA. Lithium was discontinued and thyroxine supplementation given, following which she successfully underwent right pyeloplasty.

Discussion: Methimazole-associated hypersensitivity and hepatotoxicity, though rare, can prompt consideration of second-line drugs for control of thyrotoxicosis including iodine, lithium, cholecystographic agents and cholestyramine. Lithium was logical alternative, having known synergistic effect with RAIA by increasing retention, enhancing half-life and increasing radio-ablative efficacy of I131 in the thyroid.

Conclusion: Low-dose lithium therapy, with appropriate monitoring, can be safe and viable adjunct to RAIA in management of patients with GD with adverse effects to thionamides.

Key words: Graves disease, lithium, methimazole, thionamides, thyrotoxicosis, radioiodine

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

A distinctive skill building model in the management of thyroid disorders for primary care physicians (PCPs) in India

Deepak Monga ¹, Sandeep Bhalla ¹, Pushkar Kumar ¹, Tanu Soni ¹, Arshit Koundal ¹, AG Unnikrishnan ¹, Shailesh Deshpande ¹

Background: 42 million Indians are affected by either hypothyroidism or hyperthyroidism. One third of patients with hypothyroidism remain undiagnosed due to lack of clinical awareness. PCPs play an important role in the screening and initiation evaluation in these patients. In India, understaffed and overburdened tertiary care along with ill-equipped and poorly skilled primary care system remains the unaddressed concern. This gap can be bridged through training of PCPs.

Methods: PHFI implemented a training initiative – “Certificate Course in Management of Thyroid Disorders (CCMTD) along with CDI and a 15-member national experts’ panel. This four modular course covered various aspects of management of thyroid disorders, with a prudent mix of theory, case studies and videos, and was delivered once a month on weekends by 49 faculty at various centres in India. An integrated monitoring and supervision mechanism was established to monitor and evaluate the program and assure training quality.

Results: Around 2500 PCPs from 41 cities across India were trained over three cycles; 45% were post graduates and 31% from government sector. The success rate measured by exam conducted at the end of course was 89.9%. This course has been endorsed by Asia and Oceania Thyroid Association for 10 years (2016-2025). Three State governments have already adopted this course for training of their doctors. Following a successful run in India, the model has also been adopted in Nepal, Afghanistan, Myanmar and Rwanda.

Conclusion: This course is unique since it is probably the only national level thyroid disease training to be undertaken in India. High enrolment and compliance rate reveal an acceptability by the physicians in education on thyroid management.

Key words: Capacity building, thyroid, training

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Weight change with levothyroxine treatment in newly diagnosed primary hypothyroidism: A prospective cohort study

Rekha Singh ^1,²

Introduction: Obesity is linked to hypothyroidism. We aimed to study the factors associated with weight loss with treatment in primary hypothyroidism.

Methods: This is a prospective cohort follow-up study. Newly diagnosed primary hypothyroidism patients were enrolled and followed up to euthyroidism. A complaint of weight gain was recorded on the Likert scale at enrolment and follow-up. Subclinical hypothyroidism cases were enrolled if the anti-thyroid peroxidase antibody was positive.

Result: A total of 359 cases were enrolled (266 Female, 93 Male). Ninety-eight participants complained of weight gain at diagnosis (16/96 subclinical hypothyroidism, 82/263 overt Hypothyroidism). A BMI of <18.5, 28.5-24.9, and >25 kg/m2 was seen in 6.1%, 40.7%, and 51.7% of the participants respectively. A total of 194 participants had follow-up assessments for weight change at euthyroidism. A total of 62/194 and 88/194 reported an increase and a decrease in weight post-treatment, respectively, on the Likert scale. A total of 32% had an increase, 45.5% had a decrease in weight, while 22.7% had no change (<0.5 kg) in weight at euthyroidism. Weight change correlated with pre-treatment TSH (r -0.33, p < 0.001), BMI (r -0.34, p < 0.001), and gender (Female = 1, Male =2, r -0.24, p < 0.01). On multivariable linear regression analysis, factor predicting a decrease in weight with higher TSH (p < 0.001), Male gender (p < 0.02), and higher pre-treatment BMI (p < 0.01).

Conclusion: A decrease in weight is seen in participants with higher pre-treatment Serum TSH and BMI, and Male Gender.

Key words: Weight change, primary hypothyroidism, treatment

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

A Retrospective Study of Clinical Features, Biochemical Profile and Outcome of Patients with Thyroid Storm from a south Indian Tertiary Care Centre

Venkata Sandeep Nandipati ¹, Felix Jebasingh K ¹, Julie Hephzibah ¹, Kripa Elizabeth Cherian ¹, Nitin Kapoor ¹, Asha H S ¹, Thomas V Paul ¹, Nihal Thomas ¹

Introduction: Thyroid storm (TS) is a rare life threatening complication of thyrotoxicosis. Burch-Wartofsky (BW) score of >45 is highly sensitive for the diagnosis of TS.

Objective: To describe the clinical features, biochemical profile and outcome in those with TS.

Methodology: Retrospective data of patients admitted with TS was obtained from medical records, wherein clinical, biochemical and treatment details were analysed.

Results: 35 patients with TS were identified. The mean age was 44.9 ± 10.2 years; one-third were females. Gastro-intestinal dysfunction (89%) and tachycardia (89%) were the most common manifestations, followed by fever (63%), cardiac failure (60%), CNS manifestations (40%) and Atrial fibrillation (40%). TS occurred as the index presentation in 43%. Around one-third had an episode of infection prior to TS and upto 50% were incompliant to anti-thyroid medication. Only one patient had TS following primary 131I ablation. The commonest aetiology was Graves’ disease (71%). Hypokalaemia was noted in 40% of patients. Three-fourths of patients were given steroids on presentation and all received rate limiting medications. Propylthiouracil, carbimazole and Lithium were used in twenty-two, ten and one patient, respectively. Parenteral iodine was utilized in one-third of patients. Three patients expired following TS (9%). Eleven patients received a definitive treatment (nine had radioiodine ablation while two underwent thyroidectomy). Eleven percent had recurrence of TS.

Conclusion: A high index of suspicion is needed to identify TS as it may mimic sepsis, cardiac illness or even gastrointestinal illness. More than one-third had recurrence in toxic multinodular goitre and early definitive treatment is necessary.

Key words: Burch-Wartofsky Point Scale, Graves’ disease, thyroid storm

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

PEDIATRIC ENDOCRINOLOGY: A rare case report of growth hormone insensitivity syndrome

Vivek Kyatham ¹, Krishna Reddy Thaduri ¹, Apsia Ruhi ¹, Srinivas Rao P ¹, Vijay Sheker R Danda ¹

Introduction: Laron dwarfism is a rare autosomal recessive disorder characterized by severe short stature associated with normal or high serum GH and low serum IGF-1 levels which fail to rise after exogenous GH administration.

Case Report: 13 year old boy p/w history of not gaining height since 5 years. He was born out of 3rd degree consanguinity with birth weight of 2.75 kg. Small sized penis was noticed with descended testes at birth. Developmental milestones were normal with no significant past or family history. Anthropometric measurements; height - 118 cm, Height SDS: (-4.3SDS), weight: 24 kg, Weight SDS: ( -2.3SDS), BMI: 25th-50th centile; MPH = 163.5 cm: (-3.2SDS). Examination revealed frontal bossing, saddle shaped nose, maxillary hypoplasia, prominent eyes, thin hair with fronto-temporal recession, small hands and feet, central obesity with SPL of 4 cm(-2.5 SDS) and pre-pubertal SMR.

Investigations: Routine biochemistry was normal.

Bone age was 11 years

S.T4 = 9.79 mcg/dl, TSH = 3.63 miu/ml,

S. IGF 1: 65.4 ng/ml (< -3SD).

Basal Fasting GH = 3.20 ng/ml

Clonidine stimulation test: 150 mcg/m2:

GH at 60 min => 40 ng/ml,

At 120 min = 32.8 ng/ml

IGF 1 generation test: with 33 mcg/kg rHGH: sIGF 1 = 50.1 ng/ml

MRI Pituitary was unremarkable

Discussion: diagnostic criteria by Savage et al. includes: height SDS < 3SD, basal GH > 2.5 ng/ml, basal IGF 1 < 50 ng/ml, IGFBP 3 < 2SD, post IGF generation test IGF 1 increase < 15 mcg/L, post IGF generation test IGFBP 3 increase <0.4 mg/dl and GH binding <10%. 5 / 7 should be met for diagnosis. As GH stimulation tests are routinely performed in evaluation peak stimulated values > 40 ng/ml should prompt suspicion of GH resistance.

Conclusion: High index of suspicion is required to diagnose GHIS .There is a need to increase awareness for accurate diagnosis.

Key words: Laron's syndrome, IGF1 generation test, savage criteria

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

An interesting case of polyuria presenting as short stature

Sagar A Barasara ¹, Nikhil Bhagwat ¹, Jugal Gada ¹, Prema Varthkavi ¹

Introduction: Hereditary nephrogenic Diabetes insipidus (NDI) is a rare disorder resulting in variable degrees of resistance to vasopressin action either due to mutation in the AVPR2 gene or the AQP2 gene. We are reporting an unusual presentation of hereditary NDI.

Case Report: A 14 year boy, third offspring of non-consanguineous marriage presented with short stature (height SDS = - 3.5 SD) and non-development of secondary sexual characters (Tanner Stage 2). He had a history of polyuria and polydipsia from birth which was well-compensated with oral fluids by the relatives. Urine output at admission was ~10 liters/day. There was no history of prolonged medication intake, deformity, or fractures. Serum and urinary electrolyte and osmolality analysis confirmed the diagnosis of Diabetes Insipidus. The anterior pituitary hormones were normal. The water deprivation test confirmed the diagnosis of NDI. Secondary causes of NDI were ruled out. Genetic testing confirmed the diagnosis of X-linked recessive NDI secondary to a mutation in the AVPR2 gene (2 base pair deletion in exon 3). The patient responded well to a low salt/low protein diet and hydrochlorothiazide (25 mg/day). Urine output decreased to 2.5 liters/day. At 7 months follow-up urine output remained normal and he gained height (height SDS = – 3.2 SD) and progressed through puberty (tanner stage 3).

Discussion: History of polyuria from birth clinched the diagnosis of NDI. The patient and relatives learned to match water intake equal to urine output well as he didn't suffer any neurological consequences. This was a novel mutation of the AVPR gene reported in the Indian population. Adequate control of NDI led to catch-up growth and progression of puberty.

Conclusion: Though hereditary NDI usually presents in childhood, it can present peripubertally as short stature and delayed puberty.

Key words: Nephrogenic Diabetes Insipidus, Hereditary NDI, Short stature

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Clinical, endocrinological, and molecular characterization of isolated growth hormone deficiency

Piyush Lodha ¹, Krishna Reddy Thaduri ¹, Apsia Ruhi ¹, Sandeep Reddy ¹, Srinivas P Rao ¹, Vijay Sheker R Danda ¹

Introduction: Congenital Isolated Growth Hormone Deficiency (IGHD) is a rare condition with incidence of 1:10,000 births. It is an important treatable endocrine cause of severe short stature.

Objective: To study the clinical, endocrinological and genetic characteristics of IGHD.

Materials and methods: We analyzed 23 subjects presenting with IGHD. The patients were divided into two groups: Group A (n = 12) with severe short stature (<4.5 SDs) and Group B (n = 11) with stature between -2.5SDs to -4.5SDs. Clinical, hormonal and radiological features were analyzed. Clinical exome sequencing for genetic evaluation was done for seven cases in Group A.

Results: 17 of 23 cases evaluated were male. Patient exhibited great variability in their stature, ranging from -2.5 to -6.3SDs (mean -4.7). Bone age was significantly delayed in all cases (Range: 2-10 years). All the subjects in group A, had serum IGF-I levels of less than 3SD and a peak GH at 60 min of 2.1 ± 1.3 ng/ml (mean ± SD). In group B, IGF levels were less than -2 SD and peak GH at 60 min was 4.4 ± 1.7 ng/ml.MRI of pituitary gland showed anterior pituitary hypoplasia in 10 cases (83%) in group A, and 6 cases (54%) in Group B. Normal pituitary was found in rest of the cases. Out of 7 cases screened in Group A, NGS identified GHRHR mutation in 4 cases.

Conclusion: The detailed phenotypic analysis show variable severity in patients with IGHD, reflecting the importance of genetic analysis in affected individuals. Patients with severe short stature, frequently have genetic mutations identified.

Keywords: Bone age, genetic mutations, isolated growth hormone deficiency, MRI pituitary

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Rare case of moon facies- Laurence Moon Bardet Biedl Syndrome PCMS & RC, Bhopal, India

Rohit Chhari ¹, Sushil Jindal ¹, Jaideep Khare ¹, Shaifali Bansal ¹

Introduction: Laurence Moon Bardet Biedl Syndrome which is a rare Ciliopathic and Pleiotropic Autosomal recessive disorder. The feature of LMBB ranges from central obesity, hearing difficulties, hypogonadism in males, renal involvement, postaxial polydactyly, learning disability to spectrum of ocular associations such as rod cone dystrophy, (Atypical retinitis Pigmentosa), Myopia, Astigmatism, Anisometropia, Strabismus, keratoconus, optic atrophy, Nystagmus.[1,2]^[3] The other features which may be rarely seen are hepatic fibrosis, diabetes mellitus, neurological, speech and language disorder, behavioural traits, facial dysmorphism, dental anomalies and developmental delay.^[6]

Case: 9-year-old boy presented to the endocrinology department with weakness of both lower limbs since 7 days and progressive loss of vision since from 1 year. On enquiry mother also complained of delayed milestones with progressive increase of weight with gaining height. Upon examination the height was 116 cm and weight 64 kg with BMI of 47.6 KG/m2. He had moon facies with post axial polydactyly. Neurological examination revealed low IQ with flaccid joints. The ophthalmological examination revealed squint with deteriorating vision due to the retinitis Pigmentosa. Genital examination revealed buried penis with retractile testes with tanner stage 1. Routine Investigations were within normal limits. Parents were advised life style modification and were made aware regarding the possible complications in future and need for regular medical evaluation.

Conclusion: Diagnosis of LBBS is usually missed because of its rarity. Any patient with moon facies, obesity with visual disturbances and polydactyly should be suspicious for this and must be evaluated and managed accordingly.

Key words: Laurence Moon Bardet Biedl Syndrome with obesity, loss of vision, polydactyly, learning disability

REFERENCES

1.Mariam A, Tariq A, Samer A, Rukhsana AS. Laurence Moon Bardet Biedl Syndrome with anaemia. J Ayub Med Coll Abbottabad. 2014;26:625–7. [PubMed] [Google Scholar]
2.Rajasekhar P, Parmi MK, Aalekhya PS. Int J Sci Res. 2015;4:438. [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

MRI predictors of severity of growth hormone deficiency-Both the Extra-sellar and sellar region morphologic defects on Magnetic resonance imaging are indicative of the severity of growth hormone deficiency with pituitary hypoplasia having the best predictive value

Himanshu Sharma ¹, Naincy Purwar ¹, Anshul Kumar ¹, Rahul Sahlot ¹, Umesh Garg ¹, Balram Sharma ¹, Sanjay Saran ¹, Sandeep K Mathur ¹

Background: Growth hormone deficiency (GHD) is one of the common endocrinological causes of short stature in clinical practice. However, there are no studies evaluating the presence of extrasellar brain abnormalities and a paucity of studies focusing on ectopic posterior pituitary and pituitary stalk abnormalities in the Indian context.

Aim: This study aimed to evaluate the prevalence of Extra-sellar and sellar region abnormalities, to determine which abnormalities could predict the severity of the GHD in the Indian context and ascertain the abnormality that is the best predictor of severe GHD.

Materials and methods: A total of 100 subjects presenting to our OPD and diagnosed to have idiopathic GHD after the exclusion of syndromic causes including Septo-optic dysplasia, system illness, presence of pituitary mass, and those with h/o cranial irradiation from 2017 through 2020 were included. Patients were divided into groups based on peak GH, extrasellar abnormalities (EBA), pituitary hypoplasia, and presence of ectopic posterior pituitary and/or pituitary stalk abnormalities (EPP/PSA) respectively.

