1 mg Overnight Dexamethasone Suppression Test Protocol
The 1 mg overnight dexamethasone suppression test should be performed by administering 1 mg of dexamethasone orally at 11 PM (23:00h), followed by measurement of serum cortisol at 8 AM the next morning. 1, 2, 3
Test Administration Protocol
Timing of dexamethasone administration: Give 1 mg dexamethasone orally between 11 PM and midnight (23:00h) 1, 2, 3
Timing of cortisol measurement: Draw blood for serum cortisol at 8 AM (08:00h) the following morning 1, 2, 3
Simultaneous dexamethasone level measurement: Measure serum dexamethasone concentration at the same time as the 8 AM cortisol draw to validate adequate drug absorption and patient compliance 2, 4
Interpretation Thresholds
Cortisol ≤50 nmol/L (≤1.8 μg/dL): Excludes autonomous cortisol secretion 1, 2, 3, 5
Cortisol 51-138 nmol/L (1.8-5.0 μg/dL): Suggests possible autonomous cortisol secretion; requires additional confirmatory testing 1, 2, 3, 5
Cortisol >138 nmol/L (>5.0 μg/dL): Indicates autonomous cortisol secretion 1, 2, 3, 5
The 1.8 μg/dL cutoff provides 100% sensitivity and 87% specificity for detecting Cushing's syndrome, making it the optimal threshold for screening 2, 6
Validation of Test Results
Measuring serum dexamethasone levels is critical to avoid false-positive results from inadequate drug absorption or patient non-compliance. 2, 4
Valid test: Serum dexamethasone ≥140 ng/dL (≥3.6 nmol/L) confirms adequate drug levels 4
Invalid test: Serum dexamethasone <140 ng/dL indicates inadequate suppression and requires test repetition 4
Undetectable dexamethasone (<19.5 ng/dL): Most commonly caused by failure to take medication (17%), concurrent glucocorticoid use (25%), or CYP3A4-inducing drugs like anticonvulsants (20%) 4
In a large series, 11.2% of dexamethasone suppression tests were invalid due to low serum dexamethasone levels, highlighting the importance of measuring drug levels to avoid unnecessary repetition and false-positive results 4
Confirmatory Testing for Equivocal Results (Cortisol 51-138 nmol/L)
When the 8 AM cortisol falls in the indeterminate range, additional criteria must be met to confirm autonomous cortisol secretion: 7
Basal ACTH <10 pg/mL (or poor ACTH response to CRH stimulation) 7
Evening cortisol ≥5 μg/dL measured between 21:00-23:00h 7
If both criteria are met, autonomous cortisol secretion is confirmed; if only one criterion is met, consider additional testing including DHEA-S levels, 24-hour urinary free cortisol, and clinical manifestations 7
Common Pitfalls and How to Avoid Them
CYP3A4-inducing medications: Anticonvulsants (phenytoin, carbamazepine, phenobarbital), rifampin, and St. John's wort accelerate dexamethasone metabolism, causing falsely elevated cortisol levels 2, 4
Gastrointestinal malabsorption: Prior gastric bypass, inflammatory bowel disease, or celiac disease impair dexamethasone absorption (13% of invalid tests) 4
Oral estrogen therapy: Increases corticosteroid-binding globulin, elevating total cortisol measurements and causing false-positive results 2, 5
Patient non-adherence: Failure to take dexamethasone accounts for 17% of undetectable drug levels 4
Concurrent glucocorticoid use: Exogenous steroids suppress cortisol but may be misinterpreted if dexamethasone levels are not measured 4
Patient Preparation Instructions
No fasting required: ACTH and cortisol levels are determined by hypothalamic-pituitary-adrenal axis feedback, not nutritional status 2
Discontinue interfering medications: Stop CYP3A4 inducers at least 2 weeks before testing when clinically feasible 2, 4
Verify medication compliance: Provide written and verbal instructions emphasizing the importance of taking dexamethasone at the specified time 4
Avoid exogenous glucocorticoids: Ensure patient is not using topical, inhaled, or systemic corticosteroids 2, 4
Why This Test Is Preferred
The 1 mg overnight dexamethasone suppression test is the preferred screening method because it is simple, cost-effective, and has excellent diagnostic accuracy when properly validated with serum dexamethasone levels 1, 2, 3. The conventional 2-day low-dose dexamethasone suppression test (0.5 mg every 6 hours for 48 hours) does not improve diagnostic specificity compared to the overnight test and is more cumbersome 8. The 8 mg dexamethasone suppression test largely replicates the results of the 1 mg test and adds no additional diagnostic value for screening autonomous cortisol secretion 9.