Development of a simplified new method of bone age estimation using three bones of the hand and wrist.

Though the Greulich and Pyle (GP) method is easy, inter-observer variability, differential maturation of hand bones influences ratings. The Tanner-Whitehouse (TW) method is more accurate, but cumbersome. A simpler method combining the above, such that it utilizes fewer bones without affecting accuracy, would be widely used and more applicable in clinical practice. OBJECTIVES: 1. Devising a simplified method utilizing three bones of the hand and wrist for bone age (BA) assessment. 2. Testing whether the 3 bone method gives comparable results to standard methods (GP,TW2,TW3) in Indian children. METHODS: Developmental stages and corresponding BA for radius, hamate, terminal phalanx (left middle finger) epiphyses combining stages from GP,TW3 atlases were described; BA were rated by two blinded observers. 3 bone method ratings were compared with the same dataset analyzed earlier using GP,TW2,TW3 (4 raters). RESULTS: Radiographs analysed:493 (Girls=226). Mean chronological age:9.4 ± 4.6 yrs, mean BA 3 bone:9.8 ± 4.8 yrs, GP:9.6 ± 4.8 yrs, TW3:9.3 ± 4.5 yrs, TW2:9.9 ± 5.0 yrs. The 3 bone method demonstrated no significant inter-observer variability (p = 0.3, mean difference = 0.02 ± 0.6 yrs); a strong positive correlation (p < 0.0001) with GP (r = 0.985), TW3 (r = 0.983) and TW2 (r = 0.982) was noted. Bland-Altman plots demonstrated good agreement; the root mean square errors between 3 bone and GP,TW3,TW2 ratings were 0.6,0.7,0.6 years; mean differences were 0.19,0.49,-0.14 years respectively. Greatest proportion of outliers (beyond ±1.96 SD of mean difference) was between 6 and 8 years age for difference in 3 bone and GP, and between 4-6 years for difference in 3 bone and TW3,TW2. CONCLUSION: The 3 bone method has multiple advantages; it is easier, tackles differential maturation of wrist and hand bones, has good reproducibility, without compromising on accuracy rendering it suitable for office practice.

Delayed Puberty.

Testicular volume ≥4 ml and appearance of breast budding are the first signs of puberty. Delayed puberty is diagnosed in the absence of thelarche by 13 y or menarche by 15 y in girls and absence of testicular enlargement by 14 y in boys. Delayed puberty can be due to hypogonadotrophic hypogonadism, hypergonadotrophic hypogonadism or eugonadotrophic eugonadism characterised by low, elevated and normal gonadotrophin levels, respectively. Constitutional Delay of Growth and Puberty (CDGP) and systemic illness should be considered before pathological causes. Assessment of sexual maturity by Tanner's staging and anthropometric assessment on growth chart is pivotal. Lack of menarche in girls with thelarche suggests structural abnormalities of reproductive tract or disorders of sexual development. Measurement of bone age helps to interpret hormone measurements and decide on timing of pubertal induction. Ultrasound assessment of abdomen gives valuable clues to pubertal onset (in girls) and possible underlying etiology. Karyotyping is mandatory in all girls with delayed puberty and short stature, and delayed menarche and boys with hypergonadotrophic hypogonadism. Gonadotrophin releasing hormone analogue stimulation test may help distinguish hypogonadotrophic hypogonadism from CDGP. Pubertal induction is done with intramuscular testosterone and oral estradiol in boys and girls, respectively. Hormone replacement is begun at low doses and slowly escalated over 2 y to mimic a physiological puberty process. Short course of testosterone for 3 to 6 mo is helpful in adolescent boys with CDGP and psychological distress. Attainment of adult sexual maturity by 18 y is mandatory to rule out disorders of hypothalamic pituitary gonadal axis.

Prevalence and Determinants of Occurrence of Dyslipidemia in Subjects with Type 1 Diabetes Mellitus.

