Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis. Methods: Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G. Results: Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans. Conclusion: LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.

Primary Adrenal Insufficiency Masked by an Eating Disorder Diagnosis in an Adolescent Male.

We describe a 14-year-old male who was followed for several years for the diagnoses of avoidant restrictive food intake disorder and generalized anxiety disorder before being diagnosed with primary adrenal insufficiency (PAI) or Addison disease. The patient presented multiple times to different facilities with worsening symptoms of anorexia, nausea, vomiting, and anxiety in the months leading up to diagnosis of PAI. Dehydration and hypotension, occurring relatively late in the course of his illness, were attributed to poor intake and vomiting. Hyponatremia was attributed to his psychotropic medication, olanzapine, and to dehydration. During his third hospitalization, he was diagnosed with PAI; treatment with stress-dose glucocorticoid therapy resulted in rapid clinical improvement. This case serves as a reminder that adrenal insufficiency must be considered in the differential diagnosis of eating disorders because signs and symptoms of adrenal insufficiency can overlap and progress insidiously. Additionally, we recognize that the diagnostic process is intertwined with a patient's medical history and use this opportunity to discuss cognitive, specifically anchoring, bias in academic medicine.

Ovarian follicle count by magnetic resonance imaging is greater in adolescents and young adults with polycystic ovary syndrome than in controls.

Objective: To use magnetic resonance imaging (MRI) to quantify the follicle number per ovary (FNPO) using biplanar measurements and determine the ovarian volume (OV) using three-dimensional measurements in adolescents and young adults with polycystic ovary syndrome (PCOS) and controls and compare the differences between these groups; to examine the relationships between FNPO and OV and metabolic markers associated with PCOS; to compare OV obtained by use of MRI and ultrasound between young patients with PCOS and controls. Design: Cross-sectional study. Setting: Outpatient within a major medical center in New York City. Patients: Adolescent girls and young women aged 13-25 years with PCOS (n = 16) and body mass index-, age-, and ethnicity-comparable control subjects (n = 15). Interventions: None. Main Outcome Measures: The OV and FNPO by use of MRI, OV by use of transabdominal pelvic ultrasound, anthropometric measurements, and biochemical and hormonal evaluation. Results: The FNPO was higher in participants with PCOS (23.7 ± 4.6 follicles) than in controls (15.2 ± 4 follicles) when adjusted for menstrual age. The OV by use of ultrasound was higher in participants with PCOS (11.7 ± 5.6 mL) than in controls (8.1 ± 3.4 mL); however, OV by use of MRI did not differ between the groups. The OV by use of MRI and ultrasound correlated in participants with PCOS (r = 0.62) but not in controls. Conclusions: Our results are in line with prior studies showing that FNPO may be a more sensitive measure of polycystic ovary morphology than OV. The results of this study support the use of ovarian k, a promising diagnostic tool for PCOS, in young patients.

Disorders of Puberty in Girls.

Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.

The Families Improving Health Together (FIT) Program: Initial evaluation of retention and research in a multispecialty clinic for children with obesity.

BACKGROUND: Obesity affects ∼17% of US children, with parallel increases in multiple comorbidities, especially among African-, Asian-, Hispanic-, and Native-Americans. Barriers to patient retention in pediatric obesity programs include lack of centralized care, and frequent subspecialty MD visits which conflict with patient school attendance and parental work attendance as well as with support service utilization. Lack of integration of multispecialty clinical care with interdisciplinary research is a major barrier to fuller exploration of the treatment, prevention, and understanding of obesity in childhood. OBJECTIVE: To test the hypothesis, a novel multispecialty/interdisciplinary clinical and research infrastructure with strong emphasis on a primary obesity care physician for children with early-onset (<9 years) obesity (Families Improving health Together [FIT]) could promote lower patient attrition (primary goal) and foster productive research in pediatric obesity (secondary goal). RESULTS: Data support the hypotheses. Over 15 months, FIT reported a >90% participant retention (p < 0.001 vs. expected rate based on other studies of similar programs). Though 90% of children had at least one adiposity-related comorbidity and 70% had at least two, there was no need for additional subspecialist visits with cardiologists, endocrinologists, gastroenterologists, or molecular geneticists. Three abstracts were presented at national meetings, and two manuscripts were published all with junior faculty as primary authors. CONCLUSION: This pilot study suggests that an integrated multispecialty/interdisciplinary approach to children with obesity improves patient retention and can be integrated successfully with research.

