ESPE Abstracts

Background: 17 α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia, characterized by cortisol deficiency, sex steroid deficiency, and mineralocorticoid excess. We aimed to investigate the clinical presentations and follow-up course of Korean patients with 17OHD from longitudinal cohort.

Methods: Clinical and biochemical data of 15 patients diagnosed with 17OHD during 1988-2023 were retrospectively collected from four tertiary centers across Korea. Steroid hormone profiles, genetic analysis, surgical history, and medical history were investigated.

Results: We reported 15 phenotypic females, 6 with 46,XX and 9 with XY karyotype. The mean age at diagnosis is 16.5 ± 7.4 years; 13.6 ± 7 years in XY and 20.8 ± 6.2 years in XX. All patients with XX presented with primary amenorrhea. The patients with XY visited for various presentation: abnormal external genitalia, premature thelarche, hypertension, incidental adrenal tumor, skin pigmentation and electrolyte abnormalities. The most common pathogenic variant was p.His373Leu. The median follow-up duration was 8.2 (2.4–13.3) years. At diagnosis, 8 (66.6%) had hypertension and 2 (16.7%) had pre-hypertension. The prevalence of hypertension was 73.3% (11/15) and eight (72.7%) out of the eleven patients diagnosed with hypertension were treated with hydrocortisone combined with an antihypertensive drug, and four of them successfully discontinued antihypertensive drug after normalization of blood pressure with glucocorticoid treatment. During the follow-up period, six (54.5%) out of the eleven patients achieved target blood pressure of < 140/90 mmHg with medication. Eight (57.1%) of fourteen patients manifested hypokalemia, which resolved after the treatment. Among twelve patients aged 12 years or older, all seven with available hormone profiles showed elevated gonadotropin levels. Estrogen replacement therapy was initiated at the median age of 17.3 (16.1–21.0) years. The bone mineral density was assessed in 10 patients and one showed low bone mineral density (lumbar spine z-score: -3.3). Among 9 XY patients, gonadectomy was performed in 8 patients at an average age of 16.8 (14.4–17.7) years. None of the 3 patients with XX who were aged 30 or older had offspring.

Conclusion: In patients presenting with primary amenorrhea accompanied with hypertension and hypokalemia, the diagnosis of 17OHD should be considered. Early diagnosis and appropriate hormone replacement are crucial for cardiovascular outcomes in congenital adrenal hyperplasia due to 17OHD.