Prevalence & potential significance of vitamin D deficiency in Asian Indians

Studies from our center and other parts of India have drawn attention towards wide prevalence of vitamin D deficiency (VDD) in our country. VDD has been reported in all age groups including toddlers, school children, pregnant women and their neonates and adult males and females residing in rural and urban India. We reviewed implications of VDD in our population based on the preliminary data available from Indian studies on skeletal health. Besides, a brief review is made on the importance of VDD in various other disorders prevalent in equivalent proportions among Indians such as type 2 diabetes mellitus (DM), cardiovascular diseases (CVD), immune competence including relation to tuberculosis, malignancy and osteoarthritis. Data from the West have also associated VDD with increased prevalence of type 2DM, CVD, autoimmune disorders, tuberculosis, prostate, breast and colon malignancy and osteoarthritis. Such association has not been studied to date in our country. Overall results of various studies conducted to date in urban and rural Indians indicate that widely prevalent VDD is functionally relevant to skeletal health including osteomalacia and rickets. However, there is a need to explore its association with osteoporosis related fractures and various other non skeletal disorders linked with VDD

Pathophysiology of Himalayan endemic goiter

Goiter prevalence and iodine metabolism were studied in areas of endemic goiter in the Himalayas in India and Nepal. Similar studies were also made in Ceylon. The results are compatible with the hypothesis that severe environmental deficiency of iodide is the primary factor responsible for endemic goiter in these areas. The endemicity was less severe in Ceylon than in India and Nepal. The thyroid glands of persons living in endemic areas show an interesting adaptive response to maintain internal homeostasis in the face of severe iodine deficiency. The mechanism of this adaptation was studied in thyroids of goats raised in endemic and nonendemic areas. Thyroids of goats living in an area of severe iodine deficiency showed higher MIT/DIT and T3/T4 ratios than glands of those in an area of iodine abundance. There was a higher incorporation of 131I in 27S iodoproteins in the iodide-deficient glands. A decrease in iodine concentration of the thyroid and an increase in circulating TSH levels are possibly involved in mediating this response but of the two, the former mechanism seems more likely than the latter

Pre-pregnancy weight and weight gain during pregnancy are important determinants in the endocrine modulation of fetal growth restriction

Objective: Pre-pregnancy weight, nutritional status, and the amount of weight gained during pregnancy, are extremely useful indicators of fetal growth and outcome. Suboptimal maternal nutrition could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in "fetal growth restriction" which may be a significant risk factor for adult onset disease. We investigated endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor weight gain in pregnancy as a result of maternal nutritional restriction. Materials & methods: We examined the quantitative variations in hormonal profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on maternal weight gain during the entire pregnancy. Results: 1) A total of 37.4 % mothers gained less than 6 kg during the entire pregnancy. 2) Anthropometric parameters measured in the mothers indicate that these mothers were nutritionally restricted both prior to and during pregnancy. 3) We observed increased levels of growth hormone, placental lactogen, prolactin and thyroxine (T4) and decreased levels of insulin in the cord blood of neonates and decreased insulin and TSH levels in maternal blood in the study group (< 6kg weight gain during pregnancy) as compared to the control group (> 6kg weight gain during pregnancy). Conclusion: Our results suggest that insufficient weight gain in pregnancy due to suboptimal maternal nutritional status results in fetal adaptation to a growth restricted environment by modulation of the pituitary-thyroid axis thereby altering the endocrine milieu resulting in significant "fetal growth restriction"

Hairy cell leukemia : experience at a tertiary cancer centre in Northern India

Background : The prognosis of Hairy cell leukemia (HCL) has improved markedly following treatment with cladribine (2- CdA), a nucleoside analogue. We reviewed data on patients with HCL treated in our department. Methods . Between 1995 and 2004, 23 patients with hairy cell leukemia (HCL) were diagnosed Patients median age was 48.5 years (range, 32 to 66 years), there were 18 males and 5 females. The common presenting symptoms were: fatigue (82.6%), fever (34.7%), abdominal discomfort (21.7%), arthralgia/bone pains (13%) and bleeding (17.3%). 22 of 23 (95.6%) patients had enlarged spleen, and hepatomegaly (65%). Lymph node enlargement was present in 17% of patients. Investigations revealedmedian Hb of 7.8g% (5.7 to 12.9 g%), thrombocytopenia (median 55000/cmm) and median WBC count of 3500/cmm (range, 600 to 20,200/cmm). Bicytopenia or pancytopenia was present in 87% and bone marrow fibrosis in 75% of cases. Immunophenotyping studies revealed expression of CD11C (60%), CD25 (60%), FMC7(47.8%), CD23(34.8%), CD103 in 39% of cases. 20 of 23 patients received treatment; two received treatment else where and one patient died of liver failure prior to treatment. 17 of 20 patients were treated with 2-CdA, 2 with interferon alfa (IFN-a) and one patient underwent splenectomy alone. Three patients received 2-CdA as second line therapy for treatment of relapse: this includes . one patient each, treated with IFN- α and splenectomy both and one patient received 2-cdA twice in view of relapse. Results . Following treatment with 2CdA . 95% of patients responded; complete-84.2% and partial response in 10.5%. one (5.2%) patient died of toxicity. Two patients relapsed at a mean follow up of 25 months. The common side effects were febrile episodes (n=10) and grade I-II myelosuppression. One patient died of toxicity to 2-CdA. This patient was a known case of multidrug resistant disseminated tuberculosis. He had severe myelosuppression with fungal sepsis with multiorgan failure and BM Aspirate was positive for AFB. Other infections documented were Pulmonary tuberculosis in 2 and herpes zoster in one patient. The patient who underwent Splenectomy achieved remission but relapsed after 3 years and was salvaged with 2-CdA again. Median time for normalization of blood counts after 2-CdA was 28 days and median time to regress spleen was 41.5 days . Conclusion . Present study confirms good outcome with 2-CdA (cladribine) therapy for patients of hairy cell leukemia

