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Objectives: To study the clinical and genotypic spectrum of patients with HNF-1ß deletions (MODY 5) at a tertiary care hospital., Methods: This study included four patients from the Department of Endocrinology at Sher-i-Kashmir Institute of Medical Sciences Srinagar with a strong clinical suspicion of MODY 5. Genetic analysis, including a monogenic gene panel comprising 78 genes associated with MODY and other similar forms of monogenic diabetes, was done. Dosage analysis of HNF 1B by Multiplex Ligand-dependent Probe Amplification (MLPA) was performed., Results: The mean age of patients was 22.25 years with a male-to-female ratio of 3:1. Associated phenotypic features included neurodevelopmental disorder in all four patients, insulin resistance in two patients (2/4) and alopecia in three patients (3/4). One patient had clinical and biochemical hyperandrogenism. All patients had renal malformations, and one patient had a Mullerian anomaly. Family history was present in 1 patient. All patients had pancreatic abnormalities, the most common type being dorsal agenesis of the pancreas (3/4), followed by annular pancreas (1/4). All patients had a genetic deletion of the gene HNF1B on chromosome 17 with a deletion interval of (?_37686431)_(37745059_?), (?_37687281)-(37744884_?), comprising exons 1 to 9., Conclusions: It is imperative to maintain a high index of suspicion for MODY 5 in patients presenting with renal anomalies and diabetes, even in the absence of a family history. Early identification allows for screening family members and ensures a comprehensive approach to identifying and managing other abnormalities in these patients., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Spondyloocular syndrome (SOS) is a rare autosomal recessive skeletal and ocular disorder with variable phenotypes. It is caused by pathogenic mutation in the XYLT2 gene, which encodes the enzyme xylo-transferase, necessary for the synthesis of proteoglycan. It is characterized by generalized osteoporosis, short stature, hearing impairment, eye abnormalities, and cardiac defects. Till date only 24 cases have been reported worldwide with no cases documented from India. We subjected the patient to relevant biochemical investigations and Dual Energy X-ray Absorptiometry (DEXA) scan along with Next Generation Clinical Exome Sequencing (NGCES). We report a case of 23-year-old male who presented with recurrent long bone fractures, congenital heart defects, eye abnormalities (bilateral corneal opacities and atrophic bulbi), and short stature. In addition, our patient also had genu valgum and right-sided hydrocele which have never been reported in SOS till date. On genetic analysis, NGCES revealed a novel pathogenic frameshift variant c.191_192 delCA, p.(Thr64fs*22) in the XYLT2 gene. The patient is doing well on six monthly zoledronic acid infusions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: To present the clinical data, investigative profile, management, and follow-up of patients with 46, XY gonadal dysgenesis with germ cell tumors from the endocrine unit of a tertiary care university hospital., Materials and Methods: This retrospective study included 3 cases of 46, XY gonadal dysgenesis with germ cell tumors evaluated and managed at the Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, over a period of 13 years from (September 2008 to December 2021)., Results: Over a period of 13 years, we diagnosed and managed 7 patients with 46, XY gonadal dysgenesis. This included 4 patients with pure gonadal dysgenesis (PGD; Swyer syndrome), 2 patients with mixed gonadal dysgenesis (MGD), and one patient with partial gonadal dysgenesis. Out of these 7 patients, three patients developed germ cell tumors, one patient with MGD, and two patients with pure PGD (Swyer syndrome). In all three patients, germ cell tumor was the first presentation of DSD. The patient with MGD presented with primary amenorrhea and virilization, while the two patients with PGD presented as phenotypic females with primary amenorrhea and pelvic mass. All three patients developed seminomatous cancers. Patient with MGD developed seminoma and the two patients with PGD (Swyer syndrome) developed dysgerminoma. The patients were managed with bilateral gonadectomy with removal of the tumor. In addition, the 2 patients with PGD (Swyer syndrome) received combined chemotherapy. On a follow up ranging from 1 to 10 years, all three patients are disease free., Conclusions: we conclude that germ cell tumors may be the first presentation of 46, XY gonadal dysgenesis. In all phenotypic females with primary amenorrhea and dysgerminoma, karyotype is a must to uncover the diagnosis of PGD. In addition virilization may be clue to the presence of germ cell tumor in a patient with 46, XY gonadal dysgenesis., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North India to study the clinical and biochemical features and surgical outcomes in the present era. Study design This is a cross-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus, alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were used for preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgery for complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1. The mean eGFR of patients was 99.1±30.87 ml/min, with 55 (53.4%) of them having renal disease. Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively. Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively. Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most common type was right inferior parathyroid adenoma, present in 45 cases (43.7%), followed by left inferior parathyroid adenoma in 31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countries like India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Misgar et al.)

