Normal Morning and Afternoon Cortisol Ranges
The normal morning (0900h) cortisol range is 140–700 nmol/L (5–23 μg/dL), while the afternoon/midnight range is 80–350 nmol/L at midnight, with midnight levels in sleeping individuals ideally <50 nmol/L (<1.8 μg/dL). 1, 2
Morning Cortisol Reference Values
- Morning cortisol levels typically range from 140–700 nmol/L (5–23 μg/dL) at 0900 hours, with most healthy individuals clustering between 276–552 nmol/L (10–20 μg/dL) 1, 2, 3
- Morning cortisol >386 nmol/L (>14 μg/dL) effectively excludes adrenal insufficiency 2, 3
- The morning peak reflects the circadian rhythm of cortisol secretion, which is pulsatile and follows a predictable daily pattern 1
Afternoon and Midnight Cortisol Reference Values
- Midnight serum cortisol should be <50 nmol/L (<1.8 μg/dL) in sleeping individuals 2, 3
- The reference range at midnight is 80–350 nmol/L, representing the nadir of the circadian rhythm 1
- Cortisol production follows a circadian pattern with approximately 20 mg released daily under normal conditions 1
Important Clinical Considerations
Circadian Rhythm Variability
- Cortisol secretion is both pulsatile (ultradian) and circadian, with peak levels in the morning and lowest levels at midnight 1
- Individual chronotype (morning versus evening preference) can affect cortisol timing, with morning chronotypes showing cortisol peaks approximately 55–68 minutes earlier than evening chronotypes 4, 5
Factors That Confound Interpretation
- Exogenous steroid use (oral prednisolone, dexamethasone, inhaled fluticasone) interferes with serum cortisol interpretation 2, 3
- Sleep deprivation can elevate evening cortisol levels by 37–45% and delay the onset of the quiescent period by at least 1 hour 6
- Severe obesity and alcoholism may cause false-positive results in cortisol testing 3
Clinical Pitfalls to Avoid
- Do not rely solely on single time-point measurements within the "normal range" – cortisol can reach immunosuppressive levels at various points during its 24-hour rhythm even when spot checks appear normal 7
- Plasma ACTH and serum cortisol are not useful for routine glucocorticoid dose adjustment in patients on replacement therapy 1
- When malabsorption is suspected, obtain cortisol day curves with morning postdose peak and trough predose levels rather than single measurements 1