BACKGROUND: Differences of sex development (DSD) require nuanced management, including discussions about gonadectomy for tumor risk mitigation for many diagnoses. This study investigated gonadal management strategies over time for pediatric patients with DSD cared for at a freestanding pediatric hospital’s multidisciplinary clinic.
METHODS: A retrospective review of patients with DSD diagnoses who are at risk for gonadal tumors and cared for in the multidisciplinary clinic from 2013-2023 was conducted. Patients were stratified into three groups based on tumor risk (Abaci et al., 2015): low, intermediate, and high. Descriptive statistics characterized the cohort. Gonadectomy rates were calculated overall, and by risk category. Trends over time were examined.
RESULTS: Seventy patients were included (57/70 [81%] assigned female at birth). The most frequent diagnoses were Turner syndrome + Y chromosome [TS+Y, N=19], complete [N=13] and partial [N=3] androgen insensitivity syndromes [CAIS and PAIS], and mixed [N=12], partial [N=2] and complete [N=6] gonadal dysgenesis [MGD, PGD, and CGD]). Median age at DSD diagnosis was 9.3 years for low (N=19), 4.8 years for intermediate (N=28), and 2.8 years for high tumor risk (N=23) groups. Most patients were counseled about gonadal management in a multidisciplinary fashion, with endocrinology discussion about gonadectomy documented for 64/70 (91%), psychology for 39/70 (56%), and genetics for 8/70 (11%).
Most (46/70, 66%) underwent gonadectomy, including 8/19 (42%) of low, 16/28 (57%) intermediate, and 22/23 (96%) high tumor risk patients. Of these, 33/46 (72%) underwent simultaneous, bilateral gonadectomy, 13/46 (28%) underwent unilateral gonadectomy; one patient with MGD underwent asynchronous unilateral gonadectomies (Table 1). No surgical complications were reported. Median age at gonadectomy was significantly different between groups: 5.8 years for high, 9.7 years for intermediate, and 16.2 years for low tumor risk groups (p =0.044). Accordingly, median age at gonadectomy increased significantly with decreasing tumor risk (p=0.026). No notable trends in gonadectomy rates were observed over time based on tumor risk category or age (Figure 1). Pathology revealed gonadoblastoma in the streak gonads of all 5 patients with CGD who underwent gonadectomy, and 1 patient with high tumor risk category MGD. One of the CGD patients with gonadoblastoma also had dysgerminoma on their pathology specimen. Germ cells were found in 20/46 (43%) of pathologic specimens.
CONCLUSIONS: Most patients with DSD associated with gonadal tumor risk underwent gonadectomy, particularly those with high tumor risk (96%). There were no differences over time based on age or risk category. Expected differences in age at gonadectomy were noted across risk categories. Findings support updated gonadal management recommendations, including retaining gonads in CAIS until after puberty, and TS+Y guidelines recommending discussion rather than automatic gonadectomy. Prophylactic gonadectomy should still be strongly considered for high-risk diagnoses (particularly CGD), as gonadoblastoma was seen in multiple patients with high-risk diagnoses.
