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1.  Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease 
BMJ Case Reports  2013;2013:bcr2012008035.
Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism.
PMCID: PMC3604017  PMID: 23365169
2.  Bone mineral density and factors influencing it in Asian Indian population with type 2 diabetes mellitus 
To assess bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) patients and its relation, if any, to clinical, hormonal and metabolic factors.
Materials and Methods:
A prospective evaluation of 194 T2DM patients (97 men and 97 women) was carried out. BMD was done with dual energy X-ray absorptiometry (DXA) at the lumbar spine and total hip. Physical activity, nutritional intake and sunlight exposure were calculated. Biochemical and hormonal tests included serum 25 hydroxy vitamin D [25(OH) D], parathyroid hormone, estrogen, testosterone and urinary calcium-creatinine ratio. Glycosylated hemoglobin and complete lipid profiles were done in patients with diabetes. Five hundred and seventy one non-diabetic controls (262 males and 309 females) were evaluated for BMD alone.
BMD was normal (Z score > -2) in 156 (80.5%) and low (Z score ≤ -2) in 38 (19.5%) patients in the diabetes study group. BMD in the diabetes group was significantly higher than the control group in both sexes at the hip and spine. The difference was no longer significant on analysis of a BMI matched control subgroup. Weight and BMI showed significant correlation to BMD. Duration of T2DM, degree of glycemic control, use of drugs like statins and thiazolidinediones, 25(OH) D levels, calcium intake, sunlight exposure and physical activity did not significantly affect BMD in this cohort of individuals with diabetes.
Bone mineral density of Asian Indian T2DM subjects was similar to that of healthy volunteers in this study.
PMCID: PMC4192990  PMID: 25364679
Asian Indian; bone mineral density; obesity; type 2 diabetes mellitus; vitamin D deficiency
3.  Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome 
Peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in glucose and lipid metabolism is one of the candidate genes associated with polycystic ovary syndrome (PCOS). We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women.
Genotyping of PPARγ polymorphisms in this case–control study was performed in PCOS (n = 450) and age-matched controls (n = 300) by direct sequencing. Clinical, anthropometric, hormonal and metabolic parameters were estimated in 275 women with PCOS and 169 controls. Chi-square test was used to compare the categorical data while regression analysis was used to evaluate association of genotypes with PCOS as well as its related phenotypes.
The frequencies of CC and CG + GG genotypes of Pro12Ala (χ2 = 15.3, p < 0.0001) and CC and CT + TT genotypes of His447His (χ2 = 12.7, p = 0.0004) polymorphisms were significantly different between PCOS and controls. Logistic regression analysis revealed a significant association of PCOS with Pro12Ala but not the His447His polymorphism. Carriers of variant genotypes at both PPARγ loci showed significantly reduced 2 h glucose levels while carriers of variant His447His genotype showed lower fasting insulin and HOMA-IR levels in PCOS women.
Pro12Ala polymorphism of PPARγ showed significant association with decreased PCOS susceptibility. Both polymorphisms influenced insulin related traits (2 h glucose, fasting insulin and HOMA-IR) and improved glucose metabolism in these women. This is the first report to establish that variations in PPARγ gene influence the insulin resistance pathophysiology in Indian women with PCOS.
PMCID: PMC3725223  PMID: 23748472
Peroxisome proliferator activated receptor gamma (PPARγ); Polycystic ovary syndrome (PCOS); Polymorphism; Insulin resistance; Genetic
6.  Current concepts in blood glucose monitoring 
Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.
PMCID: PMC4046592  PMID: 24910827
Blood glucose monitoring system; continuous glucose monitoring; glycated haemoglobin; glycemic variability; self-monitored blood glucose
7.  Management issues with exogenous steroid therapy 
Glucocorticoids (GCs) are extensively used for various inflammatory and autoimmune disorders, but long term use of these agents is not without complications. Almost every GC formulations (e.g. oral, topical, inhaled, etc.) can cause systemic side effects. It can range from minor side effects (e.g. weight gain) to life-threatening effects (e.g. adrenal suppression, sepsis, etc.), which may require immediate intervention. Therefore, the decision to institute steroid therapy always requires careful consideration of the relative risk and benefit in each patient. The objectives of this study are to discuss monitoring of patients on GCs and management of the complications of GCs.