Background and objective Individuals with prolactinoma exhibit elevated rates of obesity, metabolic syndrome (MS), and dyslipidemia compared to their healthy counterparts. However, there is a lack of data regarding metabolic variance between male and female prolactinoma patients. Consequently, this study aimed to investigate and compare sex-specific discrepancies in metabolic abnormalities among individuals diagnosed with prolactinoma. Methods In this prospective study, 80 treatment-naïve patients with prolactinoma (12 males and 68 females) underwent clinical assessments and laboratory investigations. The measured parameters included blood glucose, total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), urea, creatinine, uric acid, and blood glucose levels. The patients were treated with cabergoline, a dopamine agonist, and reevaluated after 12 weeks. Results Forty-eight patients had microprolactinomas (all females), and 32 had macroprolactinomas (20 females, 12 males). The mean age was 28.30±7.49 years for females and 28.91±7.12 years for males (p=0.71). The median symptom duration was 12 months (range 1-72 months, IQR 4-16 months), with no significant difference between males (median 12 months, IQR 5-54 months) and females (median 12 months, IQR 10-24 months, p=0.620). The median serum prolactin (PRL) was 988 ng/mL (IQR 471-1,439) in males and 165 ng/mL (IQR 90-425) in females (p<0.05). Males showed higher HbA1c, BGF, TC, TG, LDL-C, and higher rates of obesity, MS, and diabetes mellitus. Treatment with cabergoline resulted in significant improvements in the HbA1c, BGF, TC, TG, and LDL-C levels. Conclusion Males with prolactinomas had larger tumor sizes and higher serum PRL levels than females. Additionally, males exhibited worse metabolic parameters than females. However, there was no significant difference in the duration of symptoms or age at diagnosis between the two groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Baba et al.)

Background: Hyperprolactinemia is associated with obesity, dyslipidemia, insulin resistance, and low-grade inflammation which may promote endothelial dysfunction (EnD). Limited work has been done on EnD in prolactinomas and we, therefore, studied serum markers of inflammation and EnD in patients with prolactinomas before and after treatment with dopamine agonists., Methodology: Fifty-six treatment naïve patients with prolactinomas and fifty-three (apparently healthy age and sex-matched) controls were enrolled in the study and subjected to clinical assessment and laboratory investigations including blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urea, creatinine, uric acid, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hsCRP) and markers of EnD i.e., intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Patients were treated with a dopamine agonist (cabergoline) and parameters (like ESR, hsCRP, ICAM-1, and VCAM-1) were measured at 12 weeks., Results: The majority of the patients (84%) were female, more than half (52%) had metabolic syndrome and over a third (36%) were obese. Blood glucose fasting, HbA1c, lipid fractions, ESR, hsCRP, ICAM-1, and VCAM-1 were significantly higher in patients than in controls. Median ICAM-1 was 1331.95 ng/ml (IQR 803.43-1825.99) in patients vs 753.04 ng/ml (IQR 402.04-871.55) in controls, P < 0.001 and median VCAM-1in patients was 971.35 ng/ml (IQR 695.03-1285.23) as against 634.56 ng/ml (IQR 177.49-946.50) in controls, p 0.001. Serum ICAM-1 and VCAM-1 correlated positively with hsCRP. On multivariate regression analysis, serum hsCRP was the only significant predictor of change in ICAM-1 and VCAM-1. Normalization of serum PRL with CAB resulted in a significant decrease in metabolic parameters, ESR, hsCRP, ICAM-1, and VCAM-1., Conclusion: Hyperprolactinemia because of prolactinoma is associated with EnD secondary to systemic inflammation and metabolic abnormalities which improve after treatment with DA., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

Vitamin D (VD) deficiency (serum 25 hydroxy vitamin D (25(OH)D) concentration of < 20 ng/ml), in endemic proportions, demands a supplementation strategy with optimal dosing regimens. A randomised parallel-group, active-controlled trial was conducted among apparently healthy, VD-deficient subjects, aged 18-60 years who received 600 μg/d (Group A), 1000 μg/d (Group B), 2000 μg/d (Group C) and 60 000 μg/month (Group D) of oral cholecalciferol. The intervention was carried in two phases (I and II) of 12 weeks each, with same dose, separated by a washout phase of 12 weeks. Serum 25(OH)D, intact parathyroid hormones (iPTH), Ca, phosphorous (PO4), alkaline phosphatase (ALP) and spot urine Ca/Cr were measured at baseline, 12, 24 and 36 weeks following the intervention, and adverse events were recorded at each occurrence and at 12, 24 and 36 weeks. A statistically significant time-group interaction was found in serum 25(OH)D concentration ( P < 0·05). Serum 25(OH)D concentration increased significantly from baseline to 12 weeks ( P < 0·05) in all the groups with no change at 24 weeks but further increase at 36 weeks ( P < 0·05). At the end of the study, Group C had maximum increment in serum 25(OH)D concentration, while as Groups C and D (95 %, and 90 %) had higher proportion of subjects VD sufficient than Groups A and B (65 % and 78 %) ( P < 0·05). No significant time-dose interactions were observed in serum iPTH, Ca, PO4 and ALP or urine Ca/Cr ratio. Three subjects (two in Group C and one in Group D) developed transient hypercalciuria. Supplementation with daily 2000 μg or monthly 60 000 μg of oral cholecalciferol among adults seems optimal and safe.

Objective: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10-year probability of cardiovascular (CV) events in SS patients., Design: Case-control study Sixty-three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity-matched controls., Measurements: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16-row multislice computed tomography scanner., Results: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi-Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294)., Conclusion: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD., (© 2022 John Wiley & Sons Ltd.)

Background: This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls., Methods: This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined., Results: The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls ( P < 0.001). There was no significant difference in levels of T4 ( P = 0.83) and TSH ( P = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls ( P = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls., Conclusion: We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Endocrinology and Metabolism.)

