Endocrine dynamic function tests - dexamethasone suppression tests

Role

Dexamethasone suppression testing (overnight low-dose being the standard initial screening test) assesses whether cortisol secretion appropriately suppresses in response to exogenous glucocorticoid negative feedback - failure to suppress supports a diagnosis of Cushing syndrome, prompting further localisation testing
The standard first-line screening test whenever Cushing syndrome is clinically suspected, given its practicality as an outpatient overnight test

In health, exogenous dexamethasone suppresses pituitary ACTH secretion via negative feedback, which in turn suppresses adrenal cortisol production - in Cushing syndrome (whether from autonomous adrenal cortisol production, an ACTH-secreting pituitary adenoma relatively resistant to feedback suppression, or ectopic ACTH secretion from a source entirely outside normal feedback control), this suppression fails to occur normally, and cortisol remains inappropriately elevated the following morning

Numerous factors cause false-positive results (inadequate suppression despite no true Cushing syndrome) - obesity, depression, alcohol excess, pregnancy, and medications affecting dexamethasone metabolism (e.g. enzyme-inducing drugs reducing dexamethasone levels) - meaning an abnormal screening result requires confirmatory testing (e.g. urinary free cortisol, late-night salivary cortisol) rather than being treated as diagnostic alone
A confirmed abnormal screening test is followed by localisation testing (ACTH level, high-dose suppression testing, imaging) to distinguish the specific cause

Failed suppression on screening -> confirmatory testing with a second, different dynamic test (given the false-positive rate of any single test) before committing to extensive localisation work-up
Confirmed Cushing syndrome -> localisation testing (ACTH-dependent vs independent) directing imaging (pituitary MRI vs adrenal CT) and definitive treatment planning

Cushing syndrome screening false-positive causes (obesity, depression, alcohol, enzyme-inducing drugs), confirmatory second-test requirement, ACTH-dependent vs independent localisation

An abnormal overnight dexamethasone suppression result should never be treated as diagnostic of Cushing syndrome in isolation, given the substantial false-positive rate from common confounders (obesity, depression, alcohol excess, certain medications) - confirmation with a second, mechanistically different test is required before proceeding to extensive and costly localisation imaging

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