Thyroid Volume and Thyroid Function Parameters Are Independently Associated with Weight Status in Overweight Children.

BACKGROUND: A relation between thyroid-stimulating hormone (TSH), insulin resistance - both of which are related to obesity - and thyroid volume has been suggested. Therefore, we analyzed thyroid volume and structure in relation to thyroid function parameters, weight status, and insulin resistance. METHODS: This is a cross-sectional study in which weight status (BMI-SDS), thyroid function parameters (TSH, free tri-iodothyronine [fT3], and free thyroxine [fT4]), insulin resistance index (HOMA-IR), and thyroid volume (ultrasound) were determined in 617 overweight children (aged 10.4 ± 2.2 years, 50% male, BMI-SDS 2.5 ± 0.6) and in 27 normal-weight children of a similar age and gender. Furthermore, changes in thyroid volume and structure, and thyroid function parameters were analyzed in 83 obese children (51% male, mean age 10.3 ± 2.2) at baseline and at the end of a 1-year lifestyle intervention. RESULTS: Overweight children had a significant greater thyroid volume (4.2 ± 1.8 vs. 4.1 ± 0.5 mL) and higher TSH (3.1 ± 1.5 vs. 2.4 ± 1.1 mU/L) and fT3 (4.4 ± 0.7 vs. 4.1 ± 0.5 pg/mL) concentrations compared to normal-weight children. In multiple linear regression analyses adjusted to multiple confounders, thyroid volume was significantly related to BMI-SDS (b coefficient 0.44 ± 0.10, r2 = 0.41) but not to any thyroid function parameter or HOMA-IR. Changes in BMI-SDS were significantly associated with changes in thyroid volume (r = 0.22). The changes in thyroid volume were not correlated to changes of any thyroid function parameter or HOMA-IR. CONCLUSIONS: Thyroid volume is positively correlated to weight status in childhood obesity and the change is reversible after weight loss independently of thyroid function parameters and insulin resistance. Further studies are needed to understand why thyroid volume is increased reversibly in overweight children.

Sex Hormone Profile in Pubertal Boys With Gynecomastia and Pseudogynecomastia.

CONTENT: Gynecomastia (defined by proliferation of glandular elements) and pseudogynecomastia (defined by adipose tissue) are frequent in pubertal boys. An association with sex hormones and the growth hormone axis has been discussed. OBJECTIVE: The objective of this work is to compare sex hormones, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP-3) between boys with gynecomastia and pseudogynecomastia (separation by ultrasound). DESIGN: An observational study was performed. SETTING: The setting of this study was an outpatient clinic. PARTICIPANTS: A total of 124 pubertal boys (mean age 14 ±â€…2 years) with breast enlargement and 84 healthy boys (mean age 14 ±â€…2 years) without breast enlargement participated in this study. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURES: Measurements were taken for sex hormones (progesterone, estradiol [E2], estriol, estrone, androstendione, testosterone [T], dihydrotestosterone) measured by liquid chromatography-tandem mass spectrometry, as well as gonadotropins, prolactin, IGF-1, and IGFBP-3. RESULTS: Eighty-six boys suffered from gynecomastia and 38 from pseudogynecomastia. In boys with gynecomastia, the E2/T ratio (median 22, interquartile range [IQR] 8-75) was significantly (P < .05) higher compared to boys with pseudogynecomastia (median 12, IQR 5-21) or healthy controls without breast enlargement (median 18, IQR 6-44) even after adjustment for testes volume. T concentrations were significantly (P < .05) lower in boys with gynecomastia (median 1.8, IQR 0.7-4.2 nM/L) compared to boys with pseudogynecomastia (median 4.3, IQR 1.4-6.9 nM/L) or healthy controls without breast enlargement (median 3.1, IQR 0.6-7.6 nM/L). Boys with gynecomastia did not differ from boys with pseudogynecomastia according to other sex hormones, prolactin, IGF-1, or IGFBP-3 concentrations. CONCLUSIONS: True gynecomastia is characterized by a relative T deficiency to E2 concentrations in contrast to pseudogynecomastia.

