SAT-466 - Crinecerfont Treatment of Classic Congenital Adrenal Hyperplasia Due to 11Β-Hydroxylase Deficiency: A Case Series

Background: Classic congenital adrenal hyperplasias (CAH) are rare inherited conditions caused by deficiencies in enzymes required for cortisol biosynthesis. Approximately 5% of cases are due to 11β-hydroxylase deficiency (11OHD), which leads to cortisol deficiency, accumulation of 11-deoxycortisol (11dF) and 11-deoxycorticosterone (DOC) with excess mineralocorticoid activity and adrenal androgens. Patients with 11OHD were not included in clinical trials for crinecerfont, a first-in-class corticotropin releasing factor type 1 receptor antagonist that is FDA-approved as an adjunct to glucocorticoid (GC) replacement to control androgens in patients with classic CAH. This case series describes clinical responses to crinecerfont treatment in patients with 11OHD.

Methods: A retrospective chart review of patients with 11OHD taking crinecerfont. Four representative cases are described.

Results: Case 1, a 10-YO female, was diagnosed with 11OHD at birth due to atypical genitalia and confirmed with genetic testing. Before starting crinecerfont, she was taking 11.9 mg/m2/d hydrocortisone and had elevated DOC (636 ng/dL), 11dF (2604 ng/dL), and ACTH (227 pg/mL); androstenedione (A4) and testosterone were normal (72 ng/dL; 6 ng/dL). One month after starting crinecerfont 50 mg BID, DOC, 11dF, and ACTH decreased to normal range (18 ng/dL; 143 ng/dL; 25 pg/mL). Case 2, a 9-YO male, was diagnosed at age 6 years after presenting with precocious pubarche, advanced bone age (11.6 years), and elevated DOC (1123 ng/dL), 11dF (9981 ng/dL), ACTH (120 pg/mL), and A4 (688 ng/dL). GC treatment was initiated at 6.3 mg/m2/d, which reduced A4 to normal range. However, ACTH, DOC and 11dF remained elevated even after increasing GC dose to 10.3 mg/m2/d. At age 9 years, crinecerfont 50 mg BID was added; 1 month later, DOC, 11dF, and ACTH decreased to normal ranges (20 ng/dL; 150 ng/dL; 16 pg/mL). Case 3, a 34-YO female, was diagnosed at birth due to atypical genitalia and confirmed with genetic testing. Initially, DOC was elevated (91 ng/dL) despite a GC dose of 15 mg/m2/d (30 mg/d), and she was taking spironolactone 50 mg/d for hypertension. Two months after starting crinecerfont 100 mg BID, DOC was normal ( < 16 ng/dL), blood pressure was improved, and spironolactone was discontinued. Case 4, a 24-YO male, required hydrocortisone 10 mg TID, prednisolone 1 mg/d at bedtime, eplerenone 50 mg BID, and amlodipine 10 mg/d for hypertension. One month after starting crinecerfont 100 mg BID, A4 fell from 180 to 51 ng/dL, and 11dF fell from 4636 to 36 ng/dL (both normal). Eplerenone and prednisolone were discontinued without hypertension.

Conclusion: Patients with classic CAH due to 11OHD had improved hormone levels following initiation of crinecerfont; adult patients also had improved blood pressure. This series provides evidence of efficacy for crinecerfont treatment in patients with this rare and challenging form of classic CAH.

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