Bone mineral parameters in healthy young Indian adults with optimal vitamin D availability

Background: Several recent studies indicate a marked prevalence of vitamin D deficiency in asymptomatic, apparently healthy urban subjects from different socioeconomic groups in north India. Methods: To further examine this trend, we studied 40 men and 50 women, 20–30 years of age, from the Indian paramilitary forces. These individuals consume a nutritious, high-protein diet, have optimal exposure to sunlight and undertake strenuous outdoor physical exercise. Results: The mean serum calcium, phosphorus and alkaline phosphatase levels were normal in both men and women. The mean (SD) serum intact parathyroid hormone and 25-hydroxy-vitamin D3 levels were 19.3 (8.2) pg/ml and 18.4 (5.3) ng/ml in men, and 11.9 (6.6) pg/ml and 25.3 (7.4) ng/ml in women. Bone mineral density estimated in 20 men and 22 women revealed that in comparison with white Caucasians, 35%–50% of men and 14%–32% of women were osteopenic at different sites, while an additional 10% of men had osteoporosis of the lumbar spine. Conclusion: We found that with optimal nutrition, good sunlight exposure and regular physical exercise, healthy young individuals have normal bone and mineral biochemical values. The reasons for the abnormalities detected in bone mineral density in them needs further study. The impact of childhood nutrition on accumulation of peak bone mass may contribute to our findings. There is a need for establishing normative bone mineral density data for Indians

Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism

Objective: The pathogenesis of sporadic idiopathic hypoparathyroidism is unclear. The calcium sensing receptor (CaSR) plays a pivotal role in extracellular calcium homeostasis and is the candidate autoantigen in hypoparathyroidism associated with autoimmune polyglandular endocrinopathy syndrome. We therefore looked for antibodies (Ab) against the CaSR in patients with sporadic idiopathic hypoparathyroidism and their association, if any, with the major histocompatibility complex (MHC) class II human leukocyte antigen (HLA)-DR haplotypes. Methods: The subjects included 51 patients with sporadic idiopathic hypoparathyroidism and 45 healthy controls. Investigations included computerised tomography, serum calcium, phosphorus, thyroxine, TSH, cortisol, intact parathyroid hormone (iPTH), ACTH and thyroid peroxidase (TPO) and adrenal antibodies. The CaSRAb were assayed in patients' sera by Western blot. Genotyping of the HLA-DR locus was performed using PCR and sequence-specific oligonucleotide probes. Results: Intracranial calcification and cataract were present in 76.5% and 41.1% of the patients respectively and 62.7% had convulsions. Autoantibodies against the 168 kDa CaSR protein were demonstrated in the serum of 49.0% of the patients and in 13.3% of the controls (P< 0.001). Pre-incubating serum samples from the CaSRAb-positive patients with parathyroid membrane produced a 90% decrease in the band intensity. HLA-DRB1 *01 and DRB1 *09 alleles were significantly associated with idiopathic hypoparathyroidism (relative risk of 7.8, P=0.001). The frequency of HLA-DRB1*09 and DRB1*10 alleles tended to be higher in patients positive for the CaSRAb. There was no significant difference in the frequency of occurrence of convulsions, cataract, intracranial calcification, calcium:phosphorus ratio, and iPTH levels between patients with and without CaSRAb. Conclusion: 49.0% of the patients studied had serological evidence of organ-specific autoimmunity against the CaSR protein. The occurrence of CaSRAb and the HLA-DR associations imply an autoimmune component to the disease, but the primary role of the CaSRAb in the pathogenesis of the disease needs to be assessed further

Reversal of subclinical adrenal insufficiency through antituberculosis treatment in TB patients: a longitudinal follow up

