Advances in pharmacological treatment for congenital adrenal hyperplasia

PURPOSE OF REVIEW: Congenital adrenal hyperplasia (CAH), most commonly caused by 21-hydroxylase deficiency, remains associated with substantial morbidity despite life-saving glucocorticoid replacement. This review is timely because several novel therapies have recently emerged with the potential to improve disease control while reducing glucocorticoid burden. RECENT FINDINGS: Recent advances in CAH management include modified-release hydrocortisone, which better mimics physiological cortisol secretion and may improve androgen control with lower glucocorticoid exposure. Steroid-reducing agents have advanced rapidly, particularly the corticotropin-releasing factor type 1 receptor antagonist crinecerfont and the melanocortin 2 receptor (MC2R) antagonist atumelnant, both of which show promise in lowering adrenocorticotropic hormone (ACTH)-driven androgen excess and facilitating glucocorticoid dose reduction. Additional emerging approaches include insurmountable MC2R antagonists and the anti-ACTH monoclonal antibody Lu AG13909. Gene therapy and genome editing strategies are also progressing, although important biological and technical barriers remain, particularly for durable adrenal targeting. SUMMARY: The therapeutic landscape for CAH is evolving rapidly beyond conventional steroid replacement. These innovations may improve biochemical control and long-term outcomes, but challenges remain regarding adrenal crisis risk, long-term safety, durability, cost, and global equity of access.