Induction of adrenal suppression by megestrol acetate in patients with AIDS.

Abstract

To investigate the development of secondary adrenal suppression in a patient with the acquired immunodeficiency syndrome (AIDS) who was receiving megestrol acetate. Case report of one patient abruptly withdrawn from long-term therapy with megestrol acetate; prospective study of four patients with AIDS who were starting therapy with megestrol acetate for cachexia. Outpatient clinic of a university hospital. Study patients received megestrol acetate, 80 mg three times daily. Study patients had cosyntropin-stimulation testing and oral glucose tolerance testing before and after starting therapy with megestrol acetate. The patient described in the case report developed symptoms of adrenal insufficiency after withdrawal of megestrol acetate after 4 years of treatment. His basal cortisol and adrenocorticotropic hormone (ACTH) levels were low. He showed an abnormally diminished response to a short cosyntropin-stimulation test but did respond to a 3-day cosyntropin-stimulation test. The morning cortisol levels of the study patients decreased significantly (from 11.0 +/- 1.8 micrograms/dL to 1.5 +/- 0.9 micrograms/dL; P < 0.01), and the ACTH levels of these patients decreased to below normal (from 16.6 +/- 5.5 pg/mL to 6.3 +/- 3.3 pg/mL; P = 0.02) during treatment with megestrol acetate. Cortisol levels after administration of cosyntropin decreased significantly (from 27.3 +/- 3.3 pg/mL to 9.3 +/- 6.3 pg/mL; P = 0.01) during treatment with megestrol acetate. The results of oral glucose tolerance testing in two patients were consistent with the development of insulin resistance, and daily insulin requirements increased 10-fold in a patient who had preexisting diabetes. Prolonged administration of megestrol acetate can induce clinically significant secondary adrenal suppression, and abrupt withdrawal of megestrol acetate after prolonged administration can cause adrenal insufficiency.