Background: Maturity onset diabetes of young (MODY) is considered to be the most underdiagnosed condition. The correct diagnosis of MODY has a definite bearing on the outcome and clinical course of the disease. We aim to determine the prevalence and clinical profile of MODY among young diabetic patients attending at Department of Endocrinology, a tertiary care institute in North India., Methods: It was a cross-sectional study involving all consecutive consenting patients with diabetes and age of onset ≤35 years. A total of 1,094 patients were included in this study, of whom 858 were having age of onset of diabetes <25 years. All patients were screened for MODY using clinical criteria and MODY Probability calculator (available on diabetesgenes.org). Patients with high clinical probability of MODY having negative anti-GAD65 antibody and fasting serum C-peptide levels >0.6 ng/mL were subjected to the Ala98 Val polymorphism (SNP) in hepatocyte nuclear factor (HNF) 1a gene., Results: The prevalence of MODY among the study cohort as per clinical criteria was found to be 7.7%. Males constituted the majority of patients (male vs female, 56% vs. 44%; P < 0.001). The patients with MODY were younger ( p < 0.001), leaner ( p < 0.001), had younger age at onset of diabetes mellitus ( p < 0.001), and lower frequency of features of insulin resistance in the form of skin tags and acanthosis nigricans. Among the 40 patients who were subjected to Ala98Val polymorphism of HNF1α gene (MODY 3), the mutant genotype was seen in 20 (50%) patients., Conclusion: We report a higher prevalence of MODY in our young diabetic patients. A high index of suspicion is required to diagnose MODY as misdiagnosis and inappropriate treatment may have a significant impact on quality-of-life (QOL) with increased cost and unnecessary treatment with insulin., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

Neonatal severe hyperparathyroidism is a rare disorder arising from inherited defects in the calcium sensing receptor (CaSR) that presents early in life with severe hypercalcemia, failure to thrive, and developmental retardation. The authors describe an infant with neonatal severe hyperparathyroidism due to homozygous CaSR gene mutation presenting with recurrent episodes of severe hypercalcemia, growth retardation, and developmental delay. Medical management served as an effective bridge therapy to surgery. Total parathyroidectomy with right hemithyroidectomy was performed at 7 mo of age and resulted in successful cure and normalization of growth and developmental milestones. Timely medical and surgical management can help prevent mortality and morbidity in the form of neurodevelopmental sequelae. Life-long monitoring and treatment is mandatory for the resultant hypoparathyroidism., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Competing Interests: There are no conflicts of interest.

Purpose: Studies on cardiac structural and functional abnormalities in primary hyperparathyroidism (PHPT) have yielded conflicting and inconsistent results. In this prospective case-control study, we sought to compare cardiac structure and function in symptomatic PHPT patients and controls., Methods: One hundred consecutive symptomatic PHPT patients and 113 matched controls underwent echocardiographic evaluation by the same operator., Results: Left ventricular mass index (LVMI) was significantly higher in patients as compared to controls, (median of 90.95 g/m 2 vs 86.5 g/m 2 , p = 0.041). Patients had significantly lower early trans-mitral diastolic flow (E velocity) as compared to controls (57.13 ± 14.88 vs 64.76 ± 15.45 cm/s, p < 0.001). Patients also had significantly lower early to late mitral annular velocity (E/A) as compared to controls (0.98 ± 0.37 vs 1.10 ± 0.34, p 0.013). Patients had higher frequency of aortic valve calcification (29% vs 2.65%, p < 0.001), mitral annular calcification (23% vs. 4.42%, p < 0.001), myocardial and septal calcifications (25% vs none, p < 0.001) as compared to controls. Serum PTH, calcium and uric acid significantly correlated with calcifications. Serum calcium showed a negative correlation with E/A ratio., Conclusions: Symptomatic patients with PHPT have substantial cardiac structural and functional abnormalities. These abnormalities include elevated LVMI, diastolic dysfunction, and aortic valve, mitral annular, septal and myocardial calcifications. We strongly suggest and conclude that the evaluation of PHPT patients should not only include traditional end organs like bones and kidneys but also the cardiovascular system in the form of echocardiography to detect subclinical cardiac dysfunction so that the cardiovascular health of such patients can be optimized., (© 2021. Italian Society of Endocrinology (SIE).)

Purpose: The true association between primary hyperparathyroidism (PHPT) and pancreatitis continues to be controversial. In this study, we present clinical data, investigative profile, management and follow-up of PHPT patients with pancreatitis and compare this group with PHPT patients without pancreatitis., Methods: Records of 242 patients with PHPT managed at our center over 24 years were retrospectively analyzed for demographic and laboratory data. The diagnosis of pancreatitis was entertained in the presence of at least two of the three following features: abdominal pain, levels of serum amylase greater than three times the normal or characteristic features at imaging., Results: Fifteen (6.19%) of the 242 consecutive patients with PHPT had had pancreatitis. Fourteen patients (93.3%) had acute pancreatitis (AP), while one patient had chronic calcific pancreatitis. Over half (8 of 14) of the patients with AP had at least two episodes of pancreatitis. Pancreatitis was the presenting symptom in 14 (93.3%) patients. None of the pancreatitis cases had additional risk factors for pancreatitis. PHPT patients with pancreatitis had significantly higher serum calcium and ALP than PHPT patients without pancreatitis. After successful parathyroidectomy, 14 patients had no further attacks of pancreatitis during a median follow-up of 16 months (range 2-41 months), while recurrence of pancreatitis was seen in one patient., Conclusions: We conclude that pancreatitis can be the only presenting complaint of PHPT. Our study highlights the importance of fully investigating for PHPT in any pancreatitis patient with high normal or raised serum calcium level, especially in the absence of other common causes of pancreatitis.

