What is the protocol for a 1 milligram (mg) dexamethasone suppression test?

How to Perform the 1 mg Dexamethasone Suppression Test

Administer 1 mg of dexamethasone orally between 11:00 PM and midnight, then measure serum cortisol at 8:00 AM the following morning, with normal suppression defined as cortisol <1.8 μg/dL (50 nmol/L). 1

Test Protocol

Timing and Administration

• Give 1 mg dexamethasone orally between 11:00 PM and midnight (standard timing is 11 PM-midnight, though some protocols specify 2300-2400h) 1
• Collect blood for serum cortisol measurement at 8:00 AM the following morning 1
• The patient should take the medication at home and present for blood draw the next morning 1

Interpretation of Results

Normal Response:

• Serum cortisol **<1.8 μg/dL (50 nmol/L)** effectively rules out Cushing's syndrome with >90% sensitivity 1, 2
• This threshold provides the highest diagnostic accuracy according to current Endocrine Society guidelines 1

Abnormal Response:

• Serum cortisol ≥1.8 μg/dL (≥50 nmol/L) suggests possible Cushing's syndrome and requires further evaluation 2
• Serum cortisol >5.0 μg/dL (138 nmol/L) indicates overt autonomous cortisol secretion 2, 1

Critical Pitfalls to Avoid

Medication Interactions

• CYP3A4 inducers (phenobarbital, carbamazepine, phenytoin, rifampin, St. John's wort) accelerate dexamethasone metabolism, causing false-positive results (failure to suppress despite no Cushing's) 1, 3, 2
• CYP3A4 inhibitors (fluoxetine, cimetidine, diltiazem) slow dexamethasone metabolism, causing false-negative results (suppression despite Cushing's) 1, 3
• Oral contraceptives and estrogen therapy increase cortisol-binding globulin, falsely elevating total cortisol measurements 2

Patient Factors

• Malabsorption or rapid gut transit can cause inadequate dexamethasone absorption, leading to false-positive results 1
• Pseudo-Cushing's states (depression, alcoholism, severe obesity, polycystic ovary syndrome) can cause mild hypercortisolism that mimics true Cushing's syndrome 2, 1

Improving Test Accuracy

• Consider measuring dexamethasone levels concomitantly with cortisol to confirm adequate drug absorption and exclude false results from abnormal metabolism 1, 2
• This is particularly useful when results are equivocal or when medication interactions are suspected 2

Important Limitations

Sensitivity in Mild Disease

• The test has reduced sensitivity (as low as 18-41%) in patients with mild or cyclic Cushing's syndrome who may suppress normally despite having the disease 4
• Patients with mild hypercortisolism often suppress to values <5 μg/dL and sometimes even <1.8 μg/dL 4
• Do not use a normal result to definitively exclude Cushing's syndrome in patients with high clinical suspicion 4

When to Use Alternative Screening

• For patients with high clinical suspicion, perform 2-3 different screening tests (late-night salivary cortisol, 24-hour urinary free cortisol, and overnight dexamethasone suppression test) rather than relying on a single test 1
• The 2-day low-dose dexamethasone suppression test (0.5 mg every 6 hours for 48 hours) may be more sensitive but is more cumbersome 3, 1

Alternative Dosing Considerations

• Some evidence suggests 0.5 mg dexamethasone with a cortisol cut-off of 3 μg/dL provides 99.1% sensitivity and 98.4% specificity for ACTH-dependent Cushing's syndrome 5
• However, the 1 mg dose remains the standard recommended by major endocrine societies 1