Results: 52 patients had pituitary hypoplasia, 23 (23%) had EBA and 25 (25%) had EPP/PSA. The total no. of patients with Severe GHD was 71 and Partial GHD was 29. The patients with EBA had a significantly greater prevalence of severe GHD (91.2%). Those with EBA had a lower height SDS, lower peak stimulated GH, and lower pituitary height SDS. A higher percentage of EPP/PSA subjects had severe GHD than those with normal posterior pituitary and stalk. These patients had significantly lower height SDS, lower peak stimulated GH, and a lower pituitary height SDS as compared to patients with normal posterior pituitary and stalk. All three abnormalities predict the presence of severe GHD with pituitary hypoplasia (Odds Ratio 10.81) having the best predictive value

Conclusion: Since there is no gold standard as such to differentiate between SGHD and PGHD, the delineation of GHD patients by the presence of extrasellar brain abnormalities and hypothalamic-pituitary imaging abnormality provides valuable information, facilitating the evaluation of the severity of GHD and could be of substantial value for further management of these children.

Key words: MRI, severity, growth hormone deficiency

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Mental disability due to congenital hypothyroidism despite timely diagnosis: Study from Vellore, Tirupattur and Ranipet districts of Tamil Nadu

Parandhaman Arumugam ¹, Srilakshmi R ¹, Sudha Seshayyan ¹, Shriraam Mahadevan ²

Introduction: Congenital hypothyroidism (CH) is the one of the most common preventable causes of mental retardation. The clinical features of Congenital Hypothyroidism are so subtle that many newborn infants remain undiagnosed at birth. Delayed diagnosis leads to the most severe outcome of CH which is intellectual disability.

Aim and Objective: To find out the prevalence of Congenital hypothyroidism among intellectually disabled children in Vellore, Tirupattur and Ranipet district.

Methodology: The survey was conducted in Vellore, Tirupattur and Ranipet District. Total children covering 513670 in the above 3 district, Tamil Nadu state was conducted during the years 2014-2019 using a specially designed questionnaire. Ethical clearance was obtained from Institutional Ethical Committee (IEC), The Tamil Nadu Dr MGR Medical University, Guindy. A door-to-door survey was done in 743 village (Total 22 Blocks). Survey was done over a period of 5 years. Children between the ages of 5 and 14 years were evaluated.

Results: During the study, in the age group of 6 to 14yrs it was observed that out of 6084 disabled children 2901 (47.68%) had intellectually dysfunction. Consanguinity was common in this population. On further probing, 21 children had Congenital Hypothyroidism diagnosed in early infancy but they discontinued treatment. Reasons for discontinuation included socio-economic status, ignorance, financial burden, distance to reach the centre, testing facility, availability of medicine etc. This reveals that inspite of diagnosing hypothyroidism very early significant number of people may end with mental disability. The success of New Born Screening (NBS) program for hypothyroidism thus depends on long term follow up and regular monitoring.

Conclusion: Newborn screening for Congenital Hypothyroidism and its impact would be realized only if long term follow up is also included in the program.

Key words: Mosaicism, short stature, karyotype

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Transverse testicular ectopia in a case of persistent mullerian duct syndrome: A rare form of ‘Disorders of Sex Development'

Banerjee Abhirup ¹, Goswami Soumik ¹, Baidya Arjun ¹, Sahana Pranab K ¹, Sengupta Nilanjan ¹

Introduction: Transverse testicular ectopia(TTE) is a condition where both the testes descend into the same hemi-scrotum along with uterus and uterine tubes placed within the same hernia sac. Deficiency or resistance of Anti mullerian hormone(AMH) causes persistent mullerian duct syndrome(PMDS), an important cause of TTE.

Case Report: A 2-year-old child, reared as male sex, presented with left sided undescended testis. His postnatal period was uneventful. Examination revealed palpable right-sided testes along with reducible inguinal hernia. Left Scrotal sac was empty. There was no ambiguity. Abdominal imaging detected one testes in the right scrotal sac, karyotyping was XY. Human Chorionic Gonadotropin stimulated testosterone increment, androstenedione/testosterone, Testosterone/Dihydrotestosterone ratio were normal; AMH value was low(1.97 ng/ml). Laparoscopy revealed gonadal structure in the right inguinal canal along with uterus, fallopian tube within the hernial sac. Gonadal biopsy revealed normal testicular tissue, dilatation and calcification of few seminiferous tubules which can be attributed to cryptorchidism. A diagnosis of type 2 TTE in PMDS due to AMH deficiency was established.

Discussion: TTE occurs due to presence of flimsy broad ligament connection which allows testis, still attached to fallopian tubes, to descend towards the inguinal canal. TTE has three subtypes. It has never been observed with idiopathic PMDS. Differential diagnosis of PMDS are-Mixed gonadal dysgenesis, ovotesticular DSD, AMH deficiency and resistance, Idiopathic. Malignant transformation, torsion and infertility are the major complications. In-toto removal of mullerian duct structures are discouraged to protect testicular vascularity.

Conclusion: Multidisciplinary Team Approach is required for early diagnosis and treatment to prevent complications of TTE in PMDS.

Key words: Persistent mullerian duct syndrome, Transverse testicular ectopia

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Automation of insulin bolus dose calculation in type 1 diabetes

Rajiv Singla ¹, Jatin Bindra ¹, Ankush Singla ¹, Geetu Gupta ², Yashdeep Gupta ³, Shivam Aggarwal ¹

Background: Diabetes care in type 1 diabetes has remained a challenge over time. Ability to vary insulin bolus dose according to carbohydrate content of meals, insulin carbohydrate ratio(ICR) and insulin sensitivity factor (ISF) can widen food choices and improve quality of life of people with type 1 diabetes. While, in theory, this seems simple but a large majority of people are unable to do so in practical life due to the amount of effort needed to manually count carbohydrates in every meal and inability to understand the concept of ICR and ISF. Difficulties in prediction of bolus insulin dose may largely be solved by application of technology.

Description: This work was done at the endocrine unit of a superspeciality centre involved in care of people with type 1 diabetes. Carbohydrate counting tool for Indian foods was developed and subsequently, bolus dose calculation was automated by using the reinforcement algorithm in an android app platform named “T1-Life”. Schematic of entire process is depicted.

Impact: T1-Life has potential to transform the way children with type 1 diabetes mellitus are managed. In development phase, five patients completed 3 months of this app usage. Among five people with combined usage over 115 patient-weeks, a total of 2661 insulin dose predictions were made. This translates to 3.31 patient initiated bolus dose predictions per day. Of the total bolus dose predictions made, 82% were accepted by the participants. Time in range (70-180 mg/dl) increased by an average of 16.67% in children who used CGMS in their first week as well as last week of observation.

Conclusion: T1-life, integrated carbohydrate counting and reinforcement based insulin bolus dose prediction system, has good patient usability and acceptability.

Key words: Bolus insulin dose prediction, carbohydrate counting, Expert system, type 1 diabetes

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Allgrove syndrome: A rare cause of adrenal insufficiency - Case report

Haritha Galla ¹, M N Satya Vani ¹

Introduction: Allgrove syndrome or triple A syndrome refers to the triad of adrenal insufficiency, achalasia and alacrima. It is a very rare autosomal recessive disorder with multi system involvement.

Case Report: we report a case of 6year old girl, born of non-consanguineous marriage, second in birth order, who was referred in view of hyperpigmentation of skin and weight loss. History revealed anorexia, fatigue and darkening of face. Also, there was absence of tears while crying. There was no dysphagia. Her anthropometric findings were height-117 cm (25th to 50th centile), weight-18.25 kg (10th to 25th centile). Her blood pressure was 80/60 mmHg. External genitalia were normal. Baseline investigations including electrolytes were normal. 8Am cortisol was 4.97 μg/dl. On Synacthen stimulation, the cortisol was 2.29μg/dl. ACTH was 837 pg/ml. Schirmer's test revealed xerophthalmia. Barium swallow was not done as there was no dysphagia. She was started on Hydrocortisone at a dose of 8mg/m2/day. Fludrocortisone although started, was stopped in view of hypokalemia.

Discussion: Allgrove's syndrome is characterized by a triad of primary adrenal insufficiency due to ACTH resistance, alacrima and achalasia. Our patient had primary adrenal insufficiency and alacrima. Achalasia is rare in childhood, in less than 5% before 15 years of age.

Conclusion: Although rare, Allgrove syndrome should be considered in the differential diagnosis of Addison's disease and a history of alacrima or dysphagia should be asked for, in every patient.

Key words: Adrenal insufficiency, Alacrima, hyperpigmentation

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Van Wyk-Grumbach Syndrome due to congenital hypothyroidism in the era of newborn screening –an unfortunate reality

Nanda N ¹, Rishi Bolia ¹, Indar K Sharawat ¹, Kriti Joshi1 ¹

Introduction: Van Wyk-Grumbach syndrome (VWGS) is a rare presentation of untreated pediatric hypothyroidism leading to peripheral precocious puberty. We report two cases of VWGS due to undetected congenital hypothyroidism (CH).

Case Presentation: We report two girls, a 4 and an 11 year old, who presented with features of prolonged untreated hypothyroidism and vaginal bleeding. Both had striking growth and developmental delay, unevaluated due to poor parental education and limited availability of medical care. They had evidence of peripheral precocious puberty with discordant progression as indicated by menstrual bleeding with minimal breast development. Endocrine evaluation revealed a significantly elevated TSH with undetectable FT4 in both confirming severe primary hypothyroidism [Table 1]. An FSH predominant picture with multicystic ovaries was found in both girls. Etiological evaluation for the hypothyroidism revealed thyroid agenesis in the first and hypoplasia in the second child. Following institution of levothyroxine treatment there was regression of breast development and stopping of menses. Parents were counselled about the need of lifelong thyroxine supplementation and limited likelihood of improvement in intellectual status.

Table 1.

Table showing clinical, biochemical and radiological characteristics of the two cases

Variable	1st case	2nd case
Age at presentation	4 years	11 year
Onset of symptoms	Early infancy	Early infancy
Features of hypothyroidism	Sinus bradycardia	Depressed nasal bridge, dry skin, hoarse voice
	Coarse facial features-depressed nasal bridge, protruded tongue, dry skin, hoarse voice, short stubby hands
		IQ- 45 as per Wechsler Intelligence scale for children
	Global developmental delay with overall
	Developmental quotient of 20%
Height	85 cm (- 4 SDS)	102 cm (-6.8 SDS)
Tanner staging	B1P1A-	B3P1A-
Thyroid function test
TSH (mIU/ml)
(0.35-5.5)	699	510
FT4 (ng/dl)
(0.89-1.76)	<0.4	<0.4
LH (mIU/ml)	0.01	3.11
FSH (mIU/ml)	14.9	6.11
USG Neck	Thyroid agenesis	Hypoplastic thyroid gland
		Right lobe measures 4.5 × 5 20 mm
		(Anteroposterior × Transverse × Craniocaudal) (Thyroid volume = 0.2 ml).[1] Left lobe measures 6.4 × 7.3 × 21 mm (AP × TR × CC) (Thyroid volume =0.4 ml).[1] Isthmus measures 1 mm
Ultrasound pelvis	Bilateral multicystic ovaries with uterine size discordant with age and endometrial thickness of 5 mm	Bilateral multicystic ovaries with uterus of size 3.5 × 1.3 × 2.6 cm with Endometrial thickness of 4.3 mm
Bone age	Delayed (corresponds to 1 year)	Delayed (corresponds to 5-7 years)
99mTc Nuclear thyroid scan	No uptake suggestive of thyroid agenesis	ND

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Discussion: VWGS occurs in long-standing untreated primary hypothyroidism due to specificity spillover between TSH and FSH receptors. Our cases presented with VWGS due to untreated CH. In this modern era of newborn screening (NBS) it is unfortunate that the critical window of opportunity for treatment was missed accounting for the severe neurocognitive deficits.

Conclusion: Our cases are a clarion call for improving awareness of NBS for CH and early institution of treatment for better neurocognitive outcome.

Key words: Van Wyk-Grumbach Syndrome, Congenital hypothyroidism, Precocious puberty, Newborn screening

REFERENCE

1.Zimmermann MB, Hess SY, Molinari L, Benoist BD, Delange F, Braverman LE, et al. New reference values for thyroid volume by ultrasound in iodine sufficient schoolchildren: A World Health Organization/Nutrition for Health and Development Iodine Deficiency Study Group Report. Am J Clin Nutr. 2004;79:231–7. doi: 10.1093/ajcn/79.2.231. [DOI] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Resistant hypertension in pediatric pheochromocytoma and paraganglioma

Nanda N ¹, Kalyani Sridharan ¹, Nisha Batra ¹, Satya S Baliga ¹, Enono Yhoshu ¹, Manish K Gupta ¹, Kriti Joshi ²

Introduction: We present two cases of pediatric pheochromocytoma paraganglioma (PPGL) with sustained hypertension requiring high dose alpha blockade and multiple additive antihypertensive medications for pre-operative blood pressure control.

Case Presentation: Two male children around 13.5 years of age presented with one and four years of paroxysmal symptoms and sustained hypertension respectively. Twenty-hour urine normetanephrine was elevated in both. A right sided abdominal paraganglioma encasing the right renal artery was found in the former and bilateral pheochromocytoma in the latter. In addition to pre-operative alpha blockade both children required the addition of 2-3 more antihypertensive classes for optimization of blood pressure [Table 1]. The first child underwent right adrenalectomy and right nephrectomy. The second child underwent bilateral adrenalectomy. Genetic testing for SDHB mutation is planned for the first child and the second child had a heterozygous mutation for VHL gene.

Table 1.

Table showing clinical, biochemical & radiological characteristics of the two patients of pheochromocytoma & paraganglioma

Variable	1st child	2nd child
Age at presentation	12 year 9 months	9 year 10 months
Tumor localization	Abdominal, extra-adrenal right side PPGL encasing the right renal artery with loss of fat planes on Contrast enhanced CT abdomen	Bilateral
		Pheochromocytoma
24 hour fractionated urinary	3107.5 mcg	5192 mcg
Normetanephrine (<600 mcg/24 hours)
Duration of pre-op alpha blockade (days)	18	10
Dose of prazosin (mg/kg/day)	0.45	0.5
Other pre-op antihypertensive medications required	Amlodipine (10 mg)	Amlodipine (10 mg)
	Clonidine (0.5 mg)
	Enalapril (2.5 mg)	Enalapril (2.5 mg)

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Discussion: The higher prevalence of sustained resistant hypertension, hereditary and extra-adrenal disease in pediatric PPGL reflects the predominance of noradrenergic cluster 1 PPGL in children compared to adults. In the first child, the compression of the renal artery by the tumor probably contributed to the greater antihypertensive requirement while in the second child early onset and prolonged duration of syndromic disease resulted in sustained hypertension. Literature review shows that prolonged pre-operative alpha blockade in children can be attributed to lower dose increments and greater sympathetic activity.

Conclusion: Children with syndromic PPGL and those with associated renal artery stenosis may present with resistant hypertension requiring high dose alpha blockade and additional pre-operative antihypertensives.

Key words: Pheochromocytoma, Paraganglioma, Resistant hypertension, Sustained hypertension, Pediatrics

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

ADRENAL GLANDS: Paraganglioma of the vagina presenting with episodic hypertension

Thushanth Thomas ¹, Rafeekha ¹, Manoj KS ²

Introduction: Paragangliomas occur only very rarely in the female genital tract (ovary, broad ligament, uterus, vulva). We hereby report paraganglioma in the vagina.

Case Report: 26 year old female presented with history of accelerated hypertension on attempted removal of a vaginal mass. Per-speculum examination revealed a large mass arising from the anterior vaginal wall. Even though urine metanephrines were at the upper limit of normal, because of the typical history, it was presumed to be a functional one. After adequate preparation with alpha/beta blockers and adequate intravascular fluid expansion, surgical excision was done. Grossly, 6*4*2 cm irregular yellowish tissue mass with thin capsule. Microscopy-neoplasm composed of nests, cords and sheets of polygonal round and ovoid cells with eosinphilic granular cytoplasm and round or oval nuclei. Mild anisonucleosis seen; but no pleomorphism or mitotic activity. Immunohistochemistry-strong positive reaction for synaptophysin and chromogranin (findings consistent with paraganglioma).