Graves' disease (GD) is the commonest cause of hyperthyroidism in populations with adequate iodine intake. It results from an abnormality in the immune system, which produces unique antibodies causing over production of thyroid hormones and glandular hyperplasia in individuals with genetic susceptibility. The Cytotoxic Lymphocyte Associated Antigen-4 (CTLA4) gene product serves the important function of immunomodulation, thereby helping in maintenance of peripheral self-tolerance. Studies on the association of the CTLA4 SNPs with GD have shown variations in the results from different populations. Since no such study has been carried out in ethnic Kashmiri population, we aimed to study a possible association of the CTLA4 SNPs (+49 A/G, -318C/T, CT 60 A/G and -1661 A/G) with GD. A total of 285 individuals (135 patients with GD and 150 healthy individuals) were genotyped using PCR-RFLP method and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for + 49 A/G SNP (p=<0.001; OR = 5.14; CI = 2.17-12.19) and CT 60 A/G SNP (p = < 0.001; OR = 6.9; CI = 2.8-16.6), while -318C/T and -1661 A/G SNPs showed no significant association. We also studied the mRNA expression of the CTLA4 in patients with GD and healthy individuals by Real-Time PCR and found a decreased expression of the CTLA4 mRNA in PBMCs of patients with GD as compared to healthy controls with a -3.71-fold change. We conclude that the CTLA4 + 49 A/G and CT 60 A/G SNPs have a significant association with the risk of GD development in Kashmiri population and CTLA4 mRNA expression is significantly decreased in GD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was 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., Subjects and Methods: We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake., Results: Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%., Conclusion: Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.

Background: Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes, described from several tropical countries, including India. We described the existence of this entity in the subtropical region-the Kashmir valley of the Indian subcontinent and compared the clinical characteristics of these patients with type 2 diabetes mellitus (T2DM) patients., Aim: The present study aimed to compare the clinical characteristics of patients with FCPD and those with T2DM to identify the characteristics distinctive of FCPD., Materials and Methods: A total of 124 patients with FCPD were compared with 124 patients with T2DM matched for age and duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular complications in both groups., Results: FCPD patients had significantly lower serum cholesterol, serum triglyceride, and serum calcium levels but higher glycosylated hemoglobin levels compared to T2DM patients. FCPD participants were significantly leaner. The prevalence of retinopathy, neuropathy, and nephropathy was similar between the two. Five T2DM patients had documented cardiovascular disease compared to one in FCPD patients ( P < 0.05). Multiple logistic regression analysis revealed glycosylated hemoglobin and duration of diabetes to be significantly associated with retinopathy and nephropathy in T2DM. Among FCPD patients, glycosylated hemoglobin showed a strong association with retinopathy as well as nephropathy. BMI showed a significant negative association with nephropathy in FCPD patients. Age and age at onset showed a strong association with neuropathy in FCPD patients while the duration of diabetes showed the association with neuropathy ( P = 0.015) in T2DM., Conclusion: There are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Endocrinology and Metabolism.)

Purpose: To present the clinical data, investigative profile, and management of patients with disorders of sex development (DSD) from the endocrine unit of a tertiary care university hospital., Materials and Methods: This retrospective study included 73 cases of DSD, evaluated and managed at Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, over a period of 10 years from September 2008 to August 2018., Results: Twenty-nine patients (39.7%) had 46 XY DSD and twenty-nine patients (39.7%) had 46 XX. Sex chromosome DSD was diagnosed in 15 (20.5%) patients. Of 29 patients with 46 XY DSD, 17 (58.6%) had 5α-reductase type-2 deficiency (5α-RD) and 6 (20.7%) had complete androgen insensitivity syndrome. In our patients with 5α-RD, the history of consanguinity was documented in nine (52.9%) patients. Two patients had testosterone biosynthetic defect and one patient had partial androgen insensitivity syndrome. Of 29 patients with 46 XX DSD, 16 (55.1%) had congenital adrenal hyperplasia (CAH). Of 15 patients with sex chromosome DSD, 7 patients had Turner's syndrome, 7 had Klinefelter's syndrome, and 1 patient had mixed gonadal dysgenesis., Conclusion: In our study, equal number of patients had 46 XY DSD and 46 XX DSD. We are for the first time reporting from India that the most common cause of 46 XY DSD is 5α-RD, whereas CAH is the most common cause of 46 XX DSD as reported previously., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Endocrinology and Metabolism.)

Introduction: The management of acromegaly, a rare and potentially curable disease, has undergone a paradigm shift in the past few decades. Many of the treatment modalities recommended for acromegaly are either too expensive or not available in many parts of India. There is a dearth of treatment and outcome data in Indian patients., Aim: Our aim was to study the clinical presentation, hormonal profile, radiology, management, and outcome of the disease at our center., Materials and Methods: Fifty one patients with acromegaly who attended the Department of Endocrinology, SKIMS, Srinagar, between October 2015 and April 2017, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, and outcome were evaluated., Results: The gender distribution was equal with the mean age of 42.3 ± 10.9 years at diagnosis. The majority (41) of the patients had macroadenoma. The most common presenting manifestations were acral enlargement and headache. Hypertension was present in 23, musculoskeletal manifestations in 19, and diabetes mellitus in 11 patients. Surgery was the most common method of treatment. Preoperatively only one patient with micro-adenoma had hypocortisolism, which was persistent in postoperative period, while no patient had preoperative or postoperative hypothyroidism or hypogonadism. As per the present consensus criteria, 23.7% patients achieved disease control (40% with microadenoma and only 19.5% with macroadenoma). The surgical complications occurred in 5 patients-CSF leak in 3 meningitis in 2 patients all except one having macroadenoma., Conclusions: The presentation of disease was generally comparable to that reported in literature. Cure rates were significantly lower than those reported from many large centers., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Endocrinology and Metabolism.)

