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.

Management of nutritional rickets in Indian children: a randomized controlled trial.

INTRODUCTION: Rickets is usually attributed to vitamin D deficiency. However, recent studies have implicated dietary calcium deficiency in its etiology. Information on relative efficacy of calcium, vitamin D or both together in healing of rickets is limited. OBJECTIVE: To study effect of treatment with calcium, vitamin D or a combination of these two on healing of nutritional rickets in young children. DESIGN: Randomized controlled trial. METHODS: Sixty-seven cases of nutritional rickets in the age group of 6 months to 5 years were randomly allocated to receive vitamin D (600 000 IU single intramuscular dose), calcium (75 mg/kg/day elemental calcium orally) or a combination of the above two for a period of 12 weeks. The demographic parameters, nutritional status, dietary calcium and phytate intake were assessed for all. Radiographs (wrist and knee) and biochemical parameters (serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxycholecalciferol and parathyroid hormone) were evaluated at baseline, 6 and 12 weeks for evidence of healing. RESULTS: Mean dietary intake of calcium in all cases was low (204 ± 129 mg/day). Mean serum 25-hydroxycholecalciferol D level was 15.9 ± 12.4 ng/ml, and 82.1% of patients had serum vitamin D levels <20 ng/ml, indicative of vitamin D deficiency. After 6 and 12 weeks of treatment, radiological and biochemical evidence of healing rickets was observed in all treatment groups, albeit to a variable extent. The combined end point of normal serum alkaline phosphatase and complete radiological healing at 12 weeks was observed in 50% subjects on combination therapy as compared with 15.7% subjects on vitamin D alone and 11.7% on calcium alone. CONCLUSIONS: Children with rickets had a low serum vitamin D level and a low dietary calcium intake. The best therapeutic response was seen with a combination of vitamin D and calcium than either of them given alone. TRIAL REGISTRATION NUMBER: CTRI/2010/091/000448.

Reference range of thyroid function (FT3, FT4 and TSH) among Indian adults.

OBJECTIVES: To generate thyroid hormone reference norms using electro-chemiluminescence technique. DESIGN AND METHODS: Cross sectional study on apparently normal 4349 Delhi adults (18-86 years). Predetermined exclusion criteria (goiter, hypoechogenicity or nodularity on ultrasound, elevated anti-thyroid peroxidase antibody, hypo or hyperthyroidism and family history of thyroid dysfunction) excluded 2433 subjects leaving 1916 (916 males and 1000 females) as the reference population. RESULTS: Mean age and BMI of the reference population were 41.2 ± 18.1 years and 24.5 ± 4.4 kg/m(2) respectively. Median urinary iodine excretion was 233.6 µg/L (79-458;3rd-97th centile). The population was categorized into various age groups (18-30, 31-40, 41-50, 51-60, 61-70 and ≥ 70 years). Overall FT3 and FT4 values in the reference population irrespective of age, ranged from 2.4-8.8 (mean 4.6 ± 0.9) pmol/L and 10.1-24.8 (mean 15.40 ± 2.0) pmol/L, respectively. Mean TSH value in the reference population was 2.2 ± 0.9 mIU/L which was significantly lower than that of total population (3.8 ± 6.1; p<0.001). CONCLUSION: FT3 values were observed to be significantly higher in men than women (p=0.001). The centiles (3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th and 97th) of FT3, FT4 and TSH were derived for reference purposes in Indian adults. This community based study in Indian adults has established mean reference intervals for FT3, FT4 and TSH for different age groups for both sexes separately using strict exclusion criteria. These can be used as reference norms for Indian adults.

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.

Role of calcium deficiency in development of nutritional rickets in Indian children: a case control study.

