ESPE Abstracts

Background: 46, XY disorders of sex development (DSD) due to 17-beta-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency significantly affect male sex development. Understanding the histological changes from infancy to adulthood in these patients remains limited. This study presents six patients with 17β-HSD3 deficiency from a single center, including China’s first prenatally diagnosed and postnatally confirmed case, and conducts a systematic review to explore histological progression and malignancy risk.

Methods: Data from six patients diagnosed with 46, XY DSD and 17β-HSD3 deficiency, including five previously published cases and one new case, were analyzed. Clinical and histological features were compared across all patients. A systematic review using the terms “HSD17B3” and “17beta-HSD3 gene” was conducted to identify relevant literature.

Results: All six patients exhibited a 46, XY karyotype and atypical genitalia. Four patients underwent pathological examination. Testicular tissue in younger patients (2 years old) appeared mostly normal, contrasting with older patients (10 and 11 years old) who showed significant reductions in seminiferous tubules and spermatogenic epithelium, with no spermatogenesis observed. Notably, the younger patients had better virilization effects after receiving androgen therapy treatment. The systematic review, including the patients in our cohort, identified 273 patients with 17β-HSD3 deficiency, with 56 having detailed histological descriptions, and 7 (2.56%) having testicular tumors. Histological analysis indicated that testicular tissue in patients with 17β-HSD3 deficiency develops normally in infancy but deteriorates with age. Specifically, in infants, germ cells, Sertoli cells, and Leydig cells were normal. In prepubertal patients, 9 out of 24 (37.5%) had normal germ cells, 19 out of 24 (79.2%) had normal Sertoli cells, and 7 out of 24 (29.2%) had normal Leydig cells. Among adult patients, 5 out of 22 (22.7%) had normal germ cells, 14 out of 22 (63.6%) had normal Sertoli cells, and 5 out of 22 (22.7%) had normal Leydig cells.

Conclusion: Advances in prenatal and molecular diagnostics have enabled earlier detection of 17β-HSD3 deficiency. Our study indicates that 17β-HSD3 deficiency leads to progressively worsening testicular abnormalities with age. The low risk of testicular tumors (2.56%) may allow parents and patients more time to make informed decisions regarding gender assignment and potential testes removal. Choosing male gender assignment is relatively safe for 17β-HSD3 patients, provided they are closely monitored for malignancy. Early childhood treatment results in better virilization appearance and gender identity outcomes compared to treatment during adolescence.