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. 2012 Dec;16(Suppl 2):S514–S524.

ABSTRACTS

PMCID: PMC3603132
Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Pituitary

Sheehan′s syndrome: A single centre experience

Epuri Sunil, Gadekal Rajagopal, Vaikkakara Suresh, Pokula Laksmi1, Mustur Suchitra Manohar2, Bobbidi Phaneendra Venkata3, Sachan Alok

Departments of Endocrinology, 1Radiology, 2Biochemistry, and 3Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Corresponding Author: Epuri Sunil, Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India. E-mail: sunil_pediatric@yahoo.com

Introduction: Sheehan′s syndrome (SS) occurs as a result of ischemic pituitary necrosis due to severe postpartum haemorrhage. It is one of the most common causes of hypopituitarism in developing countries. Aim and Objective: To study the clinical profile of patients with SS attending the Endocrinology Department at a tertiary hospital in south India. Materials and Methods: All patients diagnosed as SS during the study period of 2007-2012 were identified. The clinical, biochemical, hormonal, radiological and bone mineral density (BMD) data were collected. Results: Total 18 patients were identified. Median age of diagnosis was 40 years. (Inter Quartile Range (IQR) = 32-51); median diagnostic delay was 11 years (IQR = 5-17). Failure to resume menstruation and lactation failure was the most common clinical presentation. Median total tetraiodothyronine (T4), peak stimulated cortisol, stimulated growth hormone (GH), and prolactin (PRL) were low. The gonadotropins (Follicle Stimulating Hormone (FSH), Lutinising hormone (LH)) were inappropriately normal in the presence of amenorrhea. Hyponatremia was the most common electrolyte abnormality seen in 14 patients (82%). Seven patients (41%) had anaemia and five of them (76%) had normocytic normochromic anaemia. BMD assessment done in ninepatients, was suggestive of low bone mass. Conclusion: SS resulted in panhypopituitarism in all the patients. Hyponatremia, anaemia and low bone mass were frequently seen in patients with SS.

Key words: Sheehan′syndrome, pituitary necrosis

Hypothalamic Pituitary Insufficiency Following Central Nervous System Infections: A Prospective Study from a Tertiary Care Hospital

Arun Mukka, Alok Sachan, B. Vengamma1, C. V. Harinarayan, Bindu Menon1, V. Suresh, M. Neelima

Departments of Endocrinology, and 1Neurology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India

Corresponding Author: Dr. Mukka Arun, Department of Endocrinology, SVIMS, Tirupati-517 507, India. E-mail: arunmukka@rediffmail.com

Introduction: Infectious diseases of the central nervous system may also affect the hypothalamus and pituitary functions, although this effect very often has not been reported and systemically studied. Aims and Objectives: To study the functions of the anterior pituitary gland in patients suffering with meningitis and encephalitis. Materials and Methods: Fifty patients with meningitis or encephalitis were recruited for the study, following admission to the neurology ward of our tertiary care hospital after taking the informed consent from the responsible attendant. On the day of recruitment samples were collected in the fasting state for T3, T4, Thyroid Stimulating Hormone (TSH), prolactin, estradiol, testosterone, Follicle stimulating hormone (FSH) and Lutenising hormone (LH). When the patient was recovering from the illness basal cortisol, stimulated serum cortisol and growth hormone samples were collected by performing the insulin tolerance test. Results: Mean age of the patients was 27.2 ± 10.8 years with 33 males and 17 females. Three patients (two males and one female) had elevated prolactin levels. One male patient with hyperprolactinemia had low testosterone levels. In total 18 male patients had low testosterone (<3 ng/ml) with low or inappropriately normal gonadotropins. All female patients except one were found to be having normal serum levels of estradiol. Twenty patients had growth hormone <3.0 ng/ml on stimulation. Twenty-seven patients had low stimulated cortisol (<18 μ/dl). Twenty-seven patients had features suggestive of sick euthyroid syndrome. Four patients had low T3, T4 and low or inappropriately normal TSH along with a deficiency of other hormones. Conclusions: Hyperprolactinemia (6%), gonadotropic insufficiency (50%), somatotropic insufficiency (40%), corticotropic insufficiency (54%) andabnormal thyroid profiles (14%) were evident in several patients presenting with acute meningitis and meningoencephalitis.

Key words: HP Insufficiency, CNS Infections

Autoimmune Hypophysitis: A single centre experience

Shruti Girish Khare, Anurag Lila, Tushar Bandgar, Nalini Shah

Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, India

Corresponding Author: Dr. Khare Shruti Girish, Department of Endocrinology, Seth GS Medical College and KEM Hospital, Acharya Donde Marg, Parel, Mumbai, India. E-mail: shrutigkhare@yahoo.co.in

Introduction: Autoimmune hypophysitis (AH) is a rare primary autoimmune inflammatory disorderinvolving the pituitary gland. Objective: To analyze clinical and radiological features of AH. Methods: A retrospective analysis of the clinical features, radiological features and outcome of patients diagnosed with AH between 1988 and 2012 was carried out. Results: Forty patients with AH (37 females and 3 males) were evaluated during this period. Six (15%)patients presented inthe peripartum period. The most common mode of presentation was symptoms of mass effect, i.e., headache, vomiting (70%), followed by symptoms of hypothyroidism (52.5%), menstrual irregularities (37.5%), diabetesinsipidus (25%). The most common deficient hormone was adreno corticotropic hormone (70%), followed by thyroid-stimulating hormone (52.5%) andgonadotropins (42.5%). Four (10%) patients had associated autoimmune disorder. A definite, sellar mass due to pituitary enlargement was seen in 90% of patients,on neuroimaging. It was homogenously enhancing in 86% (31/36). Wherever information about pituitary stalk was available, stalk thickening was seen in 17/17 patients. Extension was suprasellar in 82% and parasellar in 12.5%. Five patients under went trans-sphenoidal surgery. Wherever serial reimaging was available, the pituitary enlargement regressedor disappeared in 16/16 patients. Conclusion: We report low incidence of peripartum casesin our series. Symptoms of mass effect were the most common while Adrenocorticotrophic hormone (ACTH) was the most common deficient hormone. Most common imaging features were pituitary enlargement with homogenous enhancement, and suprasellar extension. Persistent stalk thickening was the most consistent feature. Surgery wasrarely needed, and most patients experienced aspontaneous resolution of the mass.

Key words: Autoimmune hypophysitis, sellar mass, stalk thickening

Gene analysis of POU1F1 and PROP1 and prenatal diagnosis in combined pituitary hormone deficiency

Shweta Birla, Garima Kachhawa1, Arundhati Sharma, Rakesh Jora2, Rajesh Khadgawat3

Departments of Anatomy, and 1Obstetrics and Gynaecology, AIIMS, New Delhi, 2Department of Pediatrics, Dr. S N Medical College, Jodhpur, 3Department of Endocrinology and Metabolism, AIIMS, New Delhi, India

Corresponding Author: Dr. Birla Shweta, Department of Anatomy, AIIMS, New Delhi, India. E-mail: sbirla84@gmail.com

Introduction: Development of the pituitary gland involves activation of series of transcription factors like POU1F1, PROP1, etc. Mutations in the genes encoding either of these factors lead to deficiency of pituitary hormones resulting in combined pituitary hormone deficiency (CPHD). Aim: To identify POU1F1 and PROP1 gene mutations and provide prenatal diagnosis (PND) for CPHD families. Materials and Methods: Two families with a previous child each, diagnosed with CPHD, were enrolled for the present study. Blood samples from the parents, and affected children were collected and subjected to DNA isolation followed by mutational analysis of the PROP1 and POU1F1 genes. One family wished for PND for the second pregnancy. Placental biopsy was planned in the 12th week of gestation after detection of a mutation in the affected child. Routine ultrasound screening before the procedure revealed the absence of cardiac activity in the fetus. The parents were counseled, and informed consent was taken to induce labor for abortion. Fetal tissue samples were collected and subjected to mutation screening. Results: Genetic analysis revealed the presence of two new mutations. Both affected individuals from the two families showed a homozygous splice site POU1F1 mutation whereas their parents were heterozygous for this change. Results of PND showed that fetus in addition to the heterozygous POU1F1 mutation had another pathogenic homozygous PROP1 mutation causing premature termination of transcription leading to a truncated PROP1 protein. Since both families belonged to the same geographical area, haplotype analysis was carried out to find out the origin of the common mutation as it may be due to founder effect. Conclusion: The present study reports on the molecular genetics characterization of two families having a previous child affected with CPHD and on providing PND, for the first time, in such cases. Molecular genetics analysis identified mutations leading to truncated PROP1 and POU1F1 proteins, which probably resulted in intra uterine death of the fetus.

