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ObjectiveTo assess the safety and efficacy of short‐term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity.MethodsAdolescents (ages 12–18 years) with severe obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m2) were recruited for this double‐blind, randomized, placebo‐controlled trial. Participants completed 4 weeks of meal replacement therapy followed by randomization (1:1) to either 24 weeks of topiramate 75 mg/day or placebo. Mean changes were compared between groups.ResultsThirty adolescents (mean age 15.2 ± 1.7 years, mean BMI 40.3 ± 4.6 kg/m2) completed the meal replacement phase and were randomized; 21 completed the study. The difference in mean percent change in BMI between the topiramate and placebo groups was not significant (−1.9%; 95% CI: −5.2% to +1.5%; P = 0.291). Significant improvements in visceral fat and very‐low‐density lipoprotein cholesterol were observed in the topiramate compared with the placebo group. There were no concerning changes in neurocognitive function or bone health.ConclusionsIn this pilot study, 4 weeks of meal replacement therapy followed by 24 weeks of low‐dose topiramate compared with meal replacement therapy alone did not result in significant BMI reduction for adolescents with severe obesity.

The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

AbstractBackgroundChildhood obesity is underdiagnosed in primary care practices. Our study aimed to compare rates of documentation of diagnosis of obesity and counselling for nutrition and physical activity at an academic primary care practice prior to and following implementation of a body mass index (BMI)‐based electronic point of care clinical reminder tool.MethodsWe performed a retrospective record review of children aged 2–18 years undergoing well child visits during any of three calendar years (2009, 2011 and 2013). The electronic clinical reminder tool was implemented in September 2010. Records of children with BMI > 95th percentile were electronically searched for terms of documentation of diagnosis of obesity and nutrition and physical activity counselling. Multivariable logistic regression models were used to adjust for potential patient and provider confounders.ResultsAmong those with BMI ≥ 95th percentile, there was a statistically significant increase in documentation of diagnosis of obesity (45.5% in 2009 vs. 52.4% in 2011; P < 0.001; adjusted odds ratio 1.36; 95% CI 1.13–1.65) and in counselling for physical activity and nutrition (66.8% in 2009 vs. 75.2% in 2011; P < 0.001; adjusted odds ratio 1.33; 95% CI 1.06–1.66) following implementation of the tool. Compared with 2011, there was no statistically significant increase in documentation of obesity (50.4%) or nutrition and physical activity counselling (77.9%) in 2013.ConclusionsThe implementation of a point of care clinical reminder tool was associated with improvement in documentation of diagnosis of obesity and counselling for nutrition and physical activity. Further studies are needed to determine the impact of these automated tools on weight outcomes in children.

SummaryBackgroundObesity in children is associated with vitamin D deficiency and endothelial dysfunction. It is not known if treatment with vitamin D improves endothelial function in obese adolescents.ObjectiveThis study aimed to determine whether treatment with vitamin D3 improves endothelial function in obese adolescents.MethodsNineteen obese adolescents, 13–18 years of age, with 25‐hydroxy vitamin D (25[OH]D) levels <75 nmol L−1 were treated with 100 000 IU vitamin D3 orally once a month for 3 months in an open‐label, single‐centre prospective trial. Endothelial function was assessed by flow‐mediated dilatation (FMD) of the brachial artery at study entry and 1 month after the third dose of vitamin D3. Biochemical parameters, including calcium, fasting lipids, glucose, insulin and high‐sensitivity C‐reactive protein, were also obtained.ResultsMean 25(OH)D levels increased from 55.9 ± 12.2 to 86.9 ± 16.7 nmol L−1 (P < 0.01). There was no correlation between 25(OH)D levels and brachial artery FMD. The brachial artery FMD (%) did not change significantly following vitamin D3 treatment (9.5 ± 3.53 vs. 10.3 ± 3.83, P = 0.83). Serum parathyroid hormone declined from 3.8 ± 1.5 to 3.1 ± 1 pmol L−1 (P = 0.01). The remainder of biochemical measurements did not show a significant change.ConclusionsTreatment with vitamin D3, 100 000 IU once a month for 3 months was effective in increasing 25(OH)D levels in obese adolescents but did not impact endothelial function.

Background: Thyrotropin (TSH) levels display a positive association with body mass index (BMI), and the prevalence of isolated hyperthyrotropinemia is higher in obese adolescents compared to their normal weight controls. However, the metabolic significance of the higher TSH in obese adolescents is less clear. The objective of this study was to determine the relationship between TSH concentrations and insulin sensitivity, lipids, and adipokines in euthyroid, non-diabetic, obese adolescents. Methods: Thirty-six euthyroid, non-diabetic, obese adolescents between the ages of 12 and 18 years underwent a 75 g oral glucose tolerance test. Insulin sensitivity (S i ) and pancreatic β-cell function as assessed by disposition index (DI) were measured using the oral glucose minimal model approach. Cholesterol (total, low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C]), triglycerides (TG), interleukin-6 (IL-6), total and high molecular weight (HMW) adiponectin, and retinol binding protein-4 (RBP4) were also determined. Associations between measures of thyroid function and S i , DI, lipids, and adipokines were computed using Pearson's correlation coefficient and multiple regression analysis. Results: The mean age of the subjects was 14.3±1.88 years, and the mean BMI was 32.5±4.65 kg/m 2 ; 97% were non-Hispanic white and 47% were male. The mean TSH was 2.7±1.2 mIU/L. Increasing serum TSH was correlated with decreasing S i (log S i ) in the entire cohort ( p =0.03), but this relationship persisted only in males ( p =0.02). The correlation between TSH and S i in males remained significant after adjusting for BMI ( p =0.02). There was no correlation between TSH and pancreatic β-cell function as assessed by DI ( p =0.48). TSH correlated positively with LDL-C ( p =0.04) and IL-6 ( p =0.03), but these associations vanished or weakened after adjusting for BMI (LDL-C p- value=0.44; IL-6 p- value=0.07). Conclusions: This study suggests a sex-specific association between TSH and insulin sensitivity in euthyroid, non-diabetic, obese adolescent males. Prospective studies are warranted to explore further this sexual dimorphism in the relationship between thyroid function and insulin sensitivity and to determine if obese adolescents with insulin resistance receiving thyroid supplements for hypothyroidism would benefit from targeting TSH levels in the lower half of normal range.

