What are normal cortisol levels?

Normal Cortisol Levels

Normal morning cortisol levels are typically >14 μg/dL (>386 nmol/L), which effectively rules out adrenal insufficiency, while values <50 nmol/L (<1.8 μg/dL) at midnight are considered normal in the circadian rhythm. 1

Morning Cortisol Reference Ranges

• Morning cortisol levels >14 μg/dL (>386 nmol/L) effectively rule out adrenal insufficiency 1, 2
• A morning cortisol level of 16.68 μg/dL is within the normal range and reflects appropriate physiological cortisol production 1
• Morning cortisol values in healthy individuals typically range from 5-23 μg/dL (138-635 nmol/L), with most values clustering between 10-20 μg/dL (276-552 nmol/L) 1

Midnight/Late Night Cortisol Reference Ranges

• Midnight serum cortisol should be <50 nmol/L (<1.8 μg/dL) in sleeping individuals 3
• Late-night salivary cortisol should be below assay-specific cutoffs, typically <0.1 μg/dL in most laboratories 4
• The 2.5th-97.5th percentile range for late-night salivary cortisol in normal subjects is 0.054-0.1827 μg/dL 4

Urinary Free Cortisol (UFC) Reference Ranges

• Normal 24-hour urinary free cortisol excretion is typically <193 nmol/24h (<70 μg/m²/24h) 3
• UFC values are assay-dependent and should be interpreted according to laboratory-specific reference ranges 3

Cortisol After Dexamethasone Suppression

• After overnight dexamethasone suppression test (1 mg at midnight), normal cortisol should be <2 μg/dL (<55 nmol/L) 5
• After low-dose dexamethasone suppression test (0.5 mg every 6 hours for 48 hours), normal cortisol should be <50 nmol/L (<1.8 μg/dL) 3

Factors Affecting Cortisol Levels

• Stress, illness, or disrupted sleep patterns can temporarily elevate cortisol levels 1
• Medications such as glucocorticoids, anticonvulsants, or CYP3A4 inducers can affect cortisol measurements 1
• Exogenous steroid use (oral prednisolone, dexamethasone, inhaled fluticasone) may confound interpretation of serum cortisol levels 3

Clinical Significance of Cortisol Measurements

• Cortisol levels follow a diurnal pattern with peak levels in early morning and nadir at midnight 6, 7
• Loss of normal diurnal rhythm (elevated midnight cortisol) is a sensitive indicator of Cushing's syndrome 7
• In the presence of confirmed hypercortisolism, ACTH levels help differentiate between ACTH-dependent and ACTH-independent causes 3
• In children and adolescents, the combination of unexplained weight gain with either growth rate deceleration or height centile decrement has high sensitivity and specificity for Cushing's syndrome 3

When Additional Testing Is Warranted

• If clinical symptoms of cortisol excess are present despite normal morning cortisol, additional testing (late-night salivary cortisol, 24h UFC, dexamethasone suppression) may be necessary 1, 6
• If symptoms of adrenal insufficiency exist despite normal morning cortisol, ACTH stimulation testing should be considered 1, 2
• For equivocal cases of adrenal insufficiency, a synacthen (tetracosactide) stimulation test with peak serum cortisol <500 nmol/L is diagnostic of primary adrenal insufficiency 3

Remember that cortisol reference ranges may vary slightly between laboratories due to different assay methods, so results should always be interpreted in the context of the specific laboratory's reference ranges.