Endocrine Abstracts

Introduction: The androgen receptor (AR) as a steroid hormone receptor is crucial for the embryological male sex differentiation and the maintenance of the phenotypical male characteristics throughout life in addition to spermatogenesis. Mutations in the AR gene can disrupt its function leading to Androgen Insensitivity Syndrome (AIS). AIS has a recessive mode of inheritance and can be broadly classified into 3 phenotypical categories: complete androgen insensitivity syndrome (CAIS), partial (PAIS) and mild (MAIS). CAIS usually presents with female external genitalia and primary amenorrhoea. Karyotyping might be very helpful in these patients. Patients with PAIS syndrome typically have ambiguous genitalia, including partial labio-scrotal fusion and hypospadias. Patients with MAIS, on the other hand, have a mild presentation with subtle secondary sexual characteristics abnormalities that can remain unnoticed for long. Due to its variable presentation, MAIS can prove challenging to diagnose clinically and biochemically.

Case presentation: We describe the case of a young man in his early 20s with normal childhood growth and development. He has been to see the Cardiologist for recurrent palpitations when he was noticed to have some degree of gynaecomastia. He was then referred to our clinic for further work up. Physical examination demonstrated sparse body hair, hypoandrogenic phenotype, gynaecoid habitus, normal penile length and small scrotum. His blood test showed a confusing picture of raised FSH, raised LH, mildly raised Prolactin, high normal Testosterone, normal SHBG and raised Oestradiol. His total HCG was normal. His Karyotype was normal 46XY. U/S scrotum showed very small testes and no masses. MRI pituitary and MRI adrenal were normal. Genomic DNA sequencing of AR gene demonstrated a missense mutation indicating MAIS.

Discussion and Conclusion: Mutations affecting the AR gene can lead to either complete, partial or mild androgen insensitivity syndrome. The case reported here is consistent with mild androgen insensitivity. Due to its subtle presentation, this was not diagnosed until early adult life. The high gonadotrophins together with high normal Testosterone raised the possibility of pituitary gonadotroph adenoma initially. Klinefelter’s and similar chromosomal disorders were also included in the differential diagnoses. The patient was also investigated for potentially secreting Adrenal and testicular tumours. Nevertheless, none would completely explain the clinical picture with small scrotum and the raised Testosterone and Oestrogen levels. Patients who present with gynaecomastia should always undergo adequate endocrine and genetic testing to reach a conclusive diagnosis.