Introduction: Thyroid hormones are essential for child development, and untreated hypothyroidism can lead to severe adverse effects, including mental retardation. However, whether thyroid hormone variation within the normal range affects developmental tests is not known. Thus, we aimed to investigate associations between physiological variations in thyroid hormone levels and the results of developmental tests in healthy children. Methods: This study included 946 children who completed the Bayley Scales of Infant and Toddler Development (BSID) III, and 1467 children who completed the developmental test for children from six months to six years old (ET 6-6-R). Using regression models, we assessed the association between TSH, FT3, and FT4 and test results as outcomes. In addition, we assessed associations between the subscales and stability across age.Results: Higher TSH-SDS were associated with lower ET 6-6-R scores in cognitive development, language development, fine and gross motor skills, with effects between ß = -0.13 to ß = -0.23 (all ps < .05). After adjusting for age, sex, and mother´s education, only language development reached significance. FT3 was positively associated with gross motor skills (ß=0.17), fine motor skills (ß=0.26), and cognition (ß=0.15) (ps <.05). After adjusting, only fine motor skills remained significant. FT4 showed positive but mostly nonsignificant associations with most subscales. We found no consistent significant associations between BSID scores and thyroid hormones. Conclusion: The differential results for the developmental tests indicate that the associations are highly specific for particular aspects of development and even developmental stages. Therefore, single measurements have very limited explanatory power.

Introduction: Thyroid hormones are essential for child development, and untreated hypothyroidism can lead to severe adverse effects, including mental retardation. However, whether thyroid hormone variation within the normal range affects developmental tests is not known. Thus, we aimed to investigate associations between physiological variations in thyroid hormone levels and the results of developmental tests in healthy children. Methods: This study included 946 children who completed the Bayley Scales of Infant and Toddler Development (BSID) III, and 1467 children who completed the developmental test for children from six months to six years old (ET 6-6-R). Using regression models, we assessed the association between TSH, FT3, and FT4 and test results as outcomes. In addition, we assessed associations between the subscales and stability across age.Results: Higher TSH-SDS were associated with lower ET 6-6-R scores in cognitive development, language development, fine and gross motor skills, with effects between ß = -0.13 to ß = -0.23 (all ps < .05). After adjusting for age, sex, and mother´s education, only language development reached significance. FT3 was positively associated with gross motor skills (ß=0.17), fine motor skills (ß=0.26), and cognition (ß=0.15) (ps <.05). After adjusting, only fine motor skills remained significant. FT4 showed positive but mostly nonsignificant associations with most subscales. We found no consistent significant associations between BSID scores and thyroid hormones. Conclusion: The differential results for the developmental tests indicate that the associations are highly specific for particular aspects of development and even developmental stages. Therefore, single measurements have very limited explanatory power.

Introduction: While the influence of various factors on classical androgen synthesis in children and adolescents and its impact on puberty has been widely investigated, there appear to be gaps and contradictory findings regarding the association of overweight and obesity with the synthesis of adrenal-derived 11-oxygenated androgen (11-OA) serum levels. With this study, we aimed to examine how overweight and obesity affect 11-OA serum levels during puberty in a large cohort of children and adolescents.Methods: Our cohort comprised 1,054 healthy children aged 6 to 19 years providing serum samples at a total of 1,734 visits. Liquid chromatography-tandem mass spectrometry was used to quantify 11-ketotestosterone (11-KT), 11-ketoandrostendione (11-KA4), 11-ß-hydroxytestosterone (11-OHT), 11-ß-hydroxyandrostendione (11-OHA4), testosterone, androstenedione, and DHEAS. In addition, we assessed BMI-SDSs; skinfold thicknesses; and Tanner stages. The significance level α was set to α=0.05.Results: Increases in 11-KT, 11-KA4, 11-OHT, and 11-OHA4 levels were observed in boys and girls during puberty. 11-KT (ß=0.2, p<0.001), 11-KA4 (ß=0.16, p<0.001) and 11-OHA4 (ß=0.12, p=0.003) were positively correlated with BMI in boys age 13 and under. 11-KT (ß=0.1, p=0.047) was positively correlated with BMI in girls age 11 and under. 11-OHT was positively correlated with BMI independent of age (boys 13 and under: ß=0.17, p<0.001; over 13 years: ß=0.14, p=0.001; girls 11 and under: ß=0.17, p<0.001; over 11 years: ß=0.18, p<0.001).Conclusion: We found increasing 11-OA serum levels throughout all Tanner stages. 11-OAs were observed to be associated with BMI and skinfold thickness, suggesting that overweight and obesity may be associated with pubertal alterations in 11-OA serum levels.