Key words: Combined pituitary hormone deficiency, POU1F1, PROP1

Genotype and phenotype correlation of idiopathic growth hormone deficiency in Asian-Indian patients

Shantanu Kale, Sweta Budyal, Anurag Lila, Tushar Bandgar, Vijaya Raghavan, Nalini Shah

Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

Corresponding Author: Dr. Sweta Budyal, Department of Endocrinology, Seth G. S. Medical College and KEM Hospital, Parel, Mumbai, India. E-mail: swetabudyal@gmail.com

Introduction: Upto 30% of patients with idiopathic growth hormone deficiency (GHD) are caused by germline mutations in the genes/transcription factors involved in the pituitary development and hypothalamopituitary axis. Aim: To study the genotype and phenotype correlation in patients with idiopathic GHD. Materials and Methods: Hundred and seven patients with idiopathic GHD enrolled over 10-year period from 2000 to 2010 were selected. In all patients, detailed clinical and hormonal evaluations were done along with dedicated Magnetic resonance Imaging (MRI) of the pituitary region to assess anterior pituitary height, stalk, posterior pituitary bright spot, midline defects and other associated brain anomalies. GH1, Growth hormone releasing hormone receptor (GHRHR), PROP1 and POU1F1 were studied. Exons with splice sites of these genes were amplified using specific primer pairs by polymerase Chain reaction (PCR). All the amplicons were subjected to column purification and sequencing by dye terminator sequencing method. Results: Out of 107 patients (median age: 11 years, 64 M/43 F), 73 had isolated GHD (IGHD) and 34 had combined pituitary hormone deficiency (CPHD). Mean height standard deviation score (SDS) at presentation was 5.6. Twenty patients had familial GHD. MRI abnormalities were seen in 76.4% of CPHD and 43.8% of IGHD. The abnormalities included hypoplastic anterior pituitary, ectopic posterior pituitary and pituitary stalk abnormality. The triad of these was seen in 17.6% subjects of CPHD and 7.8% of IGHD. The analysis of sequencing of the PCR product is awaited. Conclusion: Structural abnormalities of the pituitary gland are more common in CPHD than IGHD.

Key words: Idiopathic growth hormone deficiency,anterior pituitary abnormalities

Novel GH1 exon 1 deletion in patients with familial Idiopathic growth hormone deficiency

Shantanu Kale, Sweta Budyal, Anurag Lila, Tushar Bandgar, Vijaya Raghavan, Nalini Shah

Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

Corresponding Author: Dr. Sweta Budyal, Department of Endocrinology, Seth G. S. Medical College and KEM Hospital, Parel, Mumbai, India. E-mail: swetabudyal@gmail.com

Introduction: Upto 30% of cases with Idiopathic growth hormone deficiency (IGHD) have a genetic etiology. Genes implicated in the etiology of IGHD include Growth hormone exon 1 (GH1), growth Hormone releasing hormone receptor (GHRHR) and SOX3. Objective: To screen threepatients (Father, Mother and Son) with IGHD from a single family for mutations in GH1 and GHRHR genes. Materials and Methods: Index patient, 10-year-old male and his parents were diagnosed to have isolated growth hormone deficiency (GHD). Magnetic resonance imaging (MRI) showed Hypoplastic pituitary in all three. Genetic screening involved complete GH1 gene and exons, exon-intron boundaries anduntranslated regions (5′/3′UTRs) of GHRHR gene. All the amplicons were subjected to column purification and sequencing by dye terminator sequencing method (BigDye Terminator v3.0). Deletions were confirmed by Southern blotting. Results: Mother is homozygous for E72X nonsense mutation in GHRHR gene. We could not amplify and thus sequence exon 1 in father. Southern blot analysis showed complete deletion of exon 1 in father. Son is heterozygous for E72X nonsense mutation in GHRHR gene and exon 1 deletion of GH1 gene. Conclusion: We report a novel exon 1 deletion in GH1 in patients with familial IGHD from western part of India.

Key words: Exon1 deletion,familial idiopathic growth hormone deficiency

Phenotype and genotype of three familial isolated pituitary adenoma families

N. Bothra, A. Lila, T. Bandgar, N. Shah

Department of Endocrinology, KEM Hospital, Parel, Mumbai, India

Corresponding Author: Dr. N. Bothra Nikita, Department of Endocrinology, KEM Hospital, Mumbai, India. E-mail: nikitabothra82@gmail.com

Aim: Our aim was to analyze the clinical presentation, genealogical features and genetic mutations of three homogenous familial isolated pituitary adenoma (FIPA) families with acromegaly. Materials and Methods: Six cases from three FIPA families non multiple endocrine neoplasia (MEN1)/Carney complex (CC) were evaluated clinically, biochemically and genetically. Results: After reviewing clinical history, examination and laboratory profile (biochemical and hormonal) of all the family members, MEN1 and CC were ruled out. Median age at initial symptom was 22 years; most common presenting symptoms were acral enlargement and arthralgia. Two patients of one family (mother and son) had gigantism at presentation. All affected individuals were first-degree relatives. Index cases had either macro or micro adenomas on presentation whereas all individuals diagnosed on screening had macro adenomas. Two patients of one family (nephew and paternal uncle) had macro adenoma with cystic changes with partial empty sella on magnetic resonance imaging (MRI). All the patients except one, underwent trans-sphenoidal surgery and one required radiation post-operatively. One patient was treated with medical management. Genetic analysis is in process. Conclusion: In the absence of MEN1 or CC, somatotropinomas can occur within families as isolated pituitary adenomas. FIPA families have individuals affected across generations In this series 33% had micro adenoma, two of them had gigantism. Genetic characterization can give us further insight into their prognosis.

Key words: Familial isolated pituitary adenoma, macroadenoma, somatotropinoma

Clinical profile and treatment outcomes of patients with gigantism: A tertiary care center experience

N. Bothra Nikita, A. Lila, T. Bandgar, N. Shah

Department of Endocrinology, KEM Hospital, Parel, Mumbai, India

Corresponding Author: Dr. N. Bothra Nikita, Department of Endocrinology, KEM Hospital, Mumbai, India. E-mail: nikitabothra82@gmail.com

Introduction: Somatotropinoma leading to gigantism is a rare endocrine disorder. Materials and Methods: Medical records of 19 patients diagnosed with gigantism due to somatotropinoma from 1989-2012 were reviewed. We defined gigantism as height more than the 97thpercentile for age and ethnicity and cure as nadir post glucose growth hormone <0.4 ng/ml and/or normal insulin like growth factor-1 (IGF-1). Results: Nineteen cases (15 male, 4 female) of gigantism (17 sporadic, 2 familial), with 17 years as median age at the onset of symptoms and 27 years as median age at diagnosis had median follow-up of 8 years. At presentation, coarse facial features (48%), arthralgia (37%), tall stature (26%), vision deficit (47%), hyperglycemia (16%), and hypertension (12%) were recorded. The median final height of male patients was 187.8 cm and female patients 176 cm. Four patients had upper segment (US) to lower segment (LS) ratio lesser than 0.85 and seven had normal segments. Median post glucose growth hormone (PGGH) value was 28.8 ng/ml and one patient had hyperprolactinemia (prolactin >100 mcg/L). The median maximum tumor dimension was 28 mm. Gonadal, cortisol, and thyroid axis were affected in 72%, 68%, and 11% patients, respectively at baseline and normalized in 25%, 37%, 0%, respectively post-treatment. Single surgery in 12, surgery followed by radiation in 5 and multiple surgeries followed by radiation in 2 patients were required. On follow-up 79% patients were cured and 21% had the active disease. Conclusion: Gigantism has a male sex predilection. Indian giants sought medical attention with a median latent period of 6 years. At presentation, 72% patients had hypogonadism, but 64% had normal US:LS ratio.

