Tushar Bandgar

PILOT STUDY TO EVALUATE THE EFFECT OF SHORT-TERM IMPROVEMENT IN VITAMIN D STATUS ON GLUCOSE TOLERANCE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

OBJECTIVE To study the effect of improvement in vitamin D status on glucose tolerance in Asian Indian patients with moderately controlled type 2 diabetes mellitus (T2DM). METHODS This randomized, double-blind, placebo-controlled pilot study was conducted in 28 Asian Indian patients with T2DM. Study participants were randomly assigned to a vitamin D-treated group (group D) or a placebo group (group P). Serum 25-hydroxyvitamin D, hemoglobin A1c, and serum fructosamine levels were measured, and an oral glucose tolerance test (OGTT) was performed in all patients at baseline and 4 weeks after intervention. During the OGTT, plasma glucose and serum insulin levels were measured at 0, 30, 60, 90, and 120 minutes. The unpaired t test was used to compare the groups at baseline and to compare the differences in changes from baseline to 4 weeks between the 2 study groups. RESULTS Group D and group P were similar with respect to their fasting plasma glucose and serum insulin concentrations, post-OGTT plasma glucose and serum insulin levels, and hemoglobin A1c and fructosamine values at baseline. Serum 25-hydroxyvitamin D levels increased significantly in group D at 4 weeks. No significant differences were found between the groups at baseline and 4 weeks with respect to serum fructosamine, fasting plasma glucose and serum insulin, post-OGTT plasma glucose and serum insulin levels, and homeostasis model assessment of insulin resistance. CONCLUSION In this study, short-term improvement in vitamin D status was not associated with improvement in glucose tolerance, insulin secretion, or insulin sensitivity in Asian Indian patients with moderately controlled T2DM.

Efficacy of cabergoline in uncured (persistent or recurrent) Cushing disease after pituitary surgical treatment with or without radiotherapy.

OBJECTIVE To evaluate the efficacy of cabergoline therapy in patients with Cushing disease who remained uncured (had persistent or recurrent disease) after a pituitary surgical procedure with or without radiotherapy. METHODS We undertook a prospective, open-label, single-arm study, with short-term (5 months) and longterm (1 year) evaluations. In 20 patients with uncured Cushing disease, treatment was initiated with cabergoline at a dosage of 1 mg/wk, with a monthly increment of 1 mg, until midnight serum cortisol (MNSC) or low-dose dexamethasone suppression serum cortisol (LDSC) (or both) normalized or a maximal dosage of 5 mg/wk was reached. RESULTS Overall, 5 of 18 patients (28%) responded in terms of LDSC or MNSC (or both) at a mean dosage of 3.6 mg/wk (range, 2 to 5). When the response was defined with use of either LDSC or MNSC level as an isolated criterion, it was achieved in 4 of 16 patients (25%) and 3 of 18 patients (17%), respectively. Four patients were treated for 1 year, and the response was persistent in 2 and 3 patients on the basis of MNSC and LDSC levels, respectively. Lower baseline serum cortisol (basal, MNSC, and LDSC) values were predictive of a therapeutic response. CONCLUSION Cabergoline was an effective therapy in 28%, 25%, and 17% of patients with uncured Cushing disease in terms of LDSC or MNSC (or both), LDSC alone, and MNSC alone, respectively. Further studies are needed to address the persistence of the drug response and the effects on the dynamics of the hypothalamic-pituitary-adrenal axis.

TREATmENT Of hyPOgONADIsm wITh TEsTOsTERONE IN PATIENTs wITh TyPE 2 DIAbETEs mEllITus

OBJECTIVE To investigate the effect of testosterone treatment on insulin resistance, glycemic control, and dyslipidemia in Asian Indian men with type 2 diabetes mellitus (T2DM) and hypogonadism. METHODS We conducted a double-blind, placebo-controlled, crossover study in 22 men, 25 to 50 years old, with T2DM and hypogonadism. Patients were treated with intramuscularly administered testosterone (200 mg every 15 days) or placebo for 3 months in random order, followed by a washout period of 1 month before the alternative treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostasis model assessment [HOMA] in those patients not receiving insulin), fasting blood glucose, and hemoglobin A1c. The secondary outcomes were changes in fasting lipids, blood pressure, body mass index, waist circumference, waist-to-hip ratio, and androgen deficiency symptoms. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared with the effect of testosterone. RESULTS Treatment with testosterone did not significantly influence insulin resistance measured by the HOMA index (mean treatment effect, 1.67 +/- 4.29; confidence interval, -6.91 to 10.25; P>.05). Mean change in hemoglobin A1c (%) (-1.75 +/- 5.35; -12.46 to 8.95) and fasting blood glucose (mg/dL) (20.20 +/- 67.87; -115.54 to 155.94) also did not reach statistical significance. Testosterone treatment did not affect fasting lipids, blood pressure, and anthropometric determinations significantly. CONCLUSION In this study, testosterone treatment showed a neutral effect on insulin resistance and glycemic control and failed to improve dyslipidemia, control blood pressure, or reduce visceral fat significantly in Asian Indian men with T2DM and hypogonadism.