The Unique Role of 11-Oxygenated C19 Steroids in Both Premature Adrenarche and Premature Pubarche.

INTRODUCTION: Recent studies have shown 11-oxygenated androgens (11oAs) are the dominant androgens in premature adrenarche (PA). Our objective was to compare 11oAs and conventional androgens in a well-defined cohort of children with PA or premature pubarche (PP) and correlate these androgens with metabolic markers. METHODS: A prospective cross-sectional study was conducted at a university hospital. Fasting early morning serum steroids (including 11oAs) and metabolic biomarkers were compared and their correlations determined in children ages 3-8 years (F) or 3-9 years (M) with PA or PP (5 M and 15 F) and healthy controls (3 M and 8 F). RESULTS: There were no differences between PA, PP, and controls or between PA and PP subgroups for sex, BMI z-score, or criteria for childhood metabolic syndrome. Dehydroepiandrosterone sulfate (DHEAS) was elevated only in the PA subgroup, as defined. 11oAs were elevated versus controls in PA and PP although no differences in 11oAs were noted between PA and PP. Within the case cohort, there was high correlation of T and A4 with 11-ketotestosterone and 11ß-hydroxyandrostenedione. While lipids did not differ, median insulin and HOMA-IR were higher but not statistically different in PA and PP. CONCLUSIONS: PA and PP differ only by DHEAS and not by 11oAs or insulin sensitivity, consistent with 11oAs - rather than DHEAS - mediating the phenotypic changes of pubarche. Case correlations suggest association of 11oAs with T and A4. These data are the first to report the early morning steroid profiles including 11oAs in a well-defined group of PA, PP, and healthy children.

Obesity and Insulin Resistance, Not Polycystic Ovary Syndrome, Are Independent Predictors of Bone Mineral Density in Adolescents and Young Women.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders that affects females of reproductive age. The characteristic features of PCOS individually have opposing effects on bone mineral density (BMD); however, their cumulative effect on BMD has not been clearly defined. Adolescence and young adulthood span a crucial period in achieving peak bone mass. Thus, a better understanding of the impact of PCOS on BMD in this age group is needed. OBJECTIVES: To determine whether BMD is different between young females with PCOS and controls and to identify factors that influence BMD in this population. METHODS: Data from four cross-sectional studies with a total of 170 females aged 12-25 years with PCOS (n = 123) and controls (n = 47) with a wide range of BMIs (18.7-53.4 kg/m2) were analyzed. Participants had fasting glucose, insulin, and free and total testosterone concentrations measured. HOMA-IR was calculated. Whole-body BMD was assessed by dual-energy X-ray absorptiometry. Multiple regression analysis for predicting BMD included PCOS status, menstrual age, obesity, HOMA-IR, and free testosterone. RESULTS: HOMA-IR and total and free testosterone were significantly higher in PCOS compared to controls but there was no difference in BMD z-score between PCOS (0.8 ± 1.0) and controls (0.6 ± 1.0) (p = 0.36). Obesity (p = 0.03) and HOMA-IR (p = 0.02) were associated with BMD z-score. CONCLUSIONS: Obesity status and insulin resistance, but not PCOS status, were each independently associated with BMD in adolescents and young women who spanned a wide range of BMIs.

Deficits in Bone Geometry in Growth Hormone-Deficient Prepubertal Boys Revealed by High-Resolution Peripheral Quantitative Computed Tomography.

