Trajectory-based analysis of growth in congenital adrenal hyperplasia: therapeutic implications for final height preservation

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder resulting in a dysfunction of the steroidogenesis pathway and glucocorticoid deficiency. Proper care demands not only preventing acute complications but also optimizing growth and sexual development. This study was set out to analyze final height metrics and the factors affecting them as a long-term outcome measure in CAH patients. This observational retrospective study evaluated almost 3000 visits of 63 CAH patients treated in one center between 1996 and 2025, who reached their near-final height (nFH). The population was divided into the salt-wasting (SW, n = 45) and non-SW groups (n = 18). The main outcome measures were nFH, corrected nFH (c-nFH), and their standard deviation scores (SDSs). They were associated with numerous factors, including glucocorticoid doses, bone age (BA), height velocity (HV), occurrence of puberty, body mass index, and adiposity rebound. c-nFH SDS was compromised in both the SW (- 0.99 ± 0.87) and non-SW patients (- 0.57 ± 0.71) (p = 0.053). HV trajectories pointed to a flattened pubertal growth spurt in both populations. Maximum BA advancement (BAA) and peak ΔBAA were lower in SW than in non-SW patients, while age at peak ΔBAA and age at maximum BAA were comparable between groups. Both longitudinal and cross-sectional regression models showed negative interactions between hydrocortisone doses and height outcomes. CONCLUSION: We observed that CAH patients tend to have compromised final height, with the SW-CAH population presenting with most compromised growth. Higher hydrocortisone doses were associated with worse outcomes. The analysis of BA and HV trajectories seems to suggest a period demanding intensified care. WHAT IS KNOWN: • CAH and long-term glucocorticoid therapy may impair growth and final height, particularly in salt-wasting forms, with bone age advancement regarded as a major determinant of height outcome. • Higher hydrocortisone exposure has been associated with poorer growth outcomes in CAH patients. WHAT IS NEW: • Longitudinal analysis of 2949 visits identified a shared critical period between 6 and 10 years of age characterized by accelerated bone age advancement and altered height velocity trajectories requiring intensified disease control. • Early optimization of androgen suppression and consideration of aromatase inhibitor therapy may improve growth outcomes.