Pediatric recommendations published for glucocorticoid reduction with crinecerfont in classic CAH

New expert recommendations published in The Journal of Clinical Endocrinology & Metabolism provide pediatric-specific guidance for reducing supraphysiologic glucocorticoid (GC) doses after initiation of CRENESSITY (crinecerfont) in children and adolescents with classic congenital adrenal hyperplasia (CAH).1

According to the announcement from Neurocrine Biosciences, the recommendations are intended to help clinicians manage GC tapering in pediatric patients aged 4 to 17 years while maintaining androgen control and supporting normal growth and pubertal development.

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 aged 4 years and older with classic CAH.²

“By reducing ACTH and downstream androgen production, CRENESSITY allows patients with classic CAH, including both salt-wasting and simple virilizing forms, to move toward more physiologic, cortisol-replacing glucocorticoid dosing,” said Sanjay Keswani, MD. “Blocking excess ACTH and androgen production while maintaining necessary cortisol replacement reflects an important shift in how the disease is managed, helping to lower risks associated with long-term exposure to supraphysiologic glucocorticoid doses.”¹

Pediatric guidance emphasizes growth and development

The pediatric recommendations focus on balancing androgen control with normal growth, bone maturation, and pubertal development while minimizing complications associated with prolonged high-dose GC exposure.³

According to the publication, pediatric GC reductions are targeted toward the upper portion of the physiologic range, approximately 8 to 11 mg/m²/day in hydrocortisone equivalents, while maintaining adequate cortisol and mineralocorticoid replacement.³

The expert guidance also recommends close monitoring for symptoms of GC withdrawal, adrenal insufficiency, and androgen control during dose reductions. Biomarkers that may be followed include androstenedione, 17-hydroxyprogesterone, adrenocorticotropic hormone, testosterone, renin, and electrolyte levels.³

“In children and adolescents with classic congenital adrenal hyperplasia, treatment decisions must carefully balance disease control with normal growth and development,” said Mimi Kim, MD, MSc, associate professor of clinical pediatrics at the Keck School of Medicine of the University of Southern California. “These recommendations provide clinicians with a structured, practical approach to glucocorticoid management that helps support growth, bone maturation, and pubertal development as CRENESSITY is incorporated into care.”¹

Recommendations developed from clinical and real-world experience

The guidance was developed by a panel of endocrinologists with experience managing CAH and incorporates lessons from the phase 3 CAHtalyst clinical trial program as well as real-world clinical practice.^`

The accompanying review article noted that long-term supraphysiologic GC exposure in patients with CAH has been associated with metabolic, cardiovascular, and skeletal complications, including obesity, insulin resistance, osteoporosis, and reduced bone mineral density.³

The review also highlighted that excess androgen exposure during childhood can contribute to early puberty and advanced bone age, potentially affecting final adult height.³

Authors of the review recommended that GC dose reductions be individualized based on treatment goals, cortisol requirements, and patient tolerance.³

The recommendations further emphasize that GC reduction is not appropriate for every patient. Some patients may already be receiving physiologic GC doses and may use crinecerfont primarily for androgen control rather than dose reduction.

“CRENESSITY enables us to decouple androgen control from the need for supraphysiologic glucocorticoids in patients with classic congenital adrenal hyperplasia,” said Oksana Hamidi, DO, MSCS, associate professor of internal medicine in the division of endocrinology at UT Southwestern Medical Center. “This new framework provides an algorithm and practical steps clinicians can take to lower glucocorticoid exposure without compromising cortisol replacement, helping to realize the benefits of this novel therapeutic approach in day-to-day care.”

The recommendations caution that patients receiving crinecerfont should continue GC therapy for cortisol replacement and should be monitored for adrenal insufficiency and adrenal crisis during periods of illness or physiologic stress.³

References

1. Neurocrine Biosciences. Neurocrine Biosciences announces publication of expert recommendations for glucocorticoid dose reduction after initiating CRENESSITY® (crinecerfont) for the treatment of classic congenital adrenal hyperplasia. News release. May 6, 2026. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-publication-expert

2. FDA. FDA approves new treatment for congenital adrenal hyperplasia. U.S. Food and Drug Administration. December 13, 2024. Accessed May 6, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia.

3. Hamidi O, Auchus RJ, Correa R, et al. Glucocorticoid reduction after starting crinecerfont in adult patients with classic CAH: practical perspectives. J Clin Endocrinol Metab. Published online April 1, 2026. doi:10.1210/clinem/dgag147.