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.