Ellen L. Connor

Pediatric Obesity—Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline

Cosponsoring Associations The European Society of Endocrinology and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. Objective To formulate clinical practice guidelines for the assessment, treatment, and prevention of pediatric obesity. Participants The participants include an Endocrine Society-appointed Task Force of 6 experts, a methodologist, and a medical writer. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The Task Force commissioned 2 systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and co-sponsoring organizations reviewed and commented on preliminary drafts of this guideline. Conclusion Pediatric obesity remains an ongoing serious international health concern affecting ∼17% of US children and adolescents, threatening their adult health and longevity. Pediatric obesity has its basis in genetic susceptibilities influenced by a permissive environment starting in utero and extending through childhood and adolescence. Endocrine etiologies for obesity are rare and usually are accompanied by attenuated growth patterns. Pediatric comorbidities are common and long-term health complications often result; screening for comorbidities of obesity should be applied in a hierarchal, logical manner for early identification before more serious complications result. Genetic screening for rare syndromes is indicated only in the presence of specific historical or physical features. The psychological toll of pediatric obesity on the individual and family necessitates screening for mental health issues and counseling as indicated. The prevention of pediatric obesity by promoting healthful diet, activity, and environment should be a primary goal, as achieving effective, long-lasting results with lifestyle modification once obesity occurs is difficult. Although some behavioral and pharmacotherapy studies report modest success, additional research into accessible and effective methods for preventing and treating pediatric obesity is needed. The use of weight loss medications during childhood and adolescence should be restricted to clinical trials. Increasing evidence demonstrates the effectiveness of bariatric surgery in the most seriously affected mature teenagers who have failed lifestyle modification, but the use of surgery requires experienced teams with resources for long-term follow-up. Adolescents undergoing lifestyle therapy, medication regimens, or bariatric surgery for obesity will need cohesive planning to help them effectively transition to adult care, with continued necessary monitoring, support, and intervention. Transition programs for obesity are an uncharted area requiring further research for efficacy. Despite a significant increase in research on pediatric obesity since the initial publication of these guidelines 8 years ago, further study is needed of the genetic and biological factors that increase the risk of weight gain and influence the response to therapeutic interventions. Also needed are more studies to better understand the genetic and biological factors that cause an obese individual to manifest one comorbidity vs another or to be free of comorbidities. Furthermore, continued investigation into the most effective methods of preventing and treating obesity and into methods for changing environmental and economic factors that will lead to worldwide cultural changes in diet and activity should be priorities. Particular attention to determining ways to effect systemic changes in food environments and total daily mobility, as well as methods for sustaining healthy body mass index changes, is of importance.

Insulin desensitization with insulin lispro and an insulin pump in a 5-year-old child.

BACKGROUND AND OBJECTIVE Allergic reactions to insulin, though rare, can have serious consequences in children with type I diabetes mellitus. We report a case of insulin allergy in a 5-year-old child in whom insulin desensitization was accomplished using an insulin pump. METHODS AND RESULTS A 5-year-old girl with insulin-dependent diabetes mellitus (IDDM) developed progressive reactions to insulin and was found to have positive intradermal skin tests to regular and NPH insulin. Addition of oral antihistamine and co-administration of subcutaneous dexamethasone along with the insulin failed to control her symptoms. The patient was therefore hospitalized and desensitized to insulin using an insulin pump and insulin lispro. CONCLUSION An insulin pump can be used for insulin desensitization in selected children. The slow constant infusion rate provided by the pump may be an ideal means of achieving insulin desensitization. In addition, insulin lispro, a synthetic insulin analog, should be considered for use in insulin-allergic individuals.

Clinical Variability in Approaches to Polycystic Ovary Syndrome

STUDY OBJECTIVE The objective of this study was to evaluate methods of initial diagnosis and management of polycystic ovary syndrome (PCOS) among members of the North American Society for Pediatric and Adolescent Gynecology (NASPAG) to assess the degree of practice heterogeneity among specialist providers of adolescent care. DESIGN Cross-sectional, anonymous, internet survey PARTICIPANTS NASPAG membership (N = 326; Respondents = 127 (39%)) RESULTS Percentage of respondents who incorporated specific tests at initial diagnosis was highly variable ranging from 87% (thyroid stimulating hormone) to 17% (sex hormone binding globulin). Oral contraceptives and diet modification/exercise were the most common therapies recommended by 98% and 90% of respondents respectively. CONCLUSION Considerable practice heterogeneity was present with regards to diagnostic testing for suspected PCOS. Recommendations for first-line therapy were more consistent. Future studies should clarify the clinical utility of specific diagnostic tests for adolescents, such that selection of diagnostic testing is evidence based.

