Endocrine Abstracts

Background: Gynaecomastia results from the raised oestrogen-to-testosterone ratio caused by relative oestrogen excess or testosterone deficiency. Alterations to androgen sensitivity causes a relative testosterone deficiency that can present in a spectrum, from significant, to subtle alterations of secondary sexual characteristics. Mild androgen insensitivity syndrome (MAIS) should be considered in the differential for those presenting with gynaecomastia with elevated gonadotrophins and testosterone.

Clinical case: A 23-year-old PE teacher was referred for further assessment of right-sided gynaecomastia. Breast ultrasound via two-week wait was non-concerning. Initial biochemistry detected elevated gonadotrophins, testosterone, prolactin and SHBG. The patient reported six months of an enlarging retroareolar lump with no associated galactorrhoea or sexual dysfunction. A scrotal lump was also noticed, with no concerning features on ultrasound. HCG and AFP normal. He attended the gym up to five times weekly and denied the use of anabolic steroids or sports supplements. He used cannabis recreationally and drunk alcohol socially. There was no personal or family history of note. Clinical examination demonstrated normal BMI, musculature, and secondary sexual characteristics. Right sided 2 × 3 cm retroareolar gynaecomastia, with no cervical or supraclavicular lymphadenopathy was detected. Visual fields were intact. Biochemical investigations following six weeks abstinence from cannabis revealed an elevated 9 am testosterone 41.5 (0–29 nmol/l), LH 9.5 (1.7–8.6 u/l), FSH 3.6 (1.5–12.4 u/l) and rested prolactin 777(0–323 mU/l). Normal SHBG, oestradiol. He was euthyroid, eucortisolaemic, normal IGF-1. MRI pituitary was normal. DXA scan reported normal bone mineral density, and semen analysis, normo-ozospermia. His Karyotype was 46 XY. He awaits the results of genetic screening to confirm a diagnosis of MAIS. Given only mild gynaecomastia, he remains on a watchful wait pathway.

Discussion: The assessment of gynaecomastia is aimed at the detection and management of underlying causes. Elevated gonadotrophins and testosterone in our patient prompted ruling out a functioning gonadotroph adenoma. With no features of hypogonadism other than mild gynaecomastia, Klinefelter’s and chromosomal disorders were excluded with karyotype analyses. Clinical suspicion then pointed toward a syndrome associated with resistance to testosterone signalling. Androgen insensitivity syndrome is a rare x-linked recessive condition secondary to over 1000 described mutations in the androgen receptor gene. A range of phenotypes result, and MAIS, due to subtle clinical features may go undetected; reinforcing the importance of defined pathways for investigating gynaecomastia. Management of gynaecomastia for most, including in those with MAIS follows watchful waiting; testosterone replacement recommended only in those with testosterone deficiency, and the use of aromatase inhibitors not routinely advised.