INTRODUCTION: Although growth hormone (GH) is essential for attainment of peak bone mass, bone health in prepubertal children with GH deficiency is not routinely evaluated. The objective of this study was to evaluate bone microarchitecture in GH-deficient (GHD) boys using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Fifteen control and fifteen GHD, GH naïve pre-pubertal boys were recruited for a case-control study at a major academic center. Subjects with panhypopituitarism, chromosomal pathology, chronic steroids, or stimulant use were excluded. Volumetric bone mineral density (vBMD; total, cortical, and trabecular), bone geometry (total, cortical and trabecular cross-sectional area, cortical perimeter), bone microarchitecture, and estimated bone strength of the distal radius and tibia were assessed by HR-pQCT. Areal BMD and body composition were assessed by DXA. Insulin-like growth factor 1 (IGF-1), osteocalcin, C telopeptide, and P1NP levels were measured. RESULTS: GHD subjects had a significantly smaller cortical perimeter of the distal radius compared to controls (p < 0.001), with the difference in cortical perimeter persisting after adjusting for height z score, age, lean mass, and 25-hydroxyvitamin D level (p < 0.05).No significant differences were found in vBMD. No significant differences were found in microarchitecture, estimated strength, areal BMD, body composition, or bone turnover markers. Analysis showed significant positive correlations between IGF-1 levels and cortical parameters. DISCUSSION/CONCLUSIONS: Prepubertal GHD boys had deficits in bone geometry not evident with DXA. Larger prospective/longitudinal HR-pQCT studies are needed to determine the extent of these deficits, the need for routine bone evaluation, and the timing of GH replacement for prevention or restoration of these deficits.

Alterations in Glucose Effectiveness and Insulin Dynamics: Polycystic Ovary Syndrome or Body Mass Index.

BACKGROUND/AIMS: To delineate the relationship of polycystic ovary syndrome (PCOS), obesity, and hyperandrogenism (HA) with glucose and insulin dynamics in adolescents across a broad body mass index (BMI). METHODS: Seventy-four PCOS subjects (aged 16 years) and 82 controls (aged 16 years) were evaluated by an oral glucose tolerance test. Subjects were categorized by BMI: normal weight (21 ± 0.4), overweight/obesity (OO; 33 ± 1.0), and severe obesity (SO; 48 ± 1.4). Indices of glucose and insulin dynamics were determined. Multiple linear regression analysis was used to evaluate the contribution of PCOS, HA, and BMI to these indices. RESULTS: BMI was significantly associated with systolic and diastolic blood pressure and insulin resistance. A significant interaction between BMI and PCOS and indices of post-glucose load was observed. The mean difference in peak glucose, early glucose response, area under the curve for glucose, and glucose effectiveness (SgIo) between PCOS and control subjects was significantly different between OO and SO. In PCOS subjects, testosterone was positively associated with BMI, fasting insulin, early insulin response, and diastolic blood pressure, and negatively associated with SgIo. CONCLUSIONS: Abnormal glucose dynamics in adolescents with PCOS is mainly due to SO. The combination of PCOS and SO has a synergistic effect on glucose dynamics when compared to all other groups.

The Relationship of Metabolic Syndrome and Body Composition in Children with Premature Adrenarche: Is It Age Related?

BACKGROUND: Studies that evaluate both body composition and metabolic syndrome (MeS) risk in prepubertal children with premature adrenarche (PA) are limited. METHODS: Fifty-eight prepubertal children (aged 5-9 years, 33 female and 25 male), 30 with PA and 28 controls, were evaluated for the presence of MeS as defined by age-modified National Cholesterol Education Program Adult Treatment Panel III criteria. A subset had dual-energy X-ray absorptiometry and bone markers (n = 23/58) to evaluate the effect of hyperandrogenism on metabolic abnormalities and body composition. RESULTS: There was no difference in the prevalence of MeS between PA and controls (p = 0.138). Children with MeS were obese with an increased waist circumference (WC) and decreased high-density lipoprotein levels. Androgens were not associated with having more than one criterion for MeS (p = 0.08) but were associated with triglycerides and WC (p = 0.029 and p = 0.041, respectively). Lean mass was greater in PA subjects (p = 0.039), and androgens correlated with bone mineral density (p = 0.029) and total body fat (p = 0.008). Subjects with a higher percent of body fat were more likely to have more than one MeS risk factor (p = 0.005). CONCLUSIONS: MeS was seen only in obese subjects whether or not they had PA. Thus, it appears that obesity drives metabolic risk in the prepubertal population rather than PA. Our findings are important in determining how the prepubertal patient with PA should be evaluated for metabolic risk.

An update on childhood bone health: mineral accrual, assessment and treatment.