Discussion: Only around ten cases of vaginal paraganglioma have been reported. Vaginal paraganglioma can present with bleeding, pain, or finding a vaginal wall mass. Accelerated hypertension, tachycardia or arrhythmia may occur during attempted removal or coitus. If there is any clue in the history to it being a paraganglioma, plasma free metanephrines should be done and adequate preoperative preparation is essential. The typical hyperintense signals in MRI (image attached) also should be looked for. Definitive diagnosis is based only on histological findings.

Conclusion: Paragangliomas can very rarely occur in the vagina and should be considered in any vaginal mass associated with paroxysmal symptoms or episodic hypertension.

Keyword: Episodic hypertension, paraganglioma, vagina

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Phaeochromocytoma with primary hyperparathyroidism: Looking beyond MEN to VHL – A rare case

Parul Gupta ¹, Madhukar Mittal ¹, Gautam Ram Chaudhary ¹, M K Garg ¹

Introduction: Co-occurrence of phaeochromocytoma and primary hyperparathyroidism is usually seen in patients of MEN2A and is rare in Von Hippel Lindau disease (VHL).

Case Report: A 30-year male was admitted for evaluation of hypertension and incidentally diagnosed adrenal mass on ultrasound. 9-years back, he was diagnosed as a case of VHL (right renal clear cell carcinoma, pancreatic cystadenoma, spinal hemangioblastoma and epidydymal cysts). Right nephrectomy and pancreatic cyst excision had been done and past work-up for pheochromocytoma was normal. He also had been operated twice for recurrent renal calculi. Family history revealed surgery in mother for pancreatic mass. Current imaging revealed right adrenal mass with left renal cysts and calculi, pancreatic cysts and medullary hemangioblastoma. 24-hours urinary fractionated normetanephrines were elevated and I¹³¹ MIBG scan showed 4.7*4.6 cm concentrating lesion in right renal fossa. However his biochemical evaluation revealed hypercalcemia, low phosphorus, low 25(OH)D, and raised PTH (121 pg/ml). Ultrasound neck and Tc99m-Sestamibi localized left inferior parathyroid adenoma. DEXA scan showed severe osteoporosis. Genetic analysis confirmed VHL mutation in exon-1. Calcitonin and RET mutation were normal (ruled out MEN2A). Therapeutic approach was surgical excision of adrenal pheochromocytoma followed by parathyroidectomy.

Discussion: We report a case of pheochromocytoma with primary hyperparathyroidism (cause: left inferior parathyroid adenoma) in a patient of VHL. This is the 2^nd such case reported in literature of primary hyperparathyroidism in a genetically confirmed case of VHL with pheochromocytoma.

Conclusion: This case highlights the overlap of tumorigenesis in two rare genetically divergent syndromes and importance of long-term follow-up for sequential development of new tumors.

Keyword: Von Hippel Lindau disease (VHL), Pheochromocytoma, Primary hyperparathyroidism, Multiple Endocrine Neoplasia (MEN)

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Prevalence of adrenal insufficiency in treatment naÏve tuberculosis patients

Ajeesh T ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Background: Tubercular involvement of adrenals accounts for 20-30% of cases of Adrenal Insufficiency (AI) in developing countries.[1] Previous studies done in Pulmonary tuberculosis (PTB) patients showed varying prevalence of AI ranging from 0 to 76% and data in extrapulmonary tuberculosis is scarce.[2,3,4,5,6]

Aim of study: To assess the prevalence of AI in treatment naÏve tuberculosis (TB) patients.

Materials and methods: Adult patients with microbiologically confirmed, Human Immunodeficiency Virus negative PTB or extra-pulmonary tuberculosis (EPTB), attending the Revised National Tuberculosis Control Programme (RNTCP) clinic in Government Medical College Hospital, Thiruvananthapuram were included. Before initiation of Anti-Tuberculosis Therapy (ATT), patients were subjected to ACTH Stimulation test for diagnosing AI. Blood samples for serum cortisol drawn at 60 and 120 minutes after intramuscular administration of 0.5 ml (30 Units) of porcine ACTH (Acton Prolongatum). Peak cortisol value of 19.5 μg/dL at 120-min was taken as cut off for AI.

Results: Study population comprised of 78 TB patients (58 males and 20 females) including 66 PTB (84.8%) patients. The mean age was 49.6 ± 15.1 years. 41 (52.5%) patients showed symptoms suggestive of AI. The mean peak cortisol values were 34.7 ± 10.7 ug/dl and 39.6 ± 11.1 ug/dl at 1 and 2 hours respectively. Only one EPTB patient was found to be adrenal insufficient who presented with symptoms of AI and postural hypotension and showed subnormal response to Acton Prolongatum stimulation test.

Conclusion: Adrenal insufficiency is rare (1.28%) in treatment naÏve tuberculosis patients although many patients have symptoms mimicking AI at presentation and follow up of these patients is required to rule out development of AI during the course of illness or due to treatment.

Keywords: Acton prolongatum stimulation test, adrenal insufficiency, prevalence, tuberculosis

Table 1.

Prevalence of adrenal insufficiency in patients with tuberculosis

Adrenal Insufficiency	Present N (%)	Absent N (%)	Total N (%)
Pulmonary	0 (0)	66 (84.6)	66 (84.6)
Extrapulmonary	1 (1.3)	11 (14.1)	12 (15.4)
Total	1	77	78

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REFERENCES

1.Agarwal G, Bhatia E, Pandey R, Jain SK. Clinical profile and prognosis of Addison's disease in India. Natl Med J India. 2001;14:23–5. [PubMed] [Google Scholar]
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Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Adrenal incidentaloma: North East India tertiary care centre experience

Akash N Shah ¹, Uma K Saikia ¹, Bipul K Choudhury ¹

Introduction: Adrenal incidentaloma are seen in around 2% of apparently healthy individuals which require careful evaluation for hormone excess state and malignancy. Adenomas are most common adrenal incidentaloma (33-96%), which are most commonly non-functioning. Others include functioning adenoma, pheochromocytoma, adrenocortical carcinoma, myelolipoma, metastasis and less commonly cysts.

Aims and Objectives: To study the clinical, biochemical and imaging characteristics of the patients with adrenal incidentaloma.

Methodology: Patients with adrenal incidentaloma presenting to Endocrinology dept of GMCH between January 2017 to January 2020 were evaluated as per guidelines provided by European Society of Endocrinology. This data was retrospectively analysed for this study. Patients were given final diagnosis on the basis of imaging impression, hormonal activity and biopsy results (when applicable).

Results: 45 patients were evaluated, with 24 males and 21 females and mean age of 40.9 years (8-71), 34 (75.5%) of whom underwent surgical excision. Final diagnosis and functional status figure has been attached. Two patients with pheochromocytoma were normotensive. There was discordance between imaging and hormonal status in 2 patients, with final diagnosis of pheochromocytoma.

Discussions and Conclusion: All patients with adrenal incidentaloma should be evaluated as per guidelines and appropriate therapy should be offered. Clinicians should always rule out pheochromocytoma pre- operatively. In cases of discordance between imaging, hormonal and biopsy results, careful evaluation and follow up are of utmost importance to reach a final diagnosis and provide appropriate care.

Keywords: Adenoma, adrenal incidentaloma, adrenocortical carcinoma, myelolipoma, pheochromocytoma

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

CRITICAL CARE ENDOCRINOLOGY: A comparative study of the hematological factors determining outcome in diabetic and non-diabetic severe covid-19 patients

S L Sagar Reddy ¹, Rajesh M ¹, Johann V ¹, CM Shyam Sundar ¹, Jayanthy Ramesh ¹

Introduction: As the pandemic of Coronavirus disease 2019 continues, simple prognostic markers are need of the hour in COVID positive diabetic patients. Hematological parameters are easily and immediately accessible in remote areas. Recent studies showed correlation between NLR and poor prognosis in COVID patients1. Hence, we assessed hematological parameters in diabetic and non-diabetic hospitalized COVID patients in determining their outcome.

Study Design: This retrospective study included 81 consecutive patients admitted to KGH, Visakhapatnam admitted in month of September 2020. Hematological parameters were obtained on the day of admission and tabulated in an Excel sheet. Statistical analysis were done using SPSS 25.0.

Results: In 81 patients, 39 (48%) were diabetic and 42 (51%) were non-diabetic. 36 patients were admitted to ICU of which 22 (61%) were diabetic and 25 patients expired of which 17 (68%) were diabetic. In diabetic patients, polymorphs had positive correlation with mortality, r-value of +0.383 (p < 0.022), whereas lymphocytes had negative correlation with r-value of -0.37 (p < 0.027). Though NLR (neutrophil lymphocyte ratio) in diabetics was not statistically significant, in non-diabetics and combined population a significant positive correlation with mortality, r-value of +0.38 (p < 0.0001) was observed.

Conclusion: Neutrophilia and Lymphopenia individually and in combination as NLR can predict poor outcome in severe COVID 19 patients with diabetes mellitus.

Keywords: COVID-19, diabetes mellitus, hematological parameters, NLR

REFERENCE

1.Yang AP, Liu J, Tao W, Li HM. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol. 2020;84:106504. doi: 10.1016/j.intimp.2020.106504. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

OSTEOCRINOLOGY (METABOLIC BONE DISEASE): Trabecular bone score in primary hyperparathyroidism: A prospective cohort study

Hiya Boro ²

Introduction: Trabecular Bone Score (TBS) is a new modality of investigation that can be used as a non invasive assessment of bone microarchitecture. Our study was planned to evaluate the bone microarchitecture using TBS in Primary Hyperparathyroidism (PHPT).

Aims/Objectives: The objective of our study was to assess the bone mineral density (BMD) and TBS in PHPT at baseline and at six months and one year after successful parathyroidectomy, and compare the same with that in healthy controls.

Materials and methods: PHPT (n = 140) and healthy controls (n = 80) matched for age and sex, were recruited for our study. TBS and BMD were done at the baseline and at six months and one year after successful parathyroidectomy. Healthy controls were not followed up.

Results: The mean age of PHPT was 44.0 ± 16.0 years. In PHPT, the mean L1-L4 BMD at baseline was 0.779 ± 0.174 (g/sq cm), femoral neck BMD 0.589 ± 0.163 (g/sq cm), total hip BMD 0.715 ± 0.198 (g/sq cm) and distal radius BMD was 0.542 ± 0.134 (g/sq cm). The mean absolute TBS at baseline was 1.260 ± 0.116. After one year of successful parathyroidectomy, there were significant improvements in lumbar spine (11.9%), femoral neck (10.7%) and total hip BMD (13.6%), but no significant improvement noted in either distal radius BMD (1.7%) or TBS (1.6%).

Discussion and Conclusion: In PHPT, the BMD improvement at lumbar spine was significantly greater than the TBS. This implied that microarchitectural changes reflected by TBS required a longer time for improvement compared to bone mineral density.

Keywords: Trabecular Bone Score, Primary Hyperparathyroidism, Bone mineral density

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Every PTH-dependent hypercalcemia is not primary hyperparathyroidism: report of a kindred with type 1 familial hypocalciuric hypercalcemia

Sarah Alam ¹, Alpesh Goyal ¹, Nikhil Tandon ¹

Introduction: Measurement of serum parathyroid hormone (PTH) level is an important initial step in broad subtyping of patients with hypercalcemia. Primary hyperparathyroidism (PHPT) is the most common cause of PTH-dependent hypercalcemia.

Case Report: A 48-year old female presented for evaluation of generalized body ache of two years duration. Biochemical evaluation revealed mild PTH-dependent hypercalcemia and hypocalciuria in the face of vitamin D sufficiency [Table 1]. The work-up for end-organ manifestations of hyperparathyroidism including BMD estimation, and ultrasonography of KUB region were normal. Considering a possibility of FHH, a family screening was requested. Both her children had PTH-dependent hypercalcemia and hypocalciuria in the face of vitamin D deficiency (VDD) [Table 1]. Hypocalciuria and hypercalcemia persisted while serum PTH levels reduced after cholecalciferol supplementation, raising the suspicion for an inherited defect in calcium sensing mechanism [Table 1]. Genetic testing by NGS followed by Sanger sequencing confirmed a pathogenic variant in the exon 3 of CASR gene (c. 413 C>T; p.Thr138Met) in the index patient and her children. The family was counseled about the benign nature of this condition.

Table 1.

Biochemical data of the index patient and her children

Parameter	Index patient	Daughter (Baseline)	Daughter (after D3 suppl.)	Son (Baseline)	Son (after D3 suppl.)	Reference Range
Urea (mg/dL)	14	16	16	12	13	10-40
Creatinine (mg/dL)	0.6	0.4	0.5	0.5	0.4	0.5-1.0
Serum calcium (mg/dL)	11.4	10.6	10.5	11.6	11.5	8.5-10.5
Serum phosphate (mg/dL)	3.0	2.4	3.1	4.3	4.9	2.5-4.5
ALP (IU/L)	98	270	92	426	234	80-240
Albumin (g/dL)	4.0	4.3	4.3	4.2	4.9	3.5-5
iPTH (pg/mL)	122.4	270	63.5	351	63.9	15-65
25(OH)D (ng/mL)	57.4	4.0	24.5	6.8	30.9	20-100
Urinary calcium, mg/24 h	36	76	60	17.5	45	<100 suggests
						hypocalciuria
Urinary creatinine, mg/24 h	854	852	1080	498	877	11-20 mg/kg
Calcium to creatinine	0.002	0.003	0.002	0.001	0.001	<0.01suggests
clearance ratio						hypocalciuria

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Discussion: FHH is a rare autosomal dominant condition characterized by mild PTH-dependent hypercalcemia, hypocalciuria and a benign clinical course. Severe VDD resulting in secondary hyperparathyroidism can complicate the biochemical picture of FHH. It is prudent to replete serum 25(OH) D levels before evaluation for hypocalciuria is made.

Conclusion: Accurate diagnosis of FHH is essential to avoid unnecessary parathyroid exploration. Family screening and genetic testing should be considered in suspicious cases to confirm the diagnosis.

Key words: Familial hypocalciuric hypercalcemia, hypercalcemia, primary hyperparathyroidism

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Study on insulin storage and administration techniques in patients with type 2 diabetes mellitus

Shyam Sundar C M ¹, Vivekananda B ¹, Mythili A ¹, Subrahmanyam KAV ¹, Jayanthy Ramesh ¹

Introduction: The use of Insulin in Type 2 Diabetes Mellitus is increasing, with 15.5% using it for glycemic management. Optimal glycemic control is not achieved despite increasing dose of insulin. Proper storage and use of insulin is of prime importance.

Aims and Objectives: To Study Insulin storage and use practices.

Material and Method: Cross sectional study included consecutive 160 patients attending Endocrinology OPD in our Institute.

Results: 53% were male with mean age 51 years and mean diabetes duration of 10 years. 50% were illiterate. Only 21% had FBS/PPBS in target range. 93.8% were using premix insulin and 84.4% using two doses per day. 81.3% stored Insulin in refrigerator, 70% administered insulin immediately after it taking out. 81.3% practised rolling of insulin before administration. Only 28.3% individuals waited for 15-30 mins after injection for food intake. 46% used only single site, periumbilical being the commonest, 54% used multiple sites and among them 90% practised site rotation. 53.1% practiced proper injection technique and commonest improper method was acute angle of insulin syringe (80%). 25% used a syringe more than 10 times. 81.3% individuals administered insulin by themselves. 62.5% were able to properly identify insulin markings in syringe. In 53.1% the prescription matched the actual dose used.

Conclusion: Despite advice on insulin storage and use techniques, many improper methods are followed by patients, which can affect efficacy of prescribed Insulin. Periodic reinforcement and education preferably by educator or video demonstration in OPD will aid in obtaining maximum benefit from insulin therapy.

Keywords: Administration technique, insulin, storage, type 2 diabetes mellitus

Mean value of age, gland weight & biochemical parameters and regression analysis for gland weight

Variable	Mean ± S.D	Univariate regression for gland weight			Multivariate regression for gland weight
		ß	S.E	p-value	ß	S.E	p-value
Age (years)	37.6 ± 15.5
Gland weight (grains)	4.7 ±4.9
S. Corrected Calcium (mg/dL)	12.27 ±1.6	2.3	0.77	0.004	0.11	1.25	NS
S. Phosphorus (mg/dL)	2.56 ± 0.7
S. Alkaline Phosphatase (IU/L)	1555±1982	0.31	0.09	0.001	0.09	0.8	NS
S. PTH (pg/ml)	808 ± 639	0.54	0.1	<0.0001	0.56	0.09	<0.0001
S. 25(OH)D (ng/ml)	12.5 ± 11.4

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NS=not significant

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Spondyloarthropathy in primary hypoparathyroidism-A diagnostic dilemma

Ashima Mishra ¹, Purna Chandra Karua ¹

Introduction: Spondyloarthropathy is a rare musculoskeletal manifestation of primary hypoparathyroidism, whose clinical profile has not been elucidated much.

