Reproductive Endocrinology

SUN-177 - Clinical and Genetic Profiles of A Multicenter Cohort of Individuals with Disorder of Sex Development, Addressing Gonadectomy and Gonadoblastoma Risk Factors

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Submitting author(s)

JQ

Jie Qiao, PhD

Professor
Shanghai 9th Hospital, Jiaotong Univ, School of Medicine
Shanghai, China (People's Republic)

Abstract Poster Presenter(s)

JQ

Jie Qiao, PhD

Professor
Shanghai 9th Hospital, Jiaotong Univ, School of Medicine
Shanghai, China (People's Republic)

Submitting author(s)

YJ

Yuqing Jiang, n/a

Shanghai Jiaotong University
Shanghai, China (People's Republic)

Co-Author(s)

YJ

Yuqing Jiang, n/a

Shanghai Jiaotong University
Shanghai, China (People's Republic)
SZ

Shuangxia Zhao, n/a

Shanghai Jiaotong University，Shanghai 9th Hospital
Shanghai, China (People's Republic)
YX

Yue Xu, n/a

Shanghai Jiaotong Univ, School of Medicine, Shanghai 9th Hospital
Shanghai, United States

Senior Author/Primary Investigator(s)

HS

Huaidong Song, PhD & MD

Professor
Shanghai Ninth Hospital affiliated to Shanghai Jiaotong University School of Medicine
Shanghai, China (People's Republic)

Background: DSD (Disorders of Sex Development) exhibits a high degree of heterogeneity in terms of clinical features and molecular diagnosis. The association between the risk of gonadoblastoma and the molecular basis of DSD remains to be elucidated, particularly in large cohort studies.

Methods: A total of 522 Chinese individuals with disorders of sex development were prospectively enrolled. Next-generation sequencing was performed in 400 participants, and the resulting variants were interpreted according to the ACMG guideline. Serum targeted metabolomic profiling (UPLC-MS/MS) was conducted in 10 patients with genetically confirmed androgen-insensitivity syndrome, whereas OCT4 and TSPY immunohistochemistry was performed on gonadal tissue from 50 patients who had undergone gonadectomy. Genotypic, metabolic and histopathological findings were integrated to explore determinants of gonadoblastoma susceptibility.
Result: Among 522 individuals with DSD), including 396 with 46,XY DSD, 112 with 46,XX DSD, and 15 with chromosomal DSD, 175 46,XY cases achieved a molecular diagnosis; 45 underwent gonadectomy, and two were diagnosed with gonadoblastoma. Pathogenic variants were most frequently detected in SRD5A2 (11%), SEMA3E (4.5%), NR5A1 (4.0%), NR0B1 (2.8%), and MYRF or HSD17B3 (1.1% each) among the 395 monogenic cases. Serum targeted metabolomic profiling of 10 androgen-insensitivity syndrome (AIS) patients with confirmed AR deficiency demonstrated steroid signatures consistent with androgen blockade, whereas OCT4/TSPY immunohistochemistry of 55 gonadal specimens showed minimal germ-cell marker expression and identified two occult tumours.

Conclusion: Comprehensive genomic, metabolic and histopathological profiling of 522 Chinese DSD individuals delineated prevalent SRD5A2, SEMA3E and NR5A1 variants, confirmed androgen blockade fingerprints in AIS, and highlighted low OCT4/TSPY expression with rare occult gonadoblastoma.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*