CONTEXT: Nutritional rickets is usually attributed to vitamin D deficiency. Studies from some tropical countries have postulated low dietary intake of calcium as the cause of nutritional rickets. Both vitamin D and dietary calcium deficiency are highly prevalent in India. Information on their relative contribution in the development of rickets in Indian children is limited. OBJECTIVE: The aim was to study the role of calcium and vitamin D deficiency in causation of nutritional rickets in young Indian children. DESIGN AND METHODS: In a case-control study, 67 children with nutritional rickets and 68 age- and sex-matched healthy controls were compared for demographic factors, nutritional status, sun exposure (UV score), dietary calcium and phytate intake (for subjects not breast-fed at presentation), and biochemical parameters [serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxyvitamin D (25OHD), and PTH]. RESULTS: Mean intake of calcium (204±129 vs. 453±234 mg/d; P<0.001) and proportion of calcium from dairy sources (41.7 vs. 88.6%; P<0.001) were significantly lower in cases vs. controls. The dietary intake of phytate was also significantly higher in cases (P=0.01). Median serum 25OHD level (interquartile range) in both cases and controls was in the range of deficiency [13.7 (10; 17.9) and 19.4 (12.3; 24.6) ng/ml, respectively]. There was no significant difference in the serum 25OHD level (P=0.08) or sun exposure as measured by UV score (P=0.39) among the cases and controls. In cases with rickets, significant negative correlations were seen between dietary calcium intake and radiological score (r=-0.28; P=0.03) and PTH (r=-0.26; P=0.02). No correlation was found between serum 25OHD level and radiological score or biochemical parameters of rickets. CONCLUSIONS: Rickets develops when low dietary calcium intake coexists with a low or borderline vitamin D nutrition status.

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.

Impact of two regimens of vitamin D supplementation on calcium - vitamin D - PTH axis of schoolgirls of Delhi.

OBJECTIVE: To determine the efficacy of supplementation with oral vitamin D3 (cholecalciferol) on bone mineral biochemical parameters of school-going girls. SETTING: Government school (government-aided) and Private school (fee paying) in Delhi. DESIGN: Randomized controlled trial. INTERVENTION: Cholecalciferol granules (60,000 IU) orally with water, either once in two months (two-monthly D3 group) or once a month (one-monthly D3 group) for one year. PARTICIPANTS: 290 healthy schoolgirls (6-17 y), 124 from lower socioeconomic strata (LSES) (attending government schools) and 166 from upper socioeconomic strata (USES) (attending private schools). OUTCOME MEASURES: Serum 25(OH)D, calcium, phosphorus, parathyroid hormone, and alkaline phosphatase levels at 6 and 12 months after start of supplementation. RESULTS: At baseline, 93.7% schoolgirls were vitamin D deficient [25(OH)D<50 nmol/L]. While significant increase in serum calcium and decrease in alkaline phosphatase levels was noted in both groups with both interventions, PTH response was inconsistent. In LSES subjects, two-monthly D3 and one-monthly D3 supplementation resulted in a significant increase in serum 25(OH)D levels by 8.3 nmol/L and 11.0 nmol/L, respectively at 6 months (P<0.05). Similarly, the increase in the two intervention arms in USES subjects was 10.5 nmol/L and 16.0 nmol/L, respectively (P<0.05). In both groups, this increase in serum 25(OH)D levels persisted at 12 months (P<0.05). Despite supplementation with 60,000 IU of Vitamin D3 (monthly or two-monthly), only 47% were vitamin D sufficient at the end of one year. CONCLUSIONS: 60,000 IU of cholecalciferol, monthly or two-monthly, resulted in a significant increase in serum 25(OH)D levels in vitamin D deficient schoolgirls.

High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: a case-control study.

