What is the recommended dose of dexamethasone (Decadron) for the Dexamethasone Suppression Test (DST)?

Dexamethasone Dosing for DST

For the overnight 1-mg dexamethasone suppression test (DST), administer 1 mg orally between 11:00 PM and midnight, with serum cortisol measured at 8:00 AM the following morning. 1

Overnight 1-mg DST Protocol

• Administer 1 mg dexamethasone orally between 11:00 PM and midnight 1
• Measure serum cortisol at 8:00 AM the following morning 1
• Normal response is defined as serum cortisol < 1.8 μg/dL (50 nmol/L), which has >90% sensitivity for detecting Cushing's syndrome 1
• Serum cortisol > 5.0 μg/dL (138 nmol/L) suggests autonomous cortisol secretion 1

2-Day Low-Dose DST (LDDST) Protocol

For the 2-day LDDST, administer 0.5 mg dexamethasone orally every 6 hours (at 09:00,15:00,21:00, and 03:00) for 48 hours. 2

• Measure cortisol at 0,24, and 48 hours 2
• Normal response is cortisol suppression to < 1.8 μg/dL (50 nmol/L), which effectively rules out Cushing's syndrome 2
• This test has 95% sensitivity and 80% specificity when using the ≥50 nmol/L cutoff as diagnostic for Cushing's syndrome 2

Critical Considerations for Test Accuracy

Measure serum dexamethasone levels concomitantly with cortisol to reduce false-positive results caused by inadequate dexamethasone bioavailability or noncompliance. 1, 3

• A dexamethasone threshold of ≥4.5 nmol/L indicates adequate bioavailability after the 1-mg overnight test 4
• Approximately 6% of non-Cushing's patients fail to achieve adequate dexamethasone levels, accounting for 40% of false-positive results (cortisol >138 nmol/L) 4
• Measuring dexamethasone reduces the false-positive rate by identifying the 14% of patients with unsuppressed cortisol due to subtherapeutic dexamethasone levels 3

Common Pitfalls and Drug Interactions

CYP3A4 inducers cause false-positive results by accelerating dexamethasone metabolism, while CYP3A4 inhibitors cause false-negative results. 2, 1

• False-positive causes (failure to suppress despite no Cushing's): phenobarbital, carbamazepine, St. John's wort, rifampin 2, 1
• False-negative causes (suppression despite Cushing's): fluoxetine, cimetidine, diltiazem 2, 1
• Malabsorption or rapid gut transit can also cause false-positive results 1

Important Diagnostic Nuances

The 1-mg overnight DST has high sensitivity (>90%) but moderate specificity (63% at 50 nmol/L cutoff, increasing to 91% at 138 nmol/L cutoff). 4

• Research demonstrates that 18% of patients with proven Cushing's disease suppress cortisol to <5 μg/dL, and 8% suppress to <2 μg/dL after the 1-mg test, highlighting that low-dose DST should not be used as the sole criterion to exclude Cushing's syndrome 5
• The 2-day LDDST yields false-negative results in 38% of patients when using urine cortisol and 28% when using urinary 17-hydroxycorticosteroids 5
• Pseudo-Cushing's states (depression, alcoholism, obesity) can produce false-positive results 1

Alternative Dosing Considerations

Dexamethasone timing can be adjusted from 23:00 to 21:00 without affecting cortisol suppression in healthy subjects. 6

• The 0.5 mg dose suppresses cortisol to a similar extent as 1.0 mg in healthy subjects, while 0.25 mg provides less suppression 6
• However, the standard 1-mg dose at 11:00 PM-midnight remains the guideline-recommended protocol 1