2-deoxy-D-glucose as an adjunct to standard of care in the medical management of COVID-19: a proof-of-concept and dose-ranging randomised phase II clinical trial.

BACKGROUND: At present, no single efficacious therapeutic exists for acute COVID-19 management and a multimodal approach may be necessary. 2-deoxy-D-glucose (2-DG) is a metabolic inhibitor that has been shown to limit multiplication of SARS-CoV-2 in-vitro. We evaluated the efficacy and safety of 2-DG as adjunct to standard care in the treatment of moderate to severe COVID-19 patients. METHODS: We conducted a randomized, open-label, phase II, clinical study to evaluate the efficacy, safety, and tolerability of 2-DG administered as adjunct to standard of care (SOC). A total of 110 patients between the ages of 18 and 65 years with moderate to severe COVID-19 were included. Patients were randomized to receive 63, 90, or 126 mg/kg/day 2-DG in addition to SOC or SOC only. Times to maintaining SpO2 ≥ 94% on room air, discharge, clinical recovery, vital signs normalisation, improvement by 1 and 2 points on WHO clinical progression scale, negative conversion on RT-PCR, requirement for intensive care, and mortality were analyzed to assess the efficacy. RESULTS: Patients treated with 90 mg/kg/day 2-DG plus SOC showed better outcomes. Time to maintaining SpO2 ≥ 94% was significantly shorter in the 2-DG 90 mg compared to SOC (median 2.5 days vs. 5 days, Hazard ratio [95% confidence interval] = 2.3 [1.14, 4.64], p = 0.0201). Times to discharge from isolation ward, to clinical recovery, and to vital signs normalization were significantly shorter for the 2-DG 90 mg group. All three doses of 2-DG were well tolerated. Thirty-three (30.3%) patients reported 65 adverse events and were mostly (86%) mild. CONCLUSIONS: 2-DG 90 mg/kg/day as adjunct to SOC showed clinical benefit over SOC alone in the treatment of moderate to severe COVID-19. The promising trends observed in current phase II study is encouraging for confirmatory evaluation of the efficacy and safety of 2-DG in a larger phase III trial. TRIAL REGISTRATION: CTRI, CTRI/2020/06/025664. Registered 5th June 2020, http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=44369&EncHid=&modid=&compid=%27,%2744369det%27 .

Urinary metabolic modulation in human participants residing in Siachen: a 1H NMR metabolomics approach.

The main physiological challenge in high altitude environment is hypoxia which affects the aerobic metabolism reducing the energy supply. These changes may further progress toward extreme environment-related diseases. These are further reflected in changes in small molecular weight metabolites and metabolic pathways. In the present study, metabolic changes due to chronic environmental hypoxia were assessed using 1H NMR metabolomics by analysing the urinary metabolic profile of 70 people at sea level and 40 people at Siachen camp (3700 m) for 1 year. Multivariate statistical analysis was carried out, and PLSDA detected 15 metabolites based on VIP score > 1. ROC analysis detected cis-aconitate, Nicotinamide Mononucleotide, Tyrosine, Choline and Creatinine metabolites with a high range of sensitivity and specificity. Pathway analysis revealed 16 pathways impact > 0.05, and phenylalanine tyrosine and tryptophan biosynthesis was the most prominent altered pathway indicating metabolic remodelling to meet the energy requirements. TCA cycle, Glycine serine and Threonine metabolism, Glutathione metabolism and Cysteine alterations were other metabolic pathways affected during long-term high-altitude hypoxia exposure. Present findings will help unlock a new dimension for the potential application of NMR metabolomics to address extreme environment-related health problems, early detection and developing strategies to combat high altitude hypoxia.

Does the initial chest radiograph severity in COVID-19 impact the short- and long-term outcome? - a perspective from India.

