Endocrine Abstracts

Background: Complete gonadal dysgenesis (CGD) or Swyer syndrome is a rare genetic condition which belongs to the group of 46,XY differences of sex development (DSD), due to impaired gonad (testis) development. Diagnosis is typically in adolescence due to delayed puberty or primary amenorrhea. There is a 15%-50% reported risk for gonadal tumour development with onset greatest at or after the time of puberty. Current recommendations for CGD advise early bilateral gonadectomy upon diagnosis. The study aimed to evaluate the clinical features and risk of gonadal germ cell tumours (GGCT) in 46,XY complete gonadal dysgenesis in the Ireland over the last 22 years.

Methods: Retrospective review of patients with 46,XY complete gonadal dysgenesis who underwent gonadectomy in Children’s Health Ireland from 2003-2022 and prospectively from 2022-2025.

Results: 11 patients were diagnosed with 46,XY CGD between 2003-2025, two of whom were siblings. The most frequently reported presentation was primary amenorrhea (n = 5); followed by incidental finding on karyotype (n = 2), discordance between antenatal karyotype and external genitalia at birth (n = 1), family history (n = 1) and precocious puberty with abdominal mass (n = 1). Karyotype reported 46,XY chromosomes with presence of the SRY gene in 10 cases; one case was SRY negative. A genetic aetiology was identified in 27% of the cohort, with common gene defects in SRY and DMRT1 reported. All 11 patients underwent gonadectomy. Histopathological examination of gonadal tissue reported GGCT in 9/11 (81%) cases with malignant transformation to dysgerminoma reported in 3/9 (30%) cases. All gonadal tumours were located intra-abdominally. Median age of GGCT diagnosis was 14 years (IQR 10-16); 4/11 (36%) patients were diagnosed prepubertally, with youngest aged 2.41 years. Elevated tumour markers (HCG, LDH) were reported in 2 individuals diagnosed with dysgerminoma. 8/11 (72%) cases commenced HRT post-gonadectomy; three cases with dysgerminoma required 3-monthly surveillance with pelvic ultrasound and HCG levels.

Conclusion: There is a high estimated incidence of gonadal tumours in 46XY CGD in our cohort (81%) which is higher than reports in international literature, and a significant number reported in childhood. Early prophylactic gonadectomy should be considered as soon as the diagnosis is made in CGD to prevent development of malignancy.