Link between omentin-1, obesity and insulin resistance in children: Findings from a longitudinal intervention study.

OBJECTIVE: The adipokine omentin-1 has been suggested to be inversely associated with obesity and insulin resistance in humans. We studied the relationships between omentin-1, parameters of fat mass, insulin resistance, lipids and blood pressure in children with obesity in a longitudinal study. METHODS: We analysed omentin-1 concentrations in 23 normal-weight children and in 82 children with obesity participating in a one-year lifestyle intervention. In the children with obesity, omentin-1, bioactive and conventional leptin, thyroid hormones (thyroid-stimulating hormone, free thyroxine 4, free triiodothyronine), body mass index, waist circumference, body fat based on skin-fold measurements and bioimpedance analyses, lipids, insulin resistance as homeostatic model assessment of insulin resistance (HOMA-IR) and blood pressure were determined at baseline and 1 year later. Furthermore, we measured omentin-1 concentrations 1 year after the end of the lifestyle intervention. RESULTS: The omentin-1 concentrations were significantly (P = .008) lower in children with obesity compared to normal-weight children (296 ± 108 ng ml-1 vs. 232 ± 99 ng ml-1 ). Omentin-1 concentrations increased significantly (P < .001) in children with obesity and substantial weight loss (35 ± 55 ng ml-1 ), while omentin-1 concentrations did not change significantly (P = .750) in children with obesity without weight loss (-5 ± 108 ng ml-1 ) during the intervention. Substantial weight loss after the end of intervention led to a significant (P < .001) increase of omentin-1 concentrations (+64 ± 14 ng ml-1 ). Omentin-1 was significantly and negatively associated with HOMA-IR both in cross-sectional (r = -.27, P = .006) and longitudinal analyses (r = -.33, P = .001). Omentin-1 concentrations were not related to pubertal stage, sex or thyroid hormones. CONCLUSIONS: Our data do support the hypothesis that omentin-1 is reversibly decreased in obesity and is a link between obesity and insulin resistance.

Is there a link between progranulin, obesity, and parameters of the metabolic syndrome in children? Findings from a longitudinal intervention study.

BACKGROUND: The inflammatory cytokine progranulin has been proposed to play a role in obesity and its associated comorbidities such as insulin resistance. OBJECTIVE: In a longitudinal study, we analyzed the links between progranulin, parameters of fat mass, insulin resistance, and metabolic syndrome (MetS) in obese children. METHODS: We measured the following parameters in 88 obese children at baseline, at the end of a 1-year lifestyle intervention and 1-year later (=2 years after baseline): progranulin, bioactive leptin, body mass index-SD score (BMI-SDS), waist circumference, body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index homeostasis model assessment (HOMA), and blood pressure. As a control, we determined progranulin in 23 normal-weight children. RESULTS: The progranulin concentrations did not differ significantly (P = .795) between obese and normal-weight children. Progranulin concentrations decreased significantly during and after the lifestyle intervention in children with and without decrease of BMI-SDS. There was no relationship between progranulin concentrations and pubertal stage or gender. Progranulin was not significantly associated with insulin resistance HOMA, parameters of the MetS or transaminases both in cross-sectional and longitudinal multiple linear regression analyses adjusted to multiple confounders. Progranulin was significantly, negatively related to age (b-coefficient -1.24 ± .97, P = .012, r2 = .07). CONCLUSIONS: Our data do not support the hypothesis that progranulin is an important link between obesity, insulin resistance, and MetS in childhood.

Higher steroid sulfation is linked to successful weight loss in obese children.