PURPOSE: The chest radiograph (CXR) is among the most widely used investigations in coronavirus disease 2019 (COVID-19) patients. Little is known about its predictive role on the long-term outcome. The purpose of this study was to explore its association with the short and long-term outcome in COVID-19 patients. METHODS: A total of 1530 patients were assessed for the presence, radiographic pattern and distribution of lung lesions observed on baseline chest radiographs obtained at admission. The Brixia scoring system was applied for semiquantitative assessment of lesion severity. Short-term outcome was determined by clinical severity, duration of hospitalization and mortality. The 1415 survivors in this group were assessed after 5-6 months for the presence of residual symptoms. RESULTS: About 67% patients had an abnormal baseline CXR. Bilateral involvement with a basal preponderance was observed and ground-glass opacification was the most frequent finding. The Brixia score ranged from 0 to 16, median 2, interquartile range (IQR) [0-6]. About 36% patients were symptomatic on 5-6-month follow-up, with fatigability being the commonest symptom. A good correlation was observed between the CXR score and disease severity as well as duration of hospitalization. On multivariate analysis, the CXR score was found to be a significant independent predictor of in-patient mortality as well as presence of long-term residual symptoms in survivors. CONCLUSIONS: Disease severity as seen on the chest radiograph appears to play an important role in driving the short and long-term consequences of COVID-19 and could serve as a prognostic indicator, which influences short-term management and long-term follow-up.

Brain functional connectivity in patients with hyperthyroidism after anti-thyroid treatment.

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

Neurometabolite Changes in Hyperthyroid Patients Before and After Antithyroid Treatment: An in vivo 1H MRS Study.

Purpose: Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (1H MRS). Materials and Methods: We collected neuropsychological and 1H MRS data from posterior parietal cortex and DLPFC, in both control (N = 30) and hyperthyroid (N = 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired t-test was applied in patients at baseline and follow-up. Spearman's rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment. Results: Our results revealed a significant decrease in choline/creatine [glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr)] in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (N-acetyl aspartate + N-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment. Conclusion: The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.

Challenges faced in establishing a dedicated 250 bed COVID-19 intensive care unit in a temporary structure.

An Intensive Care Unit (ICU) is an organized system for the provision of care to critically ill patients that provides intensive and specialized medical and nursing care, an enhanced capacity for monitoring, and multiple modalities of physiologic organ support to sustain life during a period of life-threatening organ system insufficiency. While this availability of trained manpower and specialized equipment makes it possible to care for critically ill patients, it also presents singular challenges in the form of man and material management, design concerns, budgetary concerns, and protocolization of treatment. Consequently, the establishment of an ICU requires rigorous design and planning, a process that can take months to years. However, the Coronavirus disease-19 (COVID-19) epidemic has required the significant capacity building to accommodate the increased number of critically ill patients. At the peak of the pandemic, many countries were forced to resort to the building of temporary structures to house critically ill patients, to help tide over the crisis. This narrative review describes the challenges and lessons learned while establishing a 250 bedded ICU in a temporary structure and achieving functionality within a period of a fortnight.

Aberrant intra and inter network resting state functional connectivity in thyrotoxicosis.

Thyroid hormones epigenetically play an important role in the regularisation of neural networks and in neural differentiation during brain development. The present study aimed to explore the intra and inter network resting state functional connectivity changes underlying the neurobehavioural symptoms in thyrotoxicosis. To understand the pathophysiological changes, we investigated the correlation between functional connectivity and clinical and behavioural measures. Twenty-eight freshly diagnosed thyrotoxicosis patients suffering with symptoms such as palpitation, loss of weight, trembling and heat intolerance from days to weeks and 28 healthy controls were recruited for the study. Thyrotoxicosis patients showed significantly decreased functional connectivity in sensorimotor network, fronto-temporal network, default mode network, right fronto-parietal network, left fronto-parietal network and salience network. Inter network functional connectivity was significantly reduced between the basal ganglia network and sensorimotor network and increased between the salience network and fronto-temporal network in thyrotoxicosis. Cognitive functions such as visual retention, recognition of objects, mental balance and performance on neuropsychological tests (ie, the Bender Gestalt test, Nahar-Benson test and Mini Mental State Examination) also showed significant decline in thyrotoxicosis patients. The altered intrinsic resting state functional connectivity might underlie these cognitive deficits. The increased functional connectivity between the salience network and fronto-temporal network suggests the recruitment of additional neuronal circuitry needed to compensate for the neuropathology in the primary neural network in thyrotoxicosis.

Alteration in intrinsic and extrinsic functional connectivity of resting state networks associated with subclinical hypothyroid.

