Dexamethasone Suppression Test Protocol
The standard protocol for the dexamethasone suppression test includes the 1mg overnight test as an initial screening tool, with patients taking 1mg of dexamethasone at midnight and having plasma cortisol measured at 8:00 AM the following morning to diagnose Cushing's syndrome. 1
Types of Dexamethasone Suppression Tests
1. Low-Dose (Overnight) DST
- Protocol:
- Patient takes 1mg dexamethasone orally at midnight
- Blood sample collected at 8:00 AM the next morning for plasma cortisol measurement
- Normal response: Cortisol suppression below established cutoff
- Clinical Use: Initial screening test for Cushing's syndrome, especially in patients with unexplained weight gain, hypertension, and glucose intolerance 1
- Interpretation: Failure to suppress cortisol suggests hypercortisolism
2. High-Dose DST
- Protocol:
- 8mg dexamethasone administered (either as single overnight dose or divided over 2 days)
- Used for differential diagnosis of ACTH-dependent Cushing's syndrome
- Clinical Use: Differentiating between pituitary (Cushing's disease) and ectopic sources of ACTH 2
- Interpretation: Suppression of plasma cortisol to <50% of baseline suggests Cushing's disease 2
Patient Preparation and Considerations
- Patients should avoid strenuous physical activity for at least 24 hours (ideally 48 hours) before and during testing 1
- Certain medications can affect results and may need to be discontinued:
- Estrogen therapy can increase cortisol-binding globulin levels
- Medications that induce CYP3A4 can accelerate dexamethasone metabolism
- Measure dexamethasone levels when possible to confirm adequate absorption and rule out false positives due to non-compliance or altered metabolism 3
Limitations and Pitfalls
- Limited sensitivity in mild or episodic hypercortisolism (as low as 18-41% with traditional cutoffs) 4
- False positives may occur due to:
- Missed dexamethasone intake
- Insufficient dexamethasone serum exposure
- Medications affecting dexamethasone metabolism
- False negatives may occur in cyclic Cushing's syndrome if testing occurs during normal cortisol production periods
Improving Test Accuracy
- Measuring serum dexamethasone levels concurrently with cortisol can improve specificity (from 67.5% to 92.4% while maintaining 100% sensitivity) 3
- Using method-specific cortisol cutoffs (e.g., 2.4 μg/dL or 66 nmol/L for LC-MS/MS methods) 3
- Consider salivary cortisol measurement as an alternative to plasma cortisol (100% sensitivity and 94% specificity with a cutoff of 1.9 nmol/L) 5
- For patients who don't suppress with standard doses, very high-dose DST (32mg) may be considered in select cases 6
Comprehensive Diagnostic Approach
The Endocrine Society recommends confirming hypercortisolism using multiple tests:
- 24-hour urinary free cortisol measurements
- Late-night salivary cortisol
- 1mg overnight dexamethasone suppression test 1
This multi-test approach helps overcome the limitations of any single test, particularly in mild or cyclic cases of Cushing's syndrome.