Clinical Characteristics and Follow-up Course of 17α-Hydroxylase/17,20-Lyase Deficiency in Korea: the OUTSPREAD Multicenter Study

Background: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is a rare congenital adrenal hyperplasia with cortisol and sex steroid deficiency and mineralocorticoid excess. We aimed to describe the phenotypic spectrum and clinical course of Korean patients with 17OHD in a multicenter cohort. Methods: This retrospective study included 17 patients with genetically confirmed 17OHD from six tertiary centers in Korea. Demographic, biochemical, and genetic data were reviewed to evaluate clinical variability and long-term outcomes. Results: Of the 17 patients, seven had a 46,XX karyotype and 10 had a 46,XY karyotype; all had female external genitalia and were raised as females. Primary amenorrhea predominated in 46,XX patients; 46,XY patients presented variably (hypertension and hyperpigmentation). The median age at diagnosis was 16.4 years. Higher follicle-stimulating hormone levels (54.2 mIU/mL vs. 18.2 mIU/mL, P=0.003) and less frequent hypokalemia (40.0% vs. 85.7%, P=0.038) were observed in 46,XY patients compared with 46,XX. The most frequent genotype was c.1118A>T (55.9%). At diagnosis, 58.8% of the patients exhibited hypokalemia, resolved with treatment. During a median follow-up of 8.1 years, 82.4% had hypertension, and 57.1% achieved normal blood pressure with glucocorticoids and/or antihypertensives. Low bone mineral density was found in 46.2% of the patients, and improvement with sex hormone replacement was observed. Gonadectomy was performed in nine XY patients (90.0%), with no malignancies identified. Conclusion: Patients with 17OHD commonly present with hypergonadotropic hypogonadism, hypertension, and hypokalemia; however, phenotypic variability exists. Clinicians should consider 17OHD in adolescents with delayed puberty and hypertension, even without classical biochemical findings, to ensure timely diagnosis and management.