Adrenocorticotropin-Stimulated Secretion of Aldosterone and Cortisol, Computed from Plasma and Red Blood Cell Measurements*

Abstract

The dynamic response of the adrenal cortex to ACTH infusion is analyzed by simulating the distribution, binding, and metabolism of cortisol and aldosterone in a multicompartmental model. The model includes the effects of temperature and cortisol concentration on aldosterone binding in plasma and the distribution between plasma and red blood cells, as verified by new observations. The secretion rates of cortisol and aldosterone were computed from serial measurements of plasma concentrations of endogenous steroids and infused tracers. The model was validated by observations after iv injection of a bolus of cortisol. Nineteen normal volunteers were studied on the fourth day on a diet containing 10 meq sodium. Endogenous ACTH was suppressed by dexamethasone, and alpha-1-24ACTH was infused at two different rates in various sequences over a 4-h period. During each hour of constant ACTH infusion, plasma cortisol continued to increase, while plasma aldosterone rose quickly, reaching a plateau within 20--30 min. Cortisol secretion approached a maximim rate after 20--30 min of ACTH infusion; the continued increase of plasma cortisol resulted from the slow equilibrium with other compartments. Aldosterone secretion rose quickly to a peak and then declined to a lower level after 20 min of ACTH infusion; the lower rate of secretion was maintained for the duration of the constant infusion of ACTH, falling abruptly within a few minutes after stopping the infusion. The characteristic differences in plasma steroid responses to various sequences of ACTH infusions can be explained by the more rapid changes in aldosterone secretion and the different clearance rates of cortisol and aldosterone, which vary with plasma cortisol concentration. The temperature at which blood is separated significantly affects plasma aldosterone measurements.