Endocrine Abstracts

Background: Gonadal dysgenesis (GD) is a heterogeneous group of disorders of sex development caused by impaired gonadal formation. It includes complete gonadal dysgenesis with streak gonads and female phenotype, and partial gonadal dysgenesis with varying degrees of genital ambiguity. We aimed to characterize the clinical presentation, hormonal profile, and genetic determinants of patients with GD.

Methods: This observational study included patients diagnosed with gonadal dysgenesis at a tertiary referral endocrine center over a period of one year. Clinical characteristics were recorded. Hormonal evaluation included serum gonadotropins and sex steroids. Cytogenetic analysis was performed using conventional karyotyping, and targeted molecular testing was undertaken where indicated. Imaging assessed internal reproductive structures, and histopathological findings were reviewed in patients undergoing gonadectomy.

Results: Among 60 patients with 46,XY DSD, 18 patients (30%) were diagnosed with gonadal dysgenesis. The median age at presentation was 105.5 months (IQR 21–186). Ten patients were reared as female and eight as male. The predominant clinical presentations were atypical genitalia (n = 12), primary amenorrhea (n = 4), and delayed puberty (n = 2). Cytogenetic analysis demonstrated a 46,XY karyotype in 17 patients, while one patient had mosaicism. Complete gonadal dysgenesis typically presented with female phenotype and streak gonads, whereas partial gonadal dysgenesis showed variable genital ambiguity and gonadal differentiation. Biochemical evaluation revealed hypergonadotropic hypogonadism, with median LH 23.9 IU/L (IQR 17.4–30.8). Median testosterone was 0.59 nmol/l (IQR 0.087–5) and AMH 4.8 pmol/l (IQR 5–87.6). Targeted molecular testing identified pathogenic variants in genes involved in sex determination and gonadal differentiation in 50% of cases, including SRY, NR5A1, DHH, MAP3K1, MYRF, and SOX9. Gonadectomy was performed in nine patients, primarily in those with complete gonadal dysgenesis or as part of definitive gender assignment. Histopathological evaluation did not reveal premalignant or malignant germ cell tumors.

Conclusion: Gonadal dysgenesis demonstrates substantial clinical and genetic heterogeneity, highlighting the importance of integrated evaluation using clinical, hormonal, cytogenetic, and molecular approaches to guide diagnosis and multidisciplinary management.