Subclinical hypothyroidism (SCH) is characterized by mild elevation of thyroid stimulating hormone (TSH) (range 5-10 µIU/ml) and normal free triiodothyronine (FT3) and free thyroxine (FT4). The cognitive function impairment is well known in thyroid disorders such as hypothyroidism and hyperthyroidism, but little is known about deficits in brain functions in SCH subjects. Also, whether hormone-replacement treatment is necessary or not in SCH subjects is still debatable. In order to have an insight into the cognition of SCH subjects, intrinsic and extrinsic functional connectivity (FC) of the resting state networks (RSNs) was studied. For resting state data analysis we used an unbiased, data-driven approach based on Independent Component Analysis (ICA) and dual-regression that can emphasize widespread changes in FC without restricting to a set of predefined seeds. 28 SCH subjects and 28 matched healthy controls (HC) participated in the study. RSN analysis showed significantly decreased intrinsic FC in somato-motor network (SMN) and right fronto-parietal attention network (RAN) and increased intrinsic FC in default mode network (DMN) in SCH subjects as compared to control subjects. The reduced intrinsic FC in the SMN and RAN suggests neuro-cognitive alterations in SCH subjects in the corresponding functions which were also evident from the deficit in the neuropsychological performance of the SCH subjects on behavioural tests such as digit span, delayed recall, visual retention, recognition, Bender Gestalt and Mini-Mental State Examination (MMSE). We also found a significant reduction in extrinsic network FC between DMN and RAN; SMN and posterior default mode network (PDMN); and increased extrinsic FC between SMN and anterior default mode network (ADMN) in SCH subjects as compared to controls. An altered extrinsic FC in SCH suggests functional reorganization in response to neurological disruption. The partial correlation analysis between intrinsic and extrinsic RSNs FC and neuropsychological performances as well as clinical indices give interesting insights into brain-behavior relationship in SCH subjects. This article is protected by copyright. All rights reserved.

Trimester specific reference intervals for thyroid function tests in normal Indian pregnant women.

CONTEXT: Accurate assessment of thyroid function during pregnancy is critical, for initiation of thyroid hormone therapy, as well as for adjustment of thyroid hormone dose in hypothyroid cases. AIMS: We evaluated pregnant women who had no past history of thyroid disorders and studied their thyroid function in each trimester. SETTINGS AND DESIGN: 86 normal pregnant women in the first trimester of pregnancy were selected for setting reference intervals. All were healthy, euthyroid and negative for thyroid peroxidase antibody (TPOAb). These women were serially followed throughout pregnancy. 124 normal nonpregnant subjects were selected for comparison. MATERIAL AND METHODS: Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and anti-TPO were measured using Roche Elecsys 1010 analyzer. Urinary iodine content was determined by simple microplate method. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. STATISTICAL ANALYSIS: SPSS (version 14.0, SPSS Inc., Chicago, IL, USA) was used for data processing and analysis. RESULTS: The reference intervals for the first, second and third trimesters for the following parameters: TSH 0.09-6.65, 0.51-6.66, 0.91-4.86 µIU/mL, FT4 9.81-18.53, 8.52-19.43, 7.39-18.28 pM/L and FT3 3.1-6.35, 2.39-5.12, 2.57-5.68 pM/L respectively. Thyroid hormone concentrations significantly differed during pregnancy at different stages of gestation. The pregnant women in the study had median urinary iodine concentration of 150-200 µg/l during each trimester. CONCLUSIONS: The trimester-specific reference intervals for thyroid tests during pregnancy have been established for pregnant Indian women serially followed during pregnancy using 2.5th and 97.5th percentiles.

Correlation between bone mineral density measured by peripheral and central dual energy X-ray absorptiometry in healthy Indian children and adolescents aged 10-18 years.

There are few large-scale studies on the utility of peripheral dual energy X-ray absorptiometry (pDXA) in children. As central dual energy X-ray absorptiometry (cDXA) equipment is not commonly available in the developing world, we assessed the correlation of bone mineral density (BMD) with cDXA and pDXA in children to determine the optimal Z-score thresholds of pDXA for predicting two predefined Z-score cutoffs (≤-1, ≤-2) of cDXA in 844 subjects (441 boys, 403 girls) aged 10-18 years. The BMD of antero-posterior lumbar spine (L1-L4), proximal femur and forearm was measured by cDXA, while the peripheral BMD of forearm and calcaneus was estimated using pDXA. The correlation was statistically significant at all sites (p<0.01). The coefficients ranged from 0.56 to 0.79 in boys and 0.17 to 0.32 in girls. A significant positive correlation was observed between BMD by pDXA and cDXA in Indian children, with a strong gender difference in both the extent of correlation and the ability of peripheral BMD to predict central BMD.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

BACKGROUND & OBJECTIVES: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. METHODS: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. RESULTS: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. INTERPRETATION & CONCLUSIONS: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Status of thyroid function in Indian adults: two decades after universal salt iodization.