PMCID: PMC4046616  PMID: 24910822
Adrenal suppression; avascular necrosis; exogenous cushing's syndrome; glucocorticoids-induced osteoporosis
8.  Aortoarteritis: Could it be a form of catecholamine-induced vasculitis? 
Catecholamine-induced vasculitis is a well known but rarely described entity. However, aortoarteritis as a manifestation of catecholamine-induced vasculitis is not described in the literature. We have reported two patients in whom pheochromocytoma coexisted with aortoarteritis. Both patients were young females with history of bilateral pheochromocytomas in more than one first-degree relative. Both patients also had bilateral adrenal pheochromocytomas (second patient also had paraganglioma at left renal hilum) with elevation of plasma free normetanephrine levels. We conclude that there may be an association between pheochromocytoma and aortoarteritis, and that catecholamine excess may have a role in the etiopathogenesis of aortoarteritis in these patients.
PMCID: PMC3659888  PMID: 23776874
Aortoarteritis; catecholamine excess; pheochromocytoma
9.  Promise and pitfalls of molecular markers of thyroid nodules 
Thyroid nodules are common in the general population with a prevalence of 5-7% The initial evaluation of thyroid nodules commonly involves thyroid function tests, an ultrasound (USG) and fine needle aspiration biopsy (FNAB). The optimal management of patients with thyroid nodules with indeterminate cytology is plagued by the lack of highly sensitive and specific diagnostic modalities In this article we attempt to review the available literature on the molecular markers which are increasingly being studied for their diagnostic utility in assessing thyroid nodules. The various molecular markers consist of gene mutations, gene re arrangements, RNA based assays and immunohistochemical markers. The molecular markers definitely would help to optimise the management of such patients.
PMCID: PMC3603017  PMID: 23565369
Molecular markers; thyroid nodules; genetic mutations; gene rearrangements
10.  Coexistence of pheochromocytoma/praganglioma and renal artery stenosis 
Renal artery stenosis (RAS) often coexists with pheochromocytoma (Pheo)/paraganglioma (PGL) and often alters the management of patients with Pheo/PGL. We have studied the prevalence of RAS in our Pheo/PGL patients. The study included 70 consecutive, histopathologically proven Pheo/PGL patients from a tertiary health care center. In 60 patients, tumors were limited to adrenal glands (54 unilateral and 6 bilateral) while other 10 patients had extra-adrenal abdominal tumors. Five patients had RAS with an overall prevalence of 14%. Only two out of 60 patients with Pheo had RAS with a low prevalence of 3.3% while three out of 10 patients with extra-adrenal abdominal PGL had RAS with a prevalence of 30%. To conclude, RAS commonly coexists with Pheo/PGL, more often with extra-adrenal PGL.
PMCID: PMC3510927  PMID: 23226653
Paraganglioma; pheochromocytoma; renal artery stenosis
11.  Vanishing tumor in pregnancy 
A patient with microprolactinoma, who had two successful pregnancies, is described for management issues. First pregnancy was uneventful. During the second pregnancy, the tumor enlarged to macroprolactinoma with headache and blurring of vision which was managed successfully with bromocriptine. Post delivery, complete disappearance of the tumor was documented.
PMCID: PMC3510938  PMID: 23226664
Bromocriptine; pregnancy; prolactinoma
12.  Hypophosphatemic rickets 
Hypophosphatemic rickets is a disorder of bone mineralization caused due to defects (inherited/acquired) in the renal handling of phosphorus. This group includes varied conditions, X-linked hypophosphatemic rickets being the most common inheritable form of rickets. The other common forms are autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia. Although these conditions exhibit different etiologies, increased phosphatonins form a common link among them. Fibroblast growth factor 23 (FGF23) is the most widely studied phosphatonin. Genetic studies tend to show that the phosphorus homeostasis depends on a complex osteo-renal axis, whose mechanisms have been poorly understood so far. Newer disorders are being added as the mechanisms in this axis get discovered. This review focuses on the clinical, biochemical, genetic features and management of hypophosphatemic disorders leading to defective mineralization.
