Future Directions in the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Abstract Context The traditional management of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is difficult and often suboptimal. Objective To review improvements in the diagnosis and management of 21OHD. Design Literature review, synthesis, and authors’ experience. Setting United States (2 centers). Participants Not applicable. Interventions Not applicable. Main Outcomes Not applicable. Results The 11-oxygenated androgens are abundant in 21OHD, and their measurement might improve diagnosis and medication titration. Several new treatments are under development. Conclusion Circadian delivery of hydrocortisone improves disease management of 21OHD compared to conventional glucocorticoids. Glucocorticoid-sparing therapies such as crinecerfont and atumelnant offer the potential for a block-and-replace strategy, with physiologic replacement dosing of hydrocortisone. Clinical Trial Registration None.