Normal Morning Cortisol Range
The normal morning cortisol range is 3-19 μg/L (saliva) or approximately 110-500 nmol/L (serum) when measured between 6:00-8:00 AM. 1
Physiological Context
Morning cortisol levels follow a circadian rhythm with:
- Peak levels in early morning (6:00-8:00 AM)
- Progressive decline throughout the day
- Lowest levels around midnight
This pattern is critical for proper interpretation of cortisol values, as the time of measurement significantly impacts reference ranges.
Detailed Reference Ranges by Time of Day
| Time | Normal Cortisol Level |
|---|---|
| Morning (6:00-8:00 AM) | 3-19 μg/L (saliva) |
| Mid-morning (11:00-12:00) | <1-11 μg/L |
| Afternoon (4:00-6:00 PM) | <1-6 μg/L |
| Evening (7:00-8:00 PM) | <1-4.5 μg/L |
| Night (10:00 PM) | <1-2.9 μg/L |
Clinical Significance of Morning Cortisol Values
Diagnostic Thresholds
- ≥300 nmol/L: Effectively excludes adrenal insufficiency 2
- <110 nmol/L: Strongly suggests adrenal insufficiency 2
- 110-300 nmol/L: Indeterminate zone requiring further testing
Predictive Values
- A morning cortisol level ≥234 nmol/L predicts a normal cortisol response to ACTH stimulation testing with optimal sensitivity (80.6%) and specificity (91.4%) 2
- For patients with suspected central adrenal insufficiency, a morning cortisol >444.7 nmol/L predicts a normal response to insulin tolerance testing with 96.9% sensitivity 3
Factors Affecting Morning Cortisol Levels
Several factors can influence morning cortisol levels and should be considered when interpreting results:
- Sleep-wake cycle disruption: Night shift workers may have altered cortisol rhythms
- Medications: CYP3A4 inducers (phenobarbital, carbamazepine) can affect cortisol metabolism 4
- Estrogen therapy: Increases cortisol-binding globulin, elevating total cortisol levels 1
- Stress: Acute and chronic stress can elevate cortisol levels
- Age: Reference ranges may vary slightly with age
Common Pitfalls in Cortisol Testing
- Timing errors: Collecting samples outside the specified morning window
- Failure to account for shift work: Night shift workers have altered circadian rhythms
- Not considering medication effects: Oral estrogens increase CBG levels and total cortisol
- Overlooking binding protein abnormalities: Changes in CBG affect total but not free cortisol
- Using inappropriate cutoffs: Different assays may have different reference ranges
Morning cortisol measurement is a valuable screening tool, but values in the indeterminate range (110-300 nmol/L) should prompt further dynamic testing such as ACTH stimulation testing or insulin tolerance testing to definitively assess adrenal function.