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Journal of Clinical Endocrinology & Metabolism Vol. 70, No. 3 572-577
doi:10.1210/jcem-70-3-572
Copyright © 1990 by the Endocrine Society.
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Circadian Variations in Plasma Levels of Hypophyseal, Adrenocortical and Testicular Hormones in Men Infected with Human Immunodeficiency Virus*

J. M. VILLETTE, P. BOURIN, C. DOINEL, I. MANSOUR, J. FIET, P. BOUDOU, C. DREUX, R. ROUE, M. DEBORD and F. LEVI

Unité d'Hormonologie, Laboratoire de Biochimie, Hôpital Saint-Louis (J.M. V., J.F., P.B., CD.) Paris
UA 581 CNRS Chronobiologie-Chronopharmacologie et Fondation A. de Rothschild (F.L.) Paris
Laboratoire de Cytométrie en flux, CNTS, and INSERM U76 (CD., I.M.) Paris
Centre de Transfusion Sanguine des Armies (P.B.), Clamart; and Hôpital Inter-Armées Begin (R.R., M.D.) Saint-Mandé, France

Address all correspondence and requests for reprints to: J. M. Villette, Laboratoire Central de Biochimie, Service du Prof. C. Dreux, Unité d'Hormonologie, Hôpital Saint-Louis, 75475 Paris Cedex 10, France.

Alterations in the circadian time structure of the secretion of several hormones were investigated in 13 male patients infected with human immunodeficiency virus (HIV). Seven were asymptomatic (classified CDC II, according to the criteria of the Atlanta Centers for Disease Control), and 6 had acquired immunodeficiency syndrome (CDC IV). Ten healthy males volunteered as controls. Plasma levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), cortisol, testosterone, ACTH, and β-endorphin were determined by RIA in blood samples obtained every 4 h from 0830–0830 h the next morning.

Data were analyzed both by two-way analysis of variance and the cosinor method. Circadian rhythms were statistically validated for each of the six hormones in each of the three groups of subjects. Compared with the control subjects, mesors (24-h adjusted means) were significantly higher for cortisol and lower for DHEA, DHEA-S, and ACTH (P < 0.001 for all four hormones) in all HIV-infected patients. Plasma testosterone mesors were similar in controls and CDC II patients, but decreased significantly in the CDC IV patient group (P < 0.05).

Analysis of the circadian rhythms of plasma hormone levels clearly indicated an altered adrenal hormonal state in HIV-infected male patients, even during the asymptomatic period of the infection. For instance, plasma cortisol at 0430 h was more than twice as high in HIV-infected patients as it was in timequalified controls. Although patients already had elevated plasma cortisol and lowered adrenal androgen levels at this stage, hypogonadism was not observed, as gauged by plasma testosterone concentrations.

We speculate that the primary hormonal defect in HIV-infected patients is increased cortisol secretion resulting from circadian-varying stimulation of the adrenal cortex by a factor other than pituitary ACTH. This factor might be a stimulating substance secreted primarily by infected immune cells. Excess cortisol would lower adrenal androgen secretion by shifting adrenal steroid biosynthesis toward glucocorticoids and decreasing pituitary ACTH secretion via a negative feedback mechanism.

* This work was partly supported by grants from the Programme National de Recherche sur le SIDA.

Received April 5, 1989.




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