Dexamethasone is an exogenous steroid that provides negative feedback to the pituitary to suppress the secretion of ACTH. This steroid is unable to pass the blood brain barrier which allows this test to assess a specific part of the Hypothalamic-pituitary-adrenal axis. Specifically, dexamethasone binds to glucocorticoid receptors in the basal medial hypothalamus, which lies outside the blood brain barrier, resulting in regulatory modulation.
The test is given at low and high doses of dexamethasone and the levels of cortisol are measured to obtain the results. A normal result is decrease in cortisol levels upon administration of low-dose dexamethasone. Results indicative of Cushing's disease involve no change in cortisol on low-dose dexamethasone, but inhibition of cortisol on high-dose dexamethasone. If the cortisol levels are unchanged by low and high-dose dexamethasone then a cortisol secreting adrenocortical tumor is suspected or an ectopic ACTH syndrome.