Androgen insensitivity syndrome

Rationale: 46, XY disorder of sex development (46, XY DSD) is relatively rare and frequently missed in clinical practice, necessitating early standardized diagnosis and treatment. Androgen insensitivity syndrome (AIS), a major subtype, should be considered in phenotypic females with suggestive clinical clues. Patient concerns: A 29-year-old phenotypic female presented with primary amenorrhea and intermittent abdominal pain. Examination revealed normal breast development, sparse pubic hair, and female external genitalia. Pelvic ultrasonography and CT showed an absent uterus and ovaries, with bilateral inguinal masses. Diagnoses: The case met the 3 diagnostic criteria for 46, XY DSD: 46,XY karyotype, testicular tissue, and feminized external genitalia. A diagnosis clinically consistent with complete AIS was further supported by the characteristic phenotype – female appearance, normal breast development, sparse pubic hair, and absent Müllerian structures. Other etiologies of undervirilization, including 5 α -reductase deficiency and 17 β -hydroxysteroid dehydrogenase deficiency, were considered. Genetic confirmation was unavailable, limiting subtype certainty. Interventions: Following counseling, the patient underwent laparoscopic bilateral orchiectomy as prophylactic gonadectomy to reduce malignancy risk, together with inguinal hernia repair, followed by postoperative hormone replacement therapy. Postoperative histopathology confirmed testicular tissue with Leydig cell hyperplasia, absent spermatogenic cells, and no malignancy. Outcomes: Abdominal pain resolved postoperatively, with improved psychological well-being and adaptation to the diagnosis under ongoing endocrine and psychological support. Lessons: 46, XY DSD is underdiagnosed due to phenotypic variability, reliance on specialized tests, and social biases. AIS should be considered in the differential diagnosis of phenotypic females presenting with primary amenorrhea, developed secondary sexual characteristics, and an absent uterus on ultrasound. However, definitive subtyping requires AR gene sequencing, which was not available in this case. Early diagnosis requires careful assessment of newborn external genitalia, with specialist evaluation prompted by any atypical findings, and hormonal and genetic testing in adolescents with abnormal development. Multidisciplinary care – involving gynecologists, endocrinologists, surgeons, geneticists, and mental-health professionals – is essential for comprehensive management, including psychological support, hormone therapy, and timely prophylactic gonadectomy. Establishing specialized multidisciplinary centers for DSD is also recommended.