Primary hyperparathyroidism in children and adolescents

ObjectivePrimary hyperparathyroidism (PHPT) in children and adolescents is a rare condition. Awareness should improve in order to lower threshold for screening and allow intervention before serious and permanent sequelac occur.MethodsA retrospective analysis of 15 children and adolescents with PHPT (age <20 yr) seen in our clinic between 1993 and 2006.ResultsMean age of patients was 17.73 yr (Range — 13–20, Male-3: Female-12). Average duration of symptoms was 18.87 (range: 0–48) mo. Clinical features at presentation included bone pain (86.67%), proximal myopathy (46.67%), bony deformities (53.33%), fractures (60%), palpable osteitis fibrosa cystica (33.3%), renal calculi (40%), palpable neck swelling (13.3%) and acute pancreatitis (6.67%). None had positive family history or features suggestive of multiple endocrine neoplasia (MEN). After biochemical confirmation, tumor was localised in all prior to surgery. Histopathology confirmed adenoma in all cases. Post-operative hungry bone syndrome occurred in 33.3%.ConclusionPHPT is more common in females. Presentation of the disease is similar to their adult counterparts except for more severe bone disease and less severe renal disease. MEN and familial non-MEN PHPT do not constitute a major cause of pediatric PHPT as against to worldwide data. The incidence of hyperplasia as a cause of PHPT is rare in our pediatric population.

Tumor-induced osteomalacia: a single center experience.

OBJECTIVE To describe the clinical presentation, localization modalities, and management of patients with tumor-induced osteomalacia (TIO). METHODS We performed a retrospective analysis of case records of patients diagnosed with TIO between January 1996 and March 2010 at our institution in Mumbai, India. RESULTS Nine patients (6 female and 3 male) with a mean age of 37.5 ± 17.5 years with biochemical and imaging evidence of TIO were included in the study. Overall, patients presented with proximal muscle weakness and pain. Three patients had neurofibromatosis 1, one had isolated schwannoma, and one had epidermal nevus syndrome. The mean delay in diagnosis was 7.67 years. Biochemical studies revealed normal serum calcium (mean, 9.2 ± 0.8 mg/dL), low serum phosphorus (mean, 1.36 ± 0.54 mg/dL), and low maximal tubular reabsorption of phosphorus factored for glomerular filtration rate (mean, 0.94 ± 0.49 mg/dL). Fibroblast growth factor-23 was increased in 3 of the patients without neurofibromatosis but was normal or near-normal in all the patients with neurofibromas. A fludeoxyglucose F 18 positron emission tomography (FDG PET) scan helped to localize the tumors in 4 of the 5 patients with diagnoses other than neurofibromatosis. Three patients underwent surgical excision and were cured. One patient underwent biopsy and partial excision. Histopathologic findings were suggestive of phosphaturic mesenchymal tumor, benign fibrous histiocytoma, nonossifying fibroma, and sciatic nerve schwannoma. CONCLUSION There is a well-known delay in the diagnosis of TIO. FDG PET is a useful modality for localization of tumors. Preoperative localization increases the odds for cure after surgical excision.

Clinical profile of primary hyperparathyroidism from western India: a single center experience.

BACKGROUND Primary hyperparathyroidism (PHPT) has a variable clinical presentation and symptomatic PHPT is still the predominant form of the disease in India. Data from western India is lacking. AIM To present the clinical profile of PHPT from western India. SETTINGS AND DESIGN This retrospective study was conducted at a tertiary care referral center. MATERIALS AND METHODS We analyzed the clinical presentation, biochemical, radiological features, and operative findings in adult patients with PHPT (1986-2008) and compared with our published data of children and adolescent patients with PHPT. STATISTICAL ANALYSIS was done with SPSS 16 software. RESULTS Seventy-nine patients (F: M-2:1) with age ranging from 21 to 55 years (mean 33.5+/-8.82) were analyzed. Skeletal manifestations (75.5%), renal calculi (40.5%) and proximal muscle weakness (45.5%) were the most common symptoms of presentation with mean duration of symptoms being 33.70 (median: 24, range 1-120) months. Biochemical features included hypercalcemia (total corrected calcium 12.55+/-1.77 mg/dl), low inorganic phosphorus (1.81+/-0.682 mg/dl), elevated total alkaline phosphatase (mean: 762.2; median: 559; range: 50-4930IU/L) and high parathyroid hormone (PTH) (mean+/-SD: 866.61+/-799.15; median: 639.5; range: 52-3820 pg/ml). Preoperative localization was achieved in 74 patients and single adenoma was found during surgery in 72 patients. Hungry bone disease was seen in 30.3% and transient hypoparathyroidism developed in 62% patients. In comparison to PHPT in children there were no significant differences with regard to clinical, laboratory and radiological features. CONCLUSIONS PHPT in western India is symptomatic disorder with skeletal and renal manifestations at a much younger age. Clinical profile of PHPT in children is similar to that of adults.

