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Context: Treatment options for central precocious puberty (CPP) are important for individualization of therapy. Objective: We evaluated the efficacy and safety of 6-month 45-mg leuprolide acetate (LA) depot with intramuscular administration. Methods: LA depot was administered at weeks 0 and 24 to treatment-naïve (n = 27) or previously treated (n = 18) children with CPP in a phase 3, multicenter, single-arm, open-label study (NCT03695237). Week 24 peak-stimulated luteinizing hormone (LH) suppression (<4â mIU/mL) was the primary outcome. Secondary/other outcomes included basal sex hormone suppression (girls, estradiol <20â pg/mL; boys, testosterone <30â ng/dL), suppression of physical signs, height velocity, bone age, patient/parent-reported outcomes, and adverse events. Results: All patients (age, 7.8 ± 1.27 years) received both scheduled study doses. At 24 weeks, 39/45 patients (86.7%) had LH suppressed. Six were counted as unsuppressed; 2 because of missing data, 3 with LH of 4.35-5.30â mIU/mL and 1 with LH of 21.07â mIU/mL. Through 48 weeks, LH, estradiol, and testosterone suppression was achieved in ≥86.7%, ≥97.4%, and 100%, respectively (as early as week 4 for LH and estradiol and week 12 for testosterone). Physical signs were suppressed at week 48 (girls, 90.2%; boys, 75.0%). Mean height velocity ranged 5.0 to 5.3â cm/year post-baseline in previously treated patients and declined from 10.1 to 6.5â cm/year at week 20 in treatment-naïve patients. Mean bone age advanced slower than chronological age. Patient/parent-reported outcomes remained stable. No new safety signals were identified. No adverse event led to treatment discontinuation. Conclusion: Six-month intramuscular LA depot demonstrated 48-week efficacy with a safety profile consistent with other GnRH agonist formulations.
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Obesity is a complex condition that interweaves biological, developmental, environmental, behavioral, and genetic factors; it is a significant public health problem. The most common cause of obesity throughout childhood and adolescence is an inequity in energy balance; that is, excess caloric intake without appropriate caloric expenditure. Adiposity rebound (AR) in early childhood is a risk factor for obesity in adolescence and adulthood. The increasing prevalence of childhood and adolescent obesity is associated with a rise in comorbidities previously identified in the adult population, such as Type 2 Diabetes Mellitus, Hypertension, Non-alcoholic Fatty Liver disease (NAFLD), Obstructive Sleep Apnea (OSA), and Dyslipidemia. Due to the lack of a single treatment option to address obesity, clinicians have generally relied on counseling dietary changes and exercise. Due to psychosocial issues that may accompany adolescence regarding body habitus, this approach can have negative results. Teens can develop unhealthy eating habits that result in Bulimia Nervosa (BN), Binge- Eating Disorder (BED), or Night eating syndrome (NES). Others can develop Anorexia Nervosa (AN) as they attempt to restrict their diet and overshoot their goal of "being healthy." To date, lifestyle interventions have shown only modest effects on weight loss. Emerging findings from basic science as well as interventional drug trials utilizing GLP-1 agonists have demonstrated success in effective weight loss in obese adults, adolescents, and pediatric patients. However, there is limited data on the efficacy and safety of other weight-loss medications in children and adolescents. Nearly 6% of adolescents in the United States are severely obese and bariatric surgery as a treatment consideration will be discussed. In summary, this paper will overview the pathophysiology, clinical, and psychological implications, and treatment options available for obese pediatric and adolescent patients.
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BACKGROUND: To determine prevalence of abnormal glucose metabolism in Fanconi Anemia (FA). PROCEDURE: Thirty-nine children with FA underwent 2-hr oral glucose tolerance test (OGTT). Reference lean adolescents (REF) were older than FA patients (mean +/- SD: FA 8.6 +/- 3.9 years, REF 19.8 +/- 0.3 years, P < 0.001), but comparable in BMI Z-scores (FA 1.25 +/- 0.58, REF -0.02 +/- 0.24; P = 0.24). Patients had normal glucose tolerance (NGT) or abnormal glucose metabolism (AGM) by American Diabetes Association Criteria. Insulinogenic index estimated beta-cell function. Insulin resistance estimation used homeostatic model assessment (HOMA-IR). Insulin secretion estimation relative to insulin sensitivity used disposition index (DI). RESULTS: Among FA patients, 46% had AGM. Compared to REF, there were significant differences in glycemic responses (area under curve: FA-NGT 344 +/- 42, FA-AGM 596 +/- 35, REF 208 +/- 25 mM, P < 0.0001) and insulinogenic index (FA-NGT 105 +/- 29, FA-AGM 44 +/- 8, and REF 173 +/- 41 pM/mM, P < 0.05). Insulin sensitivity did not differ among NGT, AGM, and REF (HOMA-IR: FA-NGT 1.9 +/- 0.4, FA-AGM 2.2 +/- 0.5, REF 1.3 +/- 0.2, P = NS). However, DI was significantly lower in both FA groups than REF [NGT 63.6 +/- 16.5 vs. AGM 26.4 +/- 3.5 (P < 0.048); REF 132.6 +/- 24.5 (NGT and AGM vs. REF, both P < 0.0002)]. CONCLUSION: Abnormalities in glucose metabolism are frequent in young FA patients without prior diagnosis of diabetes, and are associated with marked defects in insulin secretion.
