Phenotype-genotype spectrum of AAA syndrome from Western India and systematic review of literature.

OBJECTIVE: To study genotype-phenotype spectrum of triple A syndrome (TAS). METHODS: Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications). RESULTS: Median age at presentation was 4.75 years (range: 4-10) and 5 years (range: 1-42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. CONCLUSION: Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research.

Melioidosis and pulmonary tuberculosis co-infection in a diabetic.

Burkholderia pseudomallei is the causative agent of melioidosis. It is endemic in South East Asian countries and North Australia. Sporadic cases of melioidosis have been reported from several parts of South India. Melioidosis may manifest as chronic pneumonia mimicking tuberculosis and generally be seen as a single entity. We report the first case of melioidosis and pulmonary tuberculosis co-infection in a diabetic patient. The causative agents were identified using standard methods and the patient recovered after completion of the recommended antibiotic therapy. Melioidosis is an emerging infectious disease in India. Though melioidosis and tuberculosis present with similar clinical picture, co-infections are rare. Hence, increased awareness among clinicians and microbiologists can help in diagnosing the disease even when there is no clinical suspicion.

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.

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.

Prevalence of hypogonadism in patients with type 2 diabetes mellitus in an Asian Indian study group.

OBJECTIVE: To determine the prevalence of hypogonadism in Asian Indian patients with type 2 diabetes mellitus (T2DM) and to correlate it with components of the metabolic syndrome and microvascular complications of T2DM. METHODS: One hundred consecutive male patients with T2DM between 25 and 50 years of age and 50 age-matched healthy adults without diabetes underwent assessment. Calculated free testosterone was derived by using serum total testosterone and sex hormone-binding globulin. Those patients with 2 calculated free testosterone values less than 64.8 pg/mL were diagnosed as having hypogonadism. RESULTS: Of the 100 patients with T2DM, 15 (15%) were found to have hypogonadism-7 of 29 (24%) between 31 and 40 years of age and 8 of 67 (12%) between 41 and 50 years old. None of the 4 patients between 25 and 30 years old had hypogonadism. Eleven patients (73%) had hypogonadotropic hypogonadism, and 4 (27%) had hypergonadotropic hypogonadism. Among the control subjects, the prevalence of hypogonadism was 10%. In comparison with Western data, we found a higher prevalence of hypogonadism in patients with T2DM, especially in those in the 4th decade of life. The prevalence of hypogonadism was higher in obese patients, although it did not reach statistical significance. No statistically significant correlation was observed between hypogonadism and age, duration of diabetes, glycemic control, androgen deficiency symptoms, or microvascular complications. CONCLUSION: The prevalence of hypogonadism was higher in the patients with diabetes than in the control subjects, although the difference did not reach statistical significance. There was no correlation of hypogonadism with components of the metabolic syndrome or microvascular complications of diabetes mellitus.

An unusual variant of Cushing syndrome.

OBJECTIVE: To discuss the initial clinical manifestations of primary pigmented nodular adrenocortical disease. METHODS: We present a case report of a 4-year-old boy who had the classic clinical features of Cushing syndrome. Results of hormonal investigations are reviewed, and histopathologic findings are illustrated. RESULTS: Investigations revealed adrenocorticotropic hormone (corticotropin)-independent Cushing syndrome. Findings on magnetic resonance imaging of the pituitary gland and abdomen were within normal limits. The patient underwent bilateral adrenalectomy. The histopathologic features were consistent with primary pigmented nodular adrenocortical disease. CONCLUSION: Primary pigmented nodular adrenocortical disease should be suspected in patients with corticotropin-independent Cushing syndrome who have normal findings on adrenal imaging.