Background: Vitamin D toxicity (VDT), a "not uncommon" cause of hypercalcemia, can be life-threatening and cause substantial morbidity, if not treated promptly., Aims: To describe presentation, management, and outcome in 32 patients with VDT diagnosed over 3 years., Materials and Methods: Patients presenting with VDT at a tertiary care centre in Srinagar Kashmir India were included. Evaluation included detailed history and biochemical tests including serum calcium, phosphate, creatinine, intact parathyroid hormone (iPTH), 25-hydroxy Vitamin D (25-OHD), and 24-hour urinary calcium., Results: The clinical manifestations of the 32 patients (median age 65; range 3-77 years) included gastrointestinal symptoms (constipation and vomiting), polyuria/polydipsia, altered sensorium, pancreatitis, acute kidney injury, and nephrocalcinosis. The median total serum calcium level was 13.95 (range 11.10-17.20) mg/dl and median 25-OHD level was 306 (range 105-2800) ng/ml. All patients had suppressed or low normal iPTH and hypercalciuria and 78% had azotemia. All patients had received multiple intramuscular injections of vitamin D 3 . The median cumulative dose was 4,200,000 (range, 1,800,000-30,000,000) IU. The median time to resolution of hypercalcemia was 7 months (range 4-18 months)., Conclusion: We conclude that VDT is an increasingly common cause of symptomatic hypercalcemia. VDT needs prolonged follow up as it takes months to abate its toxicity. Enhancing awareness among general practitioners regarding the toxicity resulting from high doses of vitamin D is the key to prevent VDT. We suggest that VDT be considered in patients, especially the elderly, presenting with polyuria, polydispsia, vomiting, azotemia, or encephalopathy., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Endocrinology and Metabolism.)

Isolated FSH deficiency due to mutations in the gene for β-subunit of FSH is an extremely rare autosomal recessive disease of which only eleven cases have been reported so far. The clinical features include absent breast development and primary amenorrhea in females and azoospermia with normal testosterone levels in males. In this study we report two Kashmiri sisters born to native Kashmiri consanguineous parents with failure of onset of puberty. Hormonal evaluation revealed undetectable serum FSH and estradiol and high LH. Genetic analysis of FSH β-gene identified one nonsense mutation (c.343C > T:p. Arg115Stop) in exon 3. The two sisters were homozygous for this nonsense mutation while the parents were heterozygous. Incorporation of a stop codon at 115 codon position is predicted to result in the formation of truncated FSH β protein, lacking 14 amino acid from the carboxy-terminus (p.Arg115Stop). Very recently, this same mutation was reported for the first time in a Chinese male. Ours is the first ever report of any FSH β-subunit mutation from the Indian sub-continent and this particular mutation in any female from anywhere in the world. We conclude and emphasize that this diagnosis should be considered in girls with delayed puberty and selective deficiency of FSH.

Background: Nephrolithiasis is a common complication of primary hyperparathyroidism (PHPT), and in a subgroup of patients stones are clinically silent. Patients with silent and symptomatic stones may differ biochemically. There is a scarcity of data available comparing patients with silent and symptomatic renal stones in PHPT., Aims: To characterize patients with PHPT with nephrolithiais and to compare patients with silent and symptomatic stones., Materials and Methods: We reviewed clinical data of 186 patients with PHPT managed at our center from January 1996 to December 2017. Silent renal stones were defined as ultrasonography finding of renal stones without symptoms. Symptomatic renal stones were defined as those with symptoms or a history of graveluria or any procedure for nephrolithiasis. A 5-mm diameter was set as the cut-off between micro- and macrolithiasis. We compared those with ( n = 95) and without ( n = 91) stones, and, among stone formers, those with symptoms ( n = 66) and silent ( n = 29) were compared., Results: There was no significant difference between stone formers and nonstone formers with respect to biochemical parameters. Patients with silent renal stones had significantly lower serum calcium and higher phosphate, than those with symptomatic stones. Most (75%) patients with silent renal stones had microlithiais, while only a fifth (22%) with symptomatic renal stones had microlithiasis., Conclusion: Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones had microlithiasis and biochemical features of less severe disease. Patients with silent renal stones may represent early mild stage of PHPT., Competing Interests: There are no conflicts of interest.