Objective Little information is available on the steroid sulfates profile in obese children. Therefore, we examined whether sulfated steroids are linked with weight status and associated comorbidities in obese children. Methods We analyzed 66 obese children (mean age 10.5 ± 2.5 years, 57.6% female, 53.9% prepubertal, mean BMI 27.0 ± 4.6 kg/m2, 50% with BMI-SDS reduction >0.5, 50% without BMI-SDS reduction) who participated in an outpatient 1-year intervention program based on exercise, behavior and nutrition therapy. We measured intact sulfated steroids (cholesterol sulfate (CS), pregnenolone sulfate (PregS), 17αOH pregnenolone sulfate (17OH-PregS), 16αOH dehydroepiandrosterone sulfate (16OH-DHEAS), DHEAS, androstenediol-3-sulfate, androsterone sulfate and epiandrosterone sulfate) by LC-MS/MS, and insulin resistance index HOMA, lipids, blood pressure at baseline and 1 year later. Results All sulfated steroids except 17OH-PregS, 16OH-DHEAS, androsterone sulfate and epiandrosterone sulfate were higher in boys compared to girls. Concentrations of CS before intervention were higher in children who lost weight. After 1 year of treatment, both groups showed increased levels of DHEAS, 16OH-DHEAS and androstenediol-3-sulfate, but PregS was only increased in children with weight loss. None of the steroid sulfates was significantly related to cardiovascular risk factors or HOMA except 17OH-PregS, which was associated with systolic blood pressure both in cross-sectional (ß-coefficient: 0.09 ± 0.07, P = 0.020) and longitudinal analyses (ß-coefficient: 0.06 ± 0.04, P = 0.013) in multiple linear regression analyses. Conclusions Since higher steroid sulfation capacity was associated with successful weight intervention in children disruption of sulfation may be associated with difficulties to lose weight. Future studies are necessary to prove this hypothesis.

Link between chemerin, central obesity, and parameters of the Metabolic Syndrome: findings from a longitudinal study in obese children participating in a lifestyle intervention.

OBJECTIVE: Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction. METHODS: We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children. RESULTS: Obese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (-14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI. CONCLUSIONS: Since chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.

Bioactive leptin is stronger related to parameters of fat mass and distribution than conventionally measured leptin: Findings from a longitudinal study in obese children participating in a lifestyle intervention.

OBJECTIVE: This study analyzed the relationships between bioactive leptin, conventionally measured leptin, and parameters of fat mass and distribution in obese children before and after weight reduction. METHODS: We determined bioactive leptin (bioLep), conventional measured leptin (conLep), weight, height, body fat based on skinfold measurements and bioimpedance analyses, waist circumference (wc), and pubertal stage in 88 obese children participating in a lifestyle intervention at baseline and one year later. RESULTS: We identified no child with homozygous or heterozygous status for bioinactive leptin mutations. The baseline associations between bioLep and BMI (r = 0.53), BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.61, skinfold thickness: r = 0.49), wc (r = 0.42), and waist to height ratio (whr) (r = 0.39) were stronger than the associations between conLep and BMI (r = 0.50), BMI-SDS (r = 0.44), body fat (bioimpedance: r = 0.57, skinfold thickness: r = 0.41), wc (r = 0.41), and whr (r = 0.37). The changes of bioLep were stronger related to changes of BMI-SDS (r = 0.54), body fat (bioimpedance r = 0.59, skinfold thickness: r = 0.37), wc (r = 0.22), and whr (r = 0.21) than the associations between changes of conLep and changes of BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.56, skinfold thickness: r = 0.43), wc (r = 0.20), and whr (r = 0.20). The same findings were observed in multiple linear regression analyses adjusted to multiple confounders. In contrast to changes of conLep (r = 0.22), the changes of bioLep during intervention were not related to weight regain after the end of intervention. BioLep concentrations did not differ between prepubertal girls and boys, but were higher in pubertal girls compared to pubertal boys (p = 0.031). CONCLUSIONS: Bioactive leptin was stronger related to fat mass and distribution compared to conventionally measured leptin.

Impact of discontinuation of growth hormone treatment on lipids and weight status in adolescents.

