Petryk, Anna

Summary Objectives To evaluate obesity and overweight in children with congenital adrenal hyperplasia ( CAH ) and associations with glucocorticoids, fludrocortisone and disease control. Adjusting body mass index‐for‐height‐age ( BMI HA ) percentile is proposed to correct misclassification of obese/overweight status in CAH children with advanced bone age and tall‐for‐age stature. Design Longitudinal. Patients One hundred and ninety‐four children with CAH seen from 1970 to 2013: 124 salt wasting ( SW ); 70 simple virilizing ( SV ); 102 females. Measurements Body mass index (BMI) end‐points were overweight (85–94 percentile) and obese (≥95 percentile). Results Approximately 50% of the children had at least one BMI measurement ≥95 percentile and about 70% had at least one ≥85 percentile. Using BMI HA percentiles, obesity incidence decreased slightly in SW children (47–43%) and markedly in SV children (50–33%); however, overweight status was not reduced. Only 6% of SW and 1% of SV children were persistently obese (≥3 clinic visits) when BMI HA was applied, whereas overweight status persisted in 35% of SW and 33% of SV children. Most obesity or overweight when using BMI HA occurred before age 10 and there was no association with hydrocortisone (HC) or fludrocortisone dosing. Adiposity rebound for SW children occurred by 3·3 years and in SV females by age 3·8 years, over a year earlier than the adiposity rebound for healthy children. Conclusion Children with CAH are at higher risk for early onset obesity and overweight with or without using BMI HA but rates of persistent obesity were lower than previously reported. Careful HC dosing during early childhood is needed to prevent increased weight gain and an early adiposity rebound.

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.

Summary Objectives Estimates of high blood pressure ( BP ) incidence in children with congenital adrenal hyperplasia ( CAH ) vary widely; risk factors are poorly understood. We estimated incidence of hypertension by CAH subtype and sex, and assessed its association with body mass index, hydrocortisone and fludrocortisone. Design Longitudinal. Patients Chart review of 180 paediatric CAH patients (120 salt wasting; 60 simple virilizing; 93 females) seen from 1970 to 2013. Measurements High BP was diagnosed by diastolic or systolic blood pressure measurement ≥95th percentile for age, sex and height; hypertension was diagnosed with high BP on at least three clinic visits. Results Children with classic CAH who received fludrocortisone had a significantly higher rate of hypertension (55% vs 31%) than those who did not. Hypertension incidence was higher in salt‐wasting CAH (58%) than in simple‐virilizing CAH (35%). Hypertension first occurred before age 5 years in 91% of salt‐wasting males and 50% of cases in salt‐wasting females; most simple‐virilizing cases occurred during ages 10–18 years. Rates of hypertension were higher in children who had three or more measurements with 17‐ OHP < 400 ng/dl (12·12 nmol/l), and this difference was significant in salt‐wasting males. Children on fludrocortisone who had three or more readings of 17‐ OHP < 400 ng/dl (12·12 nmol/l) had a significantly higher rate of hypertension than those who did not. Hydrocortisone dose was not associated with hypertension. Conclusion Children with CAH are at higher risk for hypertension than the general paediatric population, and incidence differs by sex and CAH subtype. Hypertension was higher in children on fludrocortisone and who were oversuppressed.

Key PointsCytokine-induced loss of murine as well as human HSPC homing during ex vivo culture can be prevented by addition of BMP4. In HSPCs, BMP4 directly regulates Integrin-α4 expression through SMAD-independent p38 MAPK-mediated signaling.