Introduction: While the influence of various factors on classical androgen synthesis in children and adolescents and its impact on puberty has been widely investigated, there appear to be gaps and contradictory findings regarding the association of overweight and obesity with the synthesis of adrenal-derived 11-oxygenated androgen (11-OA) serum levels. With this study, we aimed to examine how overweight and obesity affect 11-OA serum levels during puberty in a large cohort of children and adolescents.Methods: Our cohort comprised 1,054 healthy children aged 6 to 19 years providing serum samples at a total of 1,734 visits. Liquid chromatography-tandem mass spectrometry was used to quantify 11-ketotestosterone (11-KT), 11-ketoandrostendione (11-KA4), 11-ß-hydroxytestosterone (11-OHT), 11-ß-hydroxyandrostendione (11-OHA4), testosterone, androstenedione, and DHEAS. In addition, we assessed BMI-SDSs; skinfold thicknesses; and Tanner stages. The significance level α was set to α=0.05.Results: Increases in 11-KT, 11-KA4, 11-OHT, and 11-OHA4 levels were observed in boys and girls during puberty. 11-KT (ß=0.2, p<0.001), 11-KA4 (ß=0.16, p<0.001) and 11-OHA4 (ß=0.12, p=0.003) were positively correlated with BMI in boys age 13 and under. 11-KT (ß=0.1, p=0.047) was positively correlated with BMI in girls age 11 and under. 11-OHT was positively correlated with BMI independent of age (boys 13 and under: ß=0.17, p<0.001; over 13 years: ß=0.14, p=0.001; girls 11 and under: ß=0.17, p<0.001; over 11 years: ß=0.18, p<0.001).Conclusion: We found increasing 11-OA serum levels throughout all Tanner stages. 11-OAs were observed to be associated with BMI and skinfold thickness, suggesting that overweight and obesity may be associated with pubertal alterations in 11-OA serum levels.

Introduction: Several studies have analyzed the association between the maximal growth hormone serum level obtained during a growth hormone stimulation test (GH-Max) and the body mass index standard deviation score (BMI-SDS). However, as sample sizes were quite small, our study aimed to analyze the association between GH-Max and BMI-SDS within a large cohort of 991 children. Further, we investigated other influencing factors, like test type, age, sex, puberty and preterm birth. Methods: Children with short stature (height < 10th percentile) received growth hormone stimulation tests with arginine or glucagon at the Department of Paediatric Endocrinology of the University of Leipzig Medical Center. The study population included a total of 1,438 tests (633 tests on girls, 805 tests on boys), with the majority consisting of prepubertal children (tests = 1,138). The mean age at testing was 7.74 years. Analyses were carried out on the entire cohort as well as stratified by test types. We performed univariate and multivariate analyses using linear mixed effect models to assess the effects on GH-Max. Results: GH-Max and BMI-SDS were significantly negatively associated with an effect size of ß = -1.10 (p < 0.001), independent from the test type. The GH-Max values were significantly (p < 0.001) higher for glucagon (mean value: 9.65 ng/ml) than those for arginine tests (mean value: 8.50 ng/ml). Age, sex, premature birth, and puberty were not significantly related to GH-Max values. Conclusion: We confirmed the negative association between GH-Max and weight status of short children found in previous studies. Therefore, considering BMI-SDS may be helpful in the assessment of growth hormone stimulation tests in short-statured children, but it should not be the determining factor for a treatment decision.

Introduction: Several studies have analyzed the association between the maximal growth hormone serum level obtained during a growth hormone stimulation test (GH-Max) and the body mass index standard deviation score (BMI-SDS). However, as sample sizes were quite small, our study aimed to analyze the association between GH-Max and BMI-SDS within a large cohort of 991 children. Further, we investigated other influencing factors, like test type, age, sex, puberty and preterm birth. Methods: Children with short stature (height < 10th percentile) received growth hormone stimulation tests with arginine or glucagon at the Department of Paediatric Endocrinology of the University of Leipzig Medical Center. The study population included a total of 1,438 tests (633 tests on girls, 805 tests on boys), with the majority consisting of prepubertal children (tests = 1,138). The mean age at testing was 7.74 years. Analyses were carried out on the entire cohort as well as stratified by test types. We performed univariate and multivariate analyses using linear mixed effect models to assess the effects on GH-Max. Results: GH-Max and BMI-SDS were significantly negatively associated with an effect size of ß = -1.10 (p < 0.001), independent from the test type. The GH-Max values were significantly (p < 0.001) higher for glucagon (mean value: 9.65 ng/ml) than those for arginine tests (mean value: 8.50 ng/ml). Age, sex, premature birth, and puberty were not significantly related to GH-Max values. Conclusion: We confirmed the negative association between GH-Max and weight status of short children found in previous studies. Therefore, considering BMI-SDS may be helpful in the assessment of growth hormone stimulation tests in short-statured children, but it should not be the determining factor for a treatment decision.