OBJECTIVES: The aim was to find impact of two decades of universal salt iodization on the prevalence of goiter, thyroid autoimmunity and thyroid dysfunction in Indian adults. METHODS: This was a cross sectional study from Delhi, India. The subject population included 4409 adult members of resident welfare associations of 5 residential colonies, from 18-90 years of age, who participated in general health check-up camps. The subjects underwent a detailed evaluation including history, anthropometry, goiter grading, USG thyroid, thyroid auto-antibodies and thyroid function tests. All these subjects were regularly consuming iodized salt. RESULTS: Overall, 9.6% of subjects had clinical goiter (13.3% women and 3.3% in men). Prevalence of nodules on palpation was found to be in 1.6% which was lower in men. The nodule prevalence increased to 4.6% in men and 5.6% in women on ultrasonography. Thyroid hypoechogenicity was seen in 30.6% of subjects with severe hypoechogenicity higher in women (5.7% men and 15.5% women). TPO antibody was positive in 13.3% adults and it showed a positive correlation with age, female sex and hypothyroidism. Subclinical hypothyroidism was the commonest abnormality encountered and affected 19.3% subjects (15.9% men; 21.4% women). Thyroid dysfunction showed a rising trend with age in both genders. CONCLUSIONS: Normal UIE and low goiter prevalence, especially in males, suggest success of the universal salt iodization program in the region under review. High prevalence of subclinical hypothyroidism was not correlated with either thyroid autoimmunity or iodine intake, as reflected in urinary iodine excretion.

Thyroid function and bone mineral density among Indian subjects.

BACKGROUND: Thyroid hormones affect bone remodeling in patients with thyroid disease by acting directly or indirectly on bone cells. In view of limited information on correlation of thyroid function with bone mineral density (BMD) in euthyroid subjects, we undertook this study to evaluate the correlation between thyroid function with BMD in subjects with normal thyroid function and subclinical hypothyroidism. MATERIAL AND METHODS: A total of 1290 subjects included in this cross sectional study, were divided in Group-1 with normal thyroid function and Group-2 with subclinical hypothyroidism. Fasting blood samples were drawn for the estimation of serum 25(OH)D, intact parathyroid hormone, total and ionized calcium, inorganic phosphorus, and alkaline phosphatase. BMD at lumbar spine, femur, and forearm was measured. RESULTS: BMD at all sites (radius, femur, and spine) were comparable in both groups. There was no difference in BMD when subjects were divided in tertiles of TSH in either group. In group-1, FT4 and TSH were positively associated with BMD at 33% radius whereas FT3 was negatively associated with BMD at femoral neck in multiple regression analysis after adjustment for age, sex, BMI, 25(OH)D and PTH levels. In group-2, there was no association observed between TSH and BMD at any site. Amongst all study subjects FT4 and FT3 were positively correlated with BMD at lumbar spine and radius respectively among all subjects. CONCLUSION: TSH does not affect BMD in euthyroid subjects and subjects with subclinical hypothyroidism. Thyroid hormones appear to have more pronounced positive effect on cortical than trabecular bone in euthyroid subjects.

Thyroid status two decades after salt iodization: country-wide data in school children from India.

OBJECTIVE: Country-wide evaluation of thyroid disorders in school children following two decades of universal salt iodization (USI) has not been carried out till date. This study was planned with aim to assess thyroid status of school children two decades after the launch of USI programme. DESIGN: Population survey. PATIENTS: We collected data from 25 schools in 19 cities across five different geographical zones of India. Those children who were evaluated for anthropometry, and goitre status by palpation formed 'total population'. Children who consented to give blood samples were defined as 'study population'. MEASUREMENTS: Serum free T3, free T4, TSH, anti-TPO antibody and thyroid ultrasound. RESULTS: A total of 38,961 children aged 5-15 years formed total population. Goitre rate was 15.5% while thyroid hypoechogenicity was found in 4404 (11.3%) children. In the study population (13,790 children), 2258 (16.4%) had goitre, 505 (3.7%) had positive anti-TPO antibody titres, 1001 (7.3%) had hypothyroidism (TSH > 5.2 µIU/ml) and 41 (0.3%) had thyrotoxicosis (TSH < 0.1 µIU/ml). Among goitrous children, 203 (9.0%) had anti-TPO positivity, 365 (16.1%) had hypoechogenicity of thyroid and either of these were present in 488 (21.6%) children. CONCLUSIONS: Endemic goitre in school children persisted nationwide, despite more than two decades of USI programme. Thyroid autoimmunity only partially explains the increase in goitre prevalence.

