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Induction of Adrenal Suppression by Megestrol Acetate
- S.H. Khoo, MD;
- E.G.L. Wilkins, MD; and
- M. Abbott, MD
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TO THE EDITOR:
Leinung and colleagues [1] recorded evidence of adrenal suppression by megestrol acetate. We have made similar observations in a study of cortisol function in 49 patients positive for human immunodeficiency virus (HIV) in Manchester, United Kingdom [2].
We assessed cortisol responses to the short-stimulation cosyntrophin test in HIV-positive patients who were most vulnerable to adrenal insufficiency, that is, those with CD4 lymphocyte counts of 50 cells/mm3 or less. Forty-nine patients were recruited (42 men, 7 women; age range, 25 to 56 years; CD4 count range, 4 to 50 cells/mm3; median CD4 count, 16 cells/mm3). Plasma cortisol levels were measured before and 30 minutes after a single intramuscular injection (except in one hemophiliac patient who received the compound intravenously) of 250 µg of tetracosactrin (cosyntropin) [3]. Clinical data (including concurrent medications) were recorded. Patients were excluded if they were already receiving steroid therapy with hydrocortisone or prednisolone but were enrolled if they were only receiving megestrol acetate. A normal test result was defined as a poststimulation level of 450 nmol/L (16 µg/dL) or greater [2, 3]. An abnormal result was defined as a poststimulation cortisol level of less than 350 nmol/L (12.5 µg/dL). Any intermediate result was considered an impaired response.
Of the 49 patients, 35 (71%) had a normal cosyntropin stimulation test result, 6 (12%) had an abnormal result, and 8 (16%) had an impaired response. For the analysis, we combined the abnormal and impaired groups. No significant differences (P> 0.2) were seen between the normal group (n = 35) and the abnormal or impaired group (n = 14) in the use of antiretroviral medication (21 [60%] and 8 [57%]), cotrimoxazole (18 [51%] and 8 [57%]), azole antifungal therapy (20 [57%] and 10 [71%]) or known inducers of cytochrome p450 such as rifampin c (7 [20%] and 1 [7%]; P> 0.2). No patient admitted taking opiates. Patients with an abnormal or impaired response, however, were significantly more likely to be taking megestrol acetate (dose, 40 to 80 mg/d; n = 7 [50%]) than were those with a normal response (n = 8 [23%]) (P = 0.05).
Our results agree with those of Leinung and colleagues. Not only may adrenal insufficiency occur after abrupt discontinuation of prolonged megestrol acetate therapy, but treatment with this drug may also make results of the short cosyntropin test difficult to interpret. We urge caution in the use of megestrol acetate in patients with late-stage acquired immunodeficiency syndrome (AIDS).
S.H. Khoo, MD
E.G.L. Wilkins, MD
North Manchester General Hospital
Manchester M8 6RL, United Kingdom
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
