What is a normal cortisol level?

Normal Cortisol Levels

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

Morning Cortisol Reference Values

• Morning cortisol >14 μg/dL (>386 nmol/L) effectively rules out adrenal insufficiency, providing strong clinical reassurance 1, 2
• Values >12.4 μg/dL (>300 nmol/L) almost exclude ACTH-cortisol insufficiency in unstressed patients 2
• The typical range of 5-23 μg/dL represents the broad physiologic spectrum, but most healthy individuals cluster in the 10-20 μg/dL range 1, 2

Time-Dependent Cortisol Values

Late Night/Midnight Cortisol

• Normal midnight serum cortisol should be <1.8 μg/dL (<50 nmol/L) in sleeping individuals 1, 2
• Late-night salivary cortisol should be <3.6 nmol/L, with this threshold providing >90% sensitivity for detecting Cushing's syndrome 1
• Age-dependent cutoffs for late-night salivary cortisol (10:00 PM) range from 1.0-1.7 μg/L depending on age group 3

24-Hour Urinary Cortisol

• Normal urinary free cortisol excretion is <193 nmol/24h (<70 μg/m²/24h) 1, 2
• This measurement has significant intra-patient variability (up to 50%), requiring 2-3 collections for reliable interpretation 1

Post-Suppression Cortisol Values

• After overnight 1-mg dexamethasone suppression test, normal cortisol is <1.8 μg/dL (<50 nmol/L) 1, 2
• After low-dose dexamethasone suppression (0.5 mg every 6 hours for 48 hours), normal cortisol should similarly be <50 nmol/L 1, 2
• The traditional cutoff of <5 μg/dL is outdated; only 5 of 190 normal subjects had values >2 μg/dL after dexamethasone 4

Critical Factors That Alter Cortisol Interpretation

Medications and Hormonal States

• Oral contraceptives and estrogen-containing medications falsely elevate total cortisol by increasing cortisol-binding globulin (CBG), while free cortisol remains normal 1
• Pregnancy and chronic active hepatitis similarly increase CBG, raising total cortisol without true hypercortisolism 1
• Exogenous steroids (prednisolone, dexamethasone, inhaled fluticasone) confound serum cortisol interpretation 1, 2
• CYP3A4 inducers accelerate dexamethasone metabolism, causing false-positive suppression tests 1

Physiologic and Behavioral Factors

• Physical stressors including strenuous exercise within 24-48 hours can elevate cortisol levels 1
• Acute psychological stress, mental stressors, and stress from neurocognitive assessments transiently increase cortisol 1
• Night-shift workers and those with disrupted sleep-wake cycles have unreliable standard morning measurements 1
• Blood contamination from dental work, teeth brushing, or oral trauma within 1-2 hours falsely elevates salivary cortisol 1

Pseudo-Cushing's States

• Psychiatric disorders, alcohol use disorder, polycystic ovary syndrome, and severe obesity can activate the HPA axis, causing mildly elevated cortisol that mimics hypercortisolism 1
• These conditions can cause false-positive screening tests despite absence of true Cushing's syndrome 1

Clinical Context for Interpretation

When to Suspect Adrenal Insufficiency

• Consider cortisol measurement in patients with unexplained collapse, hypotension, vomiting, or diarrhea 1
• Hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia increase suspicion for primary adrenal insufficiency 1
• Cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1
• Cortisol <400 nmol/L with elevated ACTH in acute illness generates strong suspicion requiring further evaluation 1

When to Suspect Cushing's Syndrome

• Loss of normal circadian rhythm is the hallmark finding—elevated late-night cortisol is more specific than elevated morning cortisol 1, 5
• Morning cortisol alone shows significant overlap between normal and Cushing's patients, limiting its diagnostic utility 5
• In children and adolescents, unexplained weight gain with growth deceleration has high sensitivity and specificity for Cushing's syndrome 2

Key Clinical Pitfall

The most important pitfall is interpreting elevated total cortisol as pathologic without considering CBG status—always inquire about oral contraceptives, estrogen therapy, and pregnancy before pursuing extensive workup for hypercortisolism. 1