TO THE EDITOR:
I read with interest Dr. Carey's editorial on the causes and clinical presentations of adrenal insufficiency [1]. An additional medication that should be mentioned as a cause of iatrogenic adrenal insufficiency is megestrol acetate. A recent literature search and review of U.S. Food and Drug Administration adverse-event reports have shown that megestrol acetate has glucocorticoid-like activity that can result in clinical presentations of the Cushing syndrome, diabetes mellitus, and adrenal insufficiency [2]. The past reports suggest that clinically significant adrenal insufficiency may occur after discontinuation of therapy with the medication, but evidence indicates that this condition may also occur during therapy [3]. The mechanism of action is thought to be due to the binding of megestrol acetate to the glucocorticoid receptor and suppression of the pituitary-adrenal axis [2].
Awareness of this association is important because of the expanding use of this medication. Megestrol acetate is commonly used to treat cancer of the breast and endometrium and anorexia-cachexia syndromes in patients with cancer and HIV infection [2]. Megestrol acetate may also be useful in the treatment of anorexia-cachexia in geriatric nursing home residents [4] and hot flashes in both men and women [5].
1. Carey RM. The changing clinical spectrum of adrenal insufficiency [Editorial]. Ann Intern Med. 1997; 127:1103-5.
2. Mann M, Koller E, Murgo A, Malozowski S, Bacsanyi J, Leinung M. Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med. 1997; 157:1651-6.
3. Subramanian S, Goker H, Kanji A, Sweeney H. Clinical adrenal insufficiency in patients receiving megestrol therapy. Arch Intern Med. 1997; 157:1008-11.
4. Castle S, Nguyen C, Joaquin A, Coyne B, Heuston C, Chan A, et al. Megestrol acetate suspension therapy in the treatment of geriatric anorexia/cachexia in nursing home patients [Letter]. J Am Geriatr Soc. 1995; 43:835-6.
5. Loprinzi CL, Michalak JC, Quella SK, Hatfield AK, O'Fallon JR, Nelimark RA, et al. Megestrol acetate for the prevention of hot flashes. N Engl J Med. 1994; 331:347-52.
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