Case Report: A 27 year male presented with tetany in emergency, had an abnomal posture that developed over 3 months against a 10 years history of low backache, joint pain, stiffness, severe restriction of truncal mobility; neck rotation; mouth opening, Schobers test positive, chest excursion normal and negative family history. He had hypocalcemia, severe hypoparathyroidism, hyperphosphatemia, low 25 (OH) vit D, elevated inflammatory markers and muscle enzymes, positive serology for HLAB27 allele, positive urine culture. Imaging revealed peripheral arthritis and myositis. No sacroilitis, enthesitis or any changes in vertebra suggestive of typical spondyloarthropathy. He was previously given NSAIDS without any relief and the deformities progressed. Indomethacin, baclofen, sulfasalazine were started along with a short course of steroids and antibiotics. Calcium and vit D supplement dosage was increased subsequently, leading to better recovery.

Discussion: Primary Hypoparathyroidism, uncommon endocrinopathy can mimic spondyloarthropathy as per few case reports. This patient as per ASAS criteria confirmed to be Peripheral spondyloarthropathy. No apparent cause of primary hypoparathyroidism was found (genetic analyses have not been done). Excluding all differentials, a diagnosis of hypoparathyroidism associated peripheral spondyloarthropathy was made.

Conclusion: Presence of hypoparathyroidism in peripheral spondyloarthropathy may require additional calcium and vitamin D supplements to NSAIDs and DMARD resistant cases. Hypoparathyroidism must be included in differential spectrum of atypical spondyloarthropathy, which requires further research to validate.

Keywords: Hypoparathyroidism, myopathy, peripheral spondyloarthropathy

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

A cross-sectional study of bone mineral density in type-1 diabetes mellitus patients - a tertiary care experience

Mandeep Sharma ¹, Naresh Bansal ¹, Rakhi Malhotra ¹, Sandeep Kumar ¹, Kiraninder S Brar ¹

Introduction: Type-1 DM (T1DM) with autoimmune destruction of beta cells affects various organ systems but there is inconsistent data regarding its effect on bone health. AIM and Objectives: To analyze the epidemiological, clinico-biochemical data and BMD in T1DM patients.

Materials and methods: 50 T1DM patients, 12-45 years age and at least 2years duration of diabetes were compared with age, sex, BMI matched controls. They were subjected to thorough clinical evaluation, biochemical testing and BMD by DXA.

Results: BMD Z scores at Whole body, Hip and Lumbar spine were found to be statistically significantly low in cases compared to controls. Regression analysis revealed the duration of diabetes and HbA1c to be negatively correlated to BMD Z scores at Hip and positively correlated with Vitamin D and BMI. Duration of diabetes was negatively correlated to BMD Z score at Lumbar spine too.

Discussion and Conclusions: Our study revealed that BMD at whole body, hip and spine was lower in patients with T1DM when compared to controls. T1DM has an impact on attainment of peak bone mass in adolescents and subsequently on the bone mass accrual in adults leading to a lower BMD. Poor glycemic control and increased duration of diabetes had a negative impact on the BMD at the hip and lumbar spine. It is proposed that BMD be measured in T1DM patients with poor glycemic control and long duration of diabetes as a part of evaluation.

Keywords: DXA, fracture risk, low bone mass, T1DM.

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Observational study of osteoporosis in patients with uncomplicated type 2 diabetes mellitus

Jitendra Sahu ¹, S Viswanath ¹, Nachankar Amit ²

Objective: To assess prevalence of Osteoporosis in patients with uncomplicated Type 2 Diabetes Mellitus (T2DM) & its correlation with various factors.

Material and Methods: Prospective observational study involving 100 patients above 50years age with uncomplicated T2DM on oral antidiabetic agents (except thiazolidinediones/SGLT inhibitors) and without any comorbidity (except obesity/hypertension) were assessed by age, sex, body mass index(BMI), duration of disease, glycemic and calcium profile including vitamin-D status. Bone mineral density (BMD) by Hologic Dual Xray Absorptiometry (DXA) was carried out at lumbar spine and hip. Comparison of BMD with anthropometric and biochemical profile was done.

Results: Total 39% patients had osteoporosis while 47% osteopenia and 14.0% normal BMD was detected. Osteoporosis patients had higher mean age (61.26 ± 6.92 years) and the agedifference was significant (p = 0.014). Females had more osteoporosis (84.6%) compared to males (15.4%) which was significant (p < 0.001). No significant association between osteoporosis with BMI, duration of diabetes, current glycemic status or serum calcium was found. Majority of osteoporosis cases had vitamin-D deficiency (46.2%) or insufficiency (35.9%) and the difference was significant (p = 0.022). Conversely, normal BMD cases had a higher mean vitamin-D levels (32.68 ± 17.90 ng/ml) as compared to osteopenia (29.20 ± 13.27 ng/ml) or osteoporosis cases (22.64 ± 15.52 ng/ml) and this difference was significant (p = 0.044).

Conclusion: Prevalence of Osteoporosis in patients with uncomplicated T2DM was 39% and was independent of current glycemic status or disease duration but correlated with age, sex and vitamin-D status.

Key words: Diabetes, osteoporosis, vitamin-D

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Trabecular bone score in primary hyperparathyroidism: A prospective cohort study

Hiya Boro ¹

Introduction: Trabecular Bone Score (TBS) is a new modality of investigation that can be used as a non invasive assessment of bone microarchitecture. Our study was planned to evaluate the bone microarchitecture using TBS in Primary Hyperparathyroidism (PHPT).

Aims/Objectives: The objective of our study was to assess the bone mineral density (BMD) and TBS in PHPT at baseline and at six months and one year after successful parathyroidectomy, and compare the same with that in healthy controls.

Materials and methods: PHPT (n = 140) and healthy controls (n = 80) matched for age and sex, were recruited for our study. TBS and BMD were done at the baseline and at six months and one year after successful parathyroidectomy. Healthy controls were not followed up.

Results: The mean age of PHPT was 44.0 ± 16.0 years. In PHPT, the mean L1-L4 BMD at baseline was 0.779 ± 0.174 (g/sq cm), femoral neck BMD 0.589 ± 0.163 (g/sq cm), total hip BMD 0.715 ± 0.198 (g/sq cm) and distal radius BMD was 0.542 ± 0.134 (g/sq cm). The mean absolute TBS at baseline was 1.260 ± 0.116. After one year of successful parathyroidectomy, there were significant improvements in lumbar spine (11.9%), femoral neck (10.7%) and total hip BMD (13.6%), but no significant improvement noted in either distal radius BMD (1.7%) or TBS (1.6%).

Discussion and Conclusion: In PHPT, the BMD improvement at lumbar spine was significantly greater than the TBS. This implied that microarchitectural changes reflected by TBS required a longer time for improvement compared to bone mineral density.

Keywords: Bone mineral density, Trabecular bone score, Thyrotoxicosis

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Endocrine Week - Innovations in Endocrinology: BASIC ENDOCRINOLOGY: Prospective evaluation of dysfunctions in insulin secretion, insulin sensitivity and adiposity in new-onset diabetes associated with COVID-19 infection: A novel OGTT-based metabolic study

R Das Gupta ¹, S Mondal ¹, A Ganguly ¹

Background: Recent evidence suggests a bidirectional relationship between COVID-19 infection and new-onset diabetes (NOD), though pathogenetic mechanisms regulating glucose and lipid metabolism in them remain obscure. Given the practical difficulties in utilizing isotope-based dynamic studies in resource-poor settings, we propose an unique OGTT-based study in them to elucidate the changes in insulin secretion alongwith hepatic, peripheral and adipose-tissue insulin sensitivity over time.

Description: Our study will include age and sex-matched 20 NOD, 20 Type 2 DM, 20 Type1 DM, 20 non-obese, non-diabetic controls and 20 overweight non-diabetic controls over a period of one year. NOD subjects are defined as those with RT-PCR-positive COVID-19 infection in presence of two abnormal samples of fasting plasma glucose =126 mg/dL and/or HbA1c = 6.5% or a random glucose level =200 mg/dL with symptoms of hyperglycemia, in absence of any history of diabetes in past. Patients with hyperglycemic crisis, ARDS, Multi-organ dysfunction, requiring ventilatory or haemodynamic support, severe comorbid illness and pregnancy were excluded. All subjects will undergo a 75 g- OGTT (oral glucose tolerance test) with estimation of glucose, C-peptide and insulin levels at 0,15, 30,45, 60, 90, 120, 150 and 180 minutes. Insulin secretion rate (ISR)will be assessed by C-peptide-deconvolution technique, Hepatic insulin sensitivity will be obtained from the formula: AUC-glucose × AUC-insulin during first 30-minutes of OGTT (AUC- Area under Curve), Peripheral insulin sensitivity was estimated as: dG/dt ÷ mean plasma insulin concentration, where dG/dt is the rate of decline in plasma glucose concentration and is calculated as the slope of the least square fit to the decline in plasma glucose concentration from peak to nadir, while Adipose tissue insulin resistance index (ATIRI) is derived as: Fasting-glucose×fasting-FFA (free fatty acid) levels. All tests would be performed after strict glycemic control for at least 2-3 weeks since presentation to eliminate the effect of glucotoxicity. Further, NOD subjects will be subdivided into those with normal (NOD-N) (n = 6, 5.7%-6.4%) and elevated (NOD-E) (n = 14, >6.4%) Hba1c at inclusion, and both the sub-groups will be followed up with dynamic OGTT-studies at 3, 6, 9 and 12 months.

Impact: Ours will be the first study to comprehensively assess longitudinal changes in metabolic dysfunction of COVID-19-associated NOD, utilizing an easily reproducible, simplified OGTT-based technique. Validated against the gold-standard pancreatic clamp technique,[1] we hypothesize that our novel technique can be employed in larger, multicentre Indian studies to define this entity which is metabolically unique from T1DM or T2DM.

Conclusion: The progressively increasing threat of the COVID-19 pandemic and significant diabetes burden in India makes it imperative to gain accurate metabolic insights into COVID-associated NOD, which in turn will facilitate development of targeted therapeutic regimens.

Keywords: Covid-19, New onset, OGTT, Insulin sensitivity

REFERENCE

1.Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA. Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care. 2007;30:89–94. doi: 10.2337/dc06-1519. [DOI] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Does vitamin D play a role in uterine fibroids? A case control study

Lizann E Thomas ¹, Elizabeth Abraham ¹, Renjitha Bhaskaran ¹

Context: Uterine fibroids are monoclonal tumors of uterine smooth muscle cells. They are found in 20–40% of females in the reproductive age group. Ovarian hormones play an important role in its etiology. Recent studies have shown that low serum vitamin D levels are associated with increased risk of uterine fibroids. Our study was aimed to investigate the association between serum vitamin D levels and uterine fibroids.

Materials and methods: A case control study was conducted in a tertiary care hospital among 183 women between the age of 18 and 50 years with uterine fibroids who attended obstetrics and gynecology department and 183 women of the same age group who had no uterine fibroids attending comprehensive health checkup clinic. Serum vitamin D levels were estimated in both the groups by electrochemiluminescence immunoassay. Statistical analysis: It was performed using IBM SPSS version 20.0. p value of <0.05 was considered statistically significant.

Results: The mean serum vitamin D levels of women with uterine fibroids were 15.03 ± 6.996 ng/mL and 16.629 ± 8.020 ng/mL in women without uterine fibroids. There was no statistically significant difference in the serum vitamin D levels between women with and without uterine fibroids (p = 0.132).

Conclusion: Serum vitamin D levels were found to be deficient in both the groups irrespective of the presence or absence of uterine fibroids. Hence, it can be concluded that the study conducted in 366 women could not find a direct association between low serum vitamin D levels and uterine fibroids.

Keywords: Serum vitamin D levels, uterine fibroids, vitamin D and uterine fibroids, vitamin-D deficiency

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Micronutrient imbalances in people with type 2 diabetes- A software aided analysis of one week food diary

Shefali Bhadwaj ¹, Ruchira Ranadive ¹, Bijal Vora ¹, Arbinder Singal ¹, Tejal Lathia ¹

Objective: To evaluate the intake of micronutrients like calcium, magnesium and zinc among people with type 2 diabetes. Background: Though much is known on macronutrient imbalances in people with Type 2 diabetes mellitus little is known on the existing micronutrient imbalances. In people with Type 2 diabetes a deficiency in magnesium, calcium and zinc levels, insulin resistance is increased and oral magnesium, calcium and zinc supplementation has been found to improve insulin sensitivity and metabolic control.

Materials and methods: Sixty-five people with type 2 diabetes were enrolled on a diabetes management program -Diabefly. The clients were closely monitored using a technology platform (Fitterfly App) and followed up by the Diabefly coaches for the food diary entries. The data inputs received were analysed using the food database in the Fitterfly software to generate a nutrition report. Mann Whitney- U test was performed using SPSS software.

Results: Hundred percent of population was found to be deficient in their micronutrient intake. The median deficiency for calcium was 30% with a maximum deficiency of 72.8%. For magnesium, the median deficiency was 15% with a maximum of 82.7%. In the case of zinc, the median deficiency value was observed to be 9.4% with a maximum deficiency of 91.7%.

Conclusion: All participants in the study had micronutrient deficiencies (calcium, magnesium and zinc). This may impact insulin sensitivity and a diet plan to cover the micronutrient imbalance or supplementation may improve insulin sensitivity and metabolic control.

Key words: Micronutrients, type 2 diabetes, nutrition-analysis, Digital therapeutics

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

PUBLIC HEALTH ENDOCRINOLOGY: Are Indian cooking practices an important culprit for prevalence of iodine deficiency disorders in spite of adequate salt iodization?

Sudha Rathna Prabhu ¹, Shriraam Mahadevan ¹

Background: In spite of implementation of more than three decades of mandatory salt iodization program several Indian states are still iodine deficient.[1] A 2016 survey conducted by ICCIDD.[2] has reported iodine deficiency in most districts in Tamil Nadu as is revealed by population urinary iodine levels . As iodine has sublime nature, unique South Indian cooking practices of deep frying after adding salt may be an important reason for the same.

Description: As a part of another research study (unpublished) on iodine status of pregnant women, it was observed that most women add entire required amount of salt initially, boil for longer periods for taste purpose and then consume food . In addition the practice of intake of uncooked fresh salads with salt added at the table, fruits as chats are also very low in South India. These may be main reasons for inadequate iodine concentrations reported in clinical studies.

Impact on public health and practice: Iodization of salt alone may not solve the iodine deficiency. Regional differences in salt intake and cooking practices should be factored in public education to improve iodine status.

Conclusion: Public education on cooking practices to add salt after boiling process and to consume iodine rich diet may play a vital role in reducing the burden of iodine deficiency in our country.

Key words: Iodine and cooking practices, salt iodization program, pregnancy iodine status

REFERENCES

1.Pandav CS, Yadav K, Srivastava R, Pandav R, Karmarkar MG. Iodine deficiency disorders (IDD) control in India. Indian J Med Res. 2013;138:418. [PMC free article] [PubMed] [Google Scholar]
2.Nutrition International, ICCIDD, AIIMS (New Delhi) and Kantar, 2019. India Iodine Survey 2018-19 National Report, New Delhi, India [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Like e-GFR is there an e-VAT?: Metabolic score for visceral fat (METS-VF) estimation – A novel cost-effective method for visceral adipose tissue estimation validated in individuals with morbid obesity in Southern India

Nitin Kapoor ¹; On behalf of investigators from the Bariatric clinic at CMC, Vellore

Background: Visceral adipose tissue (VAT) assessment is limited in clinical practice due to expensive, time consuming and limited availability of MRI and DXA machines. We explored the utility of a recently developed Metabolic Score for Visceral Fat (METS-VF) to assess VAT in south Asian individuals with morbid obesity.

Methods: Individuals with BMI = 35 kg/m2 aged between 30 to 60 years were randomly selected from a database of individuals with morbid obesity, attending a multi-disciplinary bariatric clinic in a tertiary care teaching hospital in southern India. Body composition was assessed by using a Hologic Discovery A dual-energy X-ray absorptiometry (DXA) machine. METS-VF was used to estimate VAT by using a previously published algorithm.

