Megestrol acetate is a synthetic progestin that has been used since the 1970s for the treatment of advanced cancer and subsequently to treat anorexia, cachexia and weight loss in AIDS patients. It has been shown that high doses or prolonged treatment with this drug may cause Cushing's syndrome, new-onset diabetes and suppression of plasma ACTH and cortisol levels. Megestrol acetate may cause suppression of the pituitary-adrenal axis due to the affinity of this compound for the glucocorticoid receptor. Recognising the glucocorticoid-like activity of megestrol and its effects at the axis level is important for the diagnosis of sub-clinical adrenal insufficiency. We present the case of a 74-year-old woman with infiltrating ductal breast carcinoma refractory to prolonged hormonal treatment with megestrol acetate, presenting with adrenal insufficiency.