What is the primary test used for diagnosing Cushing's syndrome?

The primary test used for diagnosing Cushing's syndrome is the dexamethasone suppression test. This test is critical because it assesses the feedback regulation of cortisol production by the hypothalamic-pituitary-adrenal (HPA) axis. In a healthy individual, administration of dexamethasone, a synthetic glucocorticoid, would typically suppress cortisol secretion. However, in patients with Cushing's syndrome, this suppression does not occur due to underlying pathology, either from an adrenal tumor, pituitary adenoma, or ectopic ACTH production.

While the 24-hour urine free cortisol measurement and late-night salivary cortisol tests are also effective for diagnosing Cushing's syndrome, the dexamethasone suppression test specifically evaluates the HPA sensitivity to glucocorticoid feedback, making it a fundamental tool in the initial workup of suspected cases. The low-dose dexamethasone suppression test serves a similar purpose to the standard dexamethasone suppression test but is performed with different dosages and parameters, and is not typically regarded as the primary diagnostic approach in clinical settings.