ESPE Abstracts (2023) 97 P1-365

1Ghent University Hospital, Ghent, Belgium. 2Université libre de Bruxelles (ULB), Brussels, Belgium. 3Université Catholique de Louvain - UCLouvain, Brussels, Belgium. 4AZ Turnhout, Turnhout, Belgium. 5University Hospitals Leuven, Leuven, Belgium. 6Université catholique de Louvain, Yvoir, Belgium. 7AZ Delta, Roeselare, Belgium. 8Jessa Ziekenhuis, Hasselt, Belgium

Background: Long-term outcome studies on bilateral testicular regression (BTR) are currently lacking, hampering counseling of patients and parents. Although a vascular origin was initially reported, recent studies revealed a genetic origin in a subset of patients (i.e. DHX37 gene variants). How this relates to patient outcomes remains unclear.

Methods: Thirty-five patients with BTR were recruited in eight Belgian centers (mean age: 15.0±5.7 years). Cross-sectional exams included clinical exam in all and a DSD-LIFE questionnaire in 17 end-pubertal participants (6 missing). Exome-based panel testing of genes (n=241) involved in gonadal development and spermatogenesis and retrospective analysis of presentation/management were performed. Histological analysis of gonadal rests was done in 10 participants.

Results: Participants had presented at a median age of 1.2years [0-14years]. Gestational complications, in particular monozygotic twin pregnancy, were common (36.4% and 9.1% respectively). Heterozygous pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were identified in three participants. They had presented with a microphallus, opposed to 6/31 (19.4%) without DHX37 variant (1 missing). Childhood testosterone therapy to increase penile growth was more effective in those without versus with DHX37 variant. The three participants with a DHX37 variant developed a male, female and non-binary gender identity, respectively, whereas all other participants identified as males. Incremental testosterone replacement therapy (TRT) resulted in satisfactory pubertal development and statural growth (n=25; median age start 12.4years). Penile size remained suboptimal in 45.5% (≤-2.5 SD below the mean for adults). Five (45.5%) participants reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only 6/11 (54.5%) and 5/11 (45.5%) indicated they were well informed in the last year about the risks and potential side effects of TRT, respectively. Histological analysis of two participants with DHX37 variant revealed early disruption of gonadal development with presence of Müllerian remnants in both and undifferentiated gonadal tissue in one. In the eight other analyzed participants, no gonadal remnants were found.

Conclusion: BTR covers a broad phenotypic spectrum, with a more severe presentation in individuals with heterozygous DHX37 variants. In those without coding DHX37 variants, careful analysis of pregnancy details and clinical data suggest gestational complications as a contributing/etiological factor in 36.4%. Histological analysis supports DHX37 as a gonadal development rather than BTR-related gene. Even with adequate TRT, adult penile size often remains suboptimal. Adults indicate they needed a more thorough and understandable explanation of the treatment details, especially when initiating TRT.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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