What would an adrenocorticotropic hormone (AM) cortisol test indicate?

What an AM Cortisol Test Indicates

A morning (AM) cortisol test is a valuable screening tool that can help diagnose adrenal insufficiency, with levels below 140 nmol/L (5 μg/dL) strongly suggesting adrenal insufficiency and levels above 300-400 nmol/L generally excluding it. 1, 2

Diagnostic Value of AM Cortisol

Normal vs. Abnormal Values

• Morning cortisol levels typically peak between 7:30-8:00 AM due to the natural circadian rhythm
• Interpretation thresholds (though these may vary by laboratory and assay method):
  • <140 nmol/L: Highly suggestive of adrenal insufficiency 3
  • 140-300 nmol/L: Indeterminate range requiring further testing

  • 300 nmol/L: Generally excludes adrenal insufficiency 1

Correlation with ACTH Stimulation Test

• Morning cortisol levels correlate strongly with peak cortisol response in ACTH stimulation tests (r = 0.77, p < 0.0001) 1
• A morning cortisol ≥300 nmol/L reliably excludes adrenal insufficiency in non-acute settings 1
• A morning cortisol <110 nmol/L strongly suggests adrenal insufficiency 1

Clinical Applications

Primary vs. Secondary Adrenal Insufficiency

• In primary adrenal insufficiency:
  • Low cortisol with elevated ACTH levels
  • Often accompanied by hyponatremia and hyperkalemia 4
• In secondary adrenal insufficiency:
  • Low cortisol with low or inappropriately normal ACTH levels 4

Cushing Syndrome Evaluation

• Elevated morning cortisol levels may indicate Cushing syndrome
• 24-hour urine cortisol collection is recommended if cortisol levels are elevated 5
• Elevated ACTH with high cortisol suggests an ACTH-producing tumor (pituitary or ectopic) 5

Limitations and Pitfalls

Assay-Specific Considerations

• Different cortisol assays yield different results, requiring assay-specific reference ranges
• Newer, more specific assays (like Roche Cortisol II) produce values approximately 30% lower than older assays 6
• With newer assays, diagnostic thresholds should be adjusted (e.g., 350 nmol/L instead of traditional 500 nmol/L for ACTH stimulation tests) 6

Timing Considerations

• Morning samples (8 AM-12 PM) are most reliable
• For afternoon samples (12 PM-6 PM), lower thresholds apply (e.g., <250 nmol/L to identify adrenal insufficiency) 2
• Inpatient testing is reliable only with morning samples 2

Confounding Factors

• Stress, acute illness, medications, and exogenous steroid use can affect cortisol levels
• In sepsis, cortisol may be within normal range but inappropriately low for the disease state 5
• Medications affecting pituitary or adrenocortical function should be stopped before testing (at least 5 half-lives) 7

Follow-up Testing

When Further Testing is Needed

• Indeterminate morning cortisol (108-381 nmol/L) requires stimulation testing 3
• The high-dose (250-μg) ACTH stimulation test is preferred over the low-dose (1-μg) test due to comparable accuracy and easier administration 5
• Paired measurement of serum cortisol and plasma ACTH is the most definitive diagnostic approach for adrenal insufficiency 5, 4

Interpretation of Stimulation Tests

• Normal response: Peak cortisol >500-550 nmol/L (with traditional assays)
• With newer specific assays: Peak cortisol >350 nmol/L 6
• Adrenal insufficiency: Peak cortisol below these thresholds

AM cortisol testing provides a valuable first-line assessment of adrenal function, potentially reducing the need for more complex dynamic testing when values are clearly normal or abnormal.