PURPOSE OF REVIEW: To update the reader's knowledge about the factors that influence bone mineral accrual and to review the advances in the assessment of bone health and treatment of bone disorders. RECENT FINDINGS: Maternal vitamin D status influences neonatal calcium levels, bone mineral density (BMD) and bone size. In turn, BMD z-score tends to track in childhood. These factors highlight the importance of bone health as early as fetal life. Dual-energy x-ray absorptiometry is the mainstay of clinical bone health assessment in this population because of the availability of appropriate reference data. Recently, more information has become available about the assessment and treatment of bone disease in chronically ill pediatric patients. SUMMARY: Bone health must become a health focus starting prenatally in order to maximize peak bone mass and to prevent osteoporosis-related bone disease in adulthood. Vitamin D, calcium and weight-bearing activity are the factors of key importance throughout childhood in achieving optimal bone health as BMD z-score tracks through childhood and into adulthood. Recent updates of the International Society for Clinical Densitometry focus on the appropriate use of dual-energy x-ray absorptiometry in children of all ages, including children with chronic disease, and on the treatment of pediatric bone disease.

Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents.

OBJECTIVES: This study aimed to [1] confirm that nonobese adolescents with polycystic ovary syndrome (PCOS) have higher anti-Mullerian hormone (AMH) than controls; [2] examine the relationship of AMH with PCOS features and hormonal profile; and [3] approximate an AMH value that discriminates between adolescents with PCOS and controls. DESIGN: Case-control study. SETTING: Subspecialty ambulatory clinic. PATIENTS: Thirty-one nonobese adolescent girls (age 13-21 years), 15 with PCOS diagnosed using the National Institutes of Health (NIH) criteria and 16 healthy control subjects. Subjects and controls were comparable for body mass index z-score, age and ethnicity. MAIN OUTCOME MEASURE(S): AMH in PCOS subjects and control groups, correlation of AMH with hormonal parameters. RESULTS: AMH was higher in PCOS subjects (4.4±3.4 ng/mL) than in controls (2.4±1.3 ng/mL), when adjusted for menstrual age. In the entire group (PCOS and controls), AMH correlated with androgens, ovarian size and the presence of polycystic ovary (PCO) appearance. There was no difference in average ovarian size between PCOS (7.1±2.6 cm³) and controls (6.7±1.8 cm³). PCOS subjects were 1.49 times more likely to have AMH >3.4 ng/mL (confidence interval 0.98-2.26 ng/mL). CONCLUSIONS: Our data suggest that AMH may be a useful adjunct in the diagnosis of PCOS in adolescents.

Outcome analysis of aromatase inhibitor therapy to increase adult height in males with predicted short adult stature and/or rapid pubertal progress: a retrospective chart review.

BACKGROUND: Aromatase inhibitors (AIs) have been used off-label to increase adult height in short adolescent males. Studies have shown that AIs increase the predicted adult height (PAH) while delaying bone age (BA) maturation. We sought to determine whether AI therapy increases PAH in boys with short stature or rapid pubertal progression, and to evaluate any untoward effects. METHODS: The charts of 27 boys with BA ≥ 13 and short stature [height ≥ 2 standard deviation (SD) below the mean or ≥ 2 SD below mid-parental target height (MPTH)] or rapid pubertal progress, treated with anastrozole were reviewed. Outcome measures included anthropomorphic, hormonal, and metabolic data. RESULTS: The AI therapy averaged 21 months (range 14-30 months) for all, with Rx group 1 receiving <18 months therapy (n=7) and Rx group 2 receiving 18-30 months therapy (n=20). Post-therapy, in Rx group 1 and all subjects, there was no significant change in the PAH, height SDS, or BA/chronological age (CA). In Rx group 2, there was a small, nonsignificant increase in PAH, no change in height SDS, and a small decrease in BA/CA. Post-therapy PAH was different from MPTH in all and in both Rx groups 1 and 2, p<0.02. Eight of them achieved near-final height, averaging 6.73 ± 1.40 cm less than MPTH and 1.91 ± 0.86 cm less than the pre-therapy PAH. Post-therapy, the initially decreased estradiol did not persist but mildly increased testosterone and decreased high-density lipoprotein were noted, as was an increase in hematocrit, and decrease in growth velocity. CONCLUSIONS: We suggest that although bone age progression may be slightly delayed with longer duration of therapy, an overall short-term AI therapy does not lead to a final height that is greater than the predicted pre-therapy height.