Key words: Gigantism, somatotropinoma, radiation, surgery

Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Thyroid

Profile of paediatric hypothyroidism in a Tertiary Care Centre

D. Rajitha, E. Sunil, V. Suresh, G. Rajagopal, P. Satish Kumar, Alok Sachan

Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India

Corresponding Author: Dr. D. Rajitha, Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India. E-mail: rajithareddy005@gmail.com

Introduction: There is a paucity of Indian observational data on growth in hypothyroid children. Objectives: To study the therapeutic benefit of thyroxin (T4) on growth of children in the initial 2 years of treatment in newly diagnosed primary hypothyroidism. Materials and Methods: Paediatric patients with a diagnosis of primary hypothyroidism (i.e. Thyrotropin (TSH) >15 mIU/ml and T4 < 55 ng/ml) were included. Treatment was started with thyroxin. Dose was adjusted to maintain TSH between 0.5-5 mIU/ml. Height, height standard deviation scores (HSDS) and TSH were measured at baseline and at every follow-up visit. Height velocity in the initial couple of years was measured in cm/person year of use of thyroxin. Results: Forty-four children (female:male ratio of 2.67:1) with newly diagnosed primary hypothyroidism were included in this study. The mean duration of follow-up was 13.9 months. Mean dose of thyroxin per kg body weight required to restore euthyroidism was 4.14 ± 2.45 μg. The dose per kg fell from 4.76 ± 2 μg in preschool children to 3.04 ± 1.5 μg in adolescence (P < 0.05).The initial height SDS was –2.42 ± 2.58 and this improved by 0.45 ± 1.06 to final value of –1.86 ± 2.14 (P value < 0.05). The post-treatment catch up growth was 7.8 cm/person year of use. Conclusion: The height SDS deficit because of hypothyroidism is only partially regained in the first couple of years after treatment. However, follow-up until the attainment of final height is needed.

Key words: Pediatric hypothyroidism, clinical profile

Prevalence of celiac disease in patients with autoimmune thyroid disease

Bharat Sharma, PK Varthakavi, M Chadha, N Bhagwat, AS Joshi, TB Lathia, S Mittal, S Sheikh, J Dholye, S Rahate

Topiwala National Medical College,BYL Nair Charitable Hospital, Mumbai, India

Corresponding Author: Bharat Sharma Topiwala National Medical College, BYL Nair Charitable Hospital, Mumbai, India. bharatshakespeare@yahoo.in

Introduction: The prevalence of autoimmune thyroid disease (AITD) in India is 7 – 8% and the association of other autoimmune disorders with AITD is well documented. The concomitance of celiac disease (CD) with AITD results in poor absorption of thyroid medications and results in higher doses of the same. The institution of gluten free diet (GFD) in this cohort has helped to reduce the medication doses. Aim: To study the prevalence of celiac disease in patients with autoimmune thyroid disease Materials and Methods: A total of 300 consecutive patients with AITD attending the thyroid OPD of a tertiary care hospital run by the municipal corporation of Mumbai were screened for the presence of tissue transglutaminase antibodies (IgA TTG) using Bio-Rad enzyme linked immunoabsorbent assay (ELISA). Those with a positive titre underwent upper gastrointestinal endoscopy and duodenal mucosal biopsy for the diagnosis of CD. Results: Of the 300 patients with AITD recruited in the study, results of CA screen are available for 80 patients. Five out of these 80(6.25%) patients are positive for CA. Conclusions: CA is commonly associated with AITD and screening for the same can diagnose many cases of undiagnosed CD. The prevalence of celiac disease in all 300 recruited patients and the clinical impact will be conglomerated and presented at ESICON 2012

Cognitive function in subclinical hypothyroidism in the elderly

S. Bajaj, V. Misra, A. Varma, A. Srivastava, R. Kumar

Department of endocrinology and metabolism, M.L.N. Medical College, Allahabad, India

Corresponding Author: Dr. R. Kumar, Room No. 221, New PG Hostel, SRN Hospital, Allahabad, India. E-mail: ritesh_kumar.gsvm@rediffmail.com

Background: Thyroid hormones have profound effects on the central nervous system and the consequences of overt hypothyroidism are well known. In contrast, there is less evidence regarding cognitive effects of subclinical hypothyroidism. This unresolved issue is a problem in clinical practice because subclinical hypothyroidism is prevalent in older patients, many of whom already have some cognitive decline. Objectives: To study the association of cognitive function with subclinical hypothyroidism in elderly. Materials and Methods: Cross-sectional case-control study of 55 patients (≥65 years) who met the criteria for subclinical hypothyroidism were recruited. Similarly 55 patients age, sex and education matched healthy controls were taken. Serum TSH, free T3 and free T4 were measured. Cognitive functions were assessed by using Folstein Mini Mental Examination and clock drawing test. Results: Out of the 55 diagnosed subclinical hypothyroidism cases, cognitive impairment (by minimental score examination (MMSE)) was found in 17 (30.9%) while it was present in only 8 (14.54%) out of 55 controls but there was no association between cases and controls by using clock drawing test. Mean TSH of subclinical hypothyroidism with cognitive impairment was 7.52 ± 1.22 mIU/liter and without cognitive impairment was 6.26 ± 1.18 mIU/liter (P value = 0.0007, significant). Conclusions: Prevalence of cognitive impairment was significantly higher in subclinical hypothyroidism as compared to controls. Presence of cognitive impairment correlated to the level of TSH; as TSH increased cognitive function declined.

Key words: Cognitive impairment, elderly, subclinical hypothyroidism

Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Adrenals

Clinical profile, biochemical phenotype, functional imaging characteristic and genetic etiology of pheochromocytoma/paraganglioma patients presented to a single tertiary care center in India

Rajeev Kasliwal, V. Sarathi, R. Pandit, H. Kakade, S. Budyal, A. R. Lila, T. R. Bandgar, P. S. Menon, N. S. Shah

Department of Endocrinology, K.E.M. Hospital, Mumbai, India

Corresponding Author: Dr. Rajeev Kasliwal, Department of Endocrinology, K.E.M. Hospital, Mumbai, India. E-mail: rajeev.kasliwal@gmail.com

Introduction: Pheochromocytoma/Paragangliomas (PHEO/PGL) are rare tumor of neuroendocrine origin with underlying genetic etiology in a significant number of patients. Objective: We present clinical profile, biochemical phenotype, functional imaging characteristic and genetic etiology of PHEO/PGL patients presented to a single tertiary care center in India. Patients and Methods: Medical records of 114 patients diagnosed with PHEO/PGL from 1995 to 2012 were reviewed. Genetic testing was done in 70 PHEO/PGL patients. Results: Diagnosis of PHEO/PGL was made based on the symptomatic disease in 85 (75%) patients while 25 (22%) patients were diagnosed incidentally. Four (3%) patients were newely diagnosed during family screening at our center. Classic triad of headache, palpitation, sweating was present in 35 (31%) patients. Plasma-free metanephrine were available in 48 patients. Twenty-eight patients had noradrenergic phenotype while 12 patients adrenergic phenotype. Eight patients with PHEO/PGL had normal plasma metanepheines levels. Ten patients (9%) had malignant PHEO/PGL. VHL syndrome was clinically suspected in 19 patients, multiple endocrine neoplasia (MEN) 2A in 6 patients, MEN 2B in 2 patients, NF-1 in 1 patient. Analysis of DNA sequencing is awaited for 70 patients. Conclusion: Classic triad of symptoms was present in 31% patients. 22% of patients with PHEO/PGL were diagnosed incidentally. More and more patients are now diagnosed incidentally due to wide-spread use of CT imaging as well as during family screening. Clinically suspected syndromic association was seen in 25% of patients. Genetic analysis of 70 PHEO/PGL patients is awaited.

