Effects of endogenous and exogenous hypercortisolemia on low-dose ACTH outcome in humans
Jana Kerlik1, Adela Penesova1, Miroslav Vlcek1, Richard Imrich1, Luboslav Starka2 & Zofia Radikova1
Context: The interpretation of low-dose ACTH test during endogenous and exogenous hypercortisolemia induced by stress and glucocorticoid therapy in critically ill patients with possible relative adrenal insufficiency.
Objective: The hypothesized inhibitory effects of hypercortisolemia on adrenal responsiveness in humans were tested using two model situations in low-dose ACTH testing.
Subjects and methods: Nine young healthy women underwent minimal ACTH test in 5 modifications. In ACTH-ACTH test, ACTH (Synacthen, 1 μg i.v.) was given at 9 am and 10 am. Two control tests consisted of single ACTH bolus at 9 am or at 10 am. In HC-ACTH test, hydrocortisone (HC, 20 mg po) was orally given at 8.30 am and ACTH was injected at 10 am. Control test consisted of single HC administration at 8.30 am. The study was approved by the local Ethic Committee.
Results: Cortisol response after the 2nd ACTH test was significantly lower versus the 1st ACTH bolus (Δmax: 166±32 vs 276±15 nmol/l, P<0.05) in ACTH-ACTH test. Responses of other steroids after both ACTH injections were comparable. ACTH bolus during HC-induced hypercortisolemia caused a slight increase in cortisol level and prevented its decrease, seen after HC administration alone. Adrenal cortisol production in response to ACTH bolus under different incipient conditions (baseline, physiological and pharmacological hypercortisolemia; 180±16, 173±21, and 177±53 nmol/l/min, respectively) did not significantly differ (P=0.8).
Conclusions: Endogenous and exogenous hypercortisolemia did not influence adrenal steroids response to subsequent minimal ACTH test indicating lack of direct negative feedback of cortisol at adrenal level. Interpretations of ACTH testing based on a cortisol increment from baseline can lead to false positive results of relative adrenal insufficiency in cases with high baseline cortisol.