Dexamethasone is a potent synthetic glucocorticoid not detected by serum, urine, and salivary cortisol assays. Dexamethasone should not fully suppress ACTH and, therefore, should not decrease adrenal secretion of cortisol. Dexamethasone suppression tests are used to assess the status of the HPA axis and for the differential diagnosis of adrenal hyperfunction.
Low-dose dexamethasone suppression tests are good standard screening tests to differentiate patients with Cushing syndrome of any cause from patients who do not have Cushing syndrome. Principle: If the hypothalamic " “pituitary axis is normal, any supraphysiologic dose of dexamethasone is sufficient to suppress pituitary ACTH secretion. This should lead to reductions in cortisol secretion and its concentration in serum and saliva, as well as in the 24-hour urine excretion. Two main protocols are used: overnight 1-mg screening test and standard 2-day, 2-mg test.
High-dose suppression tests are based on the fact that ACTH secretion in Cushing disease is only relatively resistant to glucocorticoid negative feedback inhibition and does not suppress normally with either the overnight 1-mg or the 2-day low-dose test. By increasing the dose of dexamethasone four- to eightfold, ACTH secretion can be suppressed in most patients with Cushing disease. Therefore, this test is used to distinguish patients with Cushing disease (Cushing syndrome caused by pituitary hypersecretion of ACTH) from most patients with ectopic ACTH syndrome (Cushing syndrome caused by nonpituitary ACTH-secreting tumors).