OBJECTIVE: To describe the prevalence and determinants of occurrence of dyslipidemia in children and adolescents with type 1 diabetes mellitus (T1DM). METHODS: A cross-sectional study was conducted in the diabetic clinic of a tertiary care referral hospital over two years. Subjects with T1DM aged 2-18 y had assessment of Lipid profile after 12 h of fasting. Glycemic control was assessed by glycosylated hemoglobin (HbA1C). Modifiable and nonmodifiable determining factors were assessed during clinic visit as per standard criteria. Body mass index (BMI) more than 23rd adult equivalent and 27th adult equivalent were considered as overweight and obesity, respectively. Lipid parameters were considered as abnormal if: Low density lipoprotein (LDL) > 100 mg/dL, high density lipoprotein (HDL) < 40 mg/dL, triglycerides > 100 mg/dL (< 10 y) and > 130 mg/dL (> 10 y). RESULTS: A total of 171 subjects (mean age: 11.8 ± 3.5 y, M:F = 75:96) were recruited during the study period. The mean fasting LDL level, HDL level, and triglyceride level observed in the study sample were 106.6 ± 26.9 mg/dL (62% abnormal), 52.6 ± 14.3 mg/dL (9.4% abnormal), and 85.3 ± 39.4 mg/dL (10.5% abnormal), respectively; 115 (67.3%) of the subjects had at least one abnormality in the serum lipid profile. On multivariate analysis, HbA1C was the most significant factor in determining the occurrence of dyslipidemia (p < 0.05). HbA1C was 9.9 ± 1.6 in subjects with abnormal LDL versus 9.1 ± 1.5 in those with normal LDL (p < 0.05). CONCLUSION: Prevalence of dyslipidemia in the study children and adolescents with T1DM was 67.3%. HbA1C remains the most important modifiable determinant of the occurrence of dyslipidemia.

A comparison of bone age assessments using automated and manual methods in children of Indian ethnicity.

BACKGROUND: Bone age is useful for pediatric endocrinologists in evaluating various disorders related to growth and puberty. Traditional methods of bone age assessment, namely Greulich and Pyle (GP) and Tanner-Whitehouse (TW), have intra- and interobserver variations. Use of computer-automated methods like BoneXpert might overcome these subjective variations. OBJECTIVE: The aim of our study was to assess the validity of BoneXpert in comparison to manual GP and TW methods for assessing bone age in children of Asian Indian ethnicity. MATERIALS AND METHODS: We extracted from a previous study the deidentified left hand radiographs of 920 healthy children aged 2-19 years. We compared bone age as determined by four well-trained manual raters using GP and TW methods with the BoneXpert ratings. We computed accuracy using root mean square error (RMSE) to assess how close the bone age estimated by BoneXpert was to the reference rating. RESULTS: The standard deviations (SDs) of rating among the four manual raters were 0.52 years, 0.52 years and 0.47 years for GP, TW2 and TW3 methods, respectively. The RMSEs between the automated bone age estimates and the true ratings were 0.39 years, 0.41 years and 0.36 years, respectively, for the same methods. The RMSE values were significantly lower in girls than in boys (0.53, 0.5 and 0.47 vs. 0.39, 0.47 and 0.4) by all the methods; however, no such difference was noted in classification by body mass index. The best agreement between BoneXpert and manual rating was obtained by using 50% weight on carpals (GP50). The carpal bone age was retarded in Indian children, more so in boys. CONCLUSION: BoneXpert was accurate and performed well in estimating bone age by both GP and TW methods in healthy Asian Indian children; the error was larger in boys. The GP50 establishes "backward compatibility" with manual rating.

Utility of wrist circumference in recognition of metabolic syndrome in overweight and obese South Indian children and adolescents.