OBJECTIVE: The aim was to find the prevalence of polycystic ovary syndrome (PCOS) phenotype in adolescent euthyroid girls with chronic lymphocytic thyroiditis (CLT). DESIGN: This was a prospective case-control study as part of an ongoing community-wide thyroid survey in Indian schools. METHODS: One hundred and seventy-five girls with euthyroid CLT and 46 age-matched non-CLT girls underwent clinical, biochemical, hormonal, and ultrasonographic evaluation for diagnosis of PCOS by Rotterdam 2003 criteria. All subjects underwent serum sampling for LH, FSH, testosterone, DHEAS, free thyroxine, TSH, and anti-thyroid peroxidase (TPO) antibodies. Oral glucose tolerance test (OGTT) was undertaken for plasma glucose and insulin. RESULTS: Significantly higher prevalence of PCOS was noted in girls with euthyroid CLT when compared to their control counterparts (46.8 vs 4.3%, P=0.001). The CLT girls had higher body mass index, waist circumference, and systolic blood pressure (P=0.001). Mean number of menstrual cycles/year was 8.4+/-3.5 vs 10.1+/-1.4, and mean Ferriman-Gallwey score was 11.9+/-3.5 vs 3.0+/-2.4 (P=0.001) in cases versus controls respectively. The fasting and postprandial glucose and serum cholesterol were also higher in the cases (P=0.001). Homeostasis model assessment-insulin resistance was 4.4+/-4.2 vs 2.3+/-2.7 in the cases versus controls (P=0.001). CONCLUSION: Higher prevalence of PCOS characteristics in euthyroid CLT girls when compared to controls suggest possible role of autoimmune phenomenon in the etiopathogenesis of PCOS. Further studies are required to understand the pathogenic link between these two disorders.

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.

Reference range of thyroid hormones in normal Indian school-age children.

OBJECTIVE: There is an ongoing debate on narrowing the TSH reference range in adults. In view of the scarce data on normal values of thyroid function tests in children from India, we planned to establish a reference range for thyroid hormones in school-age children. DESIGN AND SUBJECTS: All children (N = 9527; 6-19 years) from six schools representing various zones of Delhi were evaluated for clinical evidence of goitre, thyroid ultrasound, serum free T3 (FT3), free T4 (FT4) and TSH and anti-thyroid peroxidase (anti-TPO) antibodies. From this sample, a reference population (N = 5122) was obtained by excluding those with a personal or family history of thyroid disease, use of thyroid medications, goitre, hypoechogenicity/nodularity on ultrasound or serum anti-TPO antibodies. MEASUREMENTS: Thyroid hormone (FT3, FT4 and TSH) reference ranges were established for each year of life for the total and reference populations. RESULTS: In the reference population, mean serum FT3 was in the range 4.19-4.84 pm/l for boys and 4.03-4.47 pm/l for girls, mean serum FT4 14.69-17.36 pm/l for boys and 14.32-15.88 pm/l for girls, and mean serum TSH 2.57-3.6 mIU/l for boys and 1.83-3.58 mIU/l for girls. For TSH, the 97th percentile was in the range 6.01-8.4 mIU/l for boys and 5.28-8.04 mIU/l for girls, suggesting that at least in children there may not be a need to reduce the upper limit of normal for serum TSH. CONCLUSIONS: This study provides mean reference intervals for FT3, FT4 and TSH for each year of life for both the sexes separately using strict exclusion criteria.

Vitamin D status of apparently healthy schoolgirls from two different socioeconomic strata in Delhi: relation to nutrition and lifestyle.

Forty to fifty per cent of skeletal mass, accumulated during childhood and adolescence, is influenced by sunlight exposure, physical activity, lifestyle, endocrine status, nutrition and gender. In view of scarce data on association of nutrition and lifestyle with hypovitaminosis D in Indian children and adolescents, an in-depth study on 3,127 apparently healthy Delhi schoolgirls (6-18 years) from the lower (LSES, n 1,477) and upper socioeconomic strata (USES, n 1650) was carried out. These girls were subjected to anthropometry and clinical examination for hypovitaminosis D. Girls randomly selected from the two strata (LSES, n 193; USES, n 211) underwent detailed lifestyle, dietary, biochemical and hormonal assessment. Clinical vitamin D deficiency was noted in 11.5 % girls (12.4 % LSES, 10.7 % USES). USES girls had significantly higher BMI than LSES counterparts. Prevalence of biochemical hypovitaminosis D (serum 25-hydroxyvitamin D < 50 nmol/l) was seen in 90.8 % of girls (89.6 % LSES, 91.9 % USES, NS). Mean intake of energy, protein, fat, Ca, vitamin D and milk/milk products was significantly higher in USES than LSES girls. Conversely, carbohydrate, fibre, phytate and cereal intakes were higher in LSES than USES girls. Physical activity and time spent outdoors was significantly higher in LSES girls (92.8 v. 64 %, P = 0.000). Significant correlation between serum 25-hydroxyvitamin D and estimated sun exposure (r 0.185, P = 0.001) and percentage body surface area exposed (r 0.146, P = 0.004) suggests that these lifestyle-related factors may contribute significantly to the vitamin D status of the apparently healthy schoolgirls. Hence, in the absence of vitamin D fortification of foods, diet alone appears to have an insignificant role.

