Early Adiposity Rebound Predicts Obesity and Adiposity in Youth with Congenital Adrenal Hyperplasia

Introduction: Youth with classical congenital adrenal hyperplasia (CAH) have higher prevalence of cardiometabolic risk factors such as obesity, abdominal adiposity, and hypertension. Patients with CAH also exhibit an earlier adiposity rebound (AR) compared to normative populations. However, the predictive relationship between AR and cardiometabolic risk factors needs to be better understood. Methods: We performed a retrospective cohort study at a US tertiary pediatric center in youth with classical CAH due to 21-hydroxylase deficiency. AR was determined by cubic polynomial modeling. A subset of participants had fasting analytes, whole-body dual-energy X-ray absorptiometry, and magnetic resonance imaging as adolescents. Results: In 42 youth with CAH (45.2% female, 54.8% Hispanic, and 90.5% salt-wasting form), the average age at AR was 3.4 ± 1.3 years. AR differed by BMI-z, with youth with obesity having an earlier AR (2.8 ± 1.0 years) compared to lean youth (4.1 ± 1.3 years, p = 0.001). However, AR did not differ by either CAH form or sex. Earlier AR predicted higher BMI-z at 7 and 12 years of age. In addition, earlier AR predicted increased central obesity (as measured by waist circumference, subcutaneous adipose tissue, and trunk fat) and total body fat in adolescence. AR was negatively correlated with bone age, and its relationships with HDL and hypertension were trending towards significance. Conclusions: AR in youth with classical CAH could serve as a useful clinical marker to identify those patients who are at higher risk for developing cardiometabolic risk factors during childhood and adolescence.