Key words: Pheochromocytoma, paraganglioma, genetics

Cushing macroadenoma: A single centre experience

Harshal Ramesh Kakade, Rajeev Kasliwal, Sweta Budyal, Shruti Khare, Anurag Lila, Tushar Bandgar, Nalini Shah

Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, India

Corresponding Author: Dr. Kakade Harshal Ramesh, Department of Endocrinology, Seth GS Medical College and KEM Hospital, Acharya Donde Marg, Parel, Mumbai, India. E-mail: dr.kakade@rediffmail.com

Introduction: Cushing syndrome due to pituitary macroadenoma is less common compared to microadenoma. Behavior of the tumor in terms of clinical profile and response to various modalities of treatment is different from microadenoma. We share our 20 years of experience of Cushing macroadenoma with the clinical profile and treatment outcome. Aim and Objective: To study clinical profile and treatment outcome of a patient of Cushing disease with macroadenoma to a single tertiary care center in India. Patients and Methods: Medical record of 40 patients diagnosed with Cushing syndrome with macroadenoma from the year 1993-2012 were reviewed and analyzed. Results: Out of 40 patients, 16 (40%) were male and 24 (60%) were female. Mean age of presentation was 27.6 ± 10.67 years. Median duration between the onset of symptoms and diagnosis was 24 months. Median adrenocorticotrophic hormone (ACTH) value was 97.1 pg/ml. 50% or more supressibility for low dose dexamethasone suppression (LDDS) was found in 10/38 patients. Visual field defects and mass effects were found in 15 patients. Mean maximum dimension of tumor was 20.7 ± 9.8 mm. All 40 patients underwent TSS. Five patients underwent early remission defined as day 5 cortisol <1.8 μg/dl (though five patients showed relapse) and 10 patients showed delayed remission defined as 6-12 weeks LDDS <1.8 μg/d (no relapses). Between 25 uncured patients and two relapses, nine lost follow-up. Among two relapsed patients, one patient underwent 2nd TSS, remined uncured and cured by radiotherapy and the second patient is on medical management. Between 18 uncured patients, two expired and two preferred medical management. Fourteen patients underwent definitive management in the form of TSS or radiotherapy, 2nd TSS was done in four patients, and three patients who remained uncured were subjected to RT and got cured. Ten patients underwent radiotherapy as 2nd line of treatment of which six patients were cured, two remained uncured and two patients lost follow-up. Between two uncured patients after radiotherapy, one patient managed with medical therapy and the other underwent 2nd and 3rd TSS, still uncured and on medical management. Conclusion: Out of 40, 15 (37.5%) patients were cured after 1st TSS. 2nd TSS was done in six patients, but only 1 (17.5%) got cured. Radiotherapy was done in 14 patients, out of which 10 (71.5%) were cured, proving as effective modality of treatment for Cushing macroadenomas.

Key Words: Cushing′s syndrome, pituitary macroadenoma

Ectopic cushing syndrome: A single center experience

Ramesh H. Kakade, Rajeev Kasliwal, Sweta Budyal, Amol Bukan, Anurag Lila, Tushar Bandgar, Nalini Shah

Department of Endocrinology, Seth GS Medical, College and KEM Hospital, Mumbai, India

Corresponding Author: Dr. Ramesh Harshal Kakade, Department of Endocrinology, Seth GS Medical, College and KEM Hospital, Acharya Donde Marg, Parel, Mumbai, India. E-mail: dr.kakade@rediffmail.com

Objective: To study clinical profile of patient presented with EAS presented to a single tertiary care center in India. Materials and Methods: Medical record of 16 patients diagnosed with EAS from 1993 to 2012 were reviewed and analyzed. Results: Out of 250 patients with endogenous hypercortisolism, 16 patients had EAS. Of 16 patients, 10 were male and 06 were female. Median age of onset of symptom was 31.5 years. Median ACTH was 141 pg/ml with the range of 53.5 to 491 pg/ml. Eight patients had bronchial carcinoid, 6 had thymic and 2 had MTC. Median lag period between consultation and diagnosis was 6 months. Patients of bronchial carcinoid had more lag period than thymic carcinoid and MTC. MRI had false positivity in 5 patients and all of them underwent TSS. IPSS was done in 7 patients, all have shown peripheral cause. Even though initial imaging was negative in 3 cases, CT scan localized lesion in all patients. Five out of 7 patients of bronchial carcinoid were cured while 2 with metastatic lesion remained uncured. Out of 6, only 2 patients with thymic carcinoid underwent surgery and both remained uncured. Two patients had MTC, out of which 1 was cured. Conclusion: Bronchial carcinoids are more indolent, difficult to localize, but amiable for surgery with less metastatic potential. Thymic carcinoids and MTC even though diagnosed easily show aggressive course. CT scan remains most useful modality for localization. MRI pituitary gives false positivity in some cases. Due to false positivity on MRI, some patient may undergo TSS. IPSS most useful investigation for localization of central verses peripheral cause.

Key words: Ectopic cushing′ s syndrome, carcinoid

To evaluate the utility of midnight salivary cortisol in endogenous cushing′s syndrome and compare it with normal population

Amol Bukan, Anurag Lila, Tushar Bandgar, Nalini Shah

Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, India

Corresponding Author: Dr. Amol Bukan, Department of Endocrinology, Seth G.S Medical College and KEM Hospital, Acharya Donde Marg, Parel, Mumbai - 400 012, India. E-mail: dramolbukan@gmail.com

Introduction: Salivary cortisol is a non-invasive and simple method. It is a good index of free serum cortisol. Aims and Objectives: To evaluate the utility of midnight salivary cortisol in endogenous Cushing′s syndrome and compare it with normal population. Materials and Methods: Twenty-six patients with the endogenous Cushings syndrome with low dose dexamethasone suppression test (LDDS) more than 1.8 μg/dl were included. 64 subjects with normal ODS cortisol were taken as controls. Saliva was collected between 11-12 pm in the plastic container with the help of cotton, which is chewed for 2-3 min. Measurement of salivary cortisol was done by ELISA method. Results: The mean midnight salivary cortisol in patients with Cushing′s syndrome and controls was 0.7230 ± 0.4573 (0.1925-2.5035) μg/dl, and 0.04878 ± 0.02281 (0.015-0.13) μg/dl, respectively. For the diagnosis of Cushing′s syndrome, the sensitivity was 100%, 96.15%, and 88.46% and specificity was 95.31%, 100%, and 100% when cut-off values used are 0.1 μg/dl, 0.2 μg/dl, and 0.3 μg/dl, respectively. Salivary cortisol values of controls with body mass index (BMI) less than 25 was 0.0462 ± 0.0270 μg/dl and in those with BMI of more than 25 was 0.06374 ± 0.0791 μg/dl. There was no correlation between salivary cortisol and BMI (r2 = 0.028). Salivary cortisol correlates with mid-night serum cortisol (r2 = 0.3951) and LDDS cortisol (r2 = 0.1604). Conclusion: Midnight salivary cortisol can be used as a screening test for the endogenous Cushing′s syndrome with a cut-off value of 0.1 μg/dl with good sensitivity without compromising specificity.

Key Words: Salivary Cortisol, Cushing′s syndrome

Case report of adrenal pheochromocytoma with coexisting thyrotoxicosis

Brahmanandam L, Vivekanand B, Giridhar, Mythili A, KAV Subrahmanyam

Andhra Medical College, King George Hospital, Visakhapatnam, India

Corresponding author: Dr. L. Brahmanandam, Andhra Medical College, King George Hospital, Visakhapatnam, India. E-mail: brahmaendo2k2@gmail.com

We report a rare case of adrenal pheochromocytoma with coexisting thyrotoxicosis. A 52 y female presented with hypertension, diabetes, hyperadrenergic symptoms, paroxysmal spells and CT abdomen revealing a left adrenal mass. Evaluation showed normal 24 hr urinary epinephrine and metanephrines with an elevation of urinary norepinephrine. Thyroid function test revealed thyrotoxicosis. The diagnosis of pheochromocytoma is delayed and the case illustrates the similarity of both the disorders. Despite existence of two disorders, the patient recovered with treatment of both pheochromocytoma and thyrotoxicosis.

Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Gynaecologic Endocrinology

High sensitive C-reactive protein as an independent cardiovascular risk marker in Indian women with polycystic ovary syndrome

Namburi R. Prasad, Aparna R. Bitla1, G. Raja Gopal2, Ponnala A. Reddy, Alok Sachan2, P. V. L. N. Srinivasa Rao1

Deparments of Endocrinology and Metabolism, Narayana Medical College and Hospital, Chinthareddy Palem, Nellore, Deparments of 1Biochemistry, and 2Endocrinology and Metabolism, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Corresponding Author: Dr. Ponnala Amaresh Reddy, Narayana Medical College and Hospital, Chinthareddy Palem, Nellore, Andhra Pradesh, India. E-mail: amareshreddy7@gmail.com

Introduction: High sensitive C-reactive protein (hsCRP), an inflammatory marker, predicts the development of cardiovascular disease (CVD). Polycystic ovary syndrome (PCOS) shares some components of the metabolic syndrome. Therefore, PCOS patients represent the largest group of women in high risk to the development of early CVD. Aims and Objectives: The aim of this study was to compare hsCRP, lipid profile levels between women with PCOS and controls with a normal menstrual cycle and to determine the factors associated with serum hsCRP levels. Materials and Methods: Forty PCOS patients and 40 healthy, regular cycling women were enrolled. We performed anthropometric measurements, and blood sampling to determine blood chemistry and levels of hsCRP, insulin and testosterone. We also conducted 75-g oral glucose-tolerance test and insulin resistance was derived using homeostatic model assessment of insulin resistance. Results and Conclusion: hsCRP concentrations were significantly higher in women with PCOS. Whereas, 65% of the PCOS patients had hsCRP levels above 5 mg/liter, only 7.5% of the controls exhibited high hsCRP levels (P < 0.01). Women with PCOS had significantly higher serum total cholesterol (P < 0.01), triglycerides (P < 0.01), low density lipoprotein –cholesterol (LDL-C) (P < 0.01), very low density lipoprotein –cholesterol C (VLDL-C) (P < 0.01) and decreased High density lipoprotein -cholesterol (HDL-C) (P < 0.01) compared to control group. hsCRP levels were significantly correlated BMI (r = 0.507, P < 0.01), systolic (r = 0.363, P < 0.05) and diastolic blood pressure (r = 0.373, P < 0.05). Therefore, elevated hsCRP levels in women with PCOS suggest as an independent cardiovascular risk marker.