The evolution of thyroid function with puberty.

OBJECTIVE: This study was planned to describe thyroid functional status in different stages of puberty. STUDY DESIGN: We collected data from five schools across different geographical zones of Delhi. All children who consented were evaluated for anthropometry, pubertal stage, goitre status, serum free T3 (FT3), free T4 (FT4), TSH, anti-TPO (thyroid peroxidase) antibodies and thyroid ultrasound. From this sample, a disease- and risk-free or 'reference population' was obtained by excluding those with history of thyroid disease or use of thyroid medications, family history of thyroid disease, goitre, hypoechogenicity or nodularity on ultrasound or positive antithyroid antibodies. RESULTS: The 'total population' comprised 3722 children; the 'reference population' comprised 2134 subjects. The mean, median, 3rd and 97th percentiles of serum FT3, FT4 and TSH for each stage of puberty were obtained. In both boys and girls, FT3 increased with entry into puberty and either stayed constant or declined marginally after stage 3 of puberty. In contrast, in both genders, FT4 decreased with entry into puberty and stayed relatively constant after stage 3 of puberty. TSH levels declined through puberty in boys, but remained largely unchanged in girls. An increased conversion of T4 to T3 is the possible explanation for this finding. CONCLUSIONS: This large community-based study in school-age children using strict exclusion criteria provides data of thyroid function in the various stages of puberty. There is no evidence of 'thyroidarche' during or preceding puberty.

Dyslipidemia in subclinical hypothyroidism in an Indian population.

OBJECTIVES: In view of inconsistent reports on the prevalence of dyslipidemia in subclinical hypothyroidism (SCH), we studied lipid abnormalities in Indian subjects with SCH. DESIGN AND METHODS: A cross sectional study of 5343 subjects divided in two groups, Group-1 (age≤18 years) and Group-2 (age>18 years) was undertaken. They were further subdivided on the basis of their thyroid functional status: Normal (Control); SCH with TSH≤10.0mIU/L (SCH-1); and SCH with TSH>10mIU/L (SCH-2). RESULTS: Prevalence of SCH was 14.7%. The only lipid abnormality in children and adolescents was low HDL in subjects with TSH>10mIU/L compared with controls. Serum total cholesterol (TC), and LDL cholesterol (LDL) were significantly higher in adults with TSH>10mIU/L compared to controls. There were no significant changes in lipid parameters in subjects with SCH having TSH≤10.0mIU/L, compared to controls. Serum TSH was positively and FT3 and FT4 were negatively correlated with TC and LDL. CONCLUSIONS: Atherogenic lipid abnormalities were observed in adult subjects with SCH-2 (TSH>10.0mIU/L), and not in subjects with SCH-1 who had TSH≤10.0mIU/L in Indian population.

Vitamin D status in healthy Indians aged 50 years and above.

INTRODUCTION: There is widespread prevalence of vitamin D deficiency from new-born to infancy, childhood and adult male and females (non-pregnant, pregnant and lactating). However, there is limited information of the vitamin D status in elderly Indians. MATERIAL AND METHODS: The study was carried in 1346 healthy subjects more than 50 years of age residing in Delhi, India. These subjects, who were divided in two groups: Group-1 (50-< 65 years) and Group-2 (> or = 65 years), underwent anthropometric, biochemical and hormonal evaluation for vitamin D status Bone mineral density was measured by dual X-ray absorptiometry. RESULTS: There were 643 males and 703 females, with a mean age of 58.0 +/- 9.5 years (range 50-84 years). Vitamin D deficiency [VDD, serum 25(OH)D levels < 20 ng/ml) was present in 1228 (91.2%) and Vitamin D insufficiency [VDI, serum 25(OH)D levels 20-< 30 ng/ml] in 92 (6.8%). There was no significant difference in prevalence of either VDD or VDI between two age groups and sexes. Serum 25(OH)D levels were negatively correlated with PTH levels (r -0.027, p <0.00001) and BMI (r -0.128, p 0.05). Prevalence of secondary hyperparathyroidism increased from 14.1% to 43.1% from VDI to severe VDD. PTH levels started rising at vitamin D level < 30 ng/ml. However, more than 50% of subjects with severe VDD had PTH levels within normal range. High prevalence of osteopenia (50.2%) and osteoporosis (31.2%) was observed in this population. CONCLUSION: Hypovitaminosis D is universal above the age of 50 years in north India. Absence of a PTH response was observed in more than 50% of individuals with VDD, the cause of which merits further evaluation. Normal bone mass was observed in only 18.6% of study subjects.

