Effects of endogenous and exogenous hypercortisolemia on low-dose adrenocorticotropin test outcome in humans

Background: The results of low-dose ACTH testing may be impaired during endogenous or exogenous hypercortisolemia in various clinical situations. Aim: The hypothesized inhibitory effects of hypercortisolemia on adrenal responsiveness to low-dose ACTH were tested in two model situations in healthy humans. Subjects and methods: Nine young healthy women underwent low-dose ACTH test in 5 modifications. In ACTH-ACTH test, ACTH (1 μg iv) was given at 09:00 h and 10:00 h. Two control tests consisted of single ACTH bolus at 09:00 h or at 10:00 h. In hydrocortisone (HC)-ACTH test, HC (20 mg po) was given at 08:30 h and ACTH was injected at 10:00 h. Control test consisted of single HC administration at 08:30 h. Results: Cortisol response after the 2nd ACTH test was significantly lower vs the 1st ACTH bolus (Amax: 166±32 nmol/l 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·min·l−1, respectively) did not significantly differ (p=0.8). Conclusions: Endogenous and exogenous hypercortisolemia did not influence adrenal cortisol response to low-dose ACTH test indicating lack of its negative feedback at adrenal level.