Endocrine Abstracts

Gonadal dysgenesis (GD) is characterised by maldevelopment of the gonads and is classified as complete (CGD) or partial (PGD) depending on gonadal morphology and function. The phenotype of PGD is variable and diagnosis is based on clinical and biochemical features, coupled with gonadal histology and genetic findings. “46,XY Gonadal Dysgenesis: diagnosis and long-term outcome” has recently been approved as an I-DSD Registry-based study. The aim is to characterise the phenotype of PGD and their pubertal development comparing with CGD. We have analysed our cohort of patients as a pilot study.

Methods: Inclusion criteria for PGD: (1) 46XY karyotype, (2) atypical genitalia, (3) at least of one of the following: (A) clinical evidence of testis dysgenesis (T level after HCG < double the basal T value, low AMH or inhibin B or Mullerian derivatives present), (B) histology consistent with dysgenesis, or (C) known gene variants associated with GD. A CGD group was analysed as a comparator.

Results: CGD, n=24; PGD assigned female, n=13; PGD assigned male, n=7. In CGD, 44% (n=8/18) presented with primary amenorrhoea, the remainder presenting earlier with, for example, an abdominal mass, inguinal hernia or a serendipitous XY karyotype. Those with PGD presented early with atypical genitalia. Mean external masculinisation scores (EMS) for CGD, PGD female and PGD male were 1.2, 3.4, and 5.3, respectively. A uterus was frequently identified (CGD, 78%; PGD assigned female, 55%; PGD assigned male, 40%). Genetic confirmation was infrequent: CGD (SRY, n=4; NR5A1, n=3) and only one PGD (male-assigned, SRY). 50% (n=3/6) of PGD assigned male showed testosterone response to hCG, despite histology consistent with dysgenesis, which is in contrast to PGD assigned female, with 14% (n=1/7) showing testosterone response.

Conclusions: This pilot study confirms heterogeneity in the collective features of PGD vs CGD. A high prevalence of uterine remnants is a simple phenotypic marker of testis dysfunction. Further studies are required to correlate this finding with definitive histology of dysgenesis. In turn, outcome studies are sparse. The I-DSD based collaborative study offers the opportunity to rectify these shortcomings.