Endocrine Abstracts

JOINT4029

Background: Differences of sex development(DSD)/Intersex are a heterogeneous group of congenital conditions affecting human sex determination and differentiation, classified based on karyotype and include: sex chromosome DSD, 46XX DSD and 46XY DSD. There is a risk of gonadal tumour development with an estimated prevalence of germ cell cancer (GCC) ranging from 0.8 to 40% depending on age and underlying condition. Gonadoblastoma (GB), is the precursor lesion of GCC in the dysgenetic gonad. Clinical recommendations and practice in DSD gonadectomy have evolved over time. International practice in DSD gonadectomy varies and optimal management of gonads is currently not well established.

Objectives: To determine the frequency and indication for childhood gonadectomy in DSD in Ireland over the last 25 years; and the incidence and clinical features of GB during this period.

Methods: From 1999 to 2024, all paediatric patients with DSD who underwent gonadectomy at the national referral centre for DSD at Children’s Health Ireland were included. Patients’ demographics, karyotype, sex of rearing, genetic results, and gonadal tissue histopathology were collected; retrospectively between 1999-2022 and prospectively between 2022-2024 as part of the International DSD registry study.

Results: A total of 57 patients with DSD (46 females) underwent gonadectomy. The main indications were risk of gonadal tumour development (41/57; 71%), GB identified on biopsy (5/57; 8%), incongruent hormone production (9/57; 15%) and concordance to sex assignment (2/57; 3%). The mean age at gonadectomy was 7.75 years (2 weeks to 18 years). GB was confirmed in 30% (17/57) of cases on histopathology of gonadal tissue, with 3 cases associated with dysgerminoma. GB was most frequently reported in 46XY complete gonadal dysgenesis (CGD) (8/17; 47%), followed by Turner syndrome Y chromosome material (7/17; 41%), and partial gonadal dysgenesis (2/17; 11%). The mean age of tumour diagnosis was 6.96 years (2 weeks to 17 years). The majority of tumours were unilateral (9/17; 52%) and located intra-abdominally (16/17; 94%). For all cases of dysgenetic gonads, the calculated risk of developing gonadal tumours was 38% (16/42). Patients with 46XY CGD demonstrated the highest risk of developing gonadal tumours (8/11; 72%).

Conclusion: The majority of gonadectomies were performed in dysgenetic gonads, either to mitigate tumour risk or remove gonadal tumours. The high incidence of gonadal tumours in dysgenetic gonads, particularly in 46XY CGD, highlights the importance of early prophylactic gonadectomy which should be performed only after multidisciplinary team discussion, which will be informed by these findings.