OBJECTIVE: To describe the utility of wrist circumference in the identification of cardiometabolic risk in overweight and obese children. METHODS: A cross-sectional study was conducted in the obesity clinic of a tertiary care referral hospital over a two year period. All children and adolescents aged 5-17 years with nutritional overweight and obesity were recruited. Data pertaining to chronological age, sex, risk factors and family history were collected. Clinical assessment of anthropometry: Weight, height, body mass index (BMI), Tanner's stage, wrist circumference, blood pressure, waist circumference and triceps skinfold thickness done as per standard criteria. Biochemical assessment of blood glucose, serum insulin, lipid profile, and Homeostatic Model for Insulin Resistance performed after 12 h of fasting. RESULTS: We recruited 118 subjects (mean age 10.9 years, 71.1% males, 87.3% obese and 12.7% overweight); 30 (25.4%) had metabolic syndrome. The mean z scores of wrist circumference of children who presented with and without metabolic syndrome was 2.7 ± 0.8 and 2.1 ± 0.7, respectively (p<0.05). We observed a fair positive correlation between wrist circumference z score and BMI z score, (r=0.5; p<0.05). On receiver operating characteristic curve analysis, 97th percentile of wrist circumference predicted metabolic syndrome among overweight and obese children with a sensitivity of 86.7% and specificity of 37.5% (AUC=0.675). CONCLUSIONS: Wrist circumference with 97th percentile as a cut-off is a useful tool to identify metabolic syndrome amongst overweight and obese children and adolescents.

Clinical Profile of Adolescents With Delayed Puberty.

One year study on forty-eight adolescents with delayed puberty revealed etiology of constitutional delay, hypogonadotrophic hypogonadism (HH), hypergonadotrophic hypogonadism, chronic systemic disease, hypothyroidism and sex reversal in 14(29.2%), 13 (27%), 12 (25%), 5 (10.4%), 3 (6.3%) and 1 (2.1%) cases, respectively. Earlier presentation, male preponderance, significant normal variants and utility of GnRH analogue testing observed .

Type 2 Diabetes Mellitus in Adolescents From Southern India - A Single Center Experience.

This 1-year follow-up study was conducted on 21 subjects with type 2 diabetes mellitus. We found reduction in glycosylated hemoglobin from 10.5% to 8.1%, and maintenance of BMI z-scores from 3.9 to 3.8. Majority of the patients could be weaned-off from insulin. Heterogeneous presentation, frequent co-morbidities and complications, and familial clustering were observed.

Care of children with type 1 diabetes mellitus in school - An interventional study.

OBJECTIVES: Paucity of data from India on care of children with Type 1 diabetes in schools. Aims: To study assess the knowledge, attitude, practices and fear of Type 1 diabetes in school teachers and to assess the impact of an educational model on the fear of teachers and care of children in Type 1 DM at school hours. METHODS: A community based study, involving school teachers and the intervention being educating them about diabetes conducted. Data pertaining to basic demography, attitude of teachers towards diabetic children, Hypoglycemia fear factor survey- parent version with worries domain and preparedness of school was collected. An education program was conducted on diabetes care in children. Immediately and after three months, the proforma details and HFSP-W scores reassessed. RESULTS: Forty two teachers (mean age: 38.7±5.4; M:F ratio 2:40) participated in the study. Post intervention, a higher willingness to have the diabetic child in class (100 vs. 57.1%; p>0.05), better support in daily care (100 vs. 92%; p>0.05), participation in sports activities (100 vs. 7.1%; p<0.05) observed. HFSP-W scores were 38.8±4.5 (pre-intervention), 22.5±4.3 (immediate post intervention) and 29.5±3.2 (at 3months) (p<0.05). To study the determinants of improvement in HFSP-W a regression analysis was performed: presence of glucometer the most likely determining factor (T=1.999, p=0.05). CONCLUSION: There is a significant element of fear in the minds of teachers towards hypoglycemia which improves with a structured education program.

A Study on New IAP 2015 Growth References in Rural South Indian Children.

