Endocrine Abstracts

Background: 46,XX testicular disorder of sex development (T-DSD) is rare. Most cases present in adulthood with infertility, fewer present at birth with genital ambiguity. SRY-positive cases typically have normal external genitalia and remain undiagnosed until adolescence. Prenatal diagnosis through karyotype analysis enables prospective characterisation and early multidisciplinary planning from birth. Recent I-DSD Registry data suggest gonadal dysfunction begins earlier than previously recognised, but serial quantitative hormonal data during adolescence remain scarce. We aimed to describe the longitudinal endocrine course and progression of gonadal dysfunction in two boys with prenatally diagnosed SRY-positive 46,XX T-DSD followed from birth.

Methods: A retrospective longitudinal analysis of two boys with prenatal diagnosis of a 46,XX karyotype and SRY/ZFY positivity by FISH, confirmed postnatally, with a male foetal phenotype on prenatal ultrasound. Both had normal male external genitalia, no cryptorchidism, and were raised male. Serial assessments from birth included auxological evaluation, Tanner staging, hormonal measurements (LH, FSH, testosterone, inhibin B, and AMH), and tumour markers. Multidisciplinary care involved paediatric endocrinology, neuropsychology, andrology, and structured family counselling.

Results: Both boys entered puberty spontaneously but developed progressive gonadal failure. Patient 1 (current age 15y): Puberty onset 14y. Serial hormones demonstrated rapid Sertoli cell failure (FSH 2.6→14.9→31 IU/L; inhibin B declined from 339 to 18 pg/mL over 14 months), followed by emerging Leydig dysfunction (testosterone 4.0→2.72 mg/L; LH 5.1→9.7 IU/L). Andrological consultation at 14y offered fertility counselling; family declined cryopreservation. Neurocognitive assessment revealed dyslexia and dysgraphia. Patient 2 (current age 12y): Puberty onset 11y, currently Tanner stage PH IV with penile activation. At age 12y showed severe Sertoli failure (FSH 26.9 IU/L, inhibin B declined from 129 to 9.9 pg/mL, AMH declined from 59.5 to 3.90 mg/L) with maintained testosterone (3.23 mg/L). Multidisciplinary counselling provided developmental guidance to family. Negative tumour markers in both patients.

Conclusions: Prenatal recognition of SRY-positive 46,XX T-DSD enables structured multidisciplinary follow-up and informs future management of progressive gonadal failure. Severe Sertoli dysfunction emerges at 12-14y with rapid progression, followed by Leydig dysfunction. These longitudinal data support structured: (1) serial hormonal monitoring from age 11-12y, (2) early fertility counselling by 12-14y, and (3) proactive multidisciplinary care including neuropsychological support.