What is considered a high post-meridiem (pm) cortisol level?

What PM Cortisol Level is Too High

A PM (evening/late-night) cortisol level ≥50 nmol/L (≥1.8 μg/dL) measured between 11 PM-1 AM is abnormally elevated and indicates loss of normal circadian rhythm, warranting formal screening for Cushing's syndrome. 1

Specific PM Cortisol Thresholds

Midnight/Late-Night Serum Cortisol (11 PM - 1 AM)

• Any value ≥50 nmol/L (≥1.8 μg/dL) is highly concerning and should prompt immediate formal Cushing's screening 1
• This threshold has 100% sensitivity for Cushing's syndrome in pediatric populations and excellent diagnostic accuracy in adults 1
• The normal circadian nadir should result in cortisol levels well below this threshold in healthy individuals 2

Late-Night Salivary Cortisol (10 PM)

The following age-specific cutoffs at 10 PM definitively diagnose Cushing's syndrome with 100% specificity 3:

• Ages 6-10 years: ≥1.9 μg/L (80% sensitivity) 3
• Ages 11-15 years: ≥1.7 μg/L (100% sensitivity) 3
• Ages 16-20 years: ≥2.5 μg/L (84.2% sensitivity) 3
• Ages 21-60 years: ≥1.9 μg/L (97.6% sensitivity) 3

Post-Dexamethasone PM Cortisol

• >50 nmol/L (>1.8 μg/dL) after overnight 1-mg dexamethasone suppression test is diagnostic of Cushing's syndrome 1
• >138 nmol/L (>5 μg/dL) is highly suggestive of autonomous cortisol production from an adrenal incidentaloma with overt Cushing's syndrome 1

Critical Interpretation Pitfalls

False Elevations to Exclude

• Oral contraceptives and estrogen therapy dramatically increase cortisol-binding globulin (CBG), falsely elevating total cortisol levels—modern oral contraceptives can cause extreme increases with total cortisol reaching 50-61 μg/dL despite normal free cortisol 4, 1
• Pregnancy and chronic active hepatitis similarly increase CBG and total cortisol 2, 1
• CYP3A4 inducers (phenobarbital, carbamazepine, St. John's wort) accelerate dexamethasone metabolism, causing false-positive suppression tests 2, 1

When PM Cortisol is Truly Elevated

The loss of normal circadian rhythm is the key pathophysiologic finding—healthy individuals should have cortisol nadir tightly entrained to sleep onset, with levels dropping to <50 nmol/L by late evening 2, 1

Recommended Action Algorithm

If PM cortisol ≥50 nmol/L (≥1.8 μg/dL):

1. Verify timing: Ensure sample was collected between 11 PM-1 AM or at usual bedtime 2, 1
2. Exclude confounders: Hold oral contraceptives for 2 months and retest if applicable; check for CYP3A4 inducers 4, 1
3. Proceed with formal Cushing's screening using at least two of the following 1:
   • 24-hour urinary free cortisol (2-3 collections)
   • Late-night salivary cortisol (2-3 occasions)
   • Overnight 1-mg dexamethasone suppression test
4. Measure 9 AM plasma ACTH once hypercortisolism is confirmed to differentiate ACTH-dependent from ACTH-independent causes 1

Special Considerations

• Night-shift workers: Do not use late-night cortisol testing due to disrupted circadian rhythm 2
• Cyclic Cushing's: Multiple sequential late-night measurements over weeks to months may be needed to capture episodic cortisol excess 2
• Exogenous steroids: Ensure 2-week washout period before interpretation, as inhaled fluticasone and other steroids can suppress the HPA axis 1