Journal of Clinical Endocrinology & Metabolism, Vol 74, 608-613, Copyright © 1992 by Endocrine Society

ARTICLES

Cortisol resistance in acquired immunodeficiency syndrome

G Norbiato, M Bevilacqua, T Vago, G Baldi, E Chebat, P Bertora, M Moroni, M Galli and N Oldenburg
Servizio di Endocrinologia, Ospedale L. Sacco Vialba, Milan, Italy.

This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism. All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis). An acquired form of peripheral resistance to glucocorticoids was suspected. We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation. Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01). The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01). [3H]Thymidine incorporation was decreased dose-dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality. In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes. Resistance to glucocorticoids implies a complex change in immune-endocrine function, which may be important in the course of immunodeficiency syndrome.

This article has been cited by other articles:

				G.U. Meduri, P. Carratu, and A.X. Freire Evidence of biological efficacy for prolonged glucocorticoid treatment in patients with unresolving ARDS Eur. Respir. J., August 1, 2003; 22(42_suppl): 57s - 64s. [Abstract] [Full Text] [PDF]

				P. E. Marik and G. P. Zaloga Adrenal Insufficiency in the Critically Ill: A New Look at an Old Problem Chest, November 1, 2002; 122(5): 1784 - 1796. [Abstract] [Full Text] [PDF]

				J. Mayo, J. Collazos, E. Martinez, and S. Ibarra Adrenal Function in the Human Immunodeficiency Virus-Infected Patient Arch Intern Med, May 27, 2002; 162(10): 1095 - 1098. [Abstract] [Full Text] [PDF]

				G. U. Meduri, E. A. Tolley, G. P. Chrousos, and F. Stentz Prolonged Methylprednisolone Treatment Suppresses Systemic Inflammation in Patients with Unresolving Acute Respiratory Distress Syndrome . Evidence for Inadequate Endogenous Glucocorticoid Secretion and Inflammation-induced Immune Cell Resistance to Glucocorticoids Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 983 - 991. [Abstract] [Full Text] [PDF]

				M. Ebrecht, A. Buske-Kirschbaum, D. Hellhammer, S. Kern, N. Rohleder, B. Walker, and C. Kirschbaum Tissue Specificity of Glucocorticoid Sensitivity in Healthy Adults J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3733 - 3739. [Abstract] [Full Text]

				T.M. O'CONNOR, D.J. O'HALLORAN, and F. SHANAHAN The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia QJM, June 1, 2000; 93(6): 323 - 333. [Abstract] [Full Text] [PDF]

				N. A. T. M. Huizenga, P. de Lange, J. W. Koper, W. W. de Herder, R. Abs, J. H. L. M. v. Kasteren, F. H. de Jong, and S. W. J. Lamberts Five Patients with Biochemical and/or Clinical Generalized Glucocorticoid Resistance without Alterations in the Glucocorticoid Receptor Gene J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 2076 - 2081. [Abstract] [Full Text]

				F. B. Hashemi, T. K. Hughes, and E. M. Smith Human Immunodeficiency Virus Induction of Corticotropin in Lymphoid Cells J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4373 - 4381. [Abstract] [Full Text]

				P. J. BARNES, S. PEDERSEN, and W. W. BUSSE Efficacy and Safety of Inhaled Corticosteroids . New Developments Am. J. Respir. Crit. Care Med., March 1, 1998; 157(3): S1 - 53. [Full Text] [PDF]

				R. H. Oakley, J. C. Webster, M. Sar, C. R. Parker Jr., and J. A. Cidlowski Expression and Subcellular Distribution of the {beta}-Isoform of the Human Glucocorticoid Receptor Endocrinology, November 1, 1997; 138(11): 5028 - 5038. [Abstract] [Full Text] [PDF]

				G. Norbiato, M. Bevilacqua, T. Vago, A. Taddei, and M. Clerici Glucocorticoids and the Immune Function in the Human Immunodeficiency Virus Infection: A Study in Hypercortisolemic and Cortisol-Resistant Patients J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3260 - 3263. [Abstract] [Full Text] [PDF]

				G. P. Chrousos The Hypothalamic-Pituitary-Adrenal Axis and Immune-Mediated Inflammation N. Engl. J. Med., May 18, 1995; 332(20): 1351 - 1363. [Full Text] [PDF]