What is a normal cortisol result after a low dose dexamethasone (Decadron) suppression test?

Normal Cortisol Result After Low-Dose Dexamethasone Suppression Test

A normal cortisol result after a low-dose dexamethasone suppression test is <1.8 μg/dL (<50 nmol/L), which effectively rules out Cushing's syndrome. 1, 2

Standard Diagnostic Thresholds

The interpretation depends on which specific low-dose protocol was used:

Overnight 1-mg Dexamethasone Suppression Test

• Normal response: cortisol <1.8 μg/dL (<50 nmol/L) measured at 08:00h after administering 1 mg dexamethasone at 23:00-24:00h 1, 2
• This threshold has >90% sensitivity for detecting Cushing's syndrome 2
• Cortisol values >5 μg/dL (>138 nmol/L) indicate overt Cushing's syndrome 2
• Values between 1.8-5 μg/dL represent a gray zone requiring further evaluation 2

2-Day Low-Dose Dexamethasone Suppression Test (LDDST)

• Normal response: cortisol <1.8 μg/dL (<50 nmol/L) after 0.5 mg dexamethasone every 6 hours for 48 hours 1, 2, 3
• This protocol has 95% sensitivity and 80% specificity for diagnosing Cushing's syndrome 1, 3
• The dexamethasone is given at 09:00,15:00,21:00, and 03:00 with cortisol measurements at 0,24, and 48 hours 3

Critical Pitfalls That Cause False Results

False-Positive Results (Failure to Suppress Despite Normal HPA Axis)

• CYP3A4 inducers (phenobarbital, carbamazepine, phenytoin, rifampin) accelerate dexamethasone metabolism, causing inadequate drug levels 1, 2, 3
• Oral estrogen/contraceptives increase cortisol-binding globulin, elevating total cortisol while free cortisol remains normal 1, 2
• Malabsorption or rapid dexamethasone metabolism results in subtherapeutic drug levels 1
• Pseudo-Cushing's states (severe obesity, depression, alcoholism, PCOS) can activate the HPA axis 1, 2, 3

False-Negative Results (Suppression Despite Cushing's Syndrome)

• CYP3A4 inhibitors (fluoxetine, cimetidine) increase dexamethasone levels, causing excessive suppression even in mild Cushing's 1, 3
• Cyclic Cushing's syndrome may be tested during a quiescent phase 3
• Some patients with mild Cushing's disease can suppress to <5 μg/dL (18% in one series) or even <2 μg/dL (8% in one series) 4

Improving Test Accuracy

Measure dexamethasone levels concomitantly with cortisol to reduce false-positive results 1, 2, 5:

• The lower limit of normal dexamethasone concentration is 4.5-4.6 nmol/L (1.8 ng/mL) 1, 5
• If cortisol is >1.8 μg/dL but dexamethasone level is <4.5 nmol/L, the test is invalid due to inadequate drug absorption/metabolism 6, 5
• This approach can reduce false-positive rates from 10% to 6% in patients without Cushing's syndrome 5
• Approximately 6% of non-Cushing's patients fail to achieve adequate dexamethasone levels, accounting for 40% of tests with cortisol >5 μg/dL 5

When to Repeat or Use Alternative Testing

• If cortisol is 1.8-5 μg/dL: Repeat the test and consider measuring dexamethasone levels, or perform 2-3 additional screening tests (late-night salivary cortisol, 24-hour urinary free cortisol) 1, 2
• If taking medications affecting CYP3A4: Either discontinue the medication if safe to do so, or measure dexamethasone levels to confirm adequate dosing 1, 3
• If taking oral estrogen: Consider alternative tests such as late-night salivary cortisol or the Dex-CRH test 1, 2
• For shift workers or disrupted circadian rhythm: DST may be preferred over late-night salivary cortisol 1

Historical Context Worth Noting

Older literature suggested a normal cutoff of <5 μg/dL, but this threshold misses cases of mild Cushing's syndrome 7. The modern standard of <1.8 μg/dL provides superior diagnostic accuracy 1, 2. However, even with this stricter threshold, the 2-day LDDST can yield false-negative results in 28-38% of Cushing's patients depending on the measurement used 4, which is why no single test should be used as the sole criterion to exclude Cushing's syndrome 4.