Glucocorticoid reduction after starting crinecerfont in pediatric patients with classic congenital adrenal hyperplasia: practical perspectives.

CONTEXT: New and emerging non-glucocorticoid therapies for classic congenital adrenal hyperplasia (CAH) can reduce adrenocorticotropic hormone-mediated androgen production, allowing for glucocorticoid (GC) dose reductions. With the approval of crinecerfont as an adjunctive treatment to GC replacement for patients with classic CAH 4 years of age and older, expert recommendations were developed to provide guidance for GC reduction in pediatric patients after starting crinecerfont.

EVIDENCE ACQUISITION: In December 2024, 11 expert endocrinologists participated in a panel to provide input on strategies and considerations when reducing GC doses after introducing crinecerfont. A smaller panel reconvened in January 2025 to review previous discussions and develop recommendations for GC dose reduction after starting crinecerfont in pediatric patients with classic CAH (4-17 years).

EVIDENCE SYNTHESIS: Approaches to GC reduction should be tailored to individual clinical goals, cortisol needs, and lifestyle. In pediatric patients, GC dose reductions should be guided by androgen concentrations, with the general goal of maintaining androgens near normal range to achieve normal growth and normalize bone age maturation while also minimizing complications from long-term GC exposure. Glucocorticoid doses should be reduced gradually with frequent monitoring and should not be decreased below the dose needed for physiologic cortisol replacement.

CONCLUSION

The approval of crinecerfont has initiated a shift in the treatment approach for classic CAH, in which GCs are used at lower doses predominantly for cortisol replacement. These recommendations will become increasingly relevant as treatment for these patients continues to shift toward a new paradigm of physiologic GC replacement with adjunctive control of androgens.