Diagnosis and challenges of polycystic ovary syndrome in adolescence.

Although the diagnostic criteria for polycystic ovary syndrome (PCOS) have become less stringent over the years, determination of the minimum diagnostic features in adolescents is still an area of controversy. Of particular concern is that many of the features considered to be diagnostic for PCOS may evolve over time and change during the first few years after menarche. Nonetheless, attempts to define young women who may be at risk for development of PCOS is pertinent since associated morbidity such as obesity, insulin resistance, and dyslipidemia may benefit from early intervention. The relative utility of diagnostic tools such as persistence of anovulatory cycles, hyperandrogenemia, hyperandrogenism (hirsutism, acne, or alopecia), or ovarian findings on ultrasound is not established in adolescents. Some suggest that even using the strictest criteria, the diagnosis of PCOS may not valid in adolescents younger than 18 years. In addition, evidence does not necessarily support that lack of treatment of PCOS in younger adolescents will result in untoward outcomes since features consistent with PCOS often resolve with time. The presented data will help determine if it is possible to establish firm criteria which may be used to reliably diagnose PCOS in adolescents.

Pediatric pulmonary arterial hypertension and hyperthyroidism: a potentially fatal combination.

CONTEXT: Patients with pulmonary arterial hypertension (PAH) who develop hyperthyroidism are at risk for acute cardiopulmonary decompensation and death. CASES AND SETTING: We present a series of eight idiopathic PAH/heritable PAH pediatric patients who developed hyperthyroidism between 1999 and 2011. Institutional Review Board approval was obtained; informed consent was waived due to the retrospective nature of the series. All eight patients were receiving iv epoprostenol; five of the eight patients presented with acute cardiopulmonary decompensation in the setting of hyperthyroidism. In the remaining three patients, hyperthyroidism was detected during routine screening of thyroid function tests. The one patient who underwent emergency thyroidectomy was the only survivor of those who presented in cardiopulmonary decline. EVIDENCE SYNTHESIS: Aggressive treatment of the hyperthyroid state, including emergency total thyroidectomy and escalation of targeted PAH therapy and ß-blockade when warranted, may prove lifesaving in these patients. Prompt thyroidectomy or radioactive iodine ablation should be considered for clinically stable PAH patients with early and/or mild hyperthyroidism to avoid potentially life-threatening cardiopulmonary decompensation. CONCLUSIONS: Although the association between hyperthyroidism and PAH remains poorly understood, the potential impact of hyperthyroidism on the cardiopulmonary status of PAH patients must not be ignored. Hyperthyroidism must be identified early in this patient population to optimize intervention before acute decompensation. Thyroid function tests should be checked routinely in patients with PAH, particularly those on iv epoprostenol, and urgently in patients with acute decompensation or symptoms of hyperthyroidism.

Metabolic manifestations of polycystic ovary syndrome in nonobese adolescents: retinol-binding protein 4 and ectopic fat deposition.

OBJECTIVE: To determine whether nonobese adolescents with polycystic ovary syndrome (PCOS) have higher levels of retinol-binding protein 4 (RBP4) and ectopic fat than controls and whether RBP4 and ectopic fat correlate with comorbidities of metabolic disease. DESIGN: Cross-sectional case-control study. SETTING: Pediatric clinical research center based in a quaternary care medical center. PATIENT(S): Twenty-four nonobese adolescents between the ages of 13 and 21 years, 13 with PCOS and 11 controls. INTERVENTION(S): Measurement of RBP4, insulin resistance, lipids, and body composition. MAIN OUTCOME MEASURE(S): Retinol-binding protein 4, reproductive and adrenal hormones, insulin resistance, intrahepatic and intramyocellular lipid levels, and visceral adipose tissue. RESULT(S): Adolescents with PCOS had higher intrahepatic lipid content and a statistical trend for higher RBP4 compared with controls. Retinol-binding protein 4 correlated with body fat, triglycerides, insulin resistance, and androgens but not intrahepatic lipid content; however, when adjusted for body fat, the correlation between RBP4 and triglycerides weakened to a statistical trend and was no longer statistically significant for the other measures. CONCLUSION(S): This small preliminary study of nonobese adolescent girls suggests that RBP4 may be involved in the dyslipidemia associated with PCOS and that there may be an independent relationship between RBP4 and triglycerides but not between RBP4 and insulin resistance. Although intrahepatic lipid content was higher in PCOS, it did not correlate with RBP4, triglycerides, or insulin resistance.

