Patricia Fechner, MD, discusses how crinecerfont may reduce glucocorticoid exposure in pediatric CAH

The approval of crinecerfont as an adjunctive treatment for classic congenital adrenal hyperplasia (CAH) in children 4 years and older is prompting a shift in how pediatric endocrinologists approach long-term glucocorticoid management, according to newly published expert recommendations.¹

Published in the Journal of Clinical Endocrinology and Metabolism, the recommendations outline strategies for reducing glucocorticoid (GC) doses after initiation of crinecerfont in pediatric patients with classic CAH. A panel of pediatric and adult endocrinologists with expertise in CAH management developed the document.

The recommendations focus on balancing androgen control while minimizing complications linked to long-term supraphysiologic glucocorticoid exposure. Authors noted that traditional CAH management often requires glucocorticoid doses above physiologic replacement levels to suppress excess adrenal androgen production, increasing the risk of growth suppression, obesity, insulin resistance, hypertension, and bone health complications.

Crinecerfont (CRENESSITY), a corticotropin-releasing factor type 1 receptor antagonist, reduces ACTH-driven androgen production and may allow clinicians to lower glucocorticoid doses closer to physiologic replacement levels.

The recommendations were developed as use of crinecerfont expands following its FDA approval in December 2024 as an adjunct to GC replacement therapy for adults and pediatric patients 4 years and older with classic CAH.²

Patricia Fechner, MD, pediatric endocrinologist at Seattle Children’s Hospital and coauthor of the recommendations, said the therapy could alter long-term management strategies for children and adolescents with CAH.

“I think that crinecerfont will allow us to use a lower dose of glucocorticoids. We now do not need to have extra glucocorticoids to suppress the adrenal androgens,” Fechner said in an interview with Contemporary Pediatrics. “By using a lower dose of glucocorticoid, we will then be able to improve a child’s growth, decrease the risk of complications from glucocorticoids, but still maintain good adrenal androgens.”

How crinecerfont may change glucocorticoid management in pediatric CAH

The manuscript highlighted evidence linking higher glucocorticoid exposure to poorer growth outcomes in children with CAH. One cited longitudinal study found adult height decreased by 0.37 cm for each 1 mg/m²/day increase in hydrocortisone dose.

Authors also described increased cardiometabolic risks among pediatric patients with CAH, including obesity, insulin resistance, and elevated fasting glucose levels.

Fechner emphasized that growth monitoring remains central in routine care.

“Most patients with CAH are followed more closely by their pediatric endocrinologist than their pediatrician, but I think that both the pediatric endocrinologist and the pediatrician should be following growth, because too much glucocorticoid use will suppress growth, insufficient use will accelerate their rate of growth,” she said.

Why reducing supraphysiologic glucocorticoid exposure matters

The recommendations advise clinicians to individualize glucocorticoid reductions based on patient goals, cortisol requirements, androgen control, and lifestyle considerations. Experts suggested dose reductions of approximately 10% to 20% at a time in patients whose androgen levels are already at or below target ranges.

The panel also recommended considering simplification of glucocorticoid regimens after crinecerfont initiation, particularly in children receiving multiple daily doses.

“I think it’s important to individualize the plan for each child,” Fechner said. “For example, if they’re taking glucocorticoids 4 times a day, simplifying their regimen by making a dose that’s given 3 times a day.”

She added that reducing high evening glucocorticoid doses may improve physiologic hormone patterns.

“If there is nonphysiologic dosing, such that the evening dose is the highest, then with crinecerfont that can be reduced, and by reducing it, we may then allow better growth hormone secretion at night, as well as improved metabolic results,” Fechner said.

Guidance emphasizes gradual, individualized dose reductions

The recommendations stressed that glucocorticoids should never be discontinued because patients with CAH still require cortisol replacement therapy. Authors also highlighted the importance of educating families about adrenal insufficiency, stress dosing, and adrenal crisis prevention during glucocorticoid reduction.

“I think it’s very critical that we discuss stress management with families,” Fechner said. “Historically, we have told them to triple the daily dose, and that may not be sufficient when we’ve decreased the daily dose of hydrocortisone.”

She added that clinicians should provide specific stress-dose instructions.

“Therefore, instead of telling them to triple the dose, I think we should give them an actual dose in milligrams, and tell them to give it every 6 to 8 hours for stress dosing,” Fechner said.

References

1. Nokoff NJ, Fechner PY, Kim MS, et al. Glucocorticoid reduction after starting crinecerfont in pediatric patients with classic CAH: practical perspectives. J Clin Endocrinol Metab. Published online May 4, 2026. doi:10.1210/clinem/dgag192

2. FDA approves new treatment for congenital adrenal hyperplasia. News release. FDA. December 13, 2024. Accessed May 6, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia.