Testing and Management for Hypercortisolism
An expert discusses the 3 main screening tests for hypercortisolism—overnight dexamethasone suppression, 24-hour urine-free cortisol, and late-night salivary cortisol—explaining their procedures, strengths, limitations, and practical use in clinical evaluation.
By
Bob Busch, MD
| Published on November 5, 2025
2 min read
The 3 most commonly used screening tests for hypercortisolism are the overnight dexamethasone suppression test (DST), the 24-hour urine-free cortisol (UFC) measurement, and the late-night salivary cortisol (LNSC) test. Each test evaluates cortisol production or regulation in a different way. The overnight DST assesses the ability of dexamethasone, a synthetic glucocorticoid, to suppress cortisol secretion. In this test, 1 mg of dexamethasone is administered orally at 11 PM, and serum cortisol is measured at 8 AM the next morning. A normal response involves cortisol suppression below a defined cutoff level, whereas a lack of suppression suggests hypercortisolism. The UFC test measures total cortisol excreted in the urine over 24 hours and reflects integrated cortisol production throughout the day. The LNSC test measures cortisol at night, when levels should be lowest, and elevated values indicate loss of normal diurnal variation.
Each test has specific strengths and limitations. The overnight DST is simple, inexpensive, and widely available, but false positives can occur with stress, obesity, alcoholism, or certain medications that affect dexamethasone metabolism. The UFC test is noninvasive and integrates cortisol levels over a day, but its accuracy depends on proper urine collection and normal kidney function. The LNSC test is convenient for home collection and highly sensitive for detecting Cushing syndrome, but contamination, shift work, or irregular sleep schedules can affect results.
In clinical practice, the overnight DST is the most commonly used initial screening test due to its convenience and cost-effectiveness. Many experts use a combination of tests to increase diagnostic accuracy and reduce false positives. In practice, screening often begins with DST, followed by confirmatory testing with UFC or LNSC when results are borderline or inconsistent with clinical findings.
