Although the adrenal is the endocrine gland most commonly involved in the acquired immunodeficiency syndrome (AIDS) [1], adrenal insufficiency is unusual [2]. Cortisol secretion in response to adrenocorticotropic hormone (ACTH) is generally normal or slightly impaired [2, 3]. Increased circadian plasma and 24-hour urinary free cortisol levels have been previously reported [2, 4, 5], but no patient had clinical symptoms of the Cushing syndrome. Further, Norbiato and colleagues' patients [5] showed Addisonian symptoms. In the latter case, hormonal changes (increased ACTH and cortisol and lack of suppression by dexamethasone) were attributed to peripheral cortisol resistance. We report the first documented case of the Cushing syndrome in a patient with AIDS.

A 22-year-old woman was hospitalized in July 1992 for hormonal evaluation. She had a history of schizophrenia, for which she was receiving psychotherapy and medical treatment consisting of flupentixol, decanoate and tropatepine. She was diagnosed as positive for antibodies to human immunodeficiency virus (HIV) type 1 in February 1990. In January 1992, therapy with zidovudine, 500 mg/d, and monthly aerosol pentamidine was administered because of a decrease in her CD4 count to levels below 0.3 x 10 (⁹/L) and the onset of fatigue, skin folliculitis, and thoracic zoster (Centers for Disease Control and Prevention group IV C2). Her resulting depression improved with trimipramine therapy. At the same time, she developed progressive signs suggestive of the Cushing syndrome: centripetal obesity, buffalo neck, moon facies, acne, thin and fragile skin, moderate hirsutism, purple striae, mycosis of the tongue, and exacerbation of psychotic reactions. She was referred for endocrine evaluation: She did not appear depressed but did have signs of the Cushing syndrome.

Her laboratory data were as follows: 24-hour urinary free cortisol, 1404 and 2007 µg/d (normal, 10 to 90 µg/d); 8-hour plasma cortisol, 261 ng/mL (normal, 50 to 290 ng/ml); ACTH, 83 pg/mL (normal, < 55 pg/mL); and testosterone, 5.9 nmol/l (normal, 0.9 to 4.9 nmol/L). A metyrapone test result was positive. A 3-mg dexamethasone suppression test result was negative (24-hour urinary free cortisol, 680 µg/d), but the 8-mg test result showed a reduction of cortisol production (24-hour urinary free cortisol, 230 µg/d).

A computed tomographic (CT) scan of the abdomen showed bilateral adrenal hyperplasia, whereas pituitary magnetic resonance imaging (MRI) showed only heterogeneity after gadolinium injection. Chest radiographs and tumor markers in plasma were normal. These results were suggestive of Cushing disease. After 6 months of mitotane therapy (1,1 dichlorodiphenyldichloro-ethane, 12 g/d), clinical symptoms of the Cushing syndrome decreased rapidly and her physical appearance returned to normal. Zidovudine was replaced by didanosine, 100 mg 4 times daily. No clinical or biologic symptom of hypercortisolism recurred after a year. Repeated MRI of the pituitary after 6 and 12 months showed no changes, but a CT scan showed normal adrenals. After 1 year, the patient was well, and no change in her CD4 count was noted.

Although this association may be due to chance, we hypothesize that in our HIV-infected patient, an increased production of interferon, interleukin-1 or other cytokines may have induced the Cushing syndrome. Infection with HIV increases the production of interleukin-1, which, at pharmacologic doses, can stimulate in vivo release of corticotropin-releasing hormone into the portal circulation. In vitro, interleukin-1 has proved to be effective in enhancing the production of ACTH by cultured AtT-20 pituitary cells and in increasing cortisol production by adrenocortical cells. Interferon therapy is another possible stimulator of the adrenals in patients with AIDS [1].