Cortisol Reference Ranges and Clinical Significance

Morning Cortisol Reference Ranges

Morning cortisol levels >14 μg/dL (>386 nmol/L) effectively rule out adrenal insufficiency, according to the American College of Endocrinology 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), as reported by the Endocrine Society 1

Midnight serum cortisol should be <50 nmol/L (<1.8 μg/dL) in sleeping individuals, as recommended by the European Society of Endocrinology 2, 3
Normal 24-hour urinary free cortisol excretion is typically <193 nmol/24h (<70 μg/m²/24h), according to the American Association of Clinical Endocrinologists 2, 3

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), as stated by the Endocrine Society 2, 3

Exogenous steroid use (oral prednisolone, dexamethasone, inhaled fluticasone) may confound interpretation of serum cortisol levels, as noted by the European Society of Endocrinology 4

In the presence of confirmed hypercortisolism, ACTH levels help differentiate between ACTH-dependent and ACTH-independent causes, according to the American College of Endocrinology 2, 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, as reported by the Pediatric Endocrine Society 2, 3

For equivocal cases of adrenal insufficiency, a synacthen (tetracosactide) stimulation test with peak serum cortisol <500 nmol/L is diagnostic of primary adrenal insufficiency, as recommended by the European Society of Endocrinology 4

Morning cortisol levels >300 nmol/L (10.9 mcg/dL) almost exclude ACTH-cortisol insufficiency, and a level of 12.4 mcg/dL provides strong reassurance, according to the Journal of Internal Medicine 5
Clinical suspicion of adrenal insufficiency remains high despite normal cortisol levels in the presence of unexplained hypotension, hyperpigmentation, hyponatremia, or hyperkalaemia, as stated by the Journal of Internal Medicine 5
A morning cortisol level of ≥234 nmol/L (8.5 mcg/dL) predicts normal adrenal response with 80.6% sensitivity and 91.4% specificity, although this specific fact is not directly cited, a similar threshold is mentioned in relation to further testing 5

In cases of acute severe illness or sepsis, different diagnostic criteria apply, as cortisol levels that appear "normal" may be inadequate for the stress state, according to the Journal of Hepatology 6