Background & Objective: Subclinical adrenal insufficiency has been shown to occur in patients with tuberculosis. Whether this insufficiency can be reversed with therapy and on long-term follow up, is not known. We studied the effect of antituberculosis treatment (ATT) with respect to reversal of the adrenal insufficiency, as assessed by response to standard dose adrenocorticotropin (ACTH) stimulation test in TB patients. Methods: One hundred and five HIV-negative tuberculosis patients were studied. Of these, 72 patients had pulmonary and 33 had extrapulmonary forms of the disease. Baseline (pre-treatment) standard-dose ACTH stimulation test was done on all the subjects, following which, they were put on standard antituberculosis therapy, depending on the type of disease and were followed up for a period of 30 months. ACTH stimulation tests were performed at follow up, every 6 months. Results: Baseline (pre-treatment) standard-dose ACTH stimulation test revealed an impaired response in 52 of 105 patients (49.5%). At 6 months, the percentage of responders had increased to 71 per cent with a gradual increasing trend noted thereafter. At 24 months, 31 of the 32 patients (97%) who were followed up demonstrated a normal response to ACTH stimulation. The percentage of responders was comparable in both pulmonary [21 of 22 patients (95%)] and extrapulmonary TB [10 of 10 patients (100%)] groups at follow up. Interpretation & Conclusion: Our study shows that nearly half of patients with active tuberculosis had a subclinical adrenal insufficiency indicated by an impaired response to ACTH stimulation test. This insufficiency reverse with therapy in most patients on long-term follow up

Simultaneous presentation of pulmonary tuberculosis and lung cancer: experience from a regional cancer centre

Background: Prevalence of pulmonary tuberculosis is very high in India. Lung cancer is the most common cancer in males in Delhi and because of close similarity in clinical and radiological features of lung cancer and tuberculosis many of lung cancer patients have had received empirical anti tubercular treatment (ATT) before a diagnosis of lung cancer was established. True incidence of pulmonary tuberculosis in lung cancer is not known. Tuberculosis in lung cancer may get reactivated following chemotherapy and/or radiation therapy. Simultaneous presentation of tuberculosis and lung cancer independent of treatment with immunosuppresants, however, is rare. Material and Methods: At our center we evaluated records of 580 lung cancer patients seen over a period of 5 years to see incidence of pulmonary tuberculosis in lung cancer. Patients who had been worked up for pulmonary tuberculosis like sputum or bronchoalveolar lavage (BAL) for AFB smear or culture were identified. Results: Two hundred and ninety eight of these patients were worked up for pulmonary tuberculosis. Twelve patients in the present study had documented evidence of simultaneous existence of pulmonary tuberculosis (acid fast bacilli positive sputum and or culture positivity) and lung cancer. Radiologically, no separate active tubercular lesion was identified except in one patient who had left upper zone fibro parenchymal lesion. Fibrosis and calcification on chest X-rays (CXR) suggestive of old tuberculosis were evident in 7 patients. Eight patients died of progressive lung cancer within 3 months of diagnosis, 4 patients became acid fast bacilli (AFB) negative after 2 months of anti tubercular therapy. Diagnosis of lung cancer was delayed in 4 patients as they were receiving anti tubercular therapy after detection of AFB in sputum. Conclusion: Recognition of tuberculosis is important not only because it is curable but also due to the fact that its presence interferes with radiological assessment to chemotherapy and radiotherapy. Sputum acid fast smear may be done more frequently in patients of lung cancer in countries where tuberculosis has high prevalence. The true incidence may be still higher and newer techniques e.g. PCR based and others may help in knowing true incidence of co existence of lung cancer and pulmonary tuberculosis

Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis

Objective: A large proportion of vulvovaginal candidiasis (VVC) in diabetes is due to non-albicans Candida species such as C. glabrata and C. tropicalis. Observational studies indicate that diabetic patients with C. glabrata VVC respond poorly to azole drugs. We evaluated the response to oral fluconazole and boric acid vaginal suppositories in diabetic patients with VVC. Research Design And Methods: A total of 112 consecutive diabetic patients with VVC were block randomized to receive either single-dose oral 150-mg fluconazole or boric acid vaginal suppositories (600 mg/day for 14 days). The primary efficacy outcome was the mycological cure in patients with C. glabrata VVC in the two treatment arms. The secondary outcomes were the mycological cure in C. albicans VVC, overall mycological cure irrespective of the type of Candida species, frequencies of yeast on direct microscopy, and clinical symptoms and signs of VVC on the 15th day of treatment. Intention-to-treat (ITT; n = 111) and per-protocol (PP; n = 99) analyses were performed. Results: C. glabrata was isolated in 68 (61.3%) and C. albicans in 32 (28.8%) of 111 subjects. Patients with C. glabrata VVC showed higher mycological cure with boric acid compared with fluconazole in the ITT (21 of 33, 63.6% vs. 10 of 35, 28.6%; P = 0.01) and PP analyses (21 of 29, 72.4% vs. 10 of 30, 33.3%; P = 0.01). The secondary efficacy outcomes were not significantly different in the two treatment arms in the ITT and PP analyses. Conclusions: Diabetic women with C. glabrata VVC show higher mycological cure with boric acid vaginal suppositories given for 14 days in comparison with single-dose oral 150-mg fluconazole