Results: The mean age and body mass index of the study subjects(N = 350) was 38.2 years and 40.1 kg/m2. The MET-VF score performed satisfactorily (AUC of 0.782 (95% CI 0.72-0.85) for predicting an increased visceral adipose tissue (VAT area = 163 cm2) as detected by DXA. A METS-VF value of 7.3 was found to have a good sensitivity and reasonable specificity in predicting elevated VAT in this population.

Conclusion: This is the first study to validate the utility of METS-VF as a surrogate measure of visceral adiposity in south Indian individuals with morbid obesity. Given the simplicity, easy availability, reliability and inexpensive nature of this obesity indicator, it may find its widespread use in lower middle-income countries.

Keywords: Metabolic obesity, morbid obesity, visceral adipose tissue

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Innovations in improving awareness of Endocrinology at local and state level

Ashok Venkatanarasu ¹, Sruthi Durgam ¹

Introduction: Awareness matters and makes the difference in hormones and its related health issues as well. Especially awareness programs designed in local tradition customized format will definitely make efforts more fruitful.

Descriptions: Once the people aware, they can take care of themselves and also guide others in preventing or approaching a qualified specialist at right time.

Ways of improving endocrine awareness locally

Books- Simple and easy understandable awareness books in local language
Collaboration with influential people- teachers, LIC agents, Asha workers, Anganwadi workers, Dwakra groups and gram panchayats
Bringing and promoting ”Endocrine awareness regional app” - It should contain all qualified local endocrinologists directory, all the details of hormones and its disorders in local languages
Local folk songs on hormones and its disorders
Local public programs to reach countryside – Burra katha, Oggu katha, Astavadhanam, Shathavadhanam and Natakam
Reaching through local festival/traditional format- Bathukamma, Rakhi, Sankranthi and Jatara.
Social media- local format crisp message, poster, video on disease symptoms, prevention tips, available tests and treatment options through Whatsapp, Facebook, YouTube, Instagram and twitter.
Electronic and print media- through radio, TV and newspaper.

Impact on present endocrine practice

Interest to take care of themselves and their beloved ones will improve
Reach and practice of our endocrine specialty will expand
Outcomes of treatment will become better

Conclusion: Innovative efforts help in improving awareness about hormones and its related problems. Public reach of endocrine practice will enhance and that may transform in to a healthy state and nation.

Key words: Collaborations, endocrine awareness, endocrine awareness regional app, local folk programs, social media

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Algorithm-based content personalisation to identify & improve patient knowledge and adherence for people with diabetes

Sudipta Satpathy ¹, Shefali Bhardwaj ¹, Arbinder Singal ¹, Jayesh Sawant ¹

Background: Patient knowledge and adherence go hand-in-hand. Current repository of knowledge (internet, hearsay) for patients might be irrelevant and non-scientific. Replacing this information overload with credible and practical content increases knowledge levels and adherence.

Description: We built a unique and personalised patient education platform based on software-driven profiling that includes their diabetes management goals and primary concern. Content personalisation is based on 9 points - medical condition, knowledge-base, lifestyle, food preference, BMI, age, gender, co-morbidities and language preference. With this, a one-of-a-kind content journey using the ‘Nudge Theory’ is planned. The content plan covers diabetes management categories like diet, exercise, medication, stress, sleep, weight, mental health and disease-specific complications. Different content types like audiovisuals, short messages, images, blogs, etc make it engaging. This content journey is part of a Digital Therapeutic Program - Diabefly - available to people with diabetes via the Fitterfly Wellness app. The software tracks patient behaviour towards all the interactions allowing us to refine our content strategy further.

Impact on current practices: A credible platform like Diabefly addresses the Doctor's challenge to answer patient queries and bridge the knowledge gap without investing time. A personalised content strategy, coupled with bite-sized, actionable content delivery methods, ensures better engagement and improved compliance on a day-on-day basis. This leads to desirable changes in patient behaviour resulting in better outcomes.

Conclusion: Diabefly's personalised content strategy uses incremental, positive and personalised reinforcements. It is aimed at making sustainable long-term behavioural changes to improve patient behaviour, thus improving diabetes and health outcomes.

Keywords: Diabetes, digital health, digital therapeutics

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

INTER-DISCIPLINARY ENDOCRINOLOGY: Perception about virtual endocrine training among endocrine residents

Sandeep Kumar ¹, Naresh Bansal ¹, KS Brar ¹, Narendra Kotwal ¹, Rakhi Malhotra ¹, Mandeep Sharma ¹

Background: COVID-19 has jolted the world order with disruption of education at all levels. Present disruption in medical education has opened doors to virtual platforms. There is dearth of studies, evaluating perception of medical students about virtual learning. We have conducted a cross sectional study to understand the perception of endocrinology residents with regards to virtual training.

Material and Methods: This study is a cross sectional online survey done in April 2020. Total 46 endocrine residents, participated in this survey. Total 05 questions were asked in this survey, whether they believe virtual endocrine training is required in present COVID-19 times or not, format of training, method of teaching, preferred topics requiring coverage and online assessment.

Results: All 46 (100%) participants agreed with need of virtual endocrine teaching. Of the total 46 participants their seniority of endocrine training was 1st year (n = 21, 45.65%); 2nd year (n = 17, 36.96%) and 3rd year (n = 8, 17.39%). Most preferred topics were endocrine imaging (n = 9, 19.57%) and nuclear medicine (n = 9, 19.57%) with pituitary as least preferred (n = 1, 2.17%). Of the total, 50% of residents wanted virtual faculty lectures, 47.8% opted for virtual clinical case discussions. Out of 46, 97.8% of residents wanted virtual platform informal assessment of students. There was no statistical significance between the choice of topic among different endocrine residents according to seniority of their training.

Conclusion: Our study have shown that there is felt need for virtual training among endocrinology residents in India. Imaging and nuclear studies are the specific topics which endocrine students wants to learn through faculty lectures, irrespective of seniority as endocrine students. This study can be used while planning virtual endocrine curriculums in future.

Keywords: Endocrine training, perception of endocrine residents, virtual learning

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Can novel anthropometric indices predict development of gestational diabetes during pregnancy and long-term metabolic impairment on postpartum followup?: A prospective, outpatient-based study amongst Indian women in early gestation

R Das Gupta ^*, J Mukhopadhyay1 ^*, S Mondal ¹, A Ganguly ^*

Background: Gestational diabetes mellitus (GDM), with it's gradually increasing prevalence worldwide and in India, portends significant metabolic risk for mother and child in short and long-term. Though invasive biochemical tests exist for it's detection and postpartum followup, there is dearth of noninvasive anthropometric measures that can be useful in resource-poor settings. Further, the traditional measures of BMI, waist circumference (WC) and Waist-Hip-Ratio (WHR) lose their predictive accuracy in pregnancy and hence the need for novel indices.

Description: In this prospective case-control study, n = 500 Asian Indian pregnant women, aged between 18-35 years, within the first 20 weeks of gestation and attending the Gynaecology OPD will be included over a period of six months. Those with pre-existing diabetes, diabetes detected for the first time within 20 weeks of pregnancy as per IADPSG criteria [Fasting glucose 92-126 mg/dl OR Hba1c 5.7-6, 5%] and high-risk pregnancies will be excluded. Anthropometric measures including BMI, WC, WHR and novel indices of Neck Circumference (NC) and Neck-height ratio (NHR) will be documented at study inclusion. Subsequently, the study group will be followed up to detect the presence of Gestational Diabetes Mellitus using a 2 hr, 75 g oral glucose tolerance test (OGTT) between 24-28 weeks of pregnancy (IADPSG criteria).[1] The study population after 24-28 weeks of gestation will comprise of those with GDM (cases) and those without GDM (controls). The anthropometric indices recorded in early gestation will be compared between these groups to estimate their potential utility in predicting GDM and also Indian population-specific predictive demarcating values for these indices will be derived using Receiver Operating Characteristic (ROC) curves. As our secondary objective, we plan to follow-up the women with GDM over next 5 years with to detect development of Type 2 Diabetes in them with annual 75 g-OGTT and Hba1c estimation and assess the ability of NC and NHR in predicting long-term metabolic dysfunction. We hypothesize that NC and NHR will have better accuracy in early prediction of GDM as also longterm development of Type 2 Diabetes in Indian women and the derived cut-of values that can be routinely used in OPD settings.

Implications of our research: Our study is the first of its kind to look at multiple novel anthropometric predictors of GDM based on neck-circumference indices in an Asian Indian population of pregnant women in early gestation. Early prediction of GDM has the potential to allow early implementation of lifestyle measures while identifying the subgroup of pregnant women who need a more invasive confirmatory test (2 hour-75-g OGTT) in later pregnancy, whereas subsequent associations with longterm development of Type 2 Diabetes in GDM mothers, if proven, can posit NC and NHR as effective, inexpensive tools of public health importance.

Conclusion: The progressively increasing burden of GDM and it's association with cardiometabolic risk in women necessitates early detection and multimodality treatment. Accurate and easily reproducible anthropometric measures may prove to be more beneficial than complex biochemical tests in resource-limited settings.

Keywords: Anthropometric, gestational diabetes, early gestation, long-term

REFERENCE

1.Blumer I, Hadar E, Hadden DR, Jovanovic L, Mestman JH, Murad MH, et al. Diabetes and pregnancy: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4227–49. doi: 10.1210/jc.2013-2465. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Affordable and accessible endocrinology for India

Ajeesh T ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Background: The major reason for misdiagnosis and improper management of endocrine disorders in the developing world are inaccessibility and unaffordability of endocrine investigations apart from lack of training and complexity of tests.

Concept: To make one of the most commonly required endocrine dynamic test accessible and affordable to major parts of the world, we have validated the accuracy of Porcine ACTH (Acton Prolongatum) stimulated cortisol test and defined its diagnostic cut-offs against the current gold standard of Synacthen Stimulation test (SST) using cortisol values at 2 hours (19.5 μg/dl) showing 100% sensitivity and 88% specificity for diagnosing Adrenal Insufficiency (AI).[1] Further we went on to standardize Acton Prolongatum stimulated salivary cortisol which offers advantage of stable transportation of samples over long distances.[2] Similarly for the diagnosis of Cushing Syndrome (CS), another condition which required a myriad of endocrine tests, we derived community derived cut off (0.25 μg/dl) for late night salivary cortisol for Indians, as evaluated by second generation Electrochemiluminescence Immunoassay (ECLIA).[3] As salivary cortisol is stable on transportation for 5 days at room temperature, this study has made the diagnosis of CS accessible to remote parts of the country.[4] Although Inferior Petrosal Sinus Sampling (IPSS) is the gold standard in localising corticotrophin source in CS, it is technically challenging. Corticotrophin Releasing Hormone, used in IPSS, is also not marketed in India. To circumvent these issues, we have tried Arginine Vasopressin (AVP) stimulated Internal Jugular Vein (IJV) sampling test at our centre.[5] In our study, IJV to Peripheral vein Adrenocorticotrophic Hormone (ACTH) ratio following AVP stimulation, showed 100% sensitivity and specificity in confirming Cushing's disease in the limited number of subjects we have studied. In the future, Acton Prolongatum stimulated 17-hydroxyprogesterone is a future prospect in diagnosing Non-classic Congenital Adrenal Hyperplasia.

Impact on current endocrine practice: Our studies have rendered the diagnosis of AI and CS accessible to most parts of the country and the developing world. The cost of AI diagnosis is brought down from USD 44 to USD 11 with our innovation.[6]

Conclusion: Affordability and accessibility are major hurdles in the evaluation of endocrine disorders and innovations like those described above and more have to be undertaken to avoid misdiagnosis, underdiagnosis and overdiagnosis of endocrine disorders.

Keywords: Acton prolongatum, arginine vasopressin, internal jugular vein sampling, porcine ACTH, salivary cortisol

REFERENCES

1.Nair A, Jayakumari C, George GS, Jabbar PK, Das DV, Jessy SJ, et al. Long acting porcine sequence ACTH in the diagnosis of adrenal insufficiency. Eur J Endocrinol. 2019;181:639–45. doi: 10.1530/EJE-19-0558. [DOI] [PubMed] [Google Scholar]
2.George GS, Jabbar PK, Jayakumari C, John M, Mini M, Thekkumkara Surendran Nair A, et al. Long-acting porcine ACTH stimulated salivary cortisol in the diagnosis of adrenal insufficiency. Clin Endocrinol (Oxf) 2020 doi: 10.1111/cen.14286. doi: 10.1111/cen.14286. [DOI] [PubMed] [Google Scholar]
3.Prasad N, Jabbar PK, Jayakumari C, John M, Ratheesh KH, Anish TS, et al. Late night salivary cortisol in healthy community dwelling Asian Indians assessed by second generation ECLIA. J Clin Endocrinol Metab. 2020;105:dgaa269. doi: 10.1210/clinem/dgaa269. [DOI] [PubMed] [Google Scholar]
4.Clements AD, Parker CR. The relationship between salivary cortisol concentrations in frozen versus mailed samples. Psychoneuroendocrinology. 1998;23:613–6. doi: 10.1016/s0306-4530(98)00031-6. [DOI] [PubMed] [Google Scholar]
5.Indian J Endocr Metab. 2019;23(Suppl S1):5–83. ESICON 2019 Abstracts. [Google Scholar]
6.Inder WJ. Long-acting porcine sequence ACTH in the diagnosis of adrenal insufficiency: A cost-effective alternative to the ACTH1-24 test. Eur J Endocrinol. 2020;182:C5–7. doi: 10.1530/EJE-19-0923. [DOI] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Patient satisfaction with the use of telemedicine in the management of thyroid disorder and diabetes mellitus

Biki K Sah ¹, Anil Acharya ¹, Robin Maskey ¹

Introduction: Previously patients of thyroid disorders and diabetes mellitus attended clinic to discuss symptoms, results and modification of dose of their medication. With this ongoing COVID-19 pandemic BPKIHS has lunched telemedicine instead of face-to-face visit all over the country. We aimed to assess the satisfaction of patients with the use of telemedicine and receive the suggestions for improvement.

Description: Material and Methods: A cross-sectional study was done in total of 62 patients, 31 each who had at least one telemedicine session for the management of thyroid disorder and diabetes mellitus during a one-month period on September 2020.

Results: 100% and 96.77% respondents were satisfied with the quality of service provided via telemedicine for the management of thyroid disorders and diabetes mellitus respectively. Impact on current endocrine practice: The role of telemedicine is vital especially in this pandemic situation as reflected by our research findings. The fear of exposure in hospital, loss of time and money, transportation problem can be overcome by proper administration of telemedicine facility.

Conclusion: This research has demonstrated the use of telemedicine in the management of thyroid disorders and diabetes mellitus in this pandemic situation is satisfying to the majority of the patients. The effectiveness can be increased by adding the facility of face-to-face consultation with specialist through video call or other means as suggested by some.

Key words: diabetes mellitus, Likert scale, patient satisfaction, telemedicine, thyroid disorders

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

PITUITARY: Expression of Programmed Death Ligand 1 (PDL-1) in pituitary adenomas: A marker for newer therapeutic target

Devyangi Paralkar ¹, Rekha Singh ¹, Adesh Shrivastava ², Ashwani Tandon ¹, Neelkamal Kapoor ¹

Introduction: PDL-1 is establishing as a diagnostic marker for immunotherapeutic targets. As PDL-1 inhibitors are new drugs for several cancers and their potential role in endocrine neoplasm, especially in pituitary adenomas (PA), are less described. We aimed to check the expression of PDL-1 in PA with a hormonal Immunohistochemistry profile.

Description: Twenty-two cases (15 male 8 female) of PA were reviewed. Growth hormone (GH), Prolactin, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and PDL-1 expression was checked with Immunohistochemistry. 6/8 female and 11/15 males showed PDL-1 expression. Five were ACTH positive, and 100% PDL1 positive. Eight were positive for Prolactin (2 invasive tumors) and 100% PDL1 positive. GH was positive in 5 cases (Prolactin co-positive in 2, 1 for ACTH, and 1 for TSH), and 100% were positive for PDL1. Five were negative for the hormonal markers, and among them, three were positive for PDL1. One case was faintly positive for TSH but PDL1 negative. A Cushing's Disease had pituitary hyperplasia with all hormonal markers positive but PDL1 negative.

