Hypothalamic-pituitary-adrenal function in non-AIDS patients with advanced HIV infection

Patients with acquired immune deficiency syndrome (AIDS) are reported to have increased basal cortisol and reduced stimulated cortisol release, but the dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis is not yet understood in patients with human immunodeficiency virus (HIV) infection during the advanced stage of disease that precedes the development of AIDS. To understand the status of the HPA axis during this phase of HIV infection, 25 non-AIDS ambulatory patients with advanced HIV infection and without evidence of adrenal or pituitary insufficiency were studied. Ovine corticotropin-releasing hormone was administered (1 microgram/kg BW) intravenously and plasma cortisol and adrenocorticotropin (ACTH) were measured over the following 120 minutes. Based on a standard response curve, obtained from CRH testing of 10 HIV negative volunteers with no HPA abnormalities, 13 patients were found to have normal response (group 1), 6 patients had reduced ACTH and cortisol response (group 2) and 6 patients had normal ACTH with reduced cortisol response (group 3). Basal cortisol and basal ACTH were comparable for control subjects and groups 1, 2, and 3. This suggests that, in advanced non-AIDS HIV patients with no clinical evidence of pituitary or adrenal disease, about 25% (group 2) have reduced pituitary reserve with high basal ACTH and cortisol, and about 25% (group 3) have reduced adrenal reserve with high basal cortisol and inappropriately normal basal ACTH, whereas about 50% (group 1) maintain normal HPA axis activity with increased basal cortisol secretion. The exact physiopathologic mechanism is not yet known, but an enhanced CRH production by the hypothalamus may explain the alterations in the HPA axis in advanced HIV disease.