OBJECTIVES: To ascertain the utility of the new pan Indian 2015 IAP references in rural South Indian children and the ability of new IAP charts to recognise children with abnormal cardiometabolic risk factors in 10 to 16 y age group. METHODS: Among school health camps conducted at two centres of Tamil Nadu- rural Vellore and rural Erode- height, weight, waist circumference, blood pressure, triceps skin-fold thickness and body fat percentage were measured by trained pediatricians and Z-scores calculated. The anthropometric measures were studied as per IAP 2015 references and compared to other national and international references. Their utility in identification of malnutrition and cardiometabolic risk ascertained. RESULTS: A total of 420 children (210 from Erode and 210 from Vellore) in the age group of 10 to 16 y were included in the study. New IAP references recognized more short stature (4.2 vs. 3%), wasting (11 vs. 1.5%) and overweight (14.2 vs. 13.2%) children compared to old IAP charts. The Z-scores of anthropometric measures as per New IAP 2015 references had significant correlation with old IAP and other international data (p < 0.05). It was noted that new IAP charts could detect 83.3%, old IAP chart 50% and WHO 83.3% of subjects with malnutrition. New IAP charts could detect 70.3% cardiometabolic risk associated with over nutrition compared to old IAP (57.4%) and WHO (51.8%). CONCLUSIONS: There is a significant prevalence of both under nutrition and overweight in rural setting. IAP 2015 reference is useful to diagnose children with under nutrition and overweight including abnormal cardiometabolic risk.

Utility of the New Indian Society of Paediatric and Adolescent Endocrinology (ISPAE) Guidelines for Congenital Hypothyroidism Screening in a High Risk Unit.

OBJECTIVE: To study the new ISPAE guidelines in neonates with congenital hypothyroidism and present authors' experience in managing these neonates. METHODS: A retrospective review of all babies who were screened for congenital hypothyroidism in the institution over a period of 5 y was conducted. Details pertaining to maternal risk factors, neonatal risk factors, screening TSH, venous TSH and details of etiological evaluation including: ultrasound thyroid, technetium 99m scintigraphy and anti thyroid peroxidase antibody estimation were retrieved. The cases were assessed using the new ISPAE guidelines. RESULTS: During the study period, 8107 babies were screened for congenital hypothyroidism, 83 cases had confirmed disease and 47 had established etiology. There is a fair correlation between screening TSH and venous TSH (r = 0.7, p < 0.05). The estimated incidence of congenital hypothyroidism in present series is 1 in 97 cases. Out of the 83 cases, 36 (43.3%), 16 (19.2%) and 31 (37.3%) cases had screening TSH >20 µIU/mL, 6-20 µIU/mL and < 6 µIU/mL, respectively. Out of the 47 babies with screening TSH <20 µIU/mL, 23 (48.9%), 25 (53.1%) and 12 (25.5%) cases had prematurity, maternal thyroid disease and illness, respectively, as risk factors (some babies had more than one risk factor). Of the 83 cases, all of them had venous TSH >10 µIU/mL and five cases had low Free T4 (<1.1 ng/dl). Thus, none of the cases with congenital hypothyroidism were missed on the new ISPAE guidelines. CONCLUSION: The new ISPAE guidelines for neonatal screening for congenital hypothyroidism are very useful and applicable in Indian neonates.

Hashimoto's Thyroiditis in South Indian Centre.

