What is the cutoff for morning serum cortisol to rule out adrenal insufficiency?

Morning Serum Cortisol Cutoffs for Ruling Out Adrenal Insufficiency

A morning serum cortisol level >13 μg/dL (>360 nmol/L) reliably rules out adrenal insufficiency and eliminates the need for further dynamic testing in outpatient settings. 1, 2, 3

Diagnostic Thresholds for Serum Cortisol

Morning serum cortisol measurements provide a valuable initial screening tool for adrenal insufficiency, with the following interpretation guidelines:

• Definitely normal (rules out adrenal insufficiency):

  • Morning cortisol >13 μg/dL (>360 nmol/L) 1
  • Some studies suggest >375 nmol/L for 95% specificity 2
  • More recent data suggests >444.7 nmol/L has 96.9% sensitivity for predicting normal response to stimulation testing 4

• Definitely abnormal (confirms adrenal insufficiency):

  • Morning cortisol <5 μg/dL (<140 nmol/L) 5
  • Some studies suggest <126.4 nmol/L has 98.7% specificity for predicting abnormal response to stimulation testing 4

• Indeterminate (requires further testing):

  • Morning cortisol between 5-13 μg/dL (140-360 nmol/L) 5, 1

Testing Considerations

• Cortisol follows a circadian rhythm with reference ranges varying from 140-700 nmol/L at 0900 to 80-350 nmol/L at midnight 6
• Timing of collection is critical for interpretation; samples should ideally be collected between 8 AM and 12 PM 3
• For afternoon samples (12 PM-6 PM), a lower cutoff of <250 nmol/L should be used to maintain sensitivity in outpatient settings 3
• For hospitalized patients, morning samples are more reliable than afternoon samples 3

When Further Testing is Needed

For patients with indeterminate morning cortisol levels (5-13 μg/dL or 140-360 nmol/L), further evaluation with a cosyntropin stimulation test (CST) is recommended:

• Standard 250 μg cosyntropin stimulation test (IV or IM administration)
• Measure cortisol before and 30-60 minutes after administration
• Normal response: post-stimulation cortisol >550 nmol/L (>20 μg/dL) 2

Clinical Pearls and Pitfalls

• Important caveat: Normal cortisol levels should not rule out adrenal crisis in a patient with suggestive clinical presentation; treatment should be initiated based on clinical suspicion rather than waiting for laboratory confirmation 6
• Primary adrenal insufficiency typically presents with low morning cortisol (<5 μg/dL) and high ACTH levels 5
• Secondary and glucocorticoid-induced adrenal insufficiency typically have low or intermediate morning cortisol (5-10 μg/dL) and low or low-normal ACTH levels 5
• The 1 μg low-dose CST has better diagnostic discrimination for secondary adrenal insufficiency but requires an extra dilution step 1
• In patients with known pituitary disease, a morning cortisol >330 nmol/L has 95% specificity for predicting normal adrenal function 2

Interpretation in Clinical Context

Always interpret cortisol levels in the context of:

• Time of measurement (circadian variation)
• Clinical presentation (fatigue, nausea, vomiting, weight loss)
• Medication history (especially recent glucocorticoid use)
• Presence of comorbidities (especially pituitary disease)
• Stress level (acute illness can falsely elevate cortisol)