Impact on current endocrine practice: Almost 25% of pituitary adenomas are invasive and often resistant to conventional treatment. Therefore, our analysis of PDL-1 expression in PA subtypes generates another therapeutic option in the form of PDL1 inhibitors.

Conclusion: We identified, 77% of PA expresses PDL-1, and analysis shows concordance with previously published data and is possibly first of its kind in India.

Keywords: Pitutary Adenoma, PDL-1, Immunohistochemistry

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

DIABETES: Is methylcobalamin or cyanocobalamin the right prescription for vitamin B12 deficiency or diabetic neuropathy?

Shriraam Mahadevan ¹, Adlyne Reena Asirvatham ¹, Subramanian Kannan ¹, Karthik Balachandran ¹, Vanitha Rani ²

Introduction: Vitamin B12 deficiency is common in diabetic patients, especially in the Indian setting. It may aggravate neuropathy and also have hematological implications. The etiology in a diabetic patient is manifold including metformin use and dietary deficiency. Vitamin B12 treatment helps in not only correcting the deficiency but also improves neuropathic symptoms in diabetic patients. Vitamin B12 should be treated with the plain preparation like cyanocobalamin. However, recently there has been a significant increase in the use of methylcobalamin. Strict review of the literature reveals evidence to the contrary.

Description: Irrespective of the source, vitamin B12 is converted to its active form methylcobalamin by the enzyme methyltransferase for its final effect intracellularly. There is no evidence that this enzyme is dysfunctional or deficient in a diabetic patient and hence there is no need to give methylcobalamin to treat our patients.

Impact on current practice: Scientifically, vitamin B12 treatment with plain cyanocobalamin is appropriate. The cost per tablet of a standard brand of cyanocobalamin (combination with other neurotropic vitamins) is around Rs 2/- and the average methylcobalamin oral preparation is at least 2 to 3 times more. Similarly the injectable form of methylcobalamin is 3 to 5 times costlier. One can imagine the enormous cost saving in the long run to the patient by the correct prescription of B12.

Conclusion: Cyanocobalamin is the most appropriate treatment for vitamin B12 deficiency/supplementation in a diabetic and this may be done at a fraction of the cost of methylcobalamin.

Keywords: B12, cyanocobalamin, methylcobalamin, neuropathy, diabetes

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Virtual systems: Shifting sands in diabetes mellitus care

Sandeep Kumar ¹, Naresh Bansal ¹, Narendra Kotwal ¹

Introduction: COVID-19 has jolted the world order and it would re-define normal for decades to come. Social distancing would be accepted way of living and virtual platform would hold key role in everyday sustenance. Conventional understanding of healthcare delivery is bound to see a strategic shift and technology would creep into heritage of healthcare infrastructure. Time is ripe that health care professionals get themselves acquainted with these virtual systems and start evolving into new era of virtual world. It is seen that in chronic diseases like diabetes mellitus (DM) health education, counselling, analysis of investigations and modification of the treatment regimen constitutes major part of out patient department (OPD) consultations. For this entire process the patients come from distantly located places, face long waiting times and travel back with their prescription to repeat the same process after a month. In these kind of consultations, there is no scope for assessment of patient during this intervening duration. Various studies have proved beyond doubt that time in range (TIR) and active patient participation is key to holistic management of diabetes mellitus.[1] Technological advancement and evolution of telehealth solutions has opened doors to new virtual realms which seem to offer promising scope in diabetes mellitus management.

Description: Virtual solutions in DM care range from simple mobile based consultations and telemedicine applications to cloud based diabetes management programmes and artificial intelligence.[2] These virtual solutions are also further catapulted by non-interventional continuous glucose monitoring systems and technologies for screening for target organ damage (TOD).[3] Summarises various virtual system available in DM care.

Impact on current endocrine/medical/health practice: It is seen that in chronic diseases like diabetes mellitus, health education, counselling, analysis of investigations and modification of the treatment regimen constitutes major part of out patient department (OPD) consultations. For this entire process the patients come from distantly located places, face long waiting times and travel back with their prescription to repeat the same process after a month. In these kind of consultations, there is no scope for assessment of patient during this intervening duration. Various studies have proved beyond doubt that time in range (TIR) and active patient participation is key to holistic management of diabetes mellitus. These virtual solutions has potential to revolutionize diabetes care. These solutions can lead to better glycemic control with capability to screen for target organ damage. Also virtual solutions in diabetes care will help in reduction of burden in conventional OPD's and save enormous time and resources.

Conclusion: Advancing technologies and COVID-19 situation has open scopes to virtual solutions. These solutions have potential for better glycemic control, better doctor patient involvement, scope for screening for TOD and saving resources. We need to educate and adapt ourselves to these technologies. Availability of these technologies also warrant to validate them in well designed prospective studies.

Keywords: Virtual systems, diabetes mellitus, telehealth

REFERENCES

1.Advani A. Positioning time in range in diabetes management. Diabetologia. 2020;63:242–52. doi: 10.1007/s00125-019-05027-0. [DOI] [PubMed] [Google Scholar]
2.Hsu WC, Lau KHK, Huang R, Ghiloni S, Le H, Gilroy S, et al. Utilization of a cloud-based diabetes management program for insulin initiation and titration enables collaborative decision making between healthcare providers and patients. Diabetes Technol Ther. 2016;18 doi: 10.1089/dia.2015.0160. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Frielitz FS, Müller-Godeffroy E, Hübner J, Eisemann N, Dördelmann J, Menrath I, et al. Monthly video-consultation for children with type 1 diabetes using a continuous glucose monitoring system: Design of ViDiKi, a multimethod intervention study to evaluate the benefit of telemedicine. J Diabetes Sci Technol. 2020;14 doi: 10.1177/1932296819861991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Community studies and intervention for prevention of type 2 diabetes mellitus and gestational diabetes mellitus (GDM)

Shameer Basheer ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Background: Prevalence of Diabetes in Indian adults is 7.3%[1] and that of gestational diabetes mellitus (GDM) 18%.[2,3] There is lack of community level interventional studies aimed to ease the burden of T2DM and GDM in India.

Concept: The first Indian study on prevalence of diabetes in community dwelling subjects =30 years by our centre concluded recently, revealed diabetes in 0.31% subjects but very high prevalence of overweight or obesity (47%) and clinical features of insulin resistance (IR) among the 1601 subjects enrolled (25%). Waist Hip Ratio (WHR) was seen to be a poor marker of hyperglycemia or IR whereas a new indicator -product of BMI with sum of abdominal circumference and hip circumference (BMI*[AC + HC]) showed the best correlation with both. Next we are assessing role of fat distribution, adipokines, inflammatory markers and genetics on IR in young non obese Indians. Third we have launched a community based cluster randomised lifestyle intervention in married nulliparous women of 18- 35 years age which will show the effect of a pre-gestational community intervention for prevention of GDM. This can be used as proof of concept to go for the larger goal of prevention of type 2 diabetes through community level lifestyle intervention.

Impact on current endocrine practice: Our study has stressed on the need for an early preventive strategy for type 2 diabetes as youth show risk markers of DM much before its diagnosis. The community level intervention may be the first trial in the world to show the impact of pre-gestational lifestyle intervention on GDM incidence. If successful same strategy may be applied to prevent type 2 diabetes benefitting millions worldwide in the form of life expectancy, quality and health economics.

Conclusion: The focus population for diabetes education (Knowledge, attitude and practice) should be youth, who hold the key in diabetes prevention. Community studies to understand risk factors of DM in youth and trials for prevention of GDM and T2DM hold the key to reducing the burden of diabetes in our country.

Keywords: Diabetes Mellitus, Gestational Diabetes Mellitus

REFERENCES

1.Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK, et al. Prevalence of diabetes and prediabetes in 15 states of India: Results from the ICMR–INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol. 2017;5:585–9. doi: 10.1016/S2213-8587(17)30174-2. [DOI] [PubMed] [Google Scholar]
2.Mohan MA, Chandrakumar A. Evaluation of prevalence and risk factors of gestational diabetes in a tertiary care hospital in Kerala. Diabetes Metab Syndr. 2016;10:68–71. doi: 10.1016/j.dsx.2015.09.002. [DOI] [PubMed] [Google Scholar]
3.Bhat M, Ramesha KN, Sarma SP, Menon S, Sowmini CV, Kumar GS. Determinants of gestational diabetes mellitus: A case control study in a district tertiary care hospital in South India. Int J Diabetes Dev Ctries. 2010;30:91–6. doi: 10.4103/0973-3930.62599. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Framework of a digital diabetes clinic

Rajiv Singla ¹, Hitesh Rastogi ¹, Soumitra Narain ¹

Background: Access to care and quality of care are continuing challenges in achieving universal diabetes goals. Glycemic control, in terms of mean HbA1c, vary from 8 to 9.1% across different parts of country. Digitalisation of diabetes care can bridge the gaps in diabetes care.

Description of intervention: Onliv Health diabetes clinic is an Indo-US venture and objective of this program is to deliver integrated diabetes care at reasonable cost to large population living with diabetes. Onliv health offers a subscription based diabetes care i.e. entire cost of physician consultations, medicines and diagnostics is included in an annual subscription fee. Patient has access to host of feature including diabetes education, personalised nutritional plans and remote monitoring devices like connected glucometer, connected sphygmomanometer and connected weighing scale. Architectural components of Onliv diabetes clinic is presented. Based on patient characteristics, a shared decision on short term and long term goals is taken at time of onboarding. Entire care team, including physician, nutritionist and personal health coach, work off a single record. With emphasis on diet, exercise and achieving ideal body weight, short term goal in each individual is reduction/optimisation of diabetes medicines and reversal of diabetes, wherever possible. Blood pressure and cholesterol goals are chased with equal vigour. Remote monitoring is structured in a way to positively reinforce healthy lifestyle decisions in the long term and promote cardiorespiratory fitness. Early detection and timely referral for diabetes complications in another important aspect of digital diabetes clinic.

Impact: Individual components of diabetes care, when delivered digitally, has been proven to improve glycemic control and diabetes distress. Preliminary data on clinic model of digital diabetes care has shown promising results.

Conclusion: Digital diabetes clinic can deliver high-touch quality diabetes care in a cost effective manner.

Keywords: Digital Diabetes Care, Access to care, Integrated diabetes care

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Using the freestyle libre pro as a flash glucose monitor using a third party application

OM LAKHANI ¹

Introduction: Continuous Glucose Monitoring (Cgm) Is Cur-Rently Available Around The World In Three Versions, They Are: A) Retrospective Cgm Devices B) Flash Cgm Devices And C) Real Time Cgm Devices. In India we have Retrospective CGM devices in the form of Abbott FreeStyle Libre Pro (FSLP) and Medtronic iPRO 2. The FSLP is different from FreeStyle Libre available in other countries since FreeStyle Libre, unlike FSLP is a Flash CGM device. In this study we have used an innovative method to use the FSLP devices as a flash CGM device using a third-party software. We have also demonstrated the accuracy of this method in a subject with diabetes and a non-diabetic subject.

Materials and methods: This study was conducted in a subject with diabetes (subject a) and a non-diabetic subject (subject b) who volunteered for this study. The fslp was applied and the sensor was activated using the standard technique as suggest-ed by the manufacturer. A third party software called ‘glimp’ was used in an android mobile phone (oneplus 6) having near-field communication (nfc) system for deriving the data from the fslp sensor. For the first 2 days after the sensor application, the subject A and B entered the glucose value obtained from a glucometer (Abbott FreeSytle Optium Neo) into the Glimp app for calibration. A total of 8 readings were entered by each of the subject for calibration. Following the calibration both subjects A and B monitored the capillary blood glucose (CBG) value using the glucometer four times in a day (before meals and bedtime). They also interrogated the FSLP device using the NFC commu-nication of the mobile phone and the Glimp app for the next 12 days at the same period of time. The gap between the CBG reading and the sensor inter-rogation was less than one minute. The glucose values obtained from the CBG and the sensor data as collected into the Glimp app were correlated. The correlation coefficient (R) was calcu-lated between the two data sets using the Pearson correlation coefficient.

Results: A total of 48 paired readings were taken in both sub-ject a and subject B. In the subject with diabetes (Subject A) the mean glucose value was 180 +/- 36 mg/dl using the glucometer and 176 +/- 38 mg/dl using the FSLP and the Glimp app. The Pearson's correlation coefficient (R value) was was 0.79. The P-Value was <0.01 suggesting a significant correlation between two sets of data. The mean glucose value in subject B (non diabetic volunteer) was 116 +/- 18 mg/dl using the glucometer and 111 +/- 20 mg/dl using the FSLP and the Glimp app. The Pearson's correlation coefficient (R value) was 0.85. The P-Value was <0.01 suggesting a significant correlation between two sets of da-ta.

Conclusion: there was a strong correlation between the glu-cometer values and the values obtained using freestyle libre pro (fslp) with the glimp app after 2 days of calibration. Using this method fslp can be used for flash glucose.

Keywords: CGM, Libre, Flash Glucose monitoring, Innovation

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

BACILLUS CALMETTE–GUÉRIN (BCG) vaccination and incidence of type 1 diabetes mellitus

Om J Lakhani ¹, Jitendra D Lakhani ¹

Backrground: The use of Bacillus Calmette–Guérin (BCG) vaccine as an immunomodulator in type 1 diabetes (T1D) has generated a lot of interest after a recent proof-of-concept trial showing injection of BCG vaccine improving C-peptide levels amongst long-standing patients with Type 1 diabetes.

Aim: The aim of the study was to compare the incidence of T1D in countries which have discontinued BCG vaccine in relation to those countries which continue to use the BCG vaccine.

Methods: This was a retrospective cohort study. Data of incidence of T1D in children =14 years in various countries was obtained from the International diabetes federation (IDF) atlas for diabetes. Data for BCG vaccination status was obtained from online atlas developed by Zwerling et. The income group of the country was obtained from World Bank data. The incidence of T1D in countries which continue to administer BCG vaccine was compared with countries which have discontinued the use of BCG vaccine. Parametric data were compared using Student's t test. p value of <0.05 was considered as statistically significant.

Results: We found higher incidence of T1D amongst children in countries that do not use BCG vaccine in comparison to those which continue to use BCG vaccine for routine immunization (p < 0.0001). The rate ratio for T1D among children in countries who received BCG vaccine as compared with unvaccinated children, was 0.31 (95 percent Confidence interval, 0.28 to 0.36). We compared the mean incidence of T1D in high or upper middle income countries which have discontinued BCG vaccination versus countries in the same income group which continue to use the BCG vaccine and we found that the incidence was higher the former (p < 0.0001). A similar difference was also found when countries of Europe alone, which give BCG were compared with those which do not give BCG vaccine (p = 0.0017).

Conclusion: Countries which have discontinued the routine use of BCG vaccine in immunization programmes have higher incidence of T1D compared to those which continue to use the BCG vaccine.

Keywords: BCG vaccine, type 1 diabetes, vaccine and diabetes

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Graphical analysis of diabetes related symptoms to identify primary and secondary linkages and corresponding first line advice – A coder's perspective

Sushant Thappa ¹, Jayesh Sawant ¹, Arbinder Singal ¹, Tejal Lathia ¹

Objective: To analyse and link manifesting symptoms of diabetes as identified by patient vernacular, to broader organ systems and represent them in a single entity graphic format that can be coded into an app interface.

Background: Among digital flowcharts for managing diabetes, we found a striking lack of any linkages or easy to follow depictions. The twofold aim was to create a map for patients to identify their symptoms and use it as a reference tool for coders to develop into a software. Having access to easy to understand information may help clinicians guide the patients and patients seeking explanation on their own for their symptoms.

Materials and methods: 45 unique symptoms e.g Tingling sensation in hands, Breathlessness or Blurring of vision etc. reported by people with type 2 diabetes were enlisted through a diabetes management program -Diabefly. The symptoms were then linked with primary or secondary causal categories ranging from Vitamin Deficiencies (Tingling Sensation in both hands) to Hyperglycaemia (Excessive Thirst) and then traced to secondary causes like OSA, Neuropathy or Obesity.

Results: 45 symptoms were found linked to nine basic casual categories like Hyperglycaemia, Hypoglycemia etc. and then secondarily linked to eleven more casual factors like OSA, Obesity or Malnutrition. By attaching weightages to each symptoms, we can pinpoint interventions and life style advice for these patients and segregate a clear treatment/advice path.

