Growth and Treatment in Congenital Adrenal Hyperplasia: An Observational Study from Diagnosis to Final Height

Abstract

Introduction: Congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase deficiency results in inadequate cortisol and aldosterone synthesis and concomitant overproduction of adrenal androgens. Despite adequate replacement, impaired growth and overweight remain a clinical challenge. The main objective was to investigate the differences in growth, final height (FH), and body mass index (BMI) between different CYP21A2 genotype groups and glucocorticoid treatment strategies during the different phases of growth. Methods: This is a population-based observational cohort study from diagnosis to FH. A total of 86 subjects were diagnosed with CAH in Sweden during 1989–1994. Eighty subjects were followed until FH. There were no interventions apart from the clinical standard of care treatment for CAH. The main outcome measure was the corrected FH standard deviation score (cFH SDS) and its correlation with genotype, accumulated total glucocorticoid dose, and treatment strategy. In addition, BMI and growth trajectories during infancy, childhood, and adolescence were studied. Results: FH was shorter in patients with the more severe CYP21A2 genotypes. Treatment doses of glucocorticoid were within the international treatment recommendations (10–15 mg/m2). Patients with the null and I2 splice genotypes lost approximately 1 SD in FH, whereas patients with the milder genotypes (I172N, P30L, and V281L) were within 0.5 to 0 SDS from target height. cFH SDS was negatively affected by the use of prednisolone but did not correlate with overall glucocorticoid treatment dose calculated as hydrocortisone equivalents. BMI at 18 years was higher in patients treated with prednisolone but did not correlate with genotype. Conclusions: Corrected FH was more affected in patients with severe CYP21A2 genotypes. The addition of a low dose of prednisolone to the hydrocortisone treatment, despite an equivalent total dose of glucocorticoids, was associated with shorter FH and higher BMI in growing subjects with CAH.