Key words: High sensitive C-reactive protein, polycystic ovary syndrome, cardiovascular disease risk

Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Bone & Mineral Metabolism

Prevalence of male osteoporosis in India

Balram Sharma, Ved Prakash, N. K. Agrawal, S. K. Singh

Departments of Endocrinology & Metabolism, IMS, BHU, Varanasi, India

Corresponding Author: Balram Sharma, Departments of Endocrinology & Metabolism, IMS, BHU, Varanasi, India. E-mail: drbalramendo@gmail.com

Introduction: Osteoporosis is a serious silent public health concern. Despite being a common cause of morbidity and mortality in males, available data on male osteoporosis in Indians are very few. Aim and Objective of Study: Study was conducted to find out the prevalence of male osteoporosis and possible etiologies in males. We evaluated 200 healthy males above 50 year′s age. Materials and Methods: Subjects were evaluated clinically including body mass index (BMI) and for bone mineral density (BMD) at right neck of the femur. T score was calculated for the diagnosis of osteoporosis or osteopenia (WHO criteria). S. calcium, S. phosphate, S. alkaline phosphates, S. creatinine, total serum proteins, S. iPTH, S. testosterone, and S. 25-OH Vitamin D were also estimated. Results: The mean age was 62.6 ± 7.6 years, and mean BMI were 23.90 ± 3.73 kg/m2. At neck of the femur, 99 (49.5%) subjects had normal BMD, 84 (42%) had osteopenia, while 17 (8.5%) had osteoporosis. Serum total testosterone was low in 16%, normal in 82%. S. iPTH was normal in 114 (57%), and high in 86 (43%) subjects. S vitamin D was low in 24.5% subjects, 33.5% were deficient, 28.5% had insufficient levels while 13.5% subjects had sufficient levels. Conclusion: The prevalence of osteoporosis was 8.5% in healthy adult Indian males. Elevated level of serum PTH was found in half while vitamin D was low in the majority of studied subjects. Despite such risks of osteoporosis, its low prevalence in the studied subjects suggested a need to redefine vitamin D deficiency.

Key Words: Male osteoporosis, BMD, vitamin D deficiency

Simultaneous expression analysis of Vitamin D receptor, calcium sensing receptor, cyclinD1 and PTH in Moderate to severe primary hyperparathyroidism in asian Indians: Implications for parathyroid tumorigenesis

Sanjay K. Bhadada

Department of Endocrinology, PGIMER, Chandigarh, India

Corresponding Author: Dr. Sanjay K. Bhadada, Department of Endocrinology, Roon No 2, fourth Floor, F Block, Nehru Hospital, Setor 12, PGIMER, Chandigarh-160012, India. E-mail: bhadadask@rediffmail.com

Background: To explore underlying molecular mechanisms in the pathogenesis of moderate. To severe sporadic primary hyperparathyroidism (PHPT). Materials and Methods: Forty one parathyroid adenomas from patients with moderate to severe PHPT and 10 normal parathyroid glands either from patients with PHPT (n =3) or from euthyroid patients without PHPT during thyroid surgery (n =7) were simultaneously analyzed for VDR , CaSR , Cyclin D1 (CD1) and PTH expressions. The protein expressions were assessed semi-quantitatively by immunohistochemistry, based on percentage of positive cells, staining intensity and confirmed by quantitative RT-PCR. Results: Immunohistochemistry revealed significant reductions in VDR (both nuclear and cytoplasmic) and CaSR, and significant increases in CD1 and PTH expressions in adenomatous compared to normal parathyroid tissue. Consistent with immunohistochemistry findings, both VDR and CaSR mRNA s were reduced by 64% and 56% (p <0.05), and CD1 and PTH mRNAs were increased by 9.4% and 17.3% respectively (p <0.05) in adenomatous parathyroid tissue. PTH mRNA correlated with serum PTH (r =0.864; p <0.05), but not with adenoma weight, while CD1 mRNA correlated with adenoma weight (r =0.715; p <0.05). There were no correlations between VDR and CaSR mRNA levels and serum Ca, PTH or 25-hydroxyvitamin D levels. In addition there was no relationship either between the decreases in VDR and CaSR mRNA expressions or the increases in PTH and CD1 mRNA expressions. Conclusions: VDR and CaSR expressions are reduced in moderate to severe PHPT in Asian Indians just as in mild PHPT in the West. In addition, CD1 expression was greatly increased and correlated with adenoma weight. Altered expression of VDR and CaSR appears to be responsible for the high growth rate, as reflected in increased CD1 and PTH expressions, and for the resultant high PTH secretary capacity in moderate to severe PHPT.

The diagnosis of osteoporosis among subjects of southern Indian origin above 50 years of age – The impact of the Indian council of medical research versus caucasian bone mineral density reference standards

Thomas V. Paul, H. S. Asha, D. M. Mahesh, Dukhabandu Naik, Simon Rajaratnam, Nihal Thomas, M. S. Seshadri

Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India

Corresponding Author: Thomas V. Paul, Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India. E-mail: thomasvpaul@yahoo.com

Introduction: In the year 2010, the Indian Council of Medical Research (ICMR) has published a normative data for bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) scanning. However, its impact on the diagnosis of osteoporosis when compared to the currently used Caucasian database has not been analyzed. Aims and Objectives: To study the effect of the newly generated ICMR database (ICMRD) on the diagnosis of osteoporosis compared with the Hologic DXA-4500 series database (HD) in subjects above 50 years of age in a tertiary care center from South India. Material and Methods: A cross-sectional study of DXA scans performed between January 2009 and December 2011 was done. The reference standards of the BMD obtained in the ICMR study for the hip and spine were used to recalculate the T-scores, and their agreement with the HD in the diagnosis of osteoporosis was ascertained. Results: A DXA scan of the lumbar spine in 4427 subjects (M:F=544:3883) and hip in 3677 subjects (M:F = 467:3210) were analyzed. The mean age of the subjects was 61.3 ± 8.4 and 59.7 ± 7.5 years in males and females, respectively. Osteoporosis at the spine and hip were diagnosed in 1859 (42.7%) and 404 (11.4%) subjects by HD and in 1186 (27.7%) and 296 (8.3%) subjects by ICMRD respectively. A significant agreement existed between the two reference databases for the diagnosis of osteoporosis of the spine (k = 0.657; P < 0.001) and hip (k = 0.808; P < 0.001). A greater proportion was diagnosed as having osteoporosis with HD over ICMRD (at the lumbar spine by 16% and hip by 3.1%). Conclusion: Though a larger proportion of subjects was diagnosed with osteoporosis using HD over ICMRD at both sites, there was a significant agreement between the two methods for the diagnosis. However, further studies are required to denote as to whether a similar degree of agreement exists for the diagnosis of osteoporosis in those subjects with fractures.

