How is a dexamethasone (corticosteroid) suppression test result interpreted?

Interpretation of Dexamethasone Suppression Test Results

The dexamethasone suppression test (DST) is interpreted as normal when cortisol levels are suppressed below 1.8 μg/dL (50 nmol/L) after administration of dexamethasone, which strongly indicates the absence of Cushing's syndrome. 1

Types of Dexamethasone Suppression Tests

• The overnight 1-mg DST is recommended as a first-line screening test for Cushing's syndrome due to its high sensitivity and ability to effectively rule out the condition when negative 1
• The 2-day Low-Dose DST (LDDST) has a sensitivity of 95% and specificity of 80% for diagnosing Cushing's syndrome, with normal response defined as cortisol suppression below 1.8 μg/dL (50 nmol/L) 1
• The overnight 8-mg DST is used for differential diagnosis of ACTH-dependent Cushing's syndrome, helping distinguish between pituitary and ectopic sources 2

Interpretation of Results

• Normal response: Cortisol suppression to <1.8 μg/dL (50 nmol/L) indicates absence of Cushing's syndrome 1, 3
• Abnormal response: Failure to suppress cortisol below 1.8 μg/dL suggests hypercortisolism and warrants further investigation 3
• Note that older literature used a higher cutoff of 5 μg/dL, but this has been shown to miss cases of Cushing's syndrome; the current accepted cutoff is 1.8 μg/dL 4

Improving Test Accuracy

• Measuring dexamethasone levels concurrently with cortisol can reduce false-positive results, with a lower limit of normal dexamethasone concentration of 1.8 ng/mL (4.6 nmol/L) 1, 5
• In patients with post-DST total cortisol between 1.8 and 5 μg/dL, measuring free cortisol can improve diagnostic accuracy and reduce false positives 6
• Multiple tests may be needed in mild or cyclic cases, as a single normal test does not exclude Cushing's syndrome 3

Factors Affecting Test Interpretation

False Positives (Abnormal Results in Patients Without Cushing's Syndrome)

• Medications that increase dexamethasone metabolism through CYP3A4 induction (phenytoin, phenobarbital, ephedrine, rifampin) 7
• Increased cortisol-binding globulin (CBG) levels, particularly in women taking oral estrogen therapy 1, 7
• Rapid dexamethasone absorption or malabsorption 1
• Indomethacin use can cause false-negative results in the DST 7
• Pseudo-Cushing states (psychiatric disorders, alcoholism, obesity, polycystic ovary syndrome) 3

False Negatives (Normal Results in Patients With Cushing's Syndrome)

• Up to 18% of patients with Cushing's disease may suppress cortisol to <5 μg/dL, and 8% may suppress to <2 μg/dL 8
• Inhibition of dexamethasone metabolism and decreased CBG levels 1

Special Considerations

• For adrenal incidentalomas, DST is particularly useful as a first-line test, with cortisol values >5 μg/dL generally identifying patients with dysregulated cortisol secretion 1
• DST may be preferred for shift workers and patients with disrupted circadian rhythm due to uneven sleep schedules 9
• DST may not be reliable in women treated with oral estrogen 9, 1
• For suspected pseudo-Cushing states, additional testing such as the Dex-CRH test may be needed 9, 3

Common Pitfalls

• Using outdated cutoff values (5 μg/dL instead of 1.8 μg/dL) can lead to missed diagnoses 4
• Failing to measure dexamethasone levels when interpreting borderline results 5
• Not accounting for medications that affect dexamethasone metabolism or cortisol binding 7
• Relying on a single test result, especially in mild or cyclic cases 3
• Not considering the possibility of false positives in patients taking oral contraceptives or estrogen therapy 6