Endocrine Abstracts

Background: Clinical recommendations in DSD gonadectomy have evolved over time due to improved knowledge of diagnosis-specific risks of gonadal germ-cell tumours (GGCT), in addition to changing societal, legal and ethical norms. There is currently a lack of established international consensus on the practice of gonadectomy in the management of gonads in DSD conditions generally, due to paucity of population incidence studies looking at risk for gonadal tumours. This study aimed to investigate DSD gonadectomy practice in Ireland over the last 26 years and to determine the risk of developing gonadal tumours in DSD conditions.

Methods: Retrospective review of patients with DSD who underwent gonadectomy in Children’s Health Ireland from 1999-2022 and also prospectively since late 2022-2025.

Results: 62 patients underwent gonadectomy [females (n = 50);males (n = 12)]. Gonadectomy was most frequently performed in mixed gonadal dysgenesis(n = 21), followed by complete gonadal dysgenesis(CGD) (n = 10), partial gonadal dysgenesis(PGD) (n = 10), mixed ovotesticular (OT) DSD(n = 8), complete androgen insensitivity syndrome(n = 7), 46,XX OT DSD (n = 3), disorder of androgen synthesis(n = 2) and LH receptor defect (n = 1). The most frequently reported indication for gonadectomy was mitigation of future tumour risk (58%), followed by biopsy/imaging indicating malignancy (18%), incongruent hormone production (16%), concordance to sex assignment (3%), rudimentary testis (3%), and patient request (2%). The median age at gonadectomy was 5.91 years (IQR 1.33 – 15.58). GGCT was confirmed in 31% (19/62) of cases on gonadal histopathology [46XY CGD (8/19; 42%), PGD (2/19; 11%), mixed GD(8/19; 42%), mixed OT DSD (1/19; 5%)]. Gonadoblastoma was reported in 84% (n = 16) of cases, with malignant transformation to dysgerminoma in 11%(n = 2) of cases, both arising in CGD. Combined GB/GCNIS was reported in mixed OT DSD (n = 1). The estimated risk of GGCT in our cohort is 80% in CGD, 20% in PGD, 38% in Mixed GD and 12.5% in mixed OT DSD.

Conclusion: The majority of gonadectomies were performed in dysgenetic gonads, to mitigate tumour risk. Given the high incidence of gonadal tumours in dysgenetic gonads in our cohort, particularly in 46XY CGD, which is higher than reports in the international literature, early prophylactic gonadectomy should be considered, only after multidisciplinary team discussion, with an emphasis on shared decision making with patients and families.