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

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.