Advances in pharmacological treatment for congenital adrenal hyperplasia

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 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.

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.