PMCID: PMC3313733  PMID: 22470852
1; 25(OH)2D3; autosomal dominant hypophosphatemic rickets; fibroblast growth factor 23; hypophosphatemia; tumor-induced osteomalacia; X-linked hypophosphatemic rickets
13.  Renal manifestations of primary hyperparathyroidism 
Primary hyperparathyroidism (PHPT) is associated with nephrolithiasis and nephrocalcinosis. Hypercalciuria is one of the multiple factors that is implicated in the complex pathophysiology of stone formation. The presence of a renal stone (symptomatic or asymptomatic) categorizes PHPT as symptomatic and is an indication for parathyroid adenomectomy. Progression of nephrocalcinosis is largely reversible after successful surgery, but the residual risk persists. PHPT is also associated with declining renal function. In case of asymptomatic mild PHPT, annual renal functional assessment is advised. Guidelines suggest that an estimated glomerular filtration rate (eGFR) < 60 ml / minute / 1.73 m2 is an indication for parathyroid adenomectomy. This article discusses how to monitor and manage renal stones and other related renal parameters in case of PHPT.
PMCID: PMC3313745  PMID: 22470864
Nephrolithiasis; primary hyperparathyroidism; renal cyst; renal stones
14.  Cushing's syndrome: Stepwise approach to diagnosis 
The projected prevalence of Cushing's syndrome (CS) inclusive of subclinical cases in the adult population ranges from 0.2–2% and it may no longer be considered as an orphan disease (2–3 cases/million/year). The recognition of CS by physicians is important for early diagnosis and treatment. Late-night salivary cortisol, dexamethasone suppressiontesti, or 24-h urine free cortisol are good screening tests. Positively screened cases need stepwise evaluation by an endocrinologist. This paper discusses the importance of screening for CS and suggests a stepwise diagnostic approach to a case of suspected hypercortisolism.
PMCID: PMC3230095  PMID: 22145134
Cushing's syndrome; dexamethasone suppression tests; hypercortisolism; salivary cortisol; urinary free cortisol
15.  Prevalence and Impact of Thyroid Disorders on Maternal Outcome in Asian-Indian Pregnant Women 
Journal of Thyroid Research  2011;2011:429097.
Aims. To establish the prevalence and the effect of thyroid dysfunction on pregnancy outcomes in Asian-Indian population. Subjects and Methods. The study cohort comprised of 483 consecutive pregnant women in the first trimester attending the antenatal clinic of a tertiary center in Mumbai, India. Thyroid hormone levels and thyroid peroxidase antibody were estimated. Patients with thyroid dysfunction were assessed periodically or treated depending on the severity. Subjects were followed until delivery. Results. The prevalence of hypothyroidism, Graves' disease, gestational transient thyrotoxicosis, and thyroid autoimmunity (TAI) was 4.8% (n = 24), 0.6% (n = 3), 6.4 % (n = 31), and 12.4% (n = 60), respectively. Forty percent of the hypothyroid patients did not have any high-risk characteristics. Hypothyroidism and TAI were associated with miscarriage (P = 0.02 and P = 0.001, resp.). Conclusions. The prevalence of hypothyroidism (4.8%) and TAI (12.4%) is high. TAI and hypothyroidism were significantly associated with miscarriage.
PMCID: PMC3140706  PMID: 21789274
16.  Prevalence of upper airway obstruction in patients with apparently asymptomatic euthyroid multi nodular goitre 
To study the prevalence of upper airway obstruction (UAO) in “apparently asymptomatic” patients with euthyroid multinodular goitre (MNG) and find correlation between clinical features, UAO on pulmonary function test (PFT) and tracheal narrowing on computerised tomography (CT).
Materials and Methods:
Consecutive patients with apparently asymptomatic euthyroid MNG attending thyroid clinic in a tertiary centre underwent clinical examination to elicit features of UAO, PFT, and CT of neck and chest.
Statistical Analysis Used:
Statistical analysis was done with SPSS version 11.5 using paired t-test, Chi square test, and Fisher's exact test. P value of <0.05 was considered to be significant.
