Primary symptomatic adrenal insufficiency induced by megestrol acetate

Megestrol acetate (MA) is a progestational agent for the treatment of metastatic breast cancer and endometrial cancer. MA has also been used to promote weight gain in malnourished elderly patients, in patients with immunodeficiency virus and in cancer-induced cachexia. In addition to thromboembolic disease, MA may induce hyperglycaemia, osteoporosis, suppression of the gonadal axis, and Cushing's syndrome. MA has also been shown to cause symptomatic suppression of the hypothalamic-pituitary-adrenal (HPA) axis owing to its intrinsic glucocorticoid-like effect. Three additional patients are presented who developed symptomatic adrenal insufficiency while they were receiving 160-320 mg MA daily. The patients were treated with cortisone acetate supplements, had clear evidence of HPA-axis suppression but recovered fully after MA was discontinued. Patients receiving MA might have an inadequate adrenal response during stressful conditions, possibly because 160-320 mg MA daily may not provide adequate protection to prevent the symptoms of adrenal insufficiency. The adverse MA effect on the HPA axis is probably not well recognised in clinical practice, and clinicians need an increased awareness of the endocrine complications secondary to MA treatment.