SAT-457 - Successful Management of Hypertension in Classic Congenital Adrenal Hyperplasia Due to 17-Hydroxylase Deficiency with Crinecerfont: A Case Report

Background:

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in steroidogenesis. The most common form is 21-hydroxylase deficiency (21OHD), whereas 17-hydroxylase deficiency (17OHD) accounts for approximately 1% of cases. Standard management involves lifelong glucocorticoid therapy (to suppress ACTH-driven mineralocorticoid excess), along with sex-steroid replacement at puberty, and management of hypertension/hypokalemia with mineralocorticoid receptor antagonists and antihypertensives as needed. Crinecerfont, a corticotropin-releasing factor 1 (CRF1) receptor antagonist, received FDA approval in 2024 for classic CAH. By reducing ACTH secretion, it mitigates excess adrenal steroid precursors. To date, its use has been limited to 21OHD. We report the first documented case of crinecerfont therapy in 17OHD.



Case:

A 26-year-old woman (46 XY karyotype) with classic 17OHD and longstanding severe hypertension was diagnosed at age 8. She underwent gonadectomy and received estrogen replacement for pubertal induction. Glucocorticoid regimens included hydrocortisone 17.5 mg/day in three divided doses until age 17, dexamethasone 0.25 mg daily for 2 years to simplify tapering, complicated by Cushingoid features, and prednisone, with persistent mineralocorticoid excess. Her regimen was eventually changed to prednisolone 4 mg in the morning and 2 mg at bedtime. Despite maximal antihypertensive therapy-including spironolactone 600 mg/day, carvedilol, valsartan, and HCTZ-blood pressure remained uncontrolled (150s/120s). Bilateral adrenalectomy was considered but declined.



Crinecerfont 100 mg twice daily was initiated, resulting in marked blood pressure improvement (120-130s/80-90s), normalization of renin, and significant reductions in deoxycorticosterone (31 ?14? < 5 ng/dL; normal < 10 ng/dL) and pregnenolone (1450?118?107 ng/dL; normal < 248 ng/dL). These biochemical changes were not achieved with prior therapies. At one-year follow-up, blood pressure remained controlled, and gradual glucocorticoid tapering was planned.



Discussion:

This is the first reported case of crinecerfont use in classic CAH due to 17OHD, demonstrating substantial clinical and biochemical benefits in a patient with refractory hypertension. CRF1 receptor antagonists may represent a promising adjunct for difficult-to-control cases, reducing mineralocorticoid excess and improving long-term outcomes. Crinecerfont may expand therapeutic options beyond 21OHD, addressing unmet needs in rare CAH subtypes.

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