As a resident in internal medicine in New York City, I treat many patients with AIDS. I was pleased to read two well-done studies describing a beneficial effect of megestrol on weight gain in patients with AIDS-related cachexia [1, 2]. My optimism is limited, however, by an encounter with a patient for whom I prescribed megestrol. Oster and colleagues [1] state that "because megestrol acetate is a derivative of progesterone, concern exists about the potential effect of megestrol on the endocrine system." This concern is well illustrated by the case of a 29-year-old woman with AIDS who had a CD4 count of 29 cells/mm³, a history of Pneumocystis carinii pneumonia, and disseminated Mycobacterium avium complex infection. Six weeks after beginning megestrol therapy (20 mg orally, thrice daily), she presented with generalized malaise and several loose bowel movements daily. She was found to be hypotensive and unresponsive to intravenous resuscitation. Further workup showed that her morning cortisol level was 1.5 µg/dL. Her thyroid function test results were normal. Results of a cosyntropin stimulation test showed that her cortisol level increased from 1.7 to 6.0 µg/dL. She was treated for adrenal insufficiency. Megestrol treatment was discontinued after a literature review [3] showed that four patients treated with megestrol (80 mg orally thrice daily) developed suppression of plasma adrenocorticotropic hormone and cortisol and significantly increased insulin requirements. After short-term treatment, the patient was given hydrocortisone (20 mg orally each morning and 10 mg each evening). Seven days after discontinuation of megestrol treatment, her cortisol level was 9.0 µg/dL and her adrenocorticotropic hormone level was 0.5 pg/mL.

This case and the four cases mentioned previously show the possible glucocorticoid properties of megestrol that can lead to suppression of pituitary function and subsequent adrenal insufficiency. In patients with AIDS who are at increased risk for impaired adrenocortical reserve secondary to many opportunistic infections, I question how Von Roenn and colleagues [2] can truly conclude that "megestrol acetate should be considered for all patients with persistent weight loss of 5% or more of ideal body weight, independent of immune status."