Hereditary distal renal tubular acidosis (dRTA) is a rare genetic disease that is caused by mutations in SLC4A1, ATP6V1B1, or ATP6V0A4. However, there are many families with hereditary dRTA in whom the disease-causing genes are unknown. Accordingly, we performed whole exome sequencing and genetic studies of the members of a family with autosomal recessive dRTA of an unknown genetic etiology. Here, we report compound heterozygous pathogenic variations in tryptophan-aspartate repeat domain 72 (WDR72) (c.1777A>G [p.R593G] and c.2522T>A [p.L841Q]) in three affected siblings of a family with dRTA. Both variants segregated with dRTA in the family and were not observed in normal control subjects. Homologous modeling and in silico mutagenesis indicated that R593G and L841Q alter the H-bond formations in the nearby residues, affecting the WDR72 protein structure. All these evidences indicate that the identified WDR72 variations were probably to have caused hereditary dRTA in the reported family. In addition, homozygous nonsense mutation (c.2686C>T [p.R896X]) was identified in another family, strongly supporting the causal role of WDR72 in dRTA. Based on our literature review, WDR72 mutations associated with dRTA have not been previously described. This is the first identification of pathogenic variations in WDR72 as a cause of hereditary dRTA., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Graves' disease is a multifactorial autoimmune disorder of the thyroid gland, with some extra-thyroidal complications like eye and skin abnormalities in some patients. GD is more prevalent in women than men and is the leading cause of hyperthyroidism worldwide. A complex interaction between genetic and environmental factors is the proposed cause which triggers immune system to produce autoantibodies stimulating the TSH receptor, leading to clinical manifestations such as hyperthyroidism, diffuse thyroid enlargement (goiter) and often ophthalmopathy in affected individuals. Various Single nucleotide gene polymorphisms (SNPs) have been associated with the risk of GD development including promoter SNPs in Forkhead Box P3 (FOXP3). FOXP3 is an important regulatory factor for T cell development and differentiation and therefore has a prominent role in suppression of autoimmune reactions which may lead to predisposition of GD. There have been some studies on the association of FOXP3 SNPs with GD, but no such investigation has been carried out in ethnic Kashmiri population. So, we aimed to study a possible association of FOXP3 promoter SNPs (-3279C/A, -2383C/T & -3499 A/G) with GD. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to genotype 285 individuals (135 GD cases and 150 healthy controls) and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for -3279C/A SNP [OR, 3.48; 95% CI (2.05-5.92); P < 0.001] and -2383C/T SNP [OR, 5.62; 95% CI (2.43-13.00); P < 0.001], while no significant association was seen in case of -3499 A/G SNP. We conclude that -3279C/A and -2383C/T SNPs have a highly significant association with the risk of GD development in Kashmiri population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Graves' disease (GD) is a multifactorial autoimmune disease with contribution from both genetic and epigenetic factors in its causation. Association of genetic factors and GD has been extensively studied. Gene "protein tyrosine phosphatase nonreceptor 22" ( PTPN22 ) is an important immunoregulatory gene preventing hyper responsiveness of T cells by negatively regulating their signal transduction. Association of single-nucleotide polymorphism (SNP) 1858 C/T within PTPN22 with some autoimmune diseases has been described., Methods: We aimed to analyze whether 1858 C/T SNP of PTPN22 gene has any association with GD in Kashmiri population. Polymerase chain reaction-restriction fragment length polymorphism was performed for genotyping 1858 C/T SNP in 135 patients with GD and 150 age- and gender-matched healthy controls., Results: Among the patients with GD, the frequencies of PTPN22 1858 CC, CT, and TT genotypes were 97.7, 2.2, and 0%, respectively, whereas in healthy controls the frequencies of CC, CT genotypes were 100 and 0%, respectively. No significant association was found between PTPN22 1858 C/T SNP and patients with GD., Conclusion: GD is not associated with PTPN22 1858 C/T SNP in Kashmiri population. Furthermore, 1858 C/T SNP in PTPN22 gene could be a part of variation in different ethnic populations across the globe., Competing Interests: There are no conflict of interest.

Purpose: Graves' disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1β has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1β gene promoter region (-511 T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population., Methods: A total of 135 Graves' disease patients and 150 healthy individuals were included in the study. PCR and PCR-based restriction analysis methods were done for IL-1RN VNTR and IL-1β gene polymorphisms respectively., Results: We found statistically significant increased frequencies of the C/C + CT genotype (P = 0.001; odds ratio (OR) = 5.04, 95% confidence interval (CI) = 3.02-8.42) and the C allele (P = 0.001; OR = 3.10, 95% CI = 2.14-4.50) in IL-1β gene promoter polymorphism (rs16944) with GD patients compared to normal controls. Also in the exon 5 (rs1143634), a significant increase in frequency of the C/C homozygous genotype (P = 0.001; OR = 0.18, 95% CI = 0.11-0.30) and C allele (P = 0.001; OR = 0.31, 95% CI = 0.20-0.48) was observed in GD cases as against controls. For IL-1RN VNTR (rs2234663), we didn't observe any significant difference in the allelic and genotypic frequencies between cases and controls., Conclusion: Our findings suggest that both promoter and exon polymorphisms of IL-1β gene have a significant role in the risk of developing GD, whereas IL-1RN VNTR has no association with GD., (Copyright © 2018. Published by Elsevier Inc.)

Objective: Growth retardation is common in children with extrahepatic portal vein obstruction (EHPVO) and growth hormone (GH) resistance may play a dominant role. The aim of this study was to ascertain growth parameters and growth-related hormones in children with EHPVO, comparing with controls and to study the response of shunt surgery on growth parameters., Materials and Methods: The auxological and growth-related hormone profile (GH; insulin-like growth factor binding protein-3 [IGFBP-3] and IGF-1) of thirty children with EHPVO were compared with controls. The effect of shunt surgery on growth parameters in 12 children was also studied., Results: The mean height standard deviation score (HSDS) of cases (-1.797 ± 1.146) was significantly lower than that of controls (-0.036 ± 0.796); the mean weight SDS of cases (-1.258 ± 0.743) was also lower than that of controls (-0.004 ± 0.533). The mean GH level of cases (5.00 ± 6.46 ng/ml) was significantly higher than that of controls (1.78 ± 2.04 ng/ml). The mean IGF-1 level of cases (100.25 ± 35.93 ng/ml) was significantly lower as compared to controls (233.53 ± 115.06 ng/ml) as was the mean IGFBP-3 level (2976.53 ± 1212.82 ng/ml in cases and 5183.28 ± 1531.28 ng/ml in controls). In 12 patients who underwent shunt surgery, growth parameters significantly improved., Conclusions: Marked decrease in weight and height SDSs associated with GH resistance is seen in children with EHPVO, which improves with shunt surgery.