Retinol-binding protein 4 correlates with triglycerides but not insulin resistance in prepubertal children with and without premature adrenarche.

BACKGROUND: Retinol-binding protein 4 (RBP4) has been proposed as an early marker for insulin resistance (IR), but no prior studies have addressed RBP4 in an exclusively prepubertal population. Children with premature adrenarche (PA) are at increased risk for IR and metabolic syndrome (MeS); thus finding an appropriate early marker for IR in this population would allow for early intervention and prevention of morbidity related to IR and MeS. OBJECTIVE: To determine whether prepubertal children with PA have higher levels of RBP4 than controls and whether RBP4 correlates with comorbidities of metabolic disease in prepubertal children. SUBJECTS: This study comprised 49 prepubertal children (24 with PA and 25 control subjects), 20 boys and 29 girls, who were between the ages of 5 and 9 years. METHODS: This was a cross-sectional, case-control study conducted in a subspecialty ambulatory clinic based in a quaternary care center. RBP4 levels, hormonal values, lipids, and response to an oral glucose tolerance test were evaluated in children with PA and controls, and body composition measures were obtained in a subset of patients (n = 18). RESULTS: RBP4 correlated with triglycerides (r = 0.57, p < 0.0001) but did not correlate with IR in a body mass index z-score-adjusted Pearson correlation analysis. There was no difference in RBP4 levels between the PA and control groups. CONCLUSIONS: These findings suggest that RBP4 may be an early marker of dyslipidemia, which may herald future onset of hepatic IR, polycystic ovary syndrome, and MeS.

Approach to the girl with early onset of pubic hair.

Premature pubarche, or the development of pubic hair before the age of 8 in girls or 9 in boys, is most commonly caused by premature adrenarche. Adrenarche is the maturation of the adrenal zona reticularis in both boys and girls, resulting in the development of pubic hair, axillary hair, and adult apocrine body odor. Although originally thought to be a benign variant of normal development, premature adrenarche has been associated with insulin resistance and the later development of metabolic syndrome and polycystic ovary syndrome. Although further studies are needed to confirm these relationships, the case presented herein argues for periodic assessment of children at risk. Indeed, recognition of these associations may allow for early preventive measures.

Bone age advancement in prepubertal children with obesity and premature adrenarche: possible potentiating factors.

Obesity and premature adrenarche (PA) are both associated with bone age (BA) advancement of unclear etiology, which may lead to earlier puberty, suboptimal final height and obesity in adulthood. Our objective was to understand the hormonal and anthropometric characteristics of BA advancement in a spectrum of prepubertal children with and without obesity and PA. In this cross-sectional study of 66 prepubertal children (35 PA, 31 control, 5-9 years), BMI z-score, hormonal values and response to an oral glucose tolerance test were the main outcome measures. Subjects were divided into tertiles by BA divided by chronological age (BA/CA), an index of BA advancement. Subjects in the top tertile for BA/CA had the highest dehydroepiandrosterone sulfate (DHEAS), free testosterone (%), hemoglobin A(1C), BMI z-score, and weight (P < 0.05). BMI z-score (r = 0.47), weight (r = 0.40), free testosterone (%) (r = 0.34), and DHEAS (r = 0.30) correlated with BA/CA (P < 0.02). Regression analysis showed greater BA/CA in PA compared to controls after controlling for weight (0.21 ± 0.56, P < 0.004). An exploratory stepwise regression model showed that weight, estradiol, and DHEAS were the strongest predictors of BA/CA accounting for 24% of its variance. Obesity was highly associated with BA advancement in this study of prepubertal children. In addition, children with PA had greater BA/CA at any given weight when compared to controls. These findings suggest a possible hormonal factor, which potentiates the effect of obesity on BA advancement in children with obesity and/or PA.