What is the protocol for a low dose dexamethasone (corticosteroid) suppression test?

Low-Dose Dexamethasone Suppression Test Protocol

The standard protocol for a low-dose dexamethasone suppression test (LDDST) involves administering 0.5 mg of dexamethasone orally every 6 hours (at 09:00,15:00,21:00, and 03:00) for 48 hours, with cortisol measurements at 0,24, and 48 hours. 1

Test Administration

• The LDDST is a key diagnostic test for confirming Cushing's syndrome, with normal suppression defined as cortisol below 50 nmol/L (1.8 μg/dL) 1
• Dexamethasone dosing schedule:
  • 0.5 mg orally every 6 hours (09:00,15:00,21:00,03:00) 1
  • Total duration: 48 hours (8 doses total) 1
• Blood sampling for cortisol measurement:
  • Baseline (before starting dexamethasone) 1
  • 24 hours after starting dexamethasone 1
  • 48 hours after starting dexamethasone (final measurement) 1

Interpretation of Results

• Normal response: Cortisol suppression below 50 nmol/L (1.8 μg/dL) at 48 hours 1
• Abnormal response (consistent with Cushing's syndrome): Cortisol remains ≥50 nmol/L (≥1.8 μg/dL) 1
• The test has approximately 95% sensitivity and 80% specificity for diagnosing Cushing's syndrome 1

Important Considerations

• False positive results (failure to suppress despite no Cushing's) can occur with:
  • Medications affecting dexamethasone metabolism (CYP3A4 inducers like phenobarbital, carbamazepine) 1, 2
  • Phenytoin, phenobarbital, ephedrine, and rifampin may enhance metabolic clearance of corticosteroids 2
• False negative results (suppression despite Cushing's) can occur with:
  • Medications inhibiting dexamethasone metabolism (fluoxetine, cimetidine) 1
  • Up to 18% of patients with Cushing's disease may suppress cortisol to <5 μg/dl after overnight dexamethasone 3
  • Up to 8% of Cushing's disease patients may show suppression to <2 μg/dl 3

Alternative Timing Considerations

• Research shows that administering dexamethasone at 21:00 instead of 23:00 does not significantly affect the degree of cortisol suppression in healthy subjects 4
• This provides flexibility in the timing of administration if the standard 03:00 dose is difficult to administer 4

Test Accuracy

• The 2-day LDDST may yield false-negative results in up to 38% of Cushing's syndrome patients when using urine cortisol and 28% when using urinary 17-hydroxycorticosteroids 3
• Serum cortisol measurement during the LDDST is considered as accurate and reliable as urinary steroid measurements 5
• In one study, serum cortisol fell below 60 nmol/L (2.2 μg/dl) in 97% of subjects without Cushing's syndrome, while remaining above 250 nmol/L (9.1 μg/dl) in those with the condition 5

The LDDST remains a valuable diagnostic tool for evaluating suspected Cushing's syndrome, but results must be interpreted in the context of other clinical findings and with awareness of potential confounding factors.