Factors Contributing to Initial Weight Loss Among Adolescents with Polycystic Ovary Syndrome

STUDY OBJECTIVE To evaluate the impact of a multidisciplinary clinic on weight management among adolescents with PCOS. DESIGN 140 adolescent females were evaluated in a multidisciplinary PCOS clinic from March 2005 to December 2008. The team included a pediatric endocrinologist, health psychologist, dietitian, and pediatric gynecologist. 110 were diagnosed with PCOS based on the Rotterdam Criteria. Height, weight, BMI, number of subspecialists seen, use of metformin, and compliance with return visits were obtained from medical records. SETTING American Family Childrens Hospital in Madison, Wisconsin. PARTICIPANTS 110 adolescent females with polycystic ovary syndrome. INTERVENTIONS Consultation with a dietitian and health psychologist. MAIN OUTCOME MEASURE Change in weight. RESULTS The average age at first visit was 15.9 years. The average BMI was 34.7 kg/m(2) (range 18.1-55.5). Seventy-six percent had an initial BMI above the 95(th) percentile. Interactions with providers at the initial visit included a pediatric endocrinologist (100%), health psychologist (60.9%), dietitian (75.5%) and gynecologist (70.9%). Seventy one percent returned for a follow-up visit, (average time of 4.5 months between visits) with 57% achieving weight loss (average 3.5 kg) and an additional 12.6% demonstrating no significant weight gain (< 1.5 kg). Thus, 69.6% demonstrated weight loss/stabilization. CONCLUSIONS In this multidisciplinary clinic for adolescents with PCOS, nearly 70% of patients succeeded in short-term weight stabilization, with 57% demonstrating weight loss. Interactions with the health psychologist and dietitian appeared to play a key role in successful weight control, supporting the importance of psychology and nutrition expertise in the management of this disorder.

Predicting Hepatic Steatosis in a Racially and Ethnically Diverse Cohort of Adolescent Girls

OBJECTIVE To develop a risk assessment model for early detection of hepatic steatosis using common anthropometric and metabolic markers. STUDY DESIGN This was a cross-sectional study of 134 adolescent and young adult females, age 11-22 years (mean 13.3±2 years) from a middle school and clinics in Madison, Wisconsin. The ethnic distribution was 27% Hispanic and 73% non-Hispanic; the racial distribution was 64% Caucasian, 31% African-American, and 5% Asian, Fasting glucose, fasting insulin, alanine aminotransferase (ALT), body mass index (BMI), waist circumference (WC), and other metabolic markers were assessed. Hepatic fat was quantified using magnetic resonance imaging proton density fat fraction (MR-PDFF). Hepatic steatosis was defined as MR-PDFF>5.5%. Outcome measures were sensitivity, specificity, and positive predictive value (PPV) of BMI, WC, ALT, fasting insulin, and ethnicity as predictors of hepatic steatosis, individually and combined, in a risk assessment model. Classification and regression tree methodology was used to construct a decision tree for predicting hepatic steatosis. RESULTS MR-PDFF revealed hepatic steatosis in 16% of subjects (27% overweight, 3% nonoverweight). Hispanic ethnicity conferred an OR of 4.26 (95% CI, 1.65-11.04; P=.003) for hepatic steatosis. BMI and ALT did not independently predict hepatic steatosis. A BMI>85% combined with ALT>65 U/L had 9% sensitivity, 100% specificity, and 100% PPV. Lowering the ALT value to 24 U/L increased the sensitivity to 68%, but reduced the PPV to 47%. A risk assessment model incorporating fasting insulin, total cholesterol, WC, and ethnicity increased sensitivity to 64%, specificity to 99% and PPV to 93%. CONCLUSION A risk assessment model can increase specificity, sensitivity, and PPV for identifying the risk of hepatic steatosis and guide the efficient use of biopsy or imaging for early detection and intervention.

Ethnic differences in the effects of hepatic fat deposition on insulin resistance in nonobese middle school girls

In nonobese youth, to investigate whether hepatic fat deposition and its metabolic consequences vary between ethnic groups.

