Endocrine Abstracts

JOINT1035

Background: Mixed Gonadal Dysgenesis (MGD) describes individuals with a chromosomal mosaicism and underdeveloped gonads, often accompanied by impaired puberty, fertility challenges and short stature. 45,X/46,XY mosaicism MGD has an estimated incidence of 5.6 per 100,000 liveborn males and median age at diagnosis is 29.1. MGD is associated with an increase in all-cause mortality and heightened risk of gonadal malignancy.

Case presentation: A 53-year-old biological male was referred to secondary endocrinology services with bilateral gynaecomastia and small testes, present since adolescence. Despite these findings, he reported normal libido, successful conception with three children, and no history of testicular infection, trauma, or steroid use. Historical sperm analysis suggested oligospermia. His past medical history includes ankylosing spondylitis (on etanercept), COPD, and benign prostatic hyperplasia. Clinical examination showed a weight of 92.6 kg, height 180 cm and BP 150/91 mmHg. He was well-virilized with male phenotypic features, bilateral gynecomastia, and small, lump-free testes. His blood tests revealed free testosterone of 134 pmol/l(163–473), total testosterone 12.2 nmol/l(6.68–25.7), LH 7.2 IU/l(1.7–8.6), FSH 13.5 IU/l(1.5–12.4), oestradiol 57 pmol/l(41–159), prolactin 167 mIU/l(86–324), cortisol 534 nmol/l(133–537), beta-HCG <0.1 IU/l, and alpha-fetoprotein 2.9 kU/L. Thyroid, renal, liver, and full blood count were unremarkable. Testicular ultrasound revealed bilateral small testes which were normal in shape and reflectivity with no visible mass or cysts. Serum PCR analysis confirmed a male sex chromosome complement with the SRY sequence on chromosome Y, excluding Klinefelter Syndrome. SNP array analysis revealed 27% monosomy X cells and 73% normal male cells, consistent with his clinical presentation of mosaicism, gonadal dysgenesis, and oligospermia. The patient has been referred for genetic counselling. A CT scan of the abdomen and pelvis is pending to evaluate for persistent Mullerian structures. He will undergo annual malignancy screenings, including testicular ultrasounds, due to the increased risk of gonadoblastoma (strongly linked to the presence of a Y chromosome).

Conclusion: This case underscores the rarity of late MGD diagnoses in older males and highlights the need for early investigations in disorders of sexual development. Awareness among paediatricians and general practitioners of MGD signs enables timely referral to specialists. While no standardized management pathway exists, early diagnosis reduces malignancy risks and addresses growth and sexual impairments. Management requires a multidisciplinary approach, including gender assignment, surgical interventions, hormone therapy, fertility considerations, and psychosocial support.