Prevalence of thyroid autoimmunity in sporadic idiopathic hypoparathyroidism in comparison to type 1 diabetes and premature ovarian failure.

CONTEXT: Thyroid autoimmunity is the most common coexistent endocrinopathy in type 1 diabetes (T1D), Addison's disease, and premature ovarian failure (POF). Although the role of autoimmunity is being investigated in patients with sporadic idiopathic hypoparathyroidism (SIH), there is little information on coexistent thyroid autoimmunity. OBJECTIVE: Our objective was to assess the prevalence of thyroid peroxidase autoantibodies (TPOAb) and thyroid dysfunction in patients with SIH and its comparison with that in T1D, POF, and Hashimoto's thyroiditis (HT) and age- and sex-matched healthy controls (for SIH). DESIGN AND SETTING: We conducted a case control study in a tertiary care setting. PATIENTS AND METHODS: Subjects were consecutive patients with SIH (n = 87), T1D (n = 100), POF (n = 58), and HT (n = 47) and healthy controls (100 females and 64 males). Serum free T3, free T4, TSH, and TPOAb (normal < or = 34 IU/ml) were measured by electrochemiluminescence assay. Subjects with 1) serum TSH at least 5 microU/ml along with TPOAb more than 34 IU/ml; 2) TSH at least 10 microU/ml but normal TPOAb titers; or 3) Graves' disease were considered to have thyroid dysfunction. RESULTS: TPOAb positivity (> 34 IU/ml) in females was 14.6% in SIH, 24.1% in POF, and 42.1% in T1D compared with 76.6% in HT and 9% in healthy controls. The frequencies of TPOAb positivity and thyroid dysfunction in patients with SIH were comparable to those in control and POF groups, but significantly less than in T1D and HT groups. CONCLUSION: The frequencies of TPOAb and thyroid dysfunction were not significantly higher in patients with SIH than in healthy controls, unlike in patients with T1D and POF.

Vitamin D and bone mineral density status of healthy schoolchildren in northern India.

BACKGROUND: Current data on the prevalence of vitamin D deficiency in India are scarce. OBJECTIVE: We assessed the calcium-vitamin D-parathyroid hormone axis in apparently healthy children from 2 different socioeconomic backgrounds in New Delhi, India. DESIGN: Clinical evaluation for evidence of vitamin D deficiency was carried out in 5137 apparently healthy schoolchildren, aged 10-18 y, attending lower (LSES) and upper (USES) socioeconomic status schools. Serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and immunoreactive parathyroid hormone were measured in 760 children randomly selected from the larger cohort. Bone mineral density of the forearm and the calcaneum was measured in 555 children by using peripheral dual-energy X-ray absorptiometry. RESULTS: Clinical evidence of vitamin D deficiency was noted in 10.8% of the children. Children in the LSES group had a significantly (P < 0.01) lower 25(OH)D concentration (10.4 +/- 0.4 ng/mL) than did those in the USES group (13.7 +/- 0.4 ng/mL). Concentrations of 25(OH)D <9 ng/mL were seen in 35.7% of the children (42.3% in LSES; 27% in USES; P < 0.01). Boys had significantly (P = 0.004) higher 25(OH)D concentrations than did girls. There was a significant negative correlation between the mean serum immunoreactive parathyroid hormone and 25(OH) D concentrations (r = -0.202, P < 0.001). Mean forearm bone mineral density was significantly (P < 0.01) higher in the USES group than in the LSES group. CONCLUSION: A high prevalence of clinical and biochemical hypovitaminosis D exists in apparently healthy schoolchildren in northern India.