What is the best test to screen for hypercortisolism (Cushing's syndrome)?

From the Guidelines

The best initial screening test for hypercortisolism (Cushing's syndrome) is the overnight 1mg dexamethasone suppression test, as recommended by the most recent and highest quality study 1. This test involves the patient taking 1mg of dexamethasone orally at 11 PM and then having their serum cortisol measured at 8 AM the following morning. A cortisol level below 1.8 μg/dL (50 nmol/L) effectively rules out hypercortisolism, while higher values suggest the need for further testing.

The reasoning behind this recommendation is based on the following key points:

• The 1mg dexamethasone suppression test is preferred due to its simplicity, convenience, and reasonable sensitivity 1.
• Alternative screening options, such as the 24-hour urinary free cortisol test and the late-night salivary cortisol test, may be used when the dexamethasone suppression test is inconclusive or as confirmatory tests 1.
• It's essential to consider clinical context when interpreting results, as false positives can occur with medications that increase dexamethasone metabolism, severe stress, depression, alcoholism, or high-estrogen states.

Some key considerations for the test include:

• The test should be performed with the patient taking 1mg of dexamethasone orally at 11 PM and then having their serum cortisol measured at 8 AM the following morning.
• A cortisol level below 1.8 μg/dL (50 nmol/L) effectively rules out hypercortisolism, while higher values suggest the need for further testing 1.
• Measuring dexamethasone level along with cortisol the morning after 1mg dexamethasone ingestion can improve test interpretability 1.

From the Research

Screening Tests for Hypercortisolism (Cushing's Syndrome)

The following are the screening tests for hypercortisolism (Cushing's syndrome):

• 1-mg dexamethasone suppression test (DST)
• Late-night salivary cortisol (LNSC)
• Urinary free cortisol (UFC) measurement

Diagnostic Performance of Screening Tests

The diagnostic performance of these tests is as follows:

• UFC measured by liquid chromatography tandem-mass spectrometry has the best accuracy in diagnosing Cushing's syndrome among patients presenting with suspected hypercortisolism 2
• LNSC is considered the best approach to screen patients suspected of having endogenous hypercortisolism (Cushing's syndrome) 3
• LNSC appears to be the most useful screening test, while UFC and DST should be performed to provide further confirmation of the diagnosis 4
• The Endocrine Society's Clinical Practice Guidelines recommend a single test with a high diagnostic accuracy, among the 1-mg DST, LNSC, and 24 h UFC 5

Comparison of Screening Tests

A comparison of the screening tests is as follows:

• The 1-mg DST has a higher proportion of unclear or abnormal results compared to the two-day low-dose DST (2d-DST) in women taking oral contraceptive agents 6
• The 2d-DST could be a better screening option than the 1-mg DST for women taking oral contraceptive agents who are reluctant to stop them 6
• UFC has a combined higher positive and a lower negative likelihood ratio among first-line tests 2
• Measuring cortisol with antibody-based immunoassays can generate false-positive results due to cross-reactivity between cortisol, cortisone and other metabolites, while structurally-based assays, such as liquid chromatography with tandem mass spectrometry, only measure cortisol 5