Conclusion: The created tool can be further refined and distilled. Reflecting patient identified symptoms and account for medication related effects. This becomes a personalised decision tree for patient care. From a coding perspective, it provides a template for writing code to create clearly defined pathways for patient to follow as an optional primary line of intervention for Diabetes related symptoms.

Key words: Diabetes symptom map, Graphical analysis, Digital flowchart, Innovation

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Predicting optimal Diabetes Drug Management using AI/ ML - Developing a prototype clinical decision support algorithm

Rajiv Singla ¹, Shivam Agarwal ¹, Ankush Singla ¹, Jatin Bindra ¹, Sweta Singla ¹

Introduction: Universal reach of diabetes care and assurance of minimum standard of care is a milestone yet to be achieved. Application of artificial intelligence/machine learning (AI/ML) for diabetes care can help solve both these aspects of diabetes care. New onset diabetes starts much earlier now and the average HbA1c of people with diabetes in India stays around 8-9%. This foretells the potentially ever-increasing burden of complications resulting from poor diabetes control. Amalgamation of AI/ML approaches in diabetes care is expected to bring a transformational change in assisting primary care physicians in decision making.

Objective: Creating a clinical decision support system using AI/ML approach for predicting best anti-diabetes drug class to be introduced to help optimally manage glycaemic control in people living with diabetes mellitus type 2.

Description: Study was conducted in an Endocrinology clinic in Delhi and data was collected from Healthvriskh electronic clinic management system. 15485 diabetes prescriptions of 4974 patients were accessed. A data subset of 1671 diabetes prescriptions information on prescription diabetes drugs, demographics (age, gender, body mass index), biochemical parameters (HbA1c, fasting blood glucose, creatinine) and patient clinical parameters (diabetes duration, compliance to diet/exercise/medications, hypoglycemia, contraindication to any drug, summary of patient self monitoring of blood glucose data, diabetes complications) was used in preliminary analysis. The patients in this data set had mean HbA1c of 7.3% +/-1.3% (median 7.05%, 25th percentile 6.5%, 75th percentile 7.89%). For analysis, 67% of the dataset was used as a training set and 33% as a testing set. An input of patient variables (current diabetes medications, demographics, biochemical parameters and patient clinical parameters) were used to predict all diabetes drug classes to be prescribed. Random forest algorithms were used to create decision trees for all diabetes drugs. Accuracy for predicting use of each individual drug class is depicted in Table 1 and varied from 85% to 99.4%. Multi-drug accuracy considering that all drug predictions in a prescription need to be correct stands at 72%. Multi drug class accuracy in clinical application may be higher than this result, as in a lot of clinical scenarios, two more diabetes drugs may be used interchangeably.

Table 1.

Individual drug class prediction accuracy

Drug Class	Training Set	Testing Set
	Accuracy (%)	Accuracy (%)
Metformin	1.0	0.978
Sulfonylureas	1.0	0.900
DPP-4 inhibitors	1.0	0.850
SGLT2-inhibitors	1.0	0.924
AGI	1.0	0.969
Pioglitazone	1.0	0.962
Meglitinides	1.0	0.993
Short acting insulin	1.0	0.994
Basal insulin	1.0	0.971
Premix Insulin	1.0	0.975

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Clinical Impact: This report presents a first positive step in developing a robust clinical decision support system to transform access and quality of diabetes care. Multi-drug accuracy is likely to improve further with time as the depth of the dataset increases over time. This clinical decision support system can accelerate last mile delivery of diabetes care by empowering local primary care physicians or a remote healthcare platform.

Key words: Type 2 Diabetes, Anti-diabetic drugs

REFERENCES

1.Unnikrishnan R, Anjana RM, Deepa M, Pradeepa R, Joshi SR, Bhansali A, et al. Glycemic control among individuals with self-reported diabetes in India--The ICMR-INDIAB Study. Diabetes Technol Ther. 2014;16:596–603. doi: 10.1089/dia.2014.0018. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Singla R, Garg A, Singla S, Gupta Y. Temporal change in profile of association between diabetes, obesity, and age of onset in urban India: A brief report and review of literature. Indian J Endocrinol Metab. 2018;22:429–32. doi: 10.4103/ijem.IJEM_601_17. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Singla R, Bindra J, Singla A, Gupta Y, Kalra S. Drug prescription patterns and cost analysis of diabetes therapy in India: Audit of an endocrine practice. Indian J Endocrinol Metab. 2019;23:40–5. doi: 10.4103/ijem.IJEM_646_18. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

OBESITY & METABOLISM: Like e-GFR is there an e-VAT?: Metabolic score for visceral fat (METS-VF) estimation – A novel cost-effective method for visceral adipose tissue estimation validated in individuals with morbid obesity in Southern India

Nitin Kapoor ¹; On behalf of investigators from the Bariatric clinic at CMC, Vellore, Tamil Nadu, India

Background: Visceral adipose tissue (VAT) assessment is limited in clinical practice due to expensive, time consuming and limited availability of MRI and DXA machines. We explored the utility of a recently developed Metabolic Score for Visceral Fat (METS-VF) to assess VAT in south Asian individuals with morbid obesity. Methods: Individuals with BMI = 35 kg/m2 aged between 30 to 60 years were randomly selected from a database of individuals with morbid obesity, attending a multi-disciplinary bariatric clinic in a tertiary care teaching hospital in southern India. Body composition was assessed by using a Hologic Discovery A dual-energy X-ray absorptiometry (DXA) machine. METS-VF was used to estimate VAT by using a previously published algorithm.

Results: The mean age and body mass index of the study subjects(N = 350) was 38.2 years and 40.1 kg/m2. The MET-VF score performed satisfactorily (AUC of 0.782 (95% CI 0.72-0.85) for predicting an increased visceral adipose tissue (VAT area = 163 cm2) as detected by DXA. A METS-VF value of 7.3 was found to have a good sensitivity and reasonable specificity in predicting elevated VAT in this population.

Conclusion: This is the first study to validate the utility of METS-VF as a surrogate measure of visceral adiposity in south Indian individuals with morbid obesity. Given the simplicity, easy availability, reliability and inexpensive nature of this obesity indicator, it may find its widespread use in lower middle-income countries.

Keywords: Metabolic obesity, morbid obesity, visceral adipose tissue

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Real-time digital tracking of food nutritive value and its association with weight loss behaviours

Samta Mittal ¹, Eesha Kanade ¹, Neeti Gulati ¹, Amrata Jaykar ¹, Prashi Mohan ¹, Priya Karkera ¹, Arbinder Singal ¹

Background: Self-monitoring of diet is one of the core aspects of behavioral weight-loss interventions. Use of technology has made the process of self-monitoring easier and quicker. However, most digital tools inaccurately focus on calorie counting alone for weight-loss. A misperception that total calorie intake is more important than the calorie source and nutrient balance, may result in an overload of nutrients correlated with the development of obesity and a lack of essential nutrients known to act against obesity.

Description: Fitterfly's powerful food database has over 200+ macro and micronutrients as defined by National Institute of Nutrition [NIN] and over 1000 ingredients with a list of nutrients linked from IFCT, USDA, and other reliable sources. Fitterfly Reset23 Program is a personalized weight management program using food tracking via this database to provide real-time tracking of nutrient details coupled with patient education on diet and physical activity. Reset23 Program is designed keeping in mind that the energy needed for catabolism differs for every kind of macronutrient during the digestion process and the main problem in obesity is accumulated fat, losing any mass other than fat may be unproductive and undesirable.

Impact on current endocrine practice: The incomplete concept of energy balance may be one of the reasons why reversing the obesity epidemic has been unsuccessful. Real-time digital tracking of the nutritive value of food can make self-monitoring more efficient and enable large-scale, personalized intervention strategies.

Conclusion: Fitterfly food database is the largest (over 9000 items) and deepest (all macro & micronutrients) dataset. Reset23 weight management program, using this database for real-time, app-based food tracking, diet, and exercise guidance using personalized reinforcements is capable of making sustainable, long-lasting behavioural changes to manage weight.

Key words: Nutrition tracking, weight loss, self-monitoring, calorie counting, behaviour management, obesity management

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

THYROID: Utility of Platelet-lymphocyte ratio (PLR) as a low-cost, novel haematological marker to differentiate thyrotoxic patients with graves’ disease from subacute thryoiditis: A cross-sectional study from South India

R Das Gupta1 ¹, A Atri ¹, F Jebasingh ¹, J Hepzhibah ¹, P Christudoss ¹, HS Asha ¹, TV Paul ¹, N Thomas ¹

Background: Thyrotoxicosis due to Graves’ disease (GD) or toxic phase of subacute thyroiditis (SAT), usually present with similar clinical and biochemical presentations despite having completely different therapeutic approaches. While clinical diagnosis remains challenging, use of expensive definitive tests is often not possible in resource-limited settings. Since thyroid hormones have been noted to affect all hematologic cell lines, we have used the platelet lymphocyte ratio (PLR) - an index usually utilized in inflammatory or malignant disorders- to compare patients with and without thyrotoxicosis and to analyse it's use in distinguishing between patients with GD and SAT prior to therapy.

Description: This cross-sectional study[1] conducted in the Department of Endocrinology, CMC Vellore, India comprised of n = 500 patients with features of thyrotoxicosis (GD or SAT), with only those who had I-131 thyroid uptake study (RAIU) and complete blood counts (CBC) at diagnosis being included. Based on the RAIU values, these were divided as GD (n = 354) and SAT (n = 146) with baseline characteristics, thyroid function tests, CBC and PLR documented in both groups. The data was compared with a group of n = 250 matched euthyroid controls. PLR showed significant reductions in both GD and SAT patients when compared to euthyroid controls (p = 0.01), with greater reductions seen in GD than SAT (74.5 ± 19 vs 84.4 ± 26, p = 0.01). Using ROC-analysis, Results showed that the PLR had an area under the curve (AUC) of 0.74 with a 95% confidence interval of 0.63-0.88 (SE = 0.03, p = 0.01). With an optimal cut off of 70.4, PLR was found to have a sensitivity of 86% and specificity of 74% in differentiating GD from SAT, with a positive predictive value (PPV) of 91.5% and a negative predictive value (NPV) of 82.7%. The likelihood ratio of having GD with a PLR < 70.4 was 2.26, with a Youden's Index of 0.60. Impact: This is the first study evaluating the utility of PLR in a relatively large cohort of Indian patients with thyrotoxicosis and provides evidence that the PLR is significantly reduced in GD and SAT patients, probably due to the effect of elevated thyroid hormones on blood cell proliferation, Further, the proposed cut-off for PLR can be used as a reliable, cost-effective and easily accessible surrogate marker for identifying GD, thus precluding the use of radio-iodine uptake studies and TSHRAb in Low and Middle Income Countries (LMIC).

Conclusion: We validated PLR against the gold-standard technique of I-131 RAIU-test, thus making it ideal for use in LMIC countries where thyroid uptake studies and TSHRAb are prohibitive due to cost and accessibility, while future prospective studies evaluating it's role in deciding treatment modalities are necessary.

Keywords: Graves’ Disease, Subacute Thyroiditis, Platelet, Lymphocyte

REFERENCES

1.Dasgupta R, Atri A, Jebasingh F, Hepzhibah J, Christudoss P, Asha HS, et al. Platelet-lymphocyte ratio (PLR) as a novel surrogate marker to differentiate thyrotoxic patients with Graves’ disease (GD) from Sub-acute thyroiditis (SAT): A cross-sectional study from South India. Endocr Pract. 2020 doi: 10.4158/EP-2020-0086. doi: 10.4158/EP-2020-0086. Online ahead of print. [DOI] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Innovations in management of hypothyroidism

Soumya S ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Background: Prevalence of hypothyroidism in India (11%), is much higher than western world.[1] Although being easy-to-detect and inexpensive-to-treat disease, significant proportion of patients are undetected or undertreated.[2] Undertreatment can result in dyslipidemia and increased risk of cardiovascular disease and impairs work performance and productivity.

Description: An open-label trial was conducted by our institution on treatment-resistant- hypothyroidism patients who were on >3 micrograms/kg/day of thyroxine, to study the efficacy of once weekly thyroxine (OWT) versus standard daily therapy (SDT). At 6 weeks, 76.5% on OWT achieved goal TSH when compared to 38.8% of those who continued on SDT (p < 0.05) and 82.6% of those who continued on OWT maintained the goal TSH at median follow up of 25 months. We have another ongoing-study on initial thyroxine dosage requirement in patients with hypothyroidism for achieving euthyroidism. In this study, TSH directed initial dose regime is used rather than 1.6 micrograms/kg as advised by guidelines. Interim analysis of 77 subjects showed that 71.4% have achieved suppression to target TSH range at 6 weeks, saving average of 25 micrograms/patient/day of thyroxine dose.

Impact on current endocrine practice: In real-world practice of treating hypothyroidism, compliance becomes an important hindrance as the patient has to take the medicine empty stomach and wait for 1 hour for food daily and space other interfering medications. OWT has helped to manage thyroxine resistant hypothyroidism in a patient- friendly way. The study on TSH directed initial thyroxine dose aims to bring forward an objective way of calculating the initial thyroxine dose considering TSH level and probably weight and thus avoiding the adverse effects of TSH oversuppression and high levels of T4 on heart and bone.

Conclusion: Innovations from our research can go a long way in patient-friendly, customized management of hypothyroidism, maintaining balance on adverse effects due to over- or underreplacement.

Keywords: Hypothyroidism, once weekly thyroxine, treatment resistant hypothyroidism, TSH

REFERENCES

2.Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M, Tewari N. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab. 2013;17:647–52. doi: 10.4103/2230-8210.113755. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Chakera AJ, Pearce SH, Vaidya B. Treatment for primary hypothyroidism: Current approaches and future possibilities. Drug Des Devel Ther. 2012;6:1–11. doi: 10.2147/DDDT.S12894. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Jayakumari C, Nair A, Puthiyaveettil Khadar J, Das DV, Prasad N, Jessy SJ. Efficacy and safety of once-weekly thyroxine for thyroxine-resistant hypothyroidism. J Endocr Soc. 2019;3:2184–93. doi: 10.1210/js.2019-00212. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

ADRENAL GLANDS: Salivary analytes in contemporary endocrinology

Karthik V ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Background: Saliva has garnered attention from researchers and clinicians alike as a non-invasive and stress-free alternative to blood. Salivary levels of unconjugated steroids like cortisol directly reflect its unbound plasma concentrations.

Concept: We have validated the accuracy of Porcine ACTH stimulated salivary cortisol in comparison with Synacthen stimulated serum cortisol and a value less than 30 nmol/L at 2 hours could diagnose adrenal insufficiency (AI) with a sensitivity and specificity of 100 and 93.4 % respectively.[1] Late-night salivary cortisol (LNSC) for screening of Cushing syndrome is a valuable yet underutilized test in our country. We pioneered the large community study which defined the upper limit of LNSC as 0.25 μg/dl in normal Indian population using a commercially available second-generation ECLIA that can be translated into clinical practice for the diagnosis and surveillance of Cushing syndrome.[2] Utilizing the superior performance of salivary cortisol in diagnosing AI in cirrhosis,[3] we are currently pursuing a study to establish the cut-offs for ACTH stimulated salivary cortisol in different stages of cirrhosis. The introduction of completely non-invasive cosyntropin stimulation test (CST) using intranasal cosyntropin and salivary cortisol and cortisone assays is set to revolutionize the way we diagnose AI.[4] The addition of 17-hydroxyprogesterone to the current panel of salivary steroids would greatly enhance the utility of non-invasive CST paradigm in both children and adults.

Impact on current endocrine practice: The addition of analyte estimation in saliva to our diagnostic repertoire is advantageous as it is non-invasive, easy to collect, store, transport and analyte levels rapidly equilibrate with changes in plasma concentrations. This is a boon especially for neonates and young children in whom testing often gets aborted due to difficulty in venous access, catheter blockade and excessive discomfort. As far as AI is concerned, the existing ambiguity regarding its true prevalence in conditions with altered CBG levels, like cirrhosis, can be unraveled. The usefulness of saliva is not limited to cortisol estimation alone and assessment of testosterone, estradiol, glucose, Insulin etc. has shown strong correlation with their plasma concentrations in respective studies and holds great promise as a non-invasive alternative.[5,6]

Conclusion: Minimally invasive testing may be the norm in the future of Diagnostic Endocrinology and saliva forms an indispensable tool vindicated by the two practice changing studies from our institution.

