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The Adrenocorticotropin Stimulation Test: Contribution of a Physiologically Based Model Developed in Horse for Its Interpretation in Different Pathophysiological Situations Encountered in Man

Unité Mixte de Recherche 181 de Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique et Ecole Nationale Vétérinaire de Toulouse, Ecole Nationale Vétérinaire de Toulouse, 31076 Toulouse cedex 03, France

Address all correspondence and requests for reprints to: Alain Bousquet-Mélou, Unité Mixte de Recherche 181 de Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique et Ecole Nationale Vétérinaire de Toulouse, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse cedex 03, France. E-mail: a.bousquet-melou{at}envt.fr.

The present study aimed to characterize the adrenal response to ACTH. A model was developed that coupled the nonlinear disposition of cortisol with a physiologically based model for cortisol secretion by the adrenals. It was assumed that the response to ACTH resulted from two mechanisms: a stimulation of the cortisol secretion rate and control of the duration of the secretion. Seven dose levels of ACTH were tested in horses, a species similar to man as regards adrenal function. The main result was that the secretion rate of the adrenal gland can be modelized by a zero order process that is maximal for a relatively low dose of ACTH (0.1 µg/kg). Beyond this dose, the increasing adrenal gland response is only due to the prolongation of the time of its secretion. The consequences of these different features were explored by simulation to reproduce classical pathophysiological situations encountered in man. Our model was able to reproduce and simply explain many adrenal gland responses that are dimmed by the different nonlinearities of the system.