Endocrine Abstracts

Background: Androgen insensitivity is classically recognised as a sex development disorder (DSD) 46,XY. However, estrogen insensitivity due to a mutation in the estrogen receptor (ESR1) is not included in current DSD classifications, probably due to its rarity and historically centred conception on the role of androgens in male differentiation.

Methods: We present the case of a 15-year-old boy referred for delayed puberty with anorchidism, initially considered to be a simple testicular cryptorchidism.

Results: The patient is the only child of consanguineous parents from Algeria. On examination, he had a marked pubertal delay, short stature, with a height below −4 DS and significant delay in bone age. Genital examination revealed a micropenis, hypoplastic scrotum with no palpable testes. Abdominal and pelvic ultrasound did not identify any testicular tissue, a result that was also confirmed by pelvic MRI. Laboratory testing revealed hypogonadism with hypergonadotrophinemia, with low inhibin B levels The LH-RH stimulation test showed a high oestradiol level reaching 200 pg/mL. Exploration by laparoscopy revealed rudimentary testicular structures. A biopsy of presumed testicular tissue revealed an absence of identifiable testicular tissue and the presence of only an embryonic relic, suggesting a major gonadal developmental anomaly. Genetic testing identified a mutation in the oestrogen receptor gene (ESR1), consistent with oestrogen insensitivity. The patient received androgen replacement therapy, leading to the progressive development of secondary sexual characteristics. Vitamin D supplementation was also initiated in view of the potential impact of impaired estrogen signaling on bone maturation.

Conclusions: Estrogen insensitivity in boys can affect initial sexual differentiation, and can alter gonadal maturation, testicular descent and pubertal progression. This picture suggests the potential involvement of this hormonal pathway in testicular development. These results support the idea that oestrogens play a major role in gonadal development, even in boys, which requires further research.