ENDO 2025: Most Patients With Classic Congenital Adrenal Hyperplasia Experience High Glucocorticoid Exposure or Suboptimal Control

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New data presented at the ENDO 2025 annual meeting illustrated the significant challenges to managing classic congenital adrenal hyperplasia (CAH). A new analysis of the CAHtalog® registry, which spanned a median of 8.6 years and involved 98 adults and children with CAH, showed that approximately 95% of participants were exposed to supraphysiologic doses of glucocorticoids (GCs), experienced suboptimal androgen control, or both at some point in their treatment course.1

The CAHtalog registry, developed by Neurocrine Biosciences in partnership with the CARES Foundation and PicnicHealth, was established to capture longitudinal real-world data on CAH due to 21-hydroxylase deficiency. This latest analysis highlights the limitations of GC monotherapy and supports the need for continued monitoring and the development of targeted therapies that can reduce androgen excess without the adverse effects associated with high-dose GC use, according to a press release from Neurocrine Biosciences.1

"These real-world findings reinforce what we know about the dynamic nature of CAH management, where patients' treatment needs are constantly evolving," Dina Matos, executive director, CARES Foundation, said in a press release. "The data clearly show that even when individuals achieve disease control with glucocorticoid treatment alone, maintaining that control over time remains a significant challenge. This highlights the importance of continued monitoring and the need for advanced therapeutic options for patients living with CAH."1

Investigators evaluated real-world data from 98 patients enrolled in the CAHtalog registry, including 37 adults, 42 children and adolescents, and 19 individuals who contributed data in both pediatric and adult stages. The analysis focused on GC treatment patterns and paired androstenedione (A4) levels collected prior to the commercial availability of crinecerfont, emphasized researchers. The first-in-class selective corticotropin-releasing factor type 1 receptor antagonist was approved by the US FDA in December 2024 for the treatment of CAH in adults and children aged 4 years and older, making it the first new therapy for the endocrine disorder in 7 decades.1,2

GC doses were categorized as higher or lower (defined as >11 mg/m²/day or ≤11 mg/m²/day hydrocortisone equivalents [HCe] for pediatric patients, and >20 mg/day or ≤20 mg/day HCe for adults). A4 values were classified as higher (≥ upper limit of normal [ULN]) or lower (< ULN), resulting in 4 defined health states. These included optimal control (lower GC/lower A4), undertreatment (lower GC/higher A4), overtreatment (higher GC/lower A4), and poor control (higher GC/higher A4).1

Among the 63 participants eligible for the longitudinal health state transition analysis, 88.9% experienced at least one change in health state, and 58.7% underwent 3 or more changes during the observation period. Nearly all participants (95.2%) entered a suboptimal health state at least once, characterized by elevated A4 levels and/or supraphysiologic GC dosing. These transitions occurred across a broad age range (aged 0–67 years).1

Although some participants achieved a state of hormonal control with lower GC exposure, these episodes were typically transient. Frequent shifts in treatment intensity and androgen control were observed throughout the patient population, reported investigators.1

References:

1. Neurocrine Biosciences Presents New Analysis of CAHtalog® Registry Showing Most Patients with Classic Congenital Adrenal Hyperplasia Experienced High Glucocorticoid Exposure, Suboptimal Disease Control or Both at ENDO 2025. News release. Neurocrine Biosciences. July 15, 2025. Accessed July 15, 2025. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-presents-new-analysis-cahtalogr-registry
2. Halsey G. FDA approves crinecerfont for congenital adrenal hyperplasia in adults and children in landmark decision. Patient Care Online. December 13, 2024. https://www.patientcareonline.com/view/fda-approves-crinecerfont-for-congenital-adrenal-hyperplasia-in-adults-and-children-in-landmark-decision