OBJECTIVE: To describe the clinical and investigatory profile of children with Hashimoto's thyroiditis (HT) presenting to the thyroid clinic of a referral children's hospital and study the course of children diagnosed as HT over a period of 6 mo. METHODS: Children aged 5-12 y with HT were recruited, their clinical and biochemical details were assessed and were started on standard therapy and followed up for a period of 6 mo. RESULTS: Ninety-seven children (89 goitrous and 8 atrophic form) with mean age: 9.90 ± 1.76 y; M:F 1:5.4 were recruited; 55.7 % were asymptomatic;14.2 % had familial clustering. The mean height, weight and BMI for age Z-scores were -1.0 ± 1.0, -0.8 ± 0.9 and -0.5 ± 1.1 respectively. 16.4 % had short stature; 4.1 % had obesity; 72.2 % had grade 2 goitre. 73.4 %, 13.2 %, 10.3 % and 3.1 % had overt hypothyroidism, sub-clinical hypothyroidism, euthyroidism and hyperthyroidism, respectively. On follow up, 38.5 % of euthyroid and 80 % of sub-clinical hypothyroid children developed overt hypothyroidism. Thyrotoxic symptoms resolved in all three Hashitoxic children by 6 mo. CONCLUSIONS: A female preponderance, less familial clustering, higher paucity of clinical manifestations and quick progression to hypothyroidism (in those without) were noted in the present series.

Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

OBJECTIVE: To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. METHODS: Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. RESULTS: Children with hypoplastic pituitary (pituitary height < 3 mm) had more severe height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p < 0.05 for both). After one year of GH therapy, height for age Z scores and percentage change in height for age Z scores were significantly higher in children with hypoplastic pituitaries (13.8 ± 3.6 and 28.7 % vs. 11.2 ± 4.1 and 21.4 %). Significant co-relation was observed between pituitary height and height for age Z-scores at baseline (r = 0.39, p < 0.05). The predicted adult height using Tanner Whitehouse-2 equations improved from 140.8 to 152.3 cm in children with hypoplastic pituitary when compared to an increase from 145.8 to 153.5 cm observed in children with normal pituitary height (p < 0.05). CONCLUSIONS: Indian growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

Growth of short children born small for gestational age and their response to growth hormone therapy.

Growth hormone [GH] is licensed for use in children born small for gestational age (SGA) who fail to catch-up. We retrospectively compared the response of twenty children born SGA (who satisfied the auxological criteria) to growth hormone (Group I) versus randomly selected age and sex matched controls from a group of SGA children with growth related complaints, not treated with GH (Group II). After 2 years of GH therapy the HAZ increased from -2.8 to -1.6 in Group I, compared 2.2 to -1.7 in group II (P-value < 0.05). The percentage of pubertal children rose from 55% to 65% in cases versus 60% to 75% in the controls (P>0.05). GH resulted in increase in growth velocity Z-score during the first year and (4.3±0.5 in Group-I versus - 0.5±0.6 in Group-II, P<0.05) second year of treatment (1.7±0.4 in cases versus -0.6±0.7 in controls, P<0.05).Thus, GH improves height of short SGA children without accelerating pubertal progression.

Performance of WHO growth standards on Indian children with growth related disorders.

OBJECTIVE: To assess performance of WHO 2006 standards on anthropometric measurements of children referred for growth related disorders to a speciality pediatric clinic in Pune, India, from June 2006 through June 2010. METHODS: Data presented in this study were collected retrospectively from case records of all children from birth to 60 mo (n=1840, mean age 2.7±1.3 y) who presented with growth related disorders; healthy age and sex matched children were recruited as controls (n=824, mean age 2.8±1.2 y). Children were divided as per their clinical diagnosis into eight different groups: growth hormone deficiency, bone disorders, syndromic short stature, familial short stature, hypothyroidism, nutritional and systemic disorder, other endocrinopathies and overgrowth disorders. Anthropometric parameters for all study subjects were converted to standard deviation scores (SD scores) using the WHO Anthro 2005. RESULTS: Mean height SD scores of children with growth related disorders were significantly lower than that of the controls, while that of the tall children were significantly higher (p<0.05). All children who were clinically very short were below the 1st percentile, while none of the children with overgrowth or normal children were classified as stunted. Weight for height SD scores of children with nutritional and systemic disorders were the lowest, while those for the obese children were the highest. CONCLUSIONS: The present results suggest that the WHO 2006 growth standards classify children with growth disorders appropriately and the classification is in concordance with the clinical assessment. They provide health practitioners in a clinical setting with an effective tool to assess growth of children.