Dexamethasone Level for an Adequate Suppression Test
For the overnight dexamethasone suppression test (DST), a serum cortisol level < 1.8 μg/dL (50 nmol/L) at 0800h the morning after 1 mg dexamethasone administration is considered a normal response indicating adequate suppression. 1
Overnight DST Protocol and Interpretation
- The standard protocol involves administering 1 mg dexamethasone between 2300h and midnight, with blood sampling for cortisol at 0800h the following morning 1
- A cortisol value < 1.8 μg/dL (50 nmol/L) strongly predicts absence of Cushing's syndrome and indicates adequate suppression 1
- Using higher cutoff points (e.g., 5 μg/dL or 138 nmol/L) reduces test sensitivity 1
- Older literature used 5 μg/dL as the cutoff, but more recent evidence supports using < 2 μg/dL as the normal value to avoid diagnostic delays 2
Measuring Dexamethasone Levels
- Measuring dexamethasone concomitantly with cortisol, using laboratory-specific ranges, can reduce the risk for false-positive results 1
- This is particularly important when false-positive DST results are suspected due to the clinical scenario 1
- Target plasma dexamethasone levels of > 3.3 nmol/L are generally considered adequate for proper test interpretation 3
Factors Affecting Test Reliability
False Positive Results (Inadequate Suppression Despite No Disease)
- Rapid absorption/malabsorption of dexamethasone due to increased gut transit time, chronic diarrhea, or celiac disease 1
- Concomitant treatment with CYP3A4 inducers (e.g., phenobarbital, carbamazepine, St. John's wort) 1
- Increased corticosteroid binding globulin (CBG) levels from oral estrogens, pregnancy, or chronic active hepatitis 1
False Negative Results (Adequate Suppression Despite Disease)
- Inhibition of dexamethasone metabolism by medications such as fluoxetine, cimetidine, or diltiazem 1
- Decreased CBG and albumin levels, as in patients with concurrent nephrotic syndrome 1
Special Considerations
Obesity
- Obese patients may have higher false-positive rates with the standard 1 mg test 4
- For obese patients, a 2 mg overnight DST may be more accurate (2% false-positive rate vs. 8% with 1 mg test) 4
- However, recent evidence suggests obesity itself does not significantly affect plasma dexamethasone levels 3
Shift Workers
- The DST is the preferred diagnostic test for evaluating cortisol status in shift workers and patients with disrupted circadian rhythms 5
- Late night salivary cortisol (LNSC) testing should not be performed in patients with disruption of the normal day/night cycle 5
Timing of Administration
- While traditionally administered at 23:00h or midnight, research shows that administering dexamethasone at 21:00h produces similar suppression results in healthy subjects 6
- This flexibility in timing may improve patient compliance and test convenience 6
Alternative Protocols
- For high-dose testing to differentiate Cushing's disease from ectopic ACTH secretion, 8 mg dexamethasone is administered at 23:00h with specific sampling protocols 7
- For patients with suspected pseudo-Cushing's syndrome, alternative tests like the low-dose 2-day dexamethasone test (LDDT) may be considered 1
Remember that measuring dexamethasone levels along with cortisol significantly improves the interpretability of the test, especially in patients with potential medication interactions or absorption issues 1.