Background: Although primary hyperparathyroidism (PHPT) has become an asymptomatic disease in the West, in India, PHPT is still an uncommonly diagnosed, overtly symptomatic disease with skeletal, muscular, and renal manifestations., Aims: To describe the profile and surgical outcome of 78 consecutive PHPT patients over a period of two decades at a single center., Materials and Methods: All patients who underwent evaluation and surgery for PHPT from January 1996 to December 2015 were included. Evaluation included measurement of serum total calcium, inorganic phosphorus, alkaline phosphatase, intact parathyroid hormone, 25-hydroxy Vitamin D, 24 hour urinary calcium and radiological survey. Ultrasonography neck and technetium-99m sestamibi scan were used for preoperative localization., Results: A total of 78 patients were identified during the two decades of whom 29 patients were studied retrospectively and 49 patients prospectively. Mean age of patients was 44.72 ± 12.46, and male:female ratio was 1:6. The most common presenting features were nephrolithiasis and/or nephrocalcinosis (64.10%), bone pain (44.1%), abdominal pain (39%), constipation (26%), and myopathy (14.10%). Fractures were present only in 10.25%, and brown tumors in 6.41% patients. The cure rate in our series was 96.15%. The mean parathyroid gland weight was 2.05 ± 3.03 g. None of the 41 patients in whom long-term follow-up was available, had recurrence of PHPT., Conclusions: The profile of PHPT is changing with older age at presentation, and emergence of renal stone disease and decline in overt skeletal disease as common presentation. The parathyroid weight in our study resembles that reported from developed countries.

Objective: Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment., Methods: Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state., Results: Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state., Conclusion: Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism., Abbreviations: ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH = postpartum hemorrhage PWd = posterior wall diameter SS = Sheehan syndrome SV = stroke volume T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.

Background: Emphysematous pyelonephritis (EPN) is a necrotizing infection which results in gas within the renal parenchyma, collecting system, or perinephric tissue. A majority of cases occur in patients with diabetes mellitus (DM). In EPN, early aggressive medical treatment may avoid nephrectomy., Aims: The aim of this study was to analyze the characteristics of patients with EPN with respect to patient demographics, clinical presentation, diagnostic investigations, microbiological findings, treatment modality and outcome, and the influence of prognostic factors on the outcome., Materials and Methods: We reviewed the hospital records of 26 patients with EPN for clinical, laboratory, radiological, and microbiological findings, treatments given, and outcome. The severity of EPN was graded as per the Huang classification. We applied the reported prognostic factors to our patients to find out whether these factors correlated with failure of conservative treatment., Results: All the study subjects had DM and all but two of them were females. The majority of our patients (61.5%) had extensive EPN (class 3 or 4) and majority (76.9%) had two or more bad prognostic factors. Escherichia coli was the most common causative organism involved in 50% of our cases. Twenty-three (88.5%) of our patients responded to conservative treatment, two required nephrectomy, and one expired on conservative treatment., Conclusions: In this series of patients with EPN, all had DM, nearly all were women, and E. coli was the most frequently isolated pathogen. Nearly a third of our patients had bilateral disease. Despite the presence of two or more bad prognostic factors and extensive EPN (class 3 or 4) in a majority of our patients, conservative treatment afforded a striking success rate of 88.5%. We recommend early aggressive medical treatment and suggest that nephrectomy should be considered only if patients deteriorate or do not improve on conservative treatment.

Introduction: Though hypoadiponectinemia and leptin resistance have been proposed as potential factors for weight gain in patients with hyperprolactinemia (HPL), the effects of HPL and cabergoline on these adipocyte-derived hormones are not clear. Aims of this study were (i) to assess the alterations of body fat, leptin, and adiponectin in patients with HPL (ii) effect of cabergoline treatment on these parameters., Methods: Nineteen consecutive patients with prolactinoma (median prolactin [PRL] 118.6 (interquartile range: 105.3) μg/L) and 20 controls were studied in a nonrandomized matched prospective design. The controls were age, gender, and body mass index (BMI) matched. Anthropometric data, metabolic variables, leptin, and adiponectin were studied at baseline and 3 and 6 months after cabergoline treatment., Results: Patients with prolactinoma had increased level of fasting plasma glucose (P < 0.001) as compared to age-, gender-, and BMI-matched healthy controls. Estradiol concentration of controls was higher than that of patients (P = 0.018). Patients with prolactinoma had higher levels of leptin (P = 0.027) as compared to healthy controls without a significant difference in adiponectin levels. There was a significant decrease of body weight at 3 months (P = 0.029), with a further decline at 6 months (P < 0.001) of cabergoline therapy. Furthermore, there was a significant decrement of BMI (P < 0.001), waist circumference (P = 0.003), waist-hip ratio (P = 0.03), total body fat (P = 0.003), plasma glucose (P < 0.001), leptin levels (P = 0.013), and an increase in estradiol concentration (P = 0.03) at 6 months of cabergoline treatment., Conclusion: Patients with prolactinoma have adverse metabolic profile compared to matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities.

Allgrove (Triple A) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrimia. It is frequently associated with neurological manifestations like polyneuropathy. Since its first description by Allgrove in 1978, approximately 100 cases have been reported in the literature. Here we report an 18-year-old boy diagnosed as having Allgrove syndrome, with ACTH resistant adrenal insufficiency, achalasia, alacrimia, and severe motor polyneuropathy. Alacrimia was the earliest feature evident at the age of 8 years. He presented with achalasia and adrenal insufficiency at 12 and 18 years respectively and developed neurological symptoms in the form of severe muscle wasting at the age of 15 years. Patients with Allgrove syndrome usually manifest adrenal insufficiency and achalasia during first decade of life. Our patient manifested adrenal insufficiency and achalasia in the second decade and manifested neurological dysfunction before adrenal dysfunction.

