What is a normal cortisol level?

Normal Cortisol Levels

Normal morning cortisol levels range from 5-23 μg/dL (138-635 nmol/L), with most values clustering between 10-20 μg/dL (276-552 nmol/L). 1

Reference Ranges by Time of Day

• Morning cortisol levels >14 μg/dL (>386 nmol/L) effectively rule out adrenal insufficiency 1, 2
• Midnight/late night serum cortisol should be <1.8 μg/dL (<50 nmol/L) in sleeping individuals 1
• Normal 24-hour urinary free cortisol excretion is typically <70 μg/m²/24h (<193 nmol/24h) 1
• Late-night salivary cortisol should be <0.21 μg/dL for reliable screening of Cushing's syndrome 3

Diurnal Variation

• Cortisol follows a distinct diurnal pattern with highest levels in the morning and lowest levels at night 4
• Morning cortisol (8:00 AM) averages 193.7 ± 35.0 ng/ml while evening cortisol (10:00 PM) averages 43.2 ± 23.3 ng/ml in healthy individuals 4
• The absence of this diurnal rhythm is a key diagnostic feature in Cushing's syndrome 5

Diagnostic Testing Reference Values

• For suspected adrenal insufficiency:

  • Morning cortisol >13 μg/dL reliably rules out adrenal insufficiency 2
  • In equivocal cases, a synacthen (tetracosactide) stimulation test with peak serum cortisol <500 nmol/L is diagnostic of primary adrenal insufficiency 6, 1
  • During acute illness, serum cortisol <250 nmol/L with increased ACTH is diagnostic of primary adrenal insufficiency 6

• For suspected Cushing's syndrome:

  • After overnight dexamethasone suppression test (1 mg), normal cortisol should be <2 μg/dL 7
  • After low-dose dexamethasone suppression test (0.5 mg every 6 hours for 48 hours), normal cortisol should be <1.8 μg/dL (<50 nmol/L) 1

Factors Affecting Cortisol Levels

• Exogenous steroid use (oral prednisolone, dexamethasone, inhaled fluticasone) may confound interpretation of serum cortisol levels 6, 1
• Estrogen therapy significantly increases total cortisol (due to increased corticosteroid-binding globulin) but unbound cortisol remains normal 4
• Conditions that can alter cortisol binding proteins include hyperthyroidism, cirrhosis, and renal disease 4

Clinical Pearls

• When interpreting cortisol levels, the time of collection is crucial due to the significant diurnal variation 4
• Free (unbound) cortisol is the biologically active form, but most laboratories measure total cortisol 4
• Late-night salivary cortisol measurement is a simple and reliable screening test for spontaneous Cushing's syndrome with high sensitivity (93%) and specificity (100%) 5, 3
• The combination of late-night salivary cortisol and 24-hour urinary free cortisol provides 100% sensitivity for detecting Cushing's syndrome 5