Effects of endogenous and exogenous hypercortisolemia on low-dose adrenocorticotropin test outcome in humans
Related Experiment Video
Updated: Jun 22, 2026

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids
Published on: April 25, 2016
J Kerlik1, A Penesova, M Vlcek
1Laboratory of Human Endocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06, Bratislava, Slovakia. jana.kerlik@savba.sk
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 microg 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 (Deltamax: 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.
Related Concept Videos
Cushing Syndrome II: Pathophysiology
Cushing Syndrome I: Introduction
Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Hypothalamic-Pituitary Axis
Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and corticosterone...
Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...