Performance of Plasma Fractionated Free Metanephrines by Enzyme Immunoassay in the Diagnosis of Pheochromocytoma and Paraganglioma in Children

OBJECTIVE To establish pediatric reference ranges for plasma fractionated free metanephrines by enzyme immunoassay (EIA) and to evaluate its performance in the diagnosis of catecholamine-secreting tumors in the pediatric population. METHODS Normotensive children and children with suspected catecholamine-secreting tumors underwent measurement of plasma fractionated metanephrines by EIA to establish pediatric reference ranges. Children with suspected pheochromocytoma or paraganglioma also underwent magnetic resonance imaging or computed tomography from the neck to the pelvis and were followed up for a minimum of 1 year. Diagnosis of pheochromocytoma/paraganglioma was confirmed by histologic examination. Pheochromocytoma/paraganglioma was excluded in children who had a histologic diagnosis other than pheochromocytoma/paraganglioma and in those who had no imaging evidence of tumor and no progression on follow-up. RESULTS Plasma fractionated metanephrines were measured in 78 normotensive children (age range, 1.5-17 years) and in 38 children with suspected catecholamine-secreting tumors. Of the 38 children (age range, 6-17 years) with suspected pheochromocytoma/paraganglioma, 17 had a histopathologically proven catecholamine-secreting tumor. The newly derived pediatric upper reference limit for metanephrine (128 pg/mL) was higher than in adults (90 pg/mL), whereas the pediatric upper reference limit for normetanephrine (149 pg/mL) was lower than in adults (180 pg/mL). The manufacturers reference range for plasma fractionated metanephrines yielded a sensitivity of 100% and a specificity of 85.7%. Use of newly established pediatric reference ranges increased the specificity to 95.2% without altering the sensitivity (100%). CONCLUSIONS Plasma fractionated metanephrines by EIA provide an accurate test with good sensitivity and specificity for the diagnosis of pheochromocytoma and paraganglioma in children. Use of pediatric reference ranges improves accuracy of the test.

GIANT PROlACTINOmA AND EFFECTIVENEss OF mEDICAl mANAGEmENT

OBJECTIVE To review our experience with long-term cabergoline and bromocriptine therapy in the treatment of giant prolactinomas. METHODS Patients with giant prolactinomas diagnosed and treated at our center in Mumbai, India, between January 2005 and January 2009 were included. Diagnostic criteria for giant prolactinoma included tumor diameter greater than 40 mm, serum prolactin concentration higher than 1000 ng/mL, and invasive tumor growth pattern with mass effects. Cabergoline was started at a dosage of 0.5 mg weekly and progressively increased as necessary up to 3.5 mg weekly. Patients were followed up with hormone measurements, sellar magnetic resonance imaging, and vision examinations. RESULTS The study group included 10 patients (5 male and 5 female), aged 17 to 50 years (mean, 36.1 years), treated for giant prolactinoma. In 8 patients, cabergoline was first-line therapy. Two patients had previously been prescribed bromocriptine, and this regimen was maintained. Mean serum prolactin concentration before treatment was 10,789 +/- 14,278 ng/mL (range, 1256-43,163 ng/mL; reference range, 5-17 ng/mL). Following treatment, levels normalized in 7 patients within 2 to 18 months (mean, 8.8 months) and decreased in 1 patient to a level 3 to 4 times that of normal. Tumor diameter, which measured from 4 to 7 cm at diagnosis, showed a mean maximal decrease of 49.28 +/- 18.27%; response was first noted about 6 months after treatment was begun. Seven patients had visual field defects at diagnosis; vision returned to normal in 3 and improved in 4. Testosterone levels, initially low in all male patients, normalized in 3. CONCLUSION Cabergoline should be first-line therapy for aggressive prolactinomas, even in those patients who present with visual field defects.

Functional imaging in primary tumour-induced osteomalacia: relative performance of FDG PET/CT vs somatostatin receptor-based functional scans: a series of nine patients.

Localization of phosphatonin‐producing mesenchymal tumours in patients with primary tumour‐induced osteomalacia (pTIO) is challenging. Functional imaging plays an important role in the localization of these tumours.

Volume interpolated 3D‐spoiled gradient echo sequence is better than dynamic contrast spin echo sequence for MRI detection of corticotropin secreting pituitary microadenomas

Various techniques have been attempted to increase the yield of magnetic resonance imaging (MRI) for localization of pituitary microadenomas in corticotropin (ACTH)‐dependent Cushings syndrome (CS).