Key Words: Osteoporosis, bone mineral density, dual energy X-ray absorptiometry

Monostotic paget΄s disease involving left radius

Kishore K. Katam, S. Yadav

Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Corresponding Author: Dr. Kishore K. Katam, Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. E-mail: kishorekatamkk@gmail.com

Introduction: Pagets's disease can be either polyostotic or monostotic. Mostly they are asymptomatic. Here we present a lady of monostotic paget's disease with minimal elevation of bone markers and subsequent monitoring of therapeutic response with imaging. Case Report: Fifty Nine year old lady presented with pain, deformity of left forearm and tingling sensation of left fingers for three months. No evidence of fever, trauma or recent fractures. No hearing loss, backache, bony swellings in other places. She was not a known case of chronic kidney disease. No similar complaints in the family members. Left forearm was warm, tender and deformed. Hand grip was full and no weakness or atrophy of muscles noticed. Investigations: Creatinine-0.85 mg/dl(0.6-1.2), ALT-23 IU/l(10-40), Calcium-9.5 mg/dl(8.4-10.5), Albumin-4.0(3.5-5.5) g/dl, Phosphorus-3.8(2.5-4.5) mg/dl, Alkaline phosphatase-167 IU/l(40-150), 25OHD-25.9 ng/ml( >32), PTH-21.8 pg/ml(10-65), beta c- telopeptide- 1 ng/ml(0. 03-0.57), Pro collagen peptide-56.62 ng/ml(16.2-73.8). Mammography and USG abdomen were normal. X- ray of left forearm showed sclerotic and deformed left radius. Tc99 MDP bone scan showed increased uptake of left radius. Left carpal tunnel syndrome was diagnosed on nerve conduction studies. Zolendronic acid 5mg was given to the patient. At the end of 6 months she became asymptomatic and repeat bone scan showed reduced uptake in the left radius. Conclusions: Monstotic paget's with normal bone markers, therapeutic response can be monitored by 25% reduction of alkaline phosphatase from baseline and by bone scan to look for decreased uptake.

Key words: Vitamin D, pregnancy, anthropometry

Vitamin D supplementation in pregnancy and its effect on cord blood 25OHD and anthropometry of the newborn

K. Kishore Kumar, V. Nair, V. Bhatia, A. Agarwal2, V. Das2, V. Ramesh1

Departments of Endocrinology, and 1Biochemistry, Sanjay Gandhi Postgraduate Institute of Medical Sciences, 2Department of Obstetrics and Gynecology, Chatrapathi Sahuji Maharaj Medical University, Lucknow, India

Corresponding Author: Dr. K. Kishore Kumar, Department of Endocrinology, Sanjay Gandhi Postgraduste Institute of Medical Sciences, Lucknow, India. E-mail: kishorekatamkk@gmail.com

Introduction: Vitamin D (D3) supplementation is essential during pregnancy in India. We previously showed that doses inadequate to keep maternal and cord 25OHD > 20 ng/ml were sufficient to improve neonatal anthropometry compared to unsupplemented mothes. Aims: To study the effect of 3 regimens of D3 supplementation in pregnant women on cord blood25OH D and newborn weight, length, and head circumfernce. SesignDesign: Pregnant women (n = 306) in early second trimester were randomized to receive oral D3 60,000 IU 8 weekly (group 1), 120,000 units 8 weekly (group 2) or no extra D3 (group 3), until the delivery. All were prescribed daily tablet containing 1000 mg calcium and 400 units D3. Serum 25OHD was measured at baseline, at term and in cord blood. Neonatal calcium was measured from day 2 o 4. Results: Median (range) term 25OHD in group 1, 2 and 3 (21.9 [4.1-53.9], 27.9 [7.5-60.9], and 16.5 [5.4-49.7] ng/ml, respectively) and in cord blood (15.4 [1.5-41.4], 22.2 [2.7-93.5], and 12.9 [2.4-32.2] ng/ml in groups 1, 2, and 3, respectively) were significantly different among the groups (P = 0.001 for both). Cord 25OHD > 20 ng/ml was achieved in 11 (26.8%), 22 (61%), and 5 (17.8%), respectively among the three groups (P = 0.005). Anthropometry the 3 three groups was not significantly diferent. Conclusions: Oral D3 dose of 120,000 units 8 weekly (but not 60,000 units 8 weekly or 400 units daily) keeps cord 25OHD > 20 ng/l in > 50 % of babie The 2 two smaller doses ensure the same anthropometry as the bigger dose.

Key words: Vitamin D, pregnancy, cord blood

Effect of vitamin D fortified milk on vitamin D status of apparently healthy school children aged 10-14 years

R. Ramot, R. Khadgawat, R. K. Marwaha1, M. K. Garg2, A. K. Oberoi, N. Gupta

department of endocrinology and metabolism, All India Institute of Medical Sciences, New Delhi, 1ILSI, Delhi, 2R and R Hospital, Delhi, India

Corresponding Author: R Ramot. E-mail: marwaha_ramank@hotmail.com

Introduction: Vitamin D deficiency (VDD) is globally well documented among school children. Objective: To study the effect of vitamin D, fortified milk on vitamin D status of apparently healthy school children (aged 10-14 years). Materials and Methods: This prospective interventional study was carried out in 713 subjects, randomized into 3 groups, group A (n =237) unfortified milk, Group B (n =243) 600 IU of vitamin D and group C (n =233) 1000 IU vitamin D for 12 weeks. Serum 25 hydroxy vitamin D (SVitD) level was measured by electrchemiluminometric assay along with serum calcium and urinary calcium creatinine ratio at baseline and 12 weeks post supplementation. Results: VDD (SVitD <20 ng/ml) reported in 92.3% subjects (boys 88%; girls 95.4%; p <0.001), with mean SVitD level 11.6 ± 5.3 ng/ml. There was no significant difference in SVitD among three groups at baseline. SVitD levels significantly improved in all 3 groups. In control group, only 5.9% had vitamin D level more than 20 ng/mL after fortification while group B and C had 69.95% and 81.11% subjects had SVitD >20 ng/mL. Similarly, vitamin D sufficiency (>30 ng/mL) was seen in 1.26% subjects in group A; 12.34% in group B and 36.05% subjects in group C after fortification. The mean improvement in serum vitamin D level in group A was 5.25% while group B had mean improvement of 137.97% and group C had mean improvement of 177.29%. Conclusion: Fortification of milk with vitamin D is effective and safe in preventing VDD in apparently healthy school children.

Key words: Vitamin D3 supplementation, healthy adults, hypovitaminosis D

Study of various vitamin D3 supplementation protocols in healthy adult volunteers with hypovitaminosis D

P. S. Pawal, B. Sharma, S. Mittal, A. Joshi, T. Lathia, N. Bhagwat, M. Chadha, P. Varthakavi

Department of Endocrinology, TN Medical College & BYL Nair Charitable Hospital, Mumbai, India

Corresponding Author: Dr. P. S. Pawal, Department of Endocrinology, 4 Floor, No. 19, College Buliding, BYL Nair Hospital, Mumbai Central - 400 008, India. E-mail: drpratibhapawal@yahoo.co.in

Introduction: Hypovitaminosis D, which has various skeletal and extraskeletal manifestations, is widely prevalent in India (70-95%). Different dosing protocols have been used for Vitamin D (VITD) supplementation. This study is designed to compare various supplemental regimens. Aim and Objectives: Comparison of serial VITD concentrations attained with various VITD supplementation protocols in VITD deficient subjects. Materials and Methods: A total of 242 healthy volunteers (20-60 years: BMI 21-26 kg/m2), were screened for vitamin D deficiency. Out of this, 139 subjects were deficient, and 105 consenting subjects with VITD <16 ng/ml were randomized to receive four different supplemental regimens, i.e., single dose 6 lac IU orally, 6 lac IU intramuscular, 60,000 IU once weekly for 8 weeks, and 2000 IU daily for 8 weeks. VITD, parathyroid hormone, calcium, phosphorus, alkaline phosphatase were monitored at 0, 1, 3, 6, 8, 12, and 16 weeks of therapy.

Results:

graphic file with name IJEM-16-514-g001.jpg

Conclusions:

  1. All groups showed rise in VITD at 1 week.

  2. At 3 weeks, there was a fall in VITD in 6 lac IU oral group, while a steady rising trend was observed in the other three groups.

  3. Six subjects in Oral 6 lac group attained toxic levels of VITD while none from other groups developed toxic levels. Final results will be presented at ESICON2012.

