Aviva B. Sopher

Classification of body fatness by body mass index-for-age categories among children.

OBJECTIVE To examine the ability of various body mass index (BMI)-for-age categories, including the Centers for Disease Control and Preventions 85th to 94th percentiles, to correctly classify the body fatness of children and adolescents. DESIGN Cross-sectional. SETTING The New York Obesity Research Center at St Lukes-Roosevelt Hospital from 1995 to 2000. PARTICIPANTS Healthy 5- to 18-year-old children and adolescents (N = 1196) were recruited in the New York City area through newspaper notices, announcements at schools and activity centers, and word of mouth. MAIN OUTCOME MEASURES Percent body fat as determined by dual-energy x-ray absorptiometry. Body fatness cutoffs were chosen so that the number of children in each category (normal, moderate, and elevated fatness) would equal the number of children in the corresponding BMI-for-age category (<85th percentile, 85th-94th percentile, and > or =95th percentile, respectively). RESULTS About 77% of the children who had a BMI for age at or above the 95th percentile had an elevated body fatness, but levels of body fatness among children who had a BMI for age between the 85th and 94th percentiles (n = 200) were more variable; about one-half of these children had a moderate level of body fatness, but 30% had a normal body fatness and 20% had an elevated body fatness. The prevalence of normal levels of body fatness among these 200 children was highest among black children (50%) and among those within the 85th to 89th percentiles of BMI for age (40%). CONCLUSION Body mass index is an appropriate screening test to identify children who should have further evaluation and follow-up, but it is not diagnostic of level of adiposity.

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 A1C, 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.

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.

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

Abstract 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.

Effect of laparoscopic adjustable gastric banding on metabolic syndrome and its risk factors in morbidly obese adolescents.

We examined the effect of laparoscopic adjustable gastric banding (LAGB) on weight loss, inflammatory markers, and components of the Metabolic Syndrome (MeS) in morbidly obese adolescents and determined if those with MeS lose less weight post-LAGB than those without. Data from 14–18 yr adolescents were obtained at baseline, 6 and 12 months following LAGB. Significant weight loss and improvements in MeS components were observed 6 months and one year following LAGB. The incidence of MeS declined 56.8% after 6 months and 69.6% after 12 months. There was no significant difference in amount of weight lost post-LAGB between those with and without MeS at either timepoint. Correlations between change in weight parameters and components of MeS in those with and without MeS at baseline were examined and found to vary by diagnostic category. LAGB is effective for short-term improvement in weight, inflammatory markers, and components of MeS in morbidly obese 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 β-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.

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

Purpose of reviewTo update the readers 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 findingsMaternal 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. SummaryBone 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.

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

Abstract 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.