Morning Cortisol Reference Range
The reference range for morning (8:00-9:00 AM) cortisol levels in adults is 140-700 nmol/L (5.1-25.4 μg/dL), with most healthy individuals having values between 276-552 nmol/L (10-20 μg/dL). 1, 2
Standard Reference Values
- Morning cortisol (0900 hours): 140-700 nmol/L (5.1-25.4 μg/dL) 1
- The optimal range in healthy individuals is more concentrated between 276-552 nmol/L (10-20 μg/dL) 2
- Midnight cortisol levels are significantly lower at 80-350 nmol/L (2.9-12.7 μg/dL), reflecting the normal circadian rhythm 1
Critical Timing Requirements
- Blood must be drawn between 8:00-9:00 AM to capture the physiologic peak of cortisol secretion 1
- This timing window is essential for accurate interpretation, as the same cortisol value may be normal at 0900 hours but pathologically elevated at midnight 1
- Shift workers and patients with disrupted circadian rhythms should not undergo standard morning cortisol testing, as their cortisol peaks occur at different times and yield unreliable results 1
Clinical Interpretation Thresholds
Ruling Out Adrenal Insufficiency
- Morning cortisol >386 nmol/L (>14 μg/dL) effectively rules out adrenal insufficiency 2
- Values >300 nmol/L (>10.9 μg/dL) exclude adrenal insufficiency in most clinical contexts 3
- Morning cortisol >236 nmol/L predicts adequate adrenal function with 84% sensitivity and 71% specificity 4
Suggesting Adrenal Insufficiency
- Morning cortisol <110 nmol/L (<4 μg/dL) suggests adrenal insufficiency and warrants further testing 3
- In critically ill patients, random cortisol <276 nmol/L (<10 μg/dL) suggests relative adrenal insufficiency 2
- Values between 110-300 nmol/L require dynamic testing (ACTH stimulation test) for definitive diagnosis 3
Factors That Falsely Elevate Total Cortisol
- Oral contraceptives and estrogen-containing medications increase cortisol-binding globulin (CBG), dramatically raising total cortisol while free cortisol remains normal 2
- Pregnancy increases CBG levels, leading to elevated total cortisol measurements that do not reflect true hypercortisolism 2
- Chronic active hepatitis can increase CBG production, falsely elevating total cortisol 2
- Physical stressors, including strenuous exercise within 24-48 hours before sampling, can elevate cortisol levels 2
- Acute psychological stress and cognitive assessments immediately before blood draw can transiently elevate cortisol 2
Critical Pitfalls to Avoid
- Never interpret a single cortisol value without documenting the exact time of collection 1
- Always inquire about oral contraceptives, estrogen therapy, and pregnancy before pursuing extensive workup for hypercortisolism 2
- Document all medications affecting CBG or cortisol metabolism, including topical hydrocortisone preparations 1, 2
- Patients should avoid strenuous exercise for 24-48 hours before testing 2
- Recent physical or mental stress significantly elevates cortisol, so avoid cognitive assessments immediately before blood draw 1