Key Words: Hypovitaminosis, D calcium, phosphorus

Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Diabetes & Metabolism

Clinical experience with liraglutide in 196 diabetics from atertiary care centre in India

S. K. Mishra, K. Kaur, A. Makkar, M. Saxena, J. S. Wasir, B. Bansal, P. Sharma1, P. Singh1, A. Mithal

Division of Endocrinology and Diabetes, and 1Medanta Institute of Education and Research, Medanta The Medicity, Gurgaon-NCR Delhi, India

Corresponding Author: Dr. S. K. Mishra,Division of Endocrinology and Diabetes, MedantaTheMedicity, Gurgaon-NCR Delhi, India. E-mail: sk mishra_run@yahoo.co.in

Background: Majority of patients with type 2 diabetes does not achieve glycemic goals. Weight gain and hypoglycemia are two most common adverse effects of currently available antidiabetic medications. Aims of the Study: (1)To evaluate the effect of liraglutide on glycemic control and weight in obese patients with type 2 diabetes mellitus. (2) To study the adverse event profile of liraglutidein this “real world” clinic population. Subjects and Methods: Liraglutide was prescribed to 196 obese patients with type 2 diabetes mellitus who had poor glycemic control on oral medications ± insulin. Baseline treatment modalities were: Metformin alone-35 (18%); sulphonylureas + metformin-57 (29%); sulphonylureas + metformin + DDP IV inhibitors/exenatide-53 (27%);sulphonylureas + metformin+ basal insulin± DPP IV inhibitors-36 (18.4%); sulphonylureas + metformin+ premix insulin 8 (4%); and sulphonyl ureas + metformin+ basal-bolus insulin regimen7 (3.6%). Initial dose of liraglutide was 0.6 mg, which was up-titrated to 1.2 mg after 1week; further up-titration to 1.8 mg was done based on tolerance and adverse event profile. DPP IV inhibitors were discontinued, and dose of other medications adjusted according to clinical judgment on initiation of liraglutide. Results: Mean age of patients was 49.9 ± 9.6 years and mean duration of diabetes was 7.56 ± 4.5 years. Twenty-one patients discontinued liraglutide before completion of 3 months for a variety of reasons. Therefore, 3-month data was available for 175 patients. At 3 months fasting plasma glucose level was 115.5 ± 25.1 versus 173.7 ± 6.3 mg/dl at baseline; post meal glucose was 177.1 ± 31.2 versus 252.5 ± 77.0 mg/dl at baseline (P< 0.001). Glycosylated hemoglobin (HbA1C) at 3 months was 7.69 ± 0.99 versus 9.24 ± 1.97% at baseline (P = 0.007). Mean body weight at 3months was 96.0 ± 16.5 versus 100.1 ± 17.5 kg at baseline (P< 0.001).HbA1C reduction was significant in all groups except in sulphonylureas + metformin and premix insulin group. Most common adverse events were nausea, burping and eructation (10%) followed by diarrhea (4.7%) and skin reactions (2.3%); this resulted in withdrawals in sevenpatients. Five patients (3%) had mild hypoglycemia. Maximal daily dose of liraglutide i.e., 1.8 mg was reached in 15% patients, and in the rest, the dose was maintained at 1.2 mg daily. Conclusions: Liraglutide significantly improves glycemic control with low risk of hypoglycaemia and is associated with significant weight loss in obese Indian patients with type 2 diabetes mellitus. Most patients on prior insulin/oral antidiabetic combinations also responded well to liraglutide. Liraglutide use was associated with gastrointestinal adverse events; these adverse events were usually mild and transient and led to only few withdrawals.

Key words: Liraglutide, diabetes

Does continuous glucose monitoring system detect diabetic range hyperglycemia in women with prediabetes?

Dinesh Garg, Asha shyamsunder Hesarghatta, Nihal Thomas, Kanakmani Jeyaraman1, Devanithi Nithya, Prasanna Samue2

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India, 1Menzies school of health research (attached to the Royal Darwin Hospital), Darwin, Australia, 2Department of Biostatistics, Christian Medical College, Vellore, India

Corresponding Author: Dr. Garg Dinesh, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India. E-mail:dinesh.garg1965@yahoo.com

Introduction: The current diagnosis of prediabetes by oral glucose tolerance test (OGTT) involves measurement of plasma glucose values at two-time points. With the availability of continuous glucose monitoring (CGM),it is now possible to record glucose values every 5min for 72 h. CGM may unravel diabetic range glucose levels in prediabetic subjects. Identification of such an unrecognized hyperglycemia will change the classification of patientsfrom prediabetes to diabetes, and will also have treatment implications. Aims and Objectives: To assess whether CGMS can detect diabetic range glucose levels in prediabetic subjects. Materials and Methods: After informed consent,prediabetic women (based on OGTT)were connected to a CGMS (Medtronic ipro) device for 72 h. Family history of diabetes and anthropometric parameters were recorded. Subjects recorded their dietary intake, physical activity, and blood-glucose levels with a glucometer periodically according to a set proforma.(IRB Min no. 7495 dated 07.06.2011). Results: Fifteen eligible women were enrolled over a period of 6months. The mean age was 36.13 years (SD 9.1), Mean Body Mass Index (BMI) was 31.54 kg/m2 (SD 7.86), and waist circumference was 103.07 cm (SD 16.05). Eight subjects were overweight and six were obese. Three subjects had impaired fasting glucose (IFG), two had impaired glucose tolerance (IGT) and ten had both IFG and IGT. The mean fasting glucose was 107.99 mg/dl (SD 8.85), 2h post 75g of glucose was 154.80 mg/dl (SD 21.90) and HbA1C was 5.74% (SD 0.33, range 5.1-6.3%). None of the subjects had diabetic range hyperglycemia. Conclusion: CGMS failed to detect diabetic range hyperglycemia in women with prediabetes (by OGTT).

Key words: CGMS, prediabetes, hyperglycemia

Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Miscellaneous

An unusual radiological manifestation in osmotic demyelination syndrome

D. Rajitha, E. Sunil, P. Satish Kumar, M. Nagasuresh1, G. Rajagopal, V. Suresh, B. Vengamma1, B. Vijayalaxmi Devi2, A. Y. Laxmi2, Alok Sachan

Departments of Endocrinology, 1Neurology, and 2Radiodiagnosis, Sri Venkateswara Institute of Medical Sciences, Tirupati, India

Corresponding Author: Dr. D. Rajitha, Departments of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India. E-mail: rajithareddy005@gmail.com

Introduction: Too rapid correction of hyponatremia leads to serious neurological complications, like osmotic demyelination syndrome (ODS). Imaging shows features of pontine myelinolysis, sometimes isolated and associated with extrapontine myelinolysis. Isolated extrapontine myelinolysis is extremely rare. Aim and Objectives: We describe a case of ODS with unusual radiological findings. Case Report: A 53-year-old female was brought to the emergency services with vomiting and altered sensorium. Patient had profound hyponatremia (110 meq/l). Correction was done with slow intravenous infusion of 3% NaCl. However, unmonitored oral administration of salt led to overcorrection with serum sodium of 150 meq/l. She developed quadriplegia, depressed level of consciousness and respiratory failure and required ventilatory support. MRI brain showed features of isolated extrapontine myelinolysis.

Key words: Osmotic demyelination syndrome, hyponatremia, MRI

Multiple endocrine neoplasia 4

T. S. Karthik, Ponnala A. Reddy, N. Rajendra Prasad, Mithun Chakravarthy, Faizal Ahmed

Department of Endocrinology, Narayana Medical College and Hospital, Chinthareddy Palem, Nellore, India

Corresponding Author: Dr. Ponnala A. Reddy, Department of Endocrinology, Narayana Medical College and Hospital, Chinthareddy Palem, Nellore, Andhra Pradesh, India. E-mail: amareshreddy7@gmail.com

Introduction: Identification of heterozygous germ-line mutations in the human CDKN1B in patients with multiple endocrine tumors leads to the identification of multiple endocrine neoplasia (MEN) 4 caused due to mutations in p27. Background: We are presenting a case of MEN 4 who presented with pituitary macroadenoma, primary hyperparathyroidism. Case Report: A 37-year-old male patient presented with a history of erectile dysfunction and recurrent headaches on and off, and no history of vomiting, or visual abnormalities. His elder sister died because of brain tumor. Serum prolactin initially was >200 ng/ml and after serial dilutions, it was 6096 ng/ml. MRI brain revealed a lobulated solid mass lesion involving the pituitary stalk extending into the right cavernous sinus and encasing the right internal carotid artery and displacing the optic chiasma. His serum calcium was 10.9 mg/dl and parathyroid hormone was 245.5 pg/ml. Ultrasound thyroid revealed a well-defined hyper echoic lesion posterior to the left lobe of thyroid and ill-defined hyper echoic heterogenous lesion in the inferior polar region of the left lobe of thyroid. His thyroid profile, 8 am cortisol, follicle stimulating hormone (FSH), growth hormone hemodynamics were normal at the initial presentation. He gave history of renal stone disease during the past. On family screening of his three younger sisters one had hyperparathyroidism, one had hyperprolactinemia and one had both. Conclusion: In view of presence only hyperparathyroidism, pituitary tumors without pancreatic tumors, and strong family history possibility of MEN 4 was kept.