BACKGROUND AND OBJECTIVE:There is ongoing concern that stimulant medications may adversely affect growth. In a sample of attention-deficit/hyperactivity disorder (ADHD) cases and controls from a population-based birth cohort, we assessed growth and the association between stimulant treatment and growth.METHODS:Subjects included childhood ADHD cases (N = 340) and controls (N = 680) from a 1976 to 1982 birth cohort (N = 5718). Height and stimulant treatment information were abstracted from medical records and obtained during a prospective, adult follow-up study. For each subject, a parametric penalized spline smoothing method modeled height over time, and the corresponding height velocity was calculated as the first derivative. Peak height velocity (PHV) age and magnitude were estimated from the velocity curves. Among stimulant-treated ADHD cases, we analyzed height Z scores at the beginning, at the end, and 24 months after the end of treatment.RESULTS:Neither ADHD itself nor treatment with stimulants was associated with differences in magnitude of PHV or final adult height. Among boys treated with stimulants, there was a positive correlation between duration of stimulant usage before PHV and age at PHV (r = 0.21, P = .01). There was no significant correlation between duration of treatment and change in height Z scores (r = −0.08 for beginning vs end change, r = 0.01 for end vs 24 months later change). Among the 59 ADHD cases treated for ≥3 years, there was a clinically insignificant decrease in mean Z score from beginning (0.48) to end (0.33) of treatment (P = .06).CONCLUSIONS:Our findings suggest that ADHD treatment with stimulant medication is not associated with differences in adult height or significant changes in growth.

SummaryBackgroundThe ideal means of identifying obesity in children and adolescents has not been determined although body mass index (BMI) is the most widely used screening tool.ObjectiveWe performed a systematic review and meta‐analysis of studies assessing the diagnostic performance of BMI to detect adiposity in children up to 18 years.MethodsData sources were EMBASE, MEDLINE, Cochrane, Database of Systematic Reviews Cochrane CENTRAL, Web of Science and SCOPUS up to March 2013. Studies providing measures of diagnostic performance of BMI and using body composition technique for body fat percentage measurement were included.ResultsThirty‐seven eligible studies that evaluated 53 521 patients, with mean age ranging from 4 to 18 years were included in the meta‐analysis. Commonly used BMI cut‐offs for obesity showed pooled sensitivity to detect high adiposity of 0.73 (confidence interval [CI] 0.67–0.79), specificity of 0.93 (CI 0.88–0.96) and diagnostic odds ratio of 36.93 (CI 20.75–65.71). Males had lower sensitivity. Moderate heterogeneity was observed (I2 = 48%) explained in meta‐regression by differences across studies in race, BMI cut‐off, BMI reference criteria (Center for Disease Control vs. International Obesity Task Force) and reference standard method assessing adiposity.ConclusionBMI has high specificity but low sensitivity to detect excess adiposity and fails to identify over a quarter of children with excess body fat percentage.

Objective: To determine the temporal trends in diagnosis and management of pediatric overweight/obesity by primary care providers at a single medical center. Patients: Children 2 to 18 years old undergoing a general medical examination during 3 calendar years (2003, 2006, and 2009). The number of visits for general medical examination were 6390 in 2003, 6646 in 2006, and 7408 in 2009. Methods: We performed a retrospective review of the electronic medical records for weight related diagnostic and/or management terms and laboratory screening in children with body mass index at or greater than the 85th percentile (n = 1630 in 2003, 1495 in 2006, and 1730 in 2009). Results: There was a significant increase in the diagnosis of obesity among obese children seen in 2009 (53.3%) compared with 2006 (36%, P < .001) and 2003 (24.3%, P < .001). Weight-related counseling was documented in a higher proportion of obese children in 2009 (49.4%) compared with 2006 (34.8%) and 2003 (26.6%). There was a significant increase in counseling regarding screen time in 2009 compared with 2006. A significant increase in screening for nonalcoholic fatty liver disease was also noted (30.5% in 2009 vs 21.9% in 2006, P = .018). Conclusions: There has been steady improvement in the rates of obesity diagnosis and obesity-related counseling by primary care providers. However, continued efforts to increase awareness of these issues are needed as nearly half of obese children remained undiagnosed and recommended laboratory screening for obesity-related comorbidities was performed in only a third of obese children.