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Female adrenal anatomy. Credit: Shutterstock.

Congenital adrenal hyperplasia (CAH) requires administration of supraphysiologial doses of steroids to reduce adrenal androgen production, increasing the likelihood of glucocorticoid-related complications. Treatment strategies that result in a reduction in steroid dose therefore have significant potential. Crinecerfont is an oral antagonist for the corticotrophin-releasing factor 1 receptor and has been demonstrated to reduce androstenedione production.

Auchus et al. report this phase 3 trial, where 182 patients with classical CAH were randomised to receive either crinecerfont or placebo for 24 weeks. Glucocorticoid treatment was reduced and optimised alongside crinecerfont, to ensure androstenedione was either ≤120% of the baseline value or within reference range. Co-administration of crinecerfont to patients with CAH resulted in a greater decrease in glucocorticoid dose compared with placebo, along with reduction in androstenedione.

Given that CAH requires lifelong treatment with glucocorticoids, crinecerfont offers an exciting potential therapeutic strategy to reduce the burden of glucocorticoid-related complications.

Read the full article in New England Journal of Medicine 391 504–514 https://doi.org/10.1056/NEJMoa2404656