Nationwide reference data for height, weight and body mass index of Indian schoolchildren.

BACKGROUND. The assessment of growth is crucial for child care and reference data are central to growth monitoring. We aimed to assess the height, weight and body mass index (BMI) of Indian schoolchildren in order to develop genderappropriate growth charts for children 5-18 years of age. METHODS. Cross-sectional evaluation of anthropometric parameters (height, weight and BMI) was done in Indian schoolchildren (3-18 years) randomly selected from both fee-paying (upper socioeconomic strata) and non-fee paying (lower socioeconomic strata) schools from 4 regions (north, south, east and west) of India. A total of 106 843 children were evaluated, of which 42 214 children (19 303 boys, 22 911 girls) were from the lower socioeconomic strata and 64 629 children (34 411 boys, 30 218 girls) were from the upper socioeconomic strata. Normative charts, using the lambda-mu-sigma (LMS) method to smoothen the curves, were drawn from children belonging to the upper socioeconomic strata, in view of the gross discrepancy between the two socioeconomic strata. RESULTS. Height, weight and BMI percentile (3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th and 97th) data were calculated and charts generated. The height of boys and girls was consistently higher at all ages when compared with earlier India data, but the final height was 2-4 cm lower than that reported in the WHO multicentre study of 2007. Weight centiles showed a rising trend both in boys and girls compared not only to earlier Indian data published in 1992, but also to that reported by the WHO multicentre study. The median weight at all ages in both boys and girls was approximately 4 kg more than that reported in affluent Indian children two decades earlier. CONCLUSION. This large nationwide study indicates secular trends in height, weight and BMI in Indian children from the upper socioeconomic strata. We suggest that the height and weight percentiles reported by us may be used as reference standards for India.

Reference range of thyroid hormones in healthy school-age children: country-wide data from India.

OBJECTIVE: This study was planned to obtain normative data of thyroid functions in school-age children from different regions of India. DESIGN AND METHODS: Students from 36 schools involving 13 states across four geographical zones of India were evaluated for goiter. Subjects who consented, underwent evaluation for serum FT3, FT4, TSH, anti-TPO antibodies and thyroid ultrasound. From this, a "reference population" was obtained by excluding those with personal or family history of thyroid disease, use of thyroid medications, goiter, hypoechogenicity or nodularity on ultrasound or positive anti-thyroid antibodies. RESULTS: Of 24,685 students clinically evaluated, 8665 formed part of the study. The reference population comprised 5343 subjects. The mean, median, 3rd and 97th percentiles of FT3, FT4 and TSH for each year (6-17 years) were obtained. CONCLUSIONS: This community based study in Indian school-age children provides reference intervals for thyroid hormones and evidence against narrowing the TSH reference range.

Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization.

We undertook this study to characterize peak bone density and evaluate its determinants in a healthy cohort of young adult male paramilitary personnel. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 473 healthy men aged 21-40 yr. The effect of anthropometry and biochemical parameters on BMD was determined. Mean BMD values of L1-L4, forearm, total hip, and femoral neck were 1.170+/-0.137, 0.755+/-0.089, 1.129+/-0.130, and 1.115+/-0.133 g/cm(2), respectively. BMD values for 31- to 40-yr age group were lower than those of 20- to 30-yr age group except for forearm, which was higher in the former. Significant positive correlation was observed between height, weight, and body mass index with BMD. On multivariate regression analysis, weight was the most consistent contributor to variance in the BMD. Compared with age-matched US males, BMD of total hip and femoral neck were higher for Indian paramilitary personnel by 3.58% and 4.2%, whereas lumbar spine BMD was lower by 4.1%. In conclusion, peak BMD in healthy Indian males was achieved by 30 yr of age at lumbar spine and hip, with weight being the most consistent contributor to variance in BMD. Peak BMD in this population was comparable to that reported in white US males.