Diurnal Variation in Suppression of Adrenal Function by Glucocorticoids

Abstract

If the functioning of the ACTH-releasing mechanism were analogous to a negative feedback system sensitive to glucocorticoids, administration of physiologic amounts of exogenous cortisol-like compounds might be expected to suppress ACTH release quantitatively and would serve, therefore, merely as replacement glucocorticoid. However, in certain circumstances it appears that this does not occur. In order to understand this paradox, normal subjects were given 0.5 mg of dexamethasone orally at 8 am in one study, at 4 PM in a second study and at midnight in the third study. Plasma and urinary 17-hydroxycorticosteroid levels were determined. Production rates of cortisol were estimated by isotope dilution. One half mg of dexamethasone administered at 8 am or 4 pm caused only temporary suppression of cortisol secretion. The same amount given at midnight, however, produced virtually complete suppression of cortisol production for a full 24-hr period. These findings appear to be attributable to a variation in the duration of suppression of ACTH release. These observations may have important therapeutic implications. By selecting the appropriate time for administration of small amounts of glucocorticoids it may be possible to selectively avoid or produce adrenal suppression.