Oxandrolone Improves Height Velocity and BMI in Patients with Cystic Fibrosis

Objective. To evaluate the effectiveness of oxandrolone in improving the nutritional status and linear growth of pediatric patients with cystic fibrosis (CF). Methods. Medical records of patients with CF treated with oxandrolone were reviewed for height z score, height velocity (HV), BMI z score, weight velocity (WV), Tanner stage, pulmonary function, liver enzyme levels, and any reported adverse events. Data were compared before (pre-Ox) and after (Ox) oxandrolone using a paired t-test. Results. 5 subjects (ages 8.5–14.5 years) were treated with oxandrolone 2.5 mg daily for 8–38 months. After 8–12 months of treatment, there was a statistically significant improvement in HV ( cm/yr,  cm/yr, ) and BMI z score (, , ). Both height z score (, , ) and WV ( kg/yr, Ox  kg/yr, ) showed beneficial trends that did not reach statistical significance. No adverse events were reported. Conclusions. In this brief clinical report, oxandrolone improved the HV and BMI z score in patients with CF. Larger studies are needed to determine if oxandrolone is an effective, safe, and affordable option to stimulate appetite, improve weight gain, and promote linear growth in patients with CF.

In Nonobese Girls, Waist Circumference as a Predictor of Insulin Resistance Is Comparable to MRI Fat Measures and Superior to BMI

Objective: The aim of this study was to investigate the degree to which waist circumference (WC), body mass index (BMI), and magnetic resonance imaging (MRI)-measured abdominal fat deposition predict insulin resistance (IR) in nonobese girls of diverse racial and ethnic backgrounds. Methods: Fifty-seven nonobese girls (12 African-American, 16 Hispanic White, and 29 non-Hispanic White girls) aged 11-14 years were assessed for WC, MRI hepatic proton density fat fraction, visceral and subcutaneous adipose tissue volume, BMI Z-score, fasting insulin, homeostasis model of assessment (HOMA)-IR, adiponectin, leptin, sex hormone-binding globulin, high-density lipoprotein cholesterol, and triglycerides. Results: Univariate and multivariate analyses adjusted for race and ethnicity indicated that only WC and visceral adipose tissue volume were independent predictors of fasting insulin and HOMA-IR, while hepatic proton density fat fraction, BMI Z-score, and subcutaneous adipose tissue volume were dependent predictors. Hispanic White girls showed significantly higher mean fasting insulin and HOMA-IR and lower sex hormone-binding globulin than non-Hispanic White girls (p < 0.01). Conclusions: In nonobese girls of diverse racial and ethnic backgrounds, WC, particularly when adjusted for race or ethnicity, is an independent predictor of IR comparable to MRI-derived measurements of fat and superior to the BMI Z-score.

Spontaneous Recovery of Ovarian Function in an Adolescent with Galactosemia and Apparent Premature Ovarian Insufficiency

BACKGROUND Galactosemia is an inborn error of metabolism resulting in premature ovarian insufficiency in 80-90% of females. There have been no reported cases of biochemical ovarian failure followed by normal menses. CASE A 12-year-old girl with galactosemia presented for gynecologic consultation. Her follicle-stimulating hormone (FSH) and estradiol levels were 52.9 U/L and less than 100 pmol/L, respectively. She started exogenous estrogen to stimulate puberty. At 16, she had spontaneous regular menstrual cycles. FSH and luteinizing hormone (LH) levels reflected normal ovarian function. Hormonal contraception was provided. One year later, she was found to be in ovarian failure (FSH 86.6 U/L, LH 33.3 U/L), and both estradiol and anti-Müllerian hormone were undetectable. SUMMARY AND CONCLUSIONS This case documents spontaneous resumption of ovarian function after galactosemia-related ovarian failure. The use of FSH and LH is potentially limited in predicting ovarian function in this population.

Polyglandular autoimmune syndrome type I - a novel AIRE mutation in a North American patient.

Abstract Autoimmune polyglandular syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autoimmune disease that results from autosomal recessive mutations of the human autoimmune regulatory (AIRE) gene. We present the case of a 17-year-old North American girl of primarily Norwegian descent with a novel AIRE gene mutation causing APS-1. In addition to the classic triad of chronic candidiasis, hypoparathyoidism and autoimmune adrenocortical insufficiency, she also has vitiligo, intestinal malabsorption, autoimmune hepatitis, autoimmune hypothyroidism, myositis, myalgias, chronic fatigue, and failure to thrive. Genetic testing revealed heterozygosity for c.20_115de196 and c.967_979del13 mutations in the AIRE gene. The AIRE gene c.20_115de196 mutation has not been previously reported.