A Case Report on 46,XX Male Difference of Sex Development

The 46,XX male syndrome is a very rare disorder/difference of sex development (DSD). Characterized by a 46,XX karyotype with a male phenotype and various abnormalities, including virilized external genitalia, small testes, hypergonadotropic hypogonadism, and azoospermia. Primarily described in small population studies and clinical reports, much remains to be understood about the prevalence of clinical manifestations, treatment outcomes, and long-term follow-up in this disorder. Here we describe a 24-year-old male who sought medical attention due to a history of erectile dysfunction, associated with a loss of libido, impaired concentration, difficulty sleeping, and bilateral gynecomastia. He and his family had no relevant medical history. On physical examination, the patient had a normal development of secondary sexual characteristics but presented with bilateral testicular atrophy with a volume of 6 ml per testis. A testicular and abdominal ultrasound were performed confirming testicular atrophy and finding no other abnormalities. Laboratory analysis revealed a hypergonadotropic hypogonadism with normal prolactin, thyroid stimulating hormone, hemoglobin, hematocrit, and kidney and liver function. The spermiogram, performed twice, revealed azoospermia. A bone densitometry was also performed, reporting osteopenia in the lumbar spine and left hip. A karyotype test was performed revealing a 46,XX (<i>SRY</i>-positive) DSD. The patient started on therapeutic supplementation with testosterone showing marked improvement of his libido, erectile dysfunction, and return of testosterone to levels within range. The patient and his partner were referred to infertility outpatient care and subsequently opted for in vitro fertilization using a sperm donor. This case report highlights the need for clinical practical awareness of this rare disorder and its wide phenotypical spectrum while also focusing on important aspects of the current literature regarding its approach and treatment. The limited data on long-term management suggest that there is a need for specialized multicenter follow-up not only to ensure a better understanding of this disorder but also to provide a better care on the quality of life and healthy well-being of this patients.