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.

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.

Betatrophin: no relation to glucose metabolism or weight status in obese children before and after lifestyle intervention.

OBJECTIVE: The influences of obesity, glucose metabolism, gender, and puberty on betatrophin levels and the longitudinal relationships between weight loss, metabolic changes and betatrophin have not yet been studied in childhood. METHODS: Cross-sectional and longitudinal analysis of weight status (standard deviation score-body mass index (SDS-BMI)), homeostasis model assessment insulin resistance (HOMA-IR), gender, and pubertal stage were evaluated in 69 obese children (51% female, age 11.9 ± 2.0 years) participating in lifestyle intervention over a 1-year period. An oral glucose tolerance test was performed in 53 of the 69 children. Twenty normal weight children (50% female, age 12.3 ± 3.0 years) served as controls. RESULTS: Circulating betatrophin did not differ significantly between obese and lean children (1.99 ± 0.90 vs 2.35 ± 0.28, mean ± SD, P = .155). At baseline, betatrophin did not differ in obese patients with vs without glucose intolerance (1.89 ± 0.96 vs 2.031 ± 0.91 ng/mL; P = .591) and obese with (delta SDS-BMI >0.4) vs without successful obesity intervention (1.89 ± 0.94 vs. 2.07 ± 0.87 ng/mL; P = 0.396). In multiple linear regression analyses, pubertal stage was associated with betatrophin (b: 0.48, P = .027), while gender, age, BMI, blood pressure, fasting glucose, HOMA-IR, triglycerides, LDL- and HDL-cholesterol were not related to betatrophin at baseline. At the end of the 1-year intervention, changes of betatrophin were not significantly associated with any parameter after controlling for multiple covariates including age and changes of pubertal stages. CONCLUSIONS: Our data do not support a relationship between betatrophin and weight status or glucose tolerance, insulin resistance, and lipid metabolism in children.

Low Treatment Adherence in Pubertal Children Treated with Thyroxin or Growth Hormone.

BACKGROUND: Treatment outcome depends largely on treatment adherence (TA). However, studies analyzing TA in chronic endocrine diseases are scarce and controversial in childhood. PATIENTS AND METHODS: We studied TA in 103 children treated subcutaneously with growth hormone (GH) and 97 children treated orally with thyroxin. TA was calculated based on the prescription refill rates. The number of GH injections was recorded by an autoinjector device in 23 children treated with GH. RESULTS: The correlation between recorded TA and calculated TA based on prescription refill rates was very good (p < 0.001, r = 0.83). TA was lower (p < 0.01) in pubertal children compared to prepubertal children and in children self-administering their medication compared to those whose drug was administered by their parents, both in GH- and thyroxin-treated children. Overall, 67% of the pubertal children treated with GH and 58% of the pubertal children treated with thyroxin missed at least 1 dose per week. TA was higher (p < 0.001) in children with thyroxin treatment compared to children treated with recombinant human GH (8 vs. 26% missed >3 doses/week). DISCUSSION: Puberty and self-administration of drugs were negative predictors of TA. Therefore, in puberty, prevention and treatment efforts should be undertaken to improve TA, especially when adolescents administer their drugs themselves.

Treatment with gonadotropin-releasing hormone analogues: different impact on body weight in normal-weight and overweight children.

OBJECTIVE: We studied the effect of gonadotropin-releasing hormone analogues (GnRHa) on weight gain as a possible side effect. METHODS: We analyzed longitudinally changes in BMI-SDS in 92 children [median age 8.0 years (IQR 7.1-8.9), 88% females, mean BMI-SDS 0.69 ± 1.30] with idiopathic central precocious puberty or early puberty treated with GnRHa. Furthermore, 25 overweight children with GnRHa were compared to 25 overweight children without GnRHa matched by age, gender, degree of overweight, and pubertal stage. RESULTS: The matched overweight children without GnRHa demonstrated a significant increase in their BMI-SDS in the course of 1 year (+0.18 ± 0.22). Normal-weight children treated with GnRHa demonstrated a significant increase in BMI-SDS in the course of 1 year (+0.32 ± 0.66) in contrast to overweight children treated with GnRHa who showed a stable BMI-SDS (-0.02 ± 0.27). This significant difference in changes in BMI-SDS between normal-weight and overweight children treated with GnRHa was also observed at the end of GnRHa treatment and 6 months later (p < 0.001). CONCLUSIONS: Change in weight status differed between overweight and normal-weight children during GnRHa treatment. We found no increased risk for the side effect of weight gain in overweight children treated with GnRHa.

Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls.

CONTEXT: Polycystic ovarian syndrome (PCOS) is associated with cardiovascular risk factors (CRF). Lifestyle intervention is regarded as therapy of choice even if studies in adolescent girls with PCOS are scarce. OBJECTIVE: Our objective was to analyze the impact of lifestyle intervention on menses irregularities, hyperandrogenemia, CRF, and intima-media thickness (IMT) in adolescent girls with PCOS. PATIENTS: Patients included 59 obese girls with PCOS aged 12-18 yr. INTERVENTION: Intervention was a 1-yr lifestyle intervention based on nutrition education, exercise training, and behavior therapy. MAIN OUTCOME MEASURES: Menses cycles, IMT, waist circumference, blood pressure, fasting lipids, insulin, glucose, testosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG were evaluated. RESULTS: In contrast to the 33 girls without weight loss, the 26 girls reducing their body mass index during the lifestyle intervention (by a mean of -3.9 kg/m(2)) improved most CRF and decreased their IMT (by a mean of -0.01 cm). Testosterone concentrations decreased (by a mean of -0.3 nmol/liter) and SHBG concentrations increased (by a mean of +8 ng/ml) significantly in girls with weight loss in contrast to girls with increasing weight. The prevalence of amenorrhea (-42%) and oligoamenorrhea (-19%) decreased in the girls with weight loss. The changes in insulin in the 1-yr follow-up were significantly correlated to changes in testosterone (r = 0.38; P = 0.002) and SHBG (r = -0.35; P = 0.048). A linear regression model with changes in IMT as dependent variable demonstrated a significant association with changes in blood pressure and weight status but not with changes in testosterone. CONCLUSIONS: Weight loss due to lifestyle intervention is effective to treat menses irregularities, normalize androgens, and improve CRF and IMT in obese adolescent girls with PCOS.

Body mass index patterns over 5 y in obese children motivated to participate in a 1-y lifestyle intervention: age as a predictor of long-term success.

BACKGROUND: Long-term outcome after lifestyle interventions in obese children is largely unknown but important to improving intervention. OBJECTIVE: The aim was to identify predictors of long-term changes in body mass index (BMI) after lifestyle intervention. DESIGN: Annual changes in the BMI SD score (BMI-SDS) over 5 y in 663 obese children (aged 4-16 y) motivated to participate in an outpatient lifestyle intervention were analyzed. Child-specific longitudinal curves based on multilevel growth curve models (MLMs) over 5 y were estimated depending on patient characteristics (age and sex). RESULTS: The mean decrease in BMI-SDS was 0.36 (95% CI: 0.33, 0.39) at the end of the 1-y intervention and 0.46 (95% CI: 0.36, 0.55) 4 y after the intervention. Change in BMI-SDS in the intervention period predicted long-term outcome after 5 y (P < 0.001). MLMs identified age but not sex as a predictor of the outcome: the youngest children (<8 y) at the onset of the intervention had the greatest decrease in BMI-SDS over 5 y, and the oldest children (>13 y) had the least decrease in BMI-SDS (P < 0.05). Whereas there was a larger reduction in BMI-SDS during the intervention in children aged 8-10 y than in children aged 11-12 y, long-term decrease in BMI-SDS was greater in 11-12-y-old children (P < 0.001). CONCLUSIONS: Younger age was associated with the best long-term outcome after participation in the lifestyle intervention, which supports the need for early intervention in childhood obesity. Children aged 8-10 y may need modified intervention, because BMI-SDS increased more in the older children in the long term. However, mean BMI-SDS was significantly lower 4 y after the end of the intervention than at baseline in all age groups. This study was registered at clinicaltrials.gov as NCT00435734.