BACKGROUND: While the main role of growth hormone (GH) replacement therapy in children is to promote linear growth, GH has also an effect on lipids and body composition. There is an ongoing discussion whether discontinuation of GH treatment is associated with deterioration of lipids. METHODS: We analyzed weight status [as body mass index-standard deviation score (BMI-SDS)], insulin like growth factor (IGF)-1, triglycerides, total, low-density liporptoein (LDL)- and high-density lipoprotein (HDL)-cholesterol at the end of GH treatment and in mean 6 months later in 90 adolescents (53 with GH deficiency, 16 with Turner syndrome [TS] and 21 born small-for-gestational age [SGA]). RESULTS: After stopping GH treatment, total cholesterol (+10±24 mg/dL vs. -4±13 mg/dL) and LDL-cholesterol (+15±20 mg/dL vs. -6±12 mg/dL) increased significantly higher in severe (defined by GH peak in stimulation test <3 ng/mL) compared to moderate GHD. In patients with TS, total cholesterol (+19±9 mg/dL), LDL-cholesterol (+9±12 mg/dL) and HDL-cholesterol (+4.3±3.5 mg/dL) increased significantly. In adolescents born SGA, triglycerides increased (+34±51 mg/dL) and HDL-cholesterol decreased significantly (-3.8±7.1 mg/dL). In multiple linear regression analyses, changes of total and LDL-cholesterol were significantly negatively related to peak GH in stimulation tests, but not to gender, age at GH start, duration of GH treatment, observation time, changes of BMI-SDS or IGF-1 after the end of GH treatment. The BMI-SDS did not change after the end of GH treatment. CONCLUSIONS: Discontinuation of GH treatment leads to a deterioration of lipids in TS, SGA and severe but not moderate GHD.

Weight loss in obese girls with polycystic ovarian syndrome is associated with a decrease in Anti-Muellerian Hormone concentrations.

OBJECTIVE: The Anti-Muellerian Hormone (AMH) has been reported as surrogate marker of antral follicles, which are the origins of hyperandrogenism in polycystic ovarian syndrome (PCOS). Therefore, AMH may be useful for the diagnosis of PCOS. The objective was to study the longitudinal changes in AMH concentrations in girls with and without PCOS. DESIGN: This is a longitudinal study of obese girls participating in a 1-year lifestyle intervention. PATIENTS: Forty obese girls aged 13-16 years (50% with PCOS) were included in the study. Girls with and without PCOS were matched to age, BMI and change in weight status. MEASUREMENTS: AMH, gonadotropins, androstenedione, testosterone, oestradiol and sex hormone-binding globulin (SHBG) were determined. RESULTS: Obese girls with PCOS demonstrated significantly (P<.001) higher AMH concentrations (5.8±3.1 ng/mL) compared to obese girls without PCOS (2.4±1.4 ng/mL). None of the girls without PCOS had AMH concentrations ≥6 ng/mL and none of the PCOS girls showed AMH concentrations ≤3 ng/mL. Weight loss in girls with PCOS was associated with a significant drop in AMH concentrations (-1.4±1.8 ng/mL, P=.045). AMH was significantly related to testosterone (cross-sectional: b-coefficient 3.7±1.7, P=.001, longitudinal: b-coefficient 0.54±0.47, P=.026) and luteinizing hormone (LH) (cross-sectional: b-coefficient 0.05±0.04, P=.039, longitudinal: b-coefficient 0.005±0.004, P=.039), but not to any other analysed parameter in multiple linear regression analyses adjusted to multiple confounders. CONCLUSIONS: AMH was increased in adolescent girls with PCOS and normalized with weight loss. AMH was cross-sectionally and longitudinally related to hyperandrogenism.

Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss.

OBJECTIVE: The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. DESIGN: This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. METHODS: We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC-MS/MS steroid profiling at baseline and one year later. RESULTS: At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. CONCLUSIONS: The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS.