Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia

Objective: Adiposity rebound is the first rise in BMI that occurs after the initial decrease during infancy. Early adiposity rebound, before age 5, is a risk factor for later obesity and metabolic problems. We investigated adiposity rebound in children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (CAH). Design: Longitudinal observational registry study. Methods: Height, weight, and BMI from patients younger than 20 years in the I-CAH Registry was described by non-linear mixed-effects models. Covariates of glucocorticoid dose, mineralocorticoid dose, 17-Hydroxyprogesterone were assessed on growth and bone age. Results: A total of 10 261 visits within 573 patients (43.6% male) showed significant variation in age at latest peak height velocity [8.4 years (SD = 3.0) in boys; 9.0 years (SD = 1.6) in girls]. Peak height velocity was more blunted in boys [7.7 cm/year (SD = 1.4)] than girls [7.4 cm/year (SD = 1.3)] in comparison to normative values. Adiposity rebound occurred earlier than age 5 years in 82% of the cohort, mean age 3.7 years (SD = 1.3) in boys and 3.9 years (SD = 0.9) in girls. Girls prescribed higher doses of glucocorticoid were associated with heavier weight in adolescence and earlier adiposity rebound. Bone age was increasingly advanced in those prescribed higher doses in both sexes. Conclusions: There is a large variation in the timing of adiposity rebound and SITAR-estimated latest peak height velocity in children with CAH. In addition to identifying individuals with CAH who may be at risk of adverse cardiometabolic outcomes these metrics may serve as early surrogate outcomes in future research investigating early-life treatment strategies.