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Anemia de Fanconi/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Teste de Tolerância a Glucose , Humanos , Lactente , Resistência à Insulina , Secreção de Insulina , MasculinoRESUMO
STUDY OBJECTIVE: Studies have suggested that low vitamin D levels may play a role in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of our study was to compare 25-hydroxyvitamin D [25(OH)D] levels in adolescent females with and without PCOS. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review at a tertiary care medical center for female adolescents aged 12-21 years with serum 25(OH)D measurements within a 5-year period. Participants were categorized as having PCOS or as controls based on National Institutes of Health PCOS diagnostic criteria. MAIN OUTCOME MEASURE: Exact logistic regression analysis was done to compare normal (≥30 ng/mL) vs low (<30 ng/mL) serum 25(OH)D levels in the PCOS and control groups. RESULTS: Two hundred ninety-nine charts were reviewed and 107 participants were included in the study. Of the included participants, 37 were in the PCOS group and 70 were in the control group, with a mean age of 15.2 years. In the PCOS group, 97.2% were obese and vitamin D deficiency was noted among 62.2% females. The mean serum 25(OH)D level was 18.4 and 21.6 ng/mL in PCOS and control groups, respectively. The difference in mean 25(OH)D levels between the 2 groups was not statistically significant (P > .05) when controlled for ethnicity, body mass index percentile, and season. CONCLUSION: In our study, there was no statistically significant difference in mean 25(OH)D levels between PCOS and control groups. The majority of participants in PCOS group were obese. Further studies in adolescent females with PCOS and normal body mass index could be helpful in delineating the role of vitamin D in the pathogenesis of PCOS.
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Síndrome do Ovário Policístico/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Síndrome do Ovário Policístico/sangue , Análise de Regressão , Estudos Retrospectivos , Estados Unidos , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Adulto JovemRESUMO
Polycystic ovary syndrome is the most common endocrinopathy recognized in women of childbearing age with a prevalence of 4-12%. The prevalence of the disorder in adolescent population is poorly defined. The pathogenesis as well as the management of this disorder is widely debated.
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Erupções Acneiformes/etiologia , Aterosclerose/prevenção & controle , Hiperandrogenismo/diagnóstico , Infertilidade Feminina/prevenção & controle , Obesidade/prevenção & controle , Síndrome do Ovário Policístico , Erupções Acneiformes/sangue , Erupções Acneiformes/tratamento farmacológico , Adolescente , Serviços de Saúde do Adolescente , Aterosclerose/sangue , Aterosclerose/etiologia , Diagnóstico Precoce , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/tratamento farmacológico , Infertilidade Feminina/sangue , Infertilidade Feminina/etiologia , Hormônio Luteinizante/sangue , Obesidade/sangue , Obesidade/complicações , Médicos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Prevalência , Testosterona/sangueRESUMO
OBJECTIVE: IGF1 is essential for human growth and mediates its effects through the type 1 IGF receptor (IGF1R). Our objective was to determine the frequency of certain previously reported IGF1R gene variants in the normal population and their effect on stature. DESIGN: A cross-sectional study was conducted in a population of 2500 children enrolled in public school grades 5 through 12 for whom DNA and anthropometric data were available. Subjects were genotyped at five previously reported loci that affect receptor abundance or function. METHODS: The frequency of the following IGF1R variants Arg108Gln, Lys115Asn, Arg59stop, Arg481Gln, and Arg605His was measured by a PCR-based assay. Circulating concentrations of IGF1 or IGF binding protein-3 (IGFBP3) were measured by ELISA in those affected and matched controls. RESULTS: A scan of 1300 subjects detected none with Arg108Gln, Lys115Asn, or Arg59stop mutations. In contrast, nucleotide changes leading to heterozygosity at codon 605 were identified in nine of 2500 subjects and six of 1800 subjects at codon 481. These individuals were, on average, 4 cm shorter than the others. There were no differences in circulating concentrations of IGF1 or IGFBP3 between those with the gene variants and controls matched for sex, ethnicity, age, and BMI. CONCLUSION: Rare IGF1R variants exerting a moderate effect on stature are present in the general population, supporting the importance of IGF1R function in growth control and indicating that variation in height within healthy individuals may be explained, in some cases, by larger effects of a small subset of gene variants.