Fifty-six patients (52 females and four males) were studied. The prevalence of UAO (PFT) and significant tracheal narrowing (CT) was 14.3%. and 9.3%, respectively. Clinical features failed to predict UAO or significant tracheal narrowing. Tracheal narrowing (CT) did not correlate with UAO (PFT). Volume of goitre significantly correlated with degree of tracheal narrowing.
Clinical features do not predict UAO on PFT or tracheal narrowing on CT in apparently asymptomatic patients with euthyroid MNG.
PMCID: PMC3169865  PMID: 21966649
Multi nodular goitre; pulmonary function test; upper airway obstruction
17.  Has experience changed the scenario in laparoscopic adrenalectomy? 
The Indian Journal of Surgery  2009;71(2):78-83.
Laparoscopic adrenalectomy (LA) is a relatively uncommon operation performed by surgeons with a specific interest in endocrine surgery as well as advanced laparoscopic surgery. LA is technically difficult and it is recommended to tackle small glands first till adequate experience is reached [1]. A minimum of 30 cases are required to master the technique [2]. The present study reviews data of 60 laparoscopic adrenalectomies comparing the later results with the first 30 cases.
Material and methods
Starting 2001, patients diagnosed to have adrenal disorders were subjected to laparoscopic approach in a graded manner. A database was maintained with respect to age, sex, duration of symptoms, co-morbid conditions, diagnosis, size of tumor, weight of tumor, blood loss, duration of surgery, conversion to open, in-hospital stay, referral pattern, morbidity (both early and late) and mortality. The database was divided into two groups. First 30 patients constituted Group A, Group B constituted the next 30 adrenalectomies and deviation in the two was noted. Statistical analysis was performed to determine the importance of deviation of factors.
Sixty adrenalectomies were performed in 49 patients (11 being bilateral) between February 2001 and July 2008. Age group varied from 12–54 years with mean of 30.73 years, Twenty four were males. Thirty-one right and 29 left LA were performed. The comparison of factors in relation to the two groups (Group A and B respectively) revealed an increase in number of adrenalectomies performed (0.4 v/s 0.76) in relation to timeline, increased incidence of pheochromocytoma (6 v/s 18) and incidentalomas (zero v/s 8), larger tumor size (4.17 cm v/s 6.6 cm), comparable blood loss (72 cc v/s 98.3 cc) and duration of surgery (122 min v/s 112 min), increased conversion to open surgery (1 v/s 6) leading to increased in-hospital stay (2.8 days v/s 3.37 days) but a comparable morbidity (2 v/s 1) and no mortality.
Though technically difficult, with increasing experience and focused approach, laparoscopic skills in adrenalectomy improves. The spectrum of indications broadens, thus making laparoscopic interventions for vascular and large adrenal glands safe and patient friendly.
PMCID: PMC3452617  PMID: 23133120
Laparoscopic adrenalectomy; Pheochromocytoma; Large adrenal tumours
18.  Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes 
Diabetes Care  2009;32(1):84-90.
OBJECTIVE—The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy.
RESEARCH DESIGN AND METHODS—In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25–79 years) had type 2 diabetes, A1C of 7–11% (previous OAD monotherapy for ≥3 months) or 7–10% (previous OAD combination therapy for ≥3 months), and BMI ≤40 kg/m2.
RESULTS—A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8–2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide (∼3%) was comparable to that with placebo but less than that with glimepiride (17%; P < 0.001). Nausea was reported by 11–19% of the liraglutide-treated subjects versus 3–4% in the placebo and glimepiride groups. The incidence of nausea declined over time.
CONCLUSIONS—In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.
PMCID: PMC2606836  PMID: 18931095
19.  Bone mineral density and disorders of mineral metabolism in chronic liver disease 
AIM: To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis.
METHODS: The study was performed on 72 Indian patients with cirrhosis (63 male, nine female; aged < 50 years). Etiology of cirrhosis was alcoholism (n = 37), hepatitis B (n = 25) and hepatitis C (n = 10). Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density (BMD) was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2.
