Case report: A 56-year old man presented with a 3 month history of painful bilateral gynaecomastia and sexual dysfunction. Investigations revealed hypogonadotrophic hypogonadism with markedly elevated serum E2, but otherwise normal baseline anterior pituitary function. Tumour markers were negative and adrenal androgens and LFTs were normal. Imaging identified a ∼6 cm right adrenal mass. Preoperative workup excluded phaechromocytoma, but identified low-grade, ACTH-independent Cushings syndrome., There were no signs of metastases at laparotomy and a 145 g adrenal tumour was removed. Post-operative cortisol and reproductive axis remain to be assessed, but E2 level normalised almost immediately (109 pmol/l), with early improvement in his gynaecomastia. Histology confirmed a completely excised adrenocortical carcinoma.
Results: LH 2.5, FSH <1.0 U/l & Prolactin 113 mU/l (NR <450), Testosterone 4.1 nmol/l (NR: 9-25),), E2 694 pmol/l (NR <180), E1 821 pmol/l (NR <330), A4 5.7 nmol/l (NR <13), DHEAS 1.9 umol/l (NR: 1.110.9), Cortisol (post 7 mg IV DST) 330 nmol/l.
Discussion: Estrogen-secreting adrenal tumours are exceedingly rare in both men and women. Although co-secretion of cortisol has been previously described, this case is virtually unique in that adrenal androgen levels were entirely normal, effectively ruling out peripheral aromatisation of androgens as the source of the elevated circulating E1 & E2 levels. It is therefore likely that the tumour itself had unusually high- level aromatase activity and was thus able to secrete E1, which was in turn further aromatised both locally and peripherally to E2. However, results of tissue aromatase expression studies are still pending.
The hypogonadotrophic hypogonadism exhibited by this patient at presentation nicely illustrates how the physiological feedback inhibition of LH & FSH secretion is predominantly mediated by E2 in men as well as in women.