Human glucocorticoid feedback inhibition is reduced in older individuals: Evening study

We have previously shown that when tested in the morning, older men and wom en, pretreated with metyrapone to block endogenous cortisol synthesis, exhi bit delayed suppression of plasma ACTH in response to cortisol infusion. To confirm this finding and to determine whether aging-related changes in fee dback responsiveness are exaggerated near the time of the circadian nadir i n adrenocortical secretion, we performed a similar study in the evening. He althy young (20-35 yr, n = 22) and old (>65 yr, n = 21) men and women were administered metyrapone orally (750 mg) at 1600 and 1900 h, followed by a c ortisol infusion of 0.06 mg/kg/h for 150 min. Blood samples were taken at 1 5-min intervals for 4 h following infusion onset for measurement of plasma ACTH, cortisol, 11-deoxycortisol, and corticosteroid binding globulin. When corrections were made for differences in circulating cortisol concentratio ns achieved among age and gender subgroups, feedback inhibition of ACTH was found to be significantly greater in young than in old subjects of both ge nders. Our studies support the hypothesis that glucocorticoid responses to stress in aging individuals are likely to be prolonged due to blunted and d elayed inhibition of ACTH secretion, thus increasing the total exposure to glucocorticoids.