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

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

Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy

Objectives: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. Methods: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffPoeso), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5±2 months. Results: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59±26 to 23±13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57±0.62 to 2.94±0.60 l), forced expiratory volume in the first second (2.21±0.49 to 2.45±0.47 l), total lung capacity (3.57±1.19 to 4.1±1.12 l), diaphragmatic movement during deep respiration (5.5±1.0 to 6.6±1.1 cm) and SniffPoeso (68.7±23 to 93.1±25.2 cmH2O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffPoeso. Conclusions: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis

Evaluation of pulmonary infiltrates in patients with haematological malignancies using fibreoptic bronchoscopy and bronchoalveolar lavage

Background : Chest infection is the major cause of morbidity and mortality among patients with haematological malignancies. Conventional diagnostic methods - chest x-ray , blood and sputum culture have limited yield . We used fibreoptic bronchoscopy and bronchoalveolar lavage to evaluate nature of pulmonary infiltrates on chest x-ray. Patients and Methods : 25 patients with haematological malignancies with fever and pulmonary infiltrates were studied. Patients median age was 32 years, ranging from 16 to 65 years. There were 21 males and 4 females. Initial evaluation included - detailed physical examination including chest to see for any focus of infection. In all patients , base line blood counts (total and differential), chest x-ray and cultures from blood and other body fluids were taken before starting broad spectrum antibiotics . Those not responding over next 48-72 hours received gram positive coverage followed by amphotericin-B therapy . Patients with persistent fever and pulmonary infiltrates were subjected to fibre-optic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) and samples were collected for bacterial, fungal, AFB and viral studies. The findings were correlated with Chest x-ray and CT scan. Results The median time for FOB and BAL was 16 days (range, 3 to 32 days) after the clinical diagnosis of chest infection.. BAL fluid examination/culture grew microbial isolates in 21 of 25 patients (84%). Of thesebacteria alone were present in 10, fungi alone in 1 and polymicrobial isolates were seen in 10 patients (40%). Later included- a combination of bacteria and fungi - in 2 patients, bacteria and AFB - 6 and a combination of bacteria, AFB and fungi were seen in 2 patients. BAL changed the radiological diagnosis in 14 patients (56% diagnostic utility). Therapy was modified according to BAL results in 6 patients (therapeutic utility of 24 %). Concordance between radiological and BAL findings were found only in 5 patients (20%). FOB procedure was tolerated well, with mild and reversible complications (throat pain, transient hypoxia, tachycardia) in some patients. Conclusions: Infections are the main cause of pulmonary infiltrates in patients with haematological malignancies. Bacterial , fungal and mycobacterium tubercular organisms are the main isolates. Isolation of ESBL positive organisms and polymicrobial isolates suggest inclusion of appropriate initial empirical antibiotics in these patients to prevent development of resistant organisms. Higher frequency of AFB isolates (32%) was the surprising finding and need to be confirmed in future studies

The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer

The role of vitamin D (VitD) in calcium and bone homeostasis is well described. In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. VitD deficiency appears to be frequent in industrialized countries. Especially patients with lung diseases have often low VitD serum levels. Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases. Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer. The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells. This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status