Key words: Pituitary macradenoma, primary hyperparathyroidism, MEN4

A rare case: Insulin autoantibody syndrome presenting with hyperinsulinemic hypogylycemia

T. S. Karthik, Ponnala A. Reddy, N. Rajendra Prasad, Mithun Chakravarthy, Faizal Ahmed

Department of Endocrinology, Narayana Medical College and Hospital, Chinthareddy Palem, Nellore, Andhra Pradesh, India

Corresponding Author: Dr. Ponnala A. Reddy, Narayana Medical College and Hospital, Chinthareddy Palem, Nellore, Andhra Pradesh, India. E-mail: amareshreddy7@gmail.com

Introduction: Autoimmune hypoglycemia is a rare cause of hyper-insulinemic hypoglycemia. Background: We report a case of 60-year-old male, non-diabetic patient who presented with insulin autoantibody syndrome. Case Report: A 60-year-old male patient admitted to our hospital with a history of recurrent episodes of sweating, giddiness, and seizures since 7 days, which was corrected after taking sugar water. The patient documented sugars of 64 mg% and 24 mg% on 2 separate days, during the attacks. There was no history of diabetes mellitus. He is a known case of hypertension and cerebrovascular accident with right hemiparesis with history of use of telmisartan and amlodepin. History of repeated use of aceclofenac with paracetamol for body aches in the past 6 months. There was no history of hepatic or renal dysfunction. The patient was initiated on 72 h extended fasting test to induce hypoglycemia. Within 4 h after initiation of the fast, patient developed hypoglycemia (25 mg/dl). During hypoglycemia, he had serum insulin of 300 μu/ml, and insulin antibody titer of 256.2 units (Normal range <18 units/ml). The patient was having normal cortisol, euthyroid, and had normal hepatic and renal functions. Conclusion: Insulin autoantibody syndrome is a rare condition characterized by antibodies directed against insulin, bind with insulin, and release insulin inappropriately when substrate (glucose) levels are normal. Many drugs have been implicated in the occurrence of this rare condition. In our case, the use of NSAIDs would have been the probable cause for the antibodies.

Key words: Insulin autoantibody syndrome, hyperinsulinemia, hypoglycemia

INSULINOMA in MEN-1

Mahesh D. M., Nihal Thomas, Asha H. S., Nitin Kapoor, Renu George1, M. J. Paul2, Philip Joseph3, Nylla Shanthly4, Anuradha C.5

Departments of Endocrinology, Diabetes and Metabolism, 1Dermatology, 2Endocrine Surgery, 3Hepatobiliary and Pancreatic Surgery, 4Nuclear Medicine, and 5Radiology, Christian Medical College, Vellore, Tamil Nadu, India

Corresponding Author: Dr. Mahesh D. M., Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore – 632 004, Tamil Nadu, India. E-mail: maheshdmendo@gmail.com

Introduction: Insulinomas are rare tumours with an annual incidence of 1 to 4 per million persons[1] and about 10% of them have multiple endocrine neoplasia-1 (MEN-1).[2] About 70-80% of insulinomas in MEN-1 are multiple[2] with a 21% recurrence rate.[1] Hence it is important to undertake a thorough preoperative and intraoperative screening to avoid incomplete surgeries. Objective: Profile the patients of Insulinoma with MEN-1 in a tertiary care centre. Materials and Methods: Clinical, biochemical and radiological data of all the patients diagnosed to have Insulinoma with MEN-1 from May-2011 to April 2012 was analysed. Results: There were 2 male and 1 female patients. The average duration of symptoms was 6 years and 2 had neuroglycopenic symptoms. Insulinoma was localized in all patients with MRI abdomen and endoscopic ultrasonography. All had double lesions with recurrence in one patient. All had hyperparathyroidism, 2 had pituitary tumours among which 1 patient had a microprolactinoma and the other had acromegaly with associated thymic carcinoid, gastrinoma with liver metastasis, and non-functioning adrenal adenoma, 2 patients had collagenomas. Two were sporadic and 1 was familial with 3 family members having hyperparathyroidism. Two patients underwent excision successfully and the third patient deferred surgical intervention. Conclusion: Screening for MEN-1 should be done in all patients with Insulinoma. Collagenomas are an important clue to MEN-1. Management of insulinoma in MEN-1 is a challenge in view of the multicentricity and increased risk of recurrence.

References

  • 1.Service FJ, McMahon MM, O’Brien PC, Ballard DJ. Functioning insulinoma-incidence, recurrence, and long-term survival of patients: A 60-year study. Mayo Clin Proc. 1991;66:711–9. doi: 10.1016/s0025-6196(12)62083-7. [DOI] [PubMed] [Google Scholar]
  • 2.Finlayson E, Clark OH. Surgical treatment of insulinomas. Surg Clin N Am. 2004;84:775–85. doi: 10.1016/j.suc.2004.02.004. [DOI] [PubMed] [Google Scholar]
Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S514–S524.

Bone & Mineral Metabolism

Recurrent bilateral nephrolithiasis as a presentation for distal renal tubular acidosis

Madhukar Mittal, Praveen Jha, Neha Jain, Apul Goel1

Department of Medicine, Endocrine Unit, KGMU, Lucknow, 1Urology, KGMU, Lucknow, UP, India

Corresponding Author: Dr. Madhukar Mittal, Department of Medicine, Endocrine Unit, KGMU, Lucknow, India. E-mail: mittalspace@gmail.com

Introduction: Renal tubular acidosis (RTA) has various clinical presentations including short stature, metabolic bone disease, and nephrolithiasis. Objective: We report three cases of distal RTA (dRTA) presenting at the urology department with bilateral nephrolithiasis who were referred to us for endocrine and metabolic evaluation. Materials and Methods: The patients with recurrent nephrolithiasis were referred to us from the urology department. Serum electrolytes, serum calcium, phosphorus, magnesium, 25-hydroxyvitamin D [25(OH)D], and parathyroid hormone (PTH) were measured. Urinary tract infection was ruled out or treated before testing for urinary pH and 24-hour urinary metabolic profile (for citrate, oxalate, magnesium, and calcium). Results: Patient 1was a 48-year-old female with a history of two admissions for hypokalemic periodic quadriparesis in 2008 and in 2011. Her ultrasonography (USG) of the abdomen revealed bilateral nephrocalcinosis along with bilateral nephrolithiasis. She was also found to have primary hypothyroidism. Patient 2 was a 40-year-old male who presented at the urology department with complaints of hematuria and reduced urinary stream. On ultrasound, the patient had bilateral nephrolithiasis with nephrocalcinosis and anemia with a hemoglobin level of 8.5 g%. The third patient was younger (26-year-old male), but had similar complaints along with dysuria. All these patients had normal serum creatinine levels. Bicarbonate treatment was given in dosages of 1–3 meq/kg/day (soda mint tablets and bicarbonate-containing syrup) along with potassium chloride. Vitamin D was supplemented in therapeutic doses. Patient 1 was given levothyroxine 62.5 μg/day after which her thyroid functions remained stable and within normal range on follow-up. All three patients have been on regular follow-up in our endocrine clinic and their serum potassium levels are normal. Patient 1(female) discontinued treatment for approximately two months during the course of the treatment. However, with regular bicarbonate treatment, the metabolic acidosis resolved and no progression in nephrocalcinosis was seen [Tables 1 and 2]. Conclusion: dRTA is an important cause for recurrent nephrolithiasis. Hypokalemic periodic paralysis may be associated with dRTA. As patients with nephrolithiasis initially report to urologists or surgeons, a co-ordinated approach involving endocrine and metabolic evaluation is necessary to prevent recurrent stone formation and a consequent need for future surgical intervention.

Table 1.

Biochemical and radiological parameters

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Table 2.

Ammonium chloride loading test confirmed the diagnosis of dRTA

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Key words: Nephrolithiasis, renal tubular acidosis, parathyroid hormone

Articles from Indian Journal of Endocrinology and Metabolism are provided here courtesy of Wolters Kluwer -- Medknow Publications

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