Endocrine Abstracts

JOINT3648

46,XX SRY-positive males are a rare DSD subset where individuals with a 46,XX karyotype develop a male phenotype due to SRY gene translocation, typically from the Y chromosome to the X chromosome. The SRY gene drives testicular development, but these individuals often exhibit mild genital ambiguity and are infertile due to missing Y-chromosomal genes needed for spermatogenesis. This case report describes the clinical management and long-term follow-up of an 18-year-old 46,XX SRY-positive male who has been under care at our clinic since the age of two. The patient initially presented with atypical external genitalia, including a mild hypospadias, a slightly bifid scrotum with an accentuated perineal raphe, and a normal penile length of approximately 4 cm. Firm gonads, each measuring around 1.5 ml, were palpable in the scrotal sacs but exhibited a tendency to ascend into the inguinal canal. No vaginal opening, excessive hair growth, or other abnormalities were observed. Genetic analysis revealed a 46,XX karyotype with a translocation of the SRY gene from the Y chromosome to the short arm of one X chromosome, confirmed via fluorescence in situ hybridization (FISH). Functional assessment of the gonads via an hCG stimulation test showed a rise in testosterone from baseline nondetectable levels to the low-normal range, confirming functional testicular tissue. In order to promote testicular descent and scrotal development, the patient was treated with hCG, resulting in favorable outcomes. Given the predominantly male phenotype and male psychosocial development, the decision to maintain male sex assignment was made. Over the years, the patient underwent priming with low-dose testosterone to support pubertal development and ensure the proper growth of secondary sexual characteristics, alongside regular hormonal monitoring and testicular ultrasounds to assess gonadal anatomy and exclude ovotestis. At age 16, testosterone therapy was discontinued while the patient was in a hypergonadotropic state. Despite normal external genitalia development to adult size, a spermogram revealed azoospermia, consistent with the expected infertility in 46,XX SRY-positive males. This case highlights the importance of a multidisciplinary approach in the diagnosis, treatment, and long-term management of individuals with DSD, emphasizing the role of genetic, endocrine, and psychosocial factors in guiding clinical decisions.