Endocrine Abstracts

A 29-year-old man presented with an 18-month history of reduced libido and lethargy. His symptoms started after cessation of anabolic steroids for three years. His childhood and development history were unremarkable with normal onset of puberty and development of secondary sexual characteristics. He had no past medical or family history of note. Clinical examination demonstrated normal BMI, musculature, distribution of body hair, testicular volume, and genital size. Biochemical investigations revealed elevated fasted early morning testosterone 42.9 nmol/l (8.4-28.7), elevated LH 11.7 U/L (2.0-9.0), FSH 2.7 U/L (1.0-18.0), DHT 4.20 nmol/l, DHEA 6.7 µmol/L, SHBG 53 nmol/l, androstenedione 4.3 nmol/l, albumin 47 g/L, IGF-1/TFTs/prolactin all normal. Elevated testosterone was re-tested at a different centre to rule out assay interference and measured separately with mass spectrometry (36.4 nmol/l and 35.4 nmol/l, respectively). Similarly, LH remained elevated on re-testing, confirming hypergonadotrophic hypergonadism. An MRI pituitary and CT thorax, abdomen and pelvis were both normal, excluding pituitary and neuroendocrine tumours. Subsequently, he was referred to genetic services for investigation. Genetic sequencing identified a hemizygous pathogenic missense variant c.2270A>G p.(Asn757Ser) in the androgen receptor (AR) gene. Combining the genetics with the clinical phenotype, a diagnosis of mild androgen insensitivity syndrome (MAIS) was reached. The patient was educated on the potential impact of MAIS on fertility and referred to the fertility services. Genetic counselling and testing were offered to his female relations and the patient was subsequently commenced on a trial of testosterone therapy for symptom relief. Androgen insensitivity syndrome (AIS) is a rare x-linked recessive condition, resulting from AR gene mutations, with a prevalence of 2-5 cases per 100,000. Over 1000 unique AR gene mutations have been identified, which result in a spectrum of phenotypes, including complete, partial, or mild androgen insensitivity syndrome. In this case, symptoms initially suspicious for hypogonadism were unmasked following cessation of hormone self-medication. The normal male clinical phenotype, with elevated gonadotrophins and testosterone, prompted initial investigation for a neuroendocrine tumour. Subsequently, genetic testing identified an AR gene mutation, clinching the diagnosis of MAIS. The prevalence of MAIS remains unclear; however, its subtle clinical and biochemical features may cause under-reporting. MAIS should be considered in patients presenting with a normal male phenotype, elevated gonadotrophins and normal/high testosterone and may present with infertility as the sole symptom. The role of testosterone replacement in MAIS remains a subject of debate.