What serum cortisol level confirms validity of a low-dose (dexamethasone) suppression test?

Dexamethasone Level for Validating Low-Dose Dexamethasone Suppression Test

The lower limit of normal dexamethasone concentration required to validate a low-dose dexamethasone suppression test is 1.8 ng/mL (4.6 nmol/L), with this threshold ensuring proper test interpretation and reducing false positive results. 1

Dexamethasone Levels and Test Validity

• Measuring dexamethasone levels concomitantly with cortisol during the dexamethasone suppression test (DST) significantly improves test accuracy by confirming adequate dexamethasone exposure 1
• The 2.5th percentile of dexamethasone in patients with excluded Cushing's syndrome (1.8 ng/mL or 4.6 nmol/L) is considered the lower limit of normal (LLN) for test validity 1
• Inadequate dexamethasone levels (<1.8 ng/mL) may lead to false positive results, incorrectly suggesting Cushing's syndrome when it is not present 1, 2
• Approximately 4% of patients may have undetectable dexamethasone levels, suggesting non-compliance with the test protocol 1

Impact on Test Interpretation

• By excluding samples with dexamethasone <1.8 ng/mL and applying method-specific cortisol cutoffs, clinical specificity for Cushing's syndrome increases from 67.5% to 92.4% while maintaining 100% sensitivity 1
• Simultaneous measurement of serum dexamethasone and cortisol reduces false-positive DST results by approximately 20% 2
• For proper interpretation, serum dexamethasone should be ≥3.3 nmol/L to ensure sufficient levels for the suppression of cortisol to <50 nmol/L in normal individuals 2

Factors Affecting Dexamethasone Levels

• Decreased glomerular filtration rate and diabetes mellitus are associated with higher serum dexamethasone concentrations, potentially affecting test interpretation 1
• Body mass index, sex, age, nicotine use, and oral contraceptives do not significantly affect dexamethasone levels 1
• Variations in dexamethasone absorption and metabolism can significantly impact test results, making dexamethasone level measurement crucial for accurate interpretation 3, 4

Cortisol Cutoff Values

• The normal cortisol value after overnight dexamethasone suppression should be less than 2 μg/dL rather than the traditionally accepted 5 μg/dL 5
• Using the higher cutoff of 5 μg/dL may lead to unnecessary delays in diagnosis, as some individuals with Cushing's syndrome partially suppress their cortisol levels to between 2 and 5 μg/dL 5
• Method-specific cortisol cutoffs (e.g., 2.4 μg/dL or 66 nmol/L) should be used in conjunction with dexamethasone levels for optimal diagnostic accuracy 1

Special Considerations

• In women taking oral contraceptives, post-DST free cortisol measurements may be more valuable than total cortisol due to altered cortisol binding 3
• The upper post-DST free cortisol range is 48 ng/dL in men and women not on oral contraceptives, and 79 ng/dL in women on oral contraceptives 3
• False-positive results are more common in patients with post-DST cortisol between 1.8 and 5 μg/dL, making this a critical range where dexamethasone level measurement adds significant value 3

Clinical Application

• Adequate dexamethasone concentrations (≥0.1 μg/dL) are observed in approximately 97% of both healthy volunteers and patients undergoing evaluation for hypercortisolism 3
• For adrenal incidentalomas, DST is particularly useful as a first-line test, with cortisol values >5 μg/dL generally identifying patients with dysregulated cortisol secretion 6
• Measuring both dexamethasone and cortisol levels simultaneously provides a more comprehensive assessment of adrenal function and improves diagnostic accuracy 2, 4