RESULTS: Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium: protein ratio and calcium: phosphorus ratio. Vitamin D deficiency was highly prevalent (92%). There was a high incidence of hypogonadism (41%). Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor (IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low (68%) and urinary deoxypyridinoline to creatinine ratio was high (79%), which demonstrated low bone formation with high resorption.
CONCLUSION: Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.
PMCID: PMC2715978  PMID: 19630107
Bone mineral density; Liver disease; Chronic disease; Cirrhosis; Bone mineral metabolism; Hepatic osteodystrophy
20.  Relation of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels to growth retardation in extrahepatic portal vein obstruction 
Hepatology International  2008;3(1):305-309.
Growth retardation has been described in patients with extrahepatic portal vein obstruction (EHPVO). An abnormal growth hormone (GH)–insulin-like growth factor (IGF) axis has been postulated as a possible etiology. We compared anthropometric parameters and IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels in patients with EHPVO with their siblings as controls.
Methods and patients
Consecutive patients diagnosed with EHPVO who presented to out-patient clinic in Department of Gastroenterology between February 2005 and February 2006 were enrolled along with their siblings whenever possible. After detailed history and clinical examination, anthropometric parameters such as age, height, weight, and mid-parental height were measured in patients and controls. IGF-1 and IGFBP-3 levels were also estimated.
Fifty-two patients (40 males, 32 adults) were enrolled. Sibling controls were available for 28 patients. Variceal bleeding was the presenting symptom in 41 of 52 (78.8%) patients. Target height was not achieved in 7 of 32 (22.6%) adults and 6 of 20 (30%) children, showing evidence of growth retardation. The mean IGF-1 levels in patients and controls were 124.71 ± 65.49 ng/ml and 233 ± 76.98 ng/ml (P < 0.01), respectively. The mean IGFBP-3 levels in patients and controls were 2.90 ± 1.07 μg/ml and 4.22 ± 0.77 μg/ml (P < 0.01), respectively. Hormonal levels between those with and without evidence of growth retardation did not differ significantly. Duration of symptoms, spleen size, platelet count, and age of presentation did not correlate with anthropometry and hormonal levels.
Growth retardation by anthropometry was documented in a quarter of patients with EHPVO. All patients had significantly low IGF-1 and IGFBP-3 levels in comparison with controls despite normal anthropometry in majority of patients (75%).
PMCID: PMC2712316  PMID: 19669381
Portal vein thrombosis; Extrahepatic portal vein obstruction
21.  Laparoscopic adrenalectomy: Gaining experience by graded approach 
Laparoscopic adrenalectomy (LA) has become a gold standard in management of most of the adrenal disorders. Though report on the first laparoscopic adrenalectomy dates back to 1992, there is no series of LA reported from India. Starting Feb 2001, a graded approach to LA was undertaken in our center. Till March 2006, a total of 34 laparoscopic adrenalectomies were performed with success.
Materials and Methods:
The endocrinology department primarily evaluated all patients. Patients were divided into Group A - unilateral LA and Group B - bilateral LA (BLA). The indications in Group A were pheochromocytoma (n=7), Conn's syndrome (n=3), Cushing's adenoma (n=2), incidentaloma (n=2); and in Group B, Cushing's disease (CD) following failed trans-sphenoid pituitary surgery (n = 8); ectopic ACTH- producing Cushing's syndrome (n=1) and congenital adrenal hyperplasia (CAH) (n=1). The lateral transabdominal route was used.
The age group varied from 12–54 years, with mean age of 28.21 years. Average duration of surgery in Group A was 166.43 min (40–270 min) and 190 min (150–310 min) in Group B. Average blood loss was 136.93 cc (20–400 cc) in Group A and 92.5 cc (40–260 cc) in Group B. There was one conversion in each group. Mean duration of surgical stay was 1.8 days (1–3 days) in Group A and 2.6 days (2–4 days) in Group B. All the patients in both groups were cured of their illness. Three patients in Group B developed Nelson's syndrome. The mean follow up was of 24.16 months (4–61 months).
LA though technically demanding, is feasible and safe. Graded approach to LA is the key to success.
PMCID: PMC2997274  PMID: 21170236
Laparoscopic adrenalectomy; graded approach

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