Serum Cortisol Timing After Dexamethasone
Serum cortisol should be measured at 8:00 AM (0800 hours), which is approximately 8-9 hours after administering 1 mg of dexamethasone between 11:00 PM and midnight. 1
Standard Overnight Dexamethasone Suppression Test Protocol
The overnight 1-mg dexamethasone suppression test (DST) follows this specific timing:
- Dexamethasone administration: 1 mg given orally between 11:00 PM (2300 hours) and midnight
- Cortisol measurement: Blood draw at 8:00 AM the following morning
- Time interval: Approximately 8-9 hours after dexamethasone dose 1
Interpretation Thresholds
The cortisol cutoff values at this 8-hour timepoint are critical for diagnosis:
- Normal response: Serum cortisol < 1.8 μg/dL (50 nmol/L) effectively excludes Cushing's syndrome 1
- Mild autonomous cortisol secretion (MACS): Cortisol > 1.8 μg/dL but < 5 μg/dL suggests autonomous cortisol production, particularly in adrenal incidentalomas 1
- Overt hypercortisolism: Cortisol > 5 μg/dL (138 nmol/L) indicates significant autonomous cortisol secretion 1
Important Caveats
Drug interactions can significantly affect results. CYP3A4 inducers (phenobarbital, carbamazepine, St. John's wort) accelerate dexamethasone metabolism, potentially causing false-positive results. Conversely, CYP3A4 inhibitors (fluoxetine, cimetidine, diltiazem) slow metabolism, potentially causing false-negative results 1.
Consider measuring dexamethasone levels concurrently if results are equivocal or drug interactions are suspected, as inadequate dexamethasone absorption occurs in approximately 3.6% of patients 2. However, even when dexamethasone levels fall below expected thresholds, the DST often remains clinically interpretable 3.
Conditions affecting cortisol-binding globulin (CBG) alter total cortisol measurements: oral estrogens, pregnancy, and chronic active hepatitis increase CBG (potentially false-positive), while nephrotic syndrome decreases CBG (potentially false-negative) 1.
Alternative Timing for Research Context
In research studies examining dexamethasone's physiologic effects on the HPA axis, cortisol suppression is maximal at approximately 24 hours post-dose 4. However, this 24-hour timepoint is not used for clinical diagnostic testing of Cushing's syndrome or autonomous cortisol secretion.