Background: Hyperprolactinemia has been associated with changes in body composition and metabolic abnormalities. Normalization of prolactin (PRL) with dopamine agonists has been found to reverse these abnormalities. This study was designed to assess the anthropometric and metabolic alterations associated with prolactinoma and response of these abnormalities to cabergoline treatment., Methods: In a non-randomised matched prospective design, 19 consecutive patients with prolactinoma (median PRL 118.6 (105.3) μg/L) and 20 controls were studied. The controls were age, gender and body mass index (BMI) matched. Anthropometric data and metabolic variables were studied at baseline, 3 and 6 months after cabergoline treatment., Results: Patients with prolactinoma had increased level of fasting plasma glucose (P < .001), LDL-cholesterol (P = .001) and triglycerides (TG) (P = .009) as compared to age, gender and BMI matched healthy controls. There was a significant decrease of body weight at 3 months (P = .029), with a further decline at 6 months (P < .001) of cabergoline therapy. In addition, there was a significant decrement of BMI (P < .001), waist circumference (P = .003), waist-hip ratio (P = .03) and total body fat (P = .003) at 6 months of cabergoline treatment. A significant decline in plasma glucose (P < .001), total cholesterol (P = .009), LDL-cholesterol (P < .001) and TG (P < .001) was seen after 6 months of cabergoline treatment., Conclusions: Patients with prolactinoma have adverse metabolic profile compared with matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities.

Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population., Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were randomized to receive in addition to standard lifestyle measures, either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly (n = 69) or no Vitamin D (n = 68). Fasting plasma glucose (FPG), 2-h plasma glucose and A1C levels were estimated at 0, 6 and 12 months. Changes in FPG, 2-h plasma glucose, A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects., Results: At 12 months, A1C levels were significantly lesser (5.7% ± 0.4%) in the Vitamin D supplemented group when compared with non-Vitamin D supplemented (6.0% ± 0.3%). Similarly, FPG (97 ± 7) and 2-h plasma glucose (132 ± 16) were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group (FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25) at 12 months. Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes., Conclusions: Vitamin D supplementation in prediabetes subjects significantly lowered FPG, 2-h plasma glucose and A1C levels.

L-asparaginase (L-Asp) is an essential component of acute lymphoblastic leukemia (ALL) treatment protocols and its use has been associated with many adverse effects. We report a case of a 15-year-old boy with ALL who developed L-Asp induced hypoglycemia. To the best of our knowledge, only one such case has been reported previously.

Background: Overt hypothyroidism is associated with abnormalities of lipid metabolism, but conflicting results regarding the degree of lipid changes in subclinical hypothyroidism (SCH) exist., Objectives: The aim of this study was to assess differences in lipid profile parameters between subjects with and without SCH in a north Indian population., Patients and Methods: Serum lipid parameters of 70 patients with subclinical hypothyroidism and 100 age and sex matched euthyroid controls were evaluated in a cross-sectional study., Results: Mean serum total cholesterol (TC), triglycerides (TG) and very low-density cholesterol (VLDL) were significantly higher in patients with SCH than controls (P < 0.05). Mean TC, TG and low-density cholesterol (LDL) concentrations were higher in patients with serum thyroid stimulating hormone (TSH) greater than 10 mU/L than those with serum TSH equal to or less than 10 mU/L, but this difference was not statistically significant. No association was found between serum high-density cholesterol (HDL-C) concentration and serum TSH level., Conclusions: High TC, TG and VLDL were observed in our patients with SCH.

Myxedema crisis is a severe life threatening form of decompensated hypothyroidism which is associated with a high mortality rate. Infections and discontinuation of thyroid supplements are the major precipitating factors while hypothermia may not play a major role in tropical countries. Low intracellular T3 leads to cardiogenic shock, respiratory depression, hypothermia and coma. Patients are identified on the basis of a low index of suspicion with a careful history and examination focused on features of hypothyroidism and precipitating factors. Arrythmias and coagulation disorders are increasingly being identified in myxedema crisis. Thyroid replacement should be initiated as early as possible with careful attention to hypotension, fluid replacement and steroid replacement in an intensive care facility. Studies have shown that replacement of thyroid hormone through ryles tube with a loading dose and maintenance therapy is as efficacious as intravenous therapy. In many countries T3 is not available and oral therapy with T4 can be used effectively without major significant difference in outcomes. Hypotension, bradycardia at presentation, need for mechanical ventilation, hypothermia unresponsive to treatment, sepsis, intake of sedative drugs, lower GCS and high APACHE II scores and Sequential Organ Failure Assessment (SOFA) scores more than 6 are significant predictors of mortality in myxedema crisis. Early intervention in hypothyroid patients developing sepsis and other precipitating factors and ensuring continued intake of thyroid supplements may prevent mortality and morbidity associated with myxedema crisis.

Fibrocalculous pancreatopathy (FCPP) is a secondary form of diabetes mellitus (DM) with obscure etiology. Recently various gene mutations have been reported in patients with FCPP from the Indian subcontinent. Initially termed tropical pancreatic diabetes, FCPP is uncommon and is characterized by pancreatic calcifications. The diagnosis is made in the third decade of life in most patients with the onset of abdominal pain and DM. We report a female child with DM diagnosed at the age of 3 years who had been managed with insulin but was ketosis resistant. The diagnosis of FCPP was made 3 years later. There were no mutations at N34S and P55S in the SPINK1 gene.