Keywords: Salivary cortisol, Adrenal insufficiency, Cushing syndrome

REFERENCES

1.George GS, Jabbar PK, Jayakumari C, John M, Mini M, Thekkumkara Surendran Nair A, et al. Long-acting porcine ACTH stimulated salivary cortisol in the diagnosis of adrenal insufficiency. Clin Endocrinol (Oxf) 2020 doi: 10.1111/cen.14286. doi: 10.1111/cen.14286. [DOI] [PubMed] [Google Scholar]
2.Prasad N, Jabbar PK, Jayakumari C, John M, Ratheesh KH, Anish TS, et al. Late-night salivary cortisol in healthy community dwelling Asian Indians assessed by second generation Eclia. J Clin Endocrinol Metab. 2020;105:dgaa269. doi: 10.1210/clinem/dgaa269. [DOI] [PubMed] [Google Scholar]
3.Galbois A, Rudler M, Massard J, Fulla Y, Bennani A, Bonnefont-Rousselot D, et al. Assessment of adrenal function in cirrhotic patients: Salivary cortisol should be preferred. J Hepatol. 2010;52:839–45. doi: 10.1016/j.jhep.2010.01.026. [DOI] [PubMed] [Google Scholar]
4.Elder CJ, Vilela R, Johnson TN, Taylor RN, Kemp EH, Keevil BG, et al. Pharmacodynamic studies of nasal tetracosactide with salivary glucocorticoids for a noninvasive Short Synacthen Test. J Clin Endocrinol Metab. 2020;105:dgaa323. doi: 10.1210/clinem/dgaa323. [DOI] [PubMed] [Google Scholar]
5.Yasuda M, Honma S, Furuya K. Diagnostic significance of salivary testosterone measurement revisited: Using liquid chromatography/mass spectrometry and enzyme-linked immunosorbent assay. J Men Heal. 2008;5:56–63. [Google Scholar]
6.Gupta S, Nayak MT, Sunitha JD, Dawar G, Sinha N, Rallan NS. Correlation of salivary glucose level with blood glucose level in diabetes mellitus. J Oral Maxillofac Pathol. 2017;21:334–9. doi: 10.4103/jomfp.JOMFP_222_15. [DOI] [PMC free article] [PubMed] [Google Scholar]

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Acton Prolongatum (ACTH - gel preparation) 0.5 ml ampoules for stimulation test

Shriraam Mahadevan ¹, Karthik Balachandran ¹, Subramanian Kannan ¹, Adlyne Reena Asirvatham ¹

Background: Adrenocorticotrophic hormone (ACTH) stimulation test is very important to diagnose adrenal insufficiency. Usually followed protocol is cortisol estimation 30 or 60 minutes after injecting ACTH (aqueous Synacthen/Cosyntropin) 250 mcg intravenously/ intramuscularly. It is well known to all endocrinologists in our country that the availability of Synacthen is variable and that too in the grey market and the cost is prohibitive.

Description: In the last few years Indian studies have been done with the long acting gel preparation of ACTH called Acton Prolongatum (AP) and published protocol for stimulation test with 0.5 ml of AP intramuscularly. Thence many centres use AP in their routine practice for suspected cases of adrenal insufficiency. Although AP is available readily in most of the Indian hospitals, it is marketed as 5 ml vial only (for other indications). Similar to several other Indian off label jugaads many physicians share one vial among more than one patients for stimulation tests. This may be done only in centres where high volume of patients and practitioners in rural and smaller centres are handicapped. It would be of immense value if AP is available as 0.5 ml ampoules specifically for stimulation test purposes.

Impact on Practice: Cost to the patient per ACTH ampoule would drastically come down. Unnecessary sharing of the same vial of ACTH and storage issues would be avoided.

Conclusion: Acton Prolongatum 0.5 ml ampoules would be of great help to endocrinologists and a noble service to our patients requiring ACTH stimulation test.

Keywords: ACTH, Acton Prolongatum, Stimulation test

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

CRITICAL CARE ENDOCRINOLOGY : New-onset diabetic ketoacidosis (DKA) in previously normoglycemic Indians with covid-19 infection: is it type 1, type 2 or atypical ketosis-prone diabetes (KPD)?

Riddhi Das Gupta ¹, R Gorai ¹, B Choudhury ¹, D Dutta ¹, A Hazra ¹, S Mondal ¹, A Ganguly ¹

Background: Ketosis-prone diabetes (KPD), an atypical form of diabetes, has emerged as a heterogeneous syndrome in multiple ethnic groups. Though viral infections have been studies as a potential etiology, possibility of the novel coronavirus precipitating KPD amongst Asian Indians remains unexplored.

Description: Consecutive, adult patients presenting to the emergency with unprovoked DKA and RT-PCR positive COVID-19 infection without pre-existing diabetes and negative for autoantibodies for Type 1 Diabetes, will be included in the study. Simultaneously, a group of Type 1A Diabetes patients (autoantibody positive) presenting with DKA without COVID-19 infection (RT-PCR negative) during the same time will be recruited as the control group. Both the groups will be prospectively studied over a period of 1-year with serial evaluations of clinical, biochemical and beta-cell secretion characteristics, the latter being assessed by fasting and stimulated C-peptide values after a standard mixed meal challenge. Glycaemic control and treatment outcomes will also be documented. We hypothesize that COVID-19 triggers an unique form of KPD (A-β+) that has a severe presentation with DKA at onset, but undergoes complete recovery of their beta-cell function with remission from insulin-dependence within 3–4 months without further recurrences of DKA.

Impact: This will be the first reported series of possible A-β+ KPD due to COVID-19 infection. Given the increasing number of new-onset DKA amongst Indian COVID-19 patients, accurate clinical and metabolic characterization is key to successful treatment. Further, possibility of future remission will necessitate careful monitoring of their beta-cell capacity and prevent unnecessary insulin use and its’ complications in resource-poor settings.

Conclusion: KPD is an unique form of diabetes that resembles T1DM at presentation, but gradually behaves more like T2DM. Understanding it's association with COVID-19 infection will prevent misclassification and help in developing rational treatment protocols.

Keywords: Covid-19, DKA, Ketosis-prone diabetes, type 1

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

OSTEOCRINOLOGY (METABOLIC BONE DISEASE) : Use of percutaneous sonography guided radiofrequency ablation in the management of parathyroid adenoma in a pregnant lady with severe hypercalcemia

Thushanth Thomas ¹, Manish Kumar Yadav ¹

Introduction: Radiofrequency ablation (RFA) is a relatively new technique for the removal of a mass. We present its use in severe refractory hypercalcemia due to parathyroid adenoma during pregnancy.

Description: 29 year old primi (IVF conception) was admitted for refractory vomiting at 7 weeks gestation (Calcium-17.3 mg/dl; PTH-360 pg/ml; Phosphorus-1 mg/dl; VitaminD-23 ng/ml). USG neck showed Right Inferior adenoma. Despite vigorous hydration, her S. Calcium could be brought down to 13.3 only and had persistent vomiting. So surgery was planned even though still in 1st trimester. But surgery was postponed as she developed influenza. It was decided that RFA could be done for the adenoma after explaining the pros and cons. RFA was done 1 week after admission (image attached). Next day, her calcium came down from 13.3 to 11.3 and then was maintained around 10-11 with PTH 94. She became much better symptomatically, vomiting subsided and regained weight. Finally in 2nd trimester, she underwent surgery as her corrected Calcium was still above normal and USG had showed 2 suspicious nodules in thyroid, which turned out to be papillary carcinoma. Her adenoma was successfully removed.

Impact on Current Endocrine Practice: RFA can be considered in primary/tertiary hyperparathyroidism in surgically unfit patients if we are sure that it is not carcinoma. Only few patients have undergone RFA for parathyroid adenoma. Long-term follow-up data is lacking. In literature, there is a report of maintaining normocalcemia for upto 2 years.

Conclusion: RFA, done by experienced Radiologist, is a safe option for parathyroid adenoma in select situations. It cannot replace surgery.

Keywords: Parathyroid adenoma, primary hyperparathyroidism, radiofrequency ablation

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

Hypercalcemia due to sarcoidosis – Case series from a tertiary endocrine care center in South India

Karthik V ¹, P K Jabbar ¹, C Jayakumari ¹, Abilash Nair ¹, Ramesh Gomez ¹, Darvin V Das ¹, Sreenath R ¹

Introduction: We present 4 patients who had hypercalcemia and were diagnosed to have sarcoidosis or its variants [Table 1].

Table 1.

Clinical, biochemical and imaging data of the 4 subjects

Case	Age (yrs)	Presenting feature	Peripheral lymphadenopathy	Peak corr.Calcium (mg/dl)	Phos mg/ dl	Creatinine on admission (mg/dl)	Creat on followup	ALP (IU/L)	PTH (pg/ ml)	25 OH Vit D (>30 ng/ml)	1,25 (OH) 2 Vit D (15-75 pg/ml)	24 hour urine Ca (mg/24 hrs)	ACE (IU/L)	CT chest	FDG PET
1	59	Abdominal pain, weight loss	No	14.1	4.2	2.1	0.9	622	7	35	60	774	116	Hilar adenopathy, ground glass opacities	Not done
2	61	Fatigue, weight loss	Yes	14	3.1	2.4	1.6	194	30	34	28.5	357	106	Hilar adenopathy, nodular parenchymal opacities	Hypermetabolic lymph nodes with lung nodules
3	72	Oliguria	Yes	15.1	3.9	2.8	1.2	105	10.2	37	42	424	66	Hilar adenopathy with subpleural, peri-fissural nodules and ground glass opacities.	Gen
4	14	skin rash, joint pain, short stature	No	12.6	3.6	0.8	0.8	316	7	64	34	124	337	Mosaic attenuation, ground glass and reticular opacities bilaterally	Not done

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Case details: Discussion: We describe the clinical details of four subjects, 3 post-menopausal Vitamin D sufficient women with age more than 50 years and a girl child with symptom onset at 4 years. All adults had renal failure at presentation. The child had symmetric, lower limb predominant arthritis and generalized erythematous papular skin eruptions from 4 years of age and was being treated as Juvenile rheumatoid arthritis with steroids. She was detected to have hypercalcemia during evaluation for short stature and delayed puberty. Serum phosphorous levels were normal and PTH levels suppressed in all 4 patients. All adults had pulmonary involvement on radiology but were asymptomatic with respect to respiratory system while the child had cough and dyspnea with CT features of Interstitial lung disease. One subject had lytic lesions in skull with normal serum immunofixation electrophoresis. Mantoux test and sputum AFB were negative in all subjects. Non-caseating granulomas were demonstrated in lymph node biopsies from adults and skin biopsy in the child. DNA sequencing identified Glu498Gly heterozygous variant in the NOD2/CARD 15 gene confirming the diagnosis of Blau syndrome in the child. All were treated with steroids 0.5-0.75 mg/kg/day and bisphosphonates administered to adult subjects. Renal failure improved even before steroid therapy and was maintained. One patient developed avascular necrosis of femoral head and hypophosphatemia following steroid therapy.

Conclusion: We report three adult subjects with biopsy proven sarcoidosis in whom severe hypercalcemia associated with renal failure was the unusual presenting feature and a child with Blau syndrome. The successful treatment and follow up is also detailed.

Keywords: Hypercalcemia, PTH independent, Sarcoidosis

Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):452–505.

GONADS : The benefit of digital therapeutics on patient-reported outcomes in girls with PCOS

Samta Mittal ¹, Tejal Lathia ¹, Eesha Kanade ¹, Amrata Jaykar ¹, Neeti Gulati ¹, Arbinder Singal ¹

Background: Lifestyle modifications are recommended as first-line therapy in polycystic ovary syndrome (PCOS), but currently, there is no structured lifestyle management program for PCOS in India. Patients often suffer from low motivation, and traditional clinical care is inadequate to address the psychosocial aspect of PCOS. The effect of lifestyle changes on patient-reported outcomes [PROs] is also largely unknown.

Description: 50 patients with PCOS were enrolled in a 3-month digital therapeutic program - Heal PCOS - focussing on education, nutrition, exercise, and motivation support. Every patient got regular calls from a dedicated nutritionist as a coach and scientific knowledge was provided using Fitterfly Wellness App in form of quizzes, blogs, audio-videos, and podcasts. Results were assessed based on patient-reported outcomes via a questionnaire. Improved outcomes were seen in self-assessment of stress management, healthier food choices, increased duration of exercise, improved knowledge about PCOS, menstrual irregularity, presence of cystic acne, and capability of managing PCOS on own.

Impact on current endocrine practice: Patient-Reported Outcomes evaluate the emotional and social impact of PCOS and its treatments. Along with traditional clinical treatment, a digital therapeutic program can help doctors overcome problems of low motivation in PCOS, provide lifestyle as well as psycho-social support, and answer patient queries without investing time. This provides holistic support for more complete management of PCOS.

Conclusion: Personalized care provided by the Heal PCOS program can help redefine care in PCOS management, provide 360° support and improve patient engagement, treatment compliance, and outcomes.

Key words: Digital therapeutics, pcos outcomes, patient support program, heal pcos

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PERMALINK

Endocrine Week - Free Paper Session

PUBLIC HEALTH ENDOCRINOLOGY: Prevalence and correlates of peripheral neuropathy among type 2 diabetes mellitus patients – A community based epidemiological study in a town of Eastern India

Sumanta Chakraborty

Anirban Mazumdar

Mental disability due to congenital hypothyroidism despite timely diagnosis: Study from Vellore, Tirupattur and Ranipet districts of Tamil Nadu

Parandhaman Arumugam

Srilakshmi R

Sudha Seshayyan

Shriraam Mahadevan

INTER-DISCIPLINARY ENDOCRINOLOGY: Intraoperative use of real time continuous glucose monitoring (rt-CGM) to predict complete insulinoma removal

Ravindra Shukla

Vaibhav Varshney

Subhash Chandra Soni

Spectrum of 21-hydroxylase deficiency congenital adrenal hyperplasia from tertiary care Centres in India

Shinjan Patra

Madhukar Mittal

Ravindra Shukla

Arun K Singh

Neeraj Gupta

MK Garg

Auto-immune Hypoglycemia: Double Trouble in Insulin Autoimmune Syndrome or Hirata Disease

Prasoon Rastogi

Shinjan Patra

Madhukar Mittal

Subhash Soni

Vaibhav K Varshney

Ravindra Shukla

MK Garg

PITUITARY: Pituitary dysfunction following snakebite envenomation: A case series

Ayan Roy

Varun Suryadevara

Nagarajan K

Sadishkumar Kamalanathan

Jayaprakash Sahoo

Dukhabandhu Naik

Nandhini Lakshmana Perumal

Niya Narayanan

Chandhana Merugu

Deepika Patel

Milind Patil

Efficacy of steroid treatment in Primary Hypophysitis: A single centre experience

Yash Chauhan

Jugal Gada

Prema Varthkavi

Nikhil Bhagwat

Table 1.

Outcomes of patients with pituitary apoplexy managed surgically or conservatively: Study from a tertiary care hospital in southern India

Pragya Gupta

Clinical characteristics, diagnostic challenges and therapeutic outcomes of thyrotropin-secreting pituitary adenomas: A case series of three patients

Prudwiraj Sanamandra

Jugal Gada

Nikhil Bhagwat

Premlata Varthkavi

Post-operative hyponatremia: Prevalence, predictors and prognosis – A study from a tertiary care center in southern India

Remya Rajan

Shivendra Verma

Nitin Kapoor

Ari G Chacko

Thomas V Paul

Nihal Thomas

Felix Jebasingh

Kripa Elizabeth Cherian

Shalini Sahu

HS Asha

Sheehan syndrome; experience from a tertiary care center from Central India

Jaideep Khare

Sushil Jindal

Saifali Bansal

Table 1.

Snake bite related panhypopituitarism, addisons disease (multiple endocrine apoplexy)

Ayan Roy

S Jayaram

Avascular osteonecrosis of femoral head in a patient cured of pituitary Cushing's disease

Raj Mohan Lekshmi Narayanan

Thushant Thomas

Thyroid Stimulating Hormone (TSH) secreting pituitary adenoma. A diagnostic and therapeutic challenge – A series of 4 cases

Kumar Thulasidass

Muthukumaran Jayapaul

Velayudham P