What is the AM (Ante Meridiem) cortisol test used for?

AM Cortisol Test: Clinical Applications

The AM (morning) cortisol test is primarily used to screen for adrenal insufficiency and autonomous cortisol secretion from adrenal masses, with specific diagnostic thresholds guiding the need for further dynamic testing. 1

Primary Diagnostic Applications

Screening for Adrenal Insufficiency

Morning cortisol is the first-line screening test when adrenal insufficiency is suspected. The test should be performed between 8 AM and 12 PM to capture peak physiologic cortisol levels. 1

Diagnostic thresholds for morning cortisol:

• ≥300 nmol/L (≥10.9 μg/dL): Excludes adrenal insufficiency - no further testing needed in most cases 2, 3
• <110 nmol/L (<4.0 μg/dL): Highly suggestive of adrenal insufficiency - proceed directly to treatment or confirmatory ACTH stimulation test 2
• 110-300 nmol/L (4.0-10.9 μg/dL): Indeterminate - requires ACTH stimulation test for definitive diagnosis 2, 3

A validated threshold of <275 nmol/L identifies subnormal cortisol response with 96.2% sensitivity in outpatient morning samples. 3

Evaluating Adrenal Incidentalomas

All patients with adrenal incidentalomas should be screened for autonomous cortisol secretion, though the 1 mg dexamethasone suppression test (DST) is preferred over AM cortisol alone for this indication. 1 The AM cortisol measured after overnight dexamethasone suppression helps identify:

• <50 nmol/L (<1.8 μg/dL): Excludes autonomous cortisol secretion 1
• 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous cortisol secretion 1
• >138 nmol/L (>5.0 μg/dL): Evidence of autonomous cortisol secretion 1

Distinguishing Primary from Secondary Adrenal Insufficiency

AM cortisol must be paired with simultaneous ACTH measurement to differentiate primary (adrenal) from secondary (pituitary/hypothalamic) causes. 1

• Low cortisol + High ACTH: Primary adrenal insufficiency (Addison's disease) 1
• Low cortisol + Low/normal ACTH: Secondary adrenal insufficiency (hypophysitis, pituitary dysfunction) 1

Critical Clinical Caveats

When AM Cortisol Cannot Be Interpreted

AM cortisol is NOT diagnostic in patients currently taking corticosteroids because therapeutic steroids interfere with cortisol assays to varying degrees. 1 Hydrocortisone must be held for 24 hours and other synthetic steroids for longer periods before endogenous cortisol function can be accurately assessed. 1

In critically ill patients, AM cortisol interpretation is unreliable due to altered cortisol-binding globulin levels and stress-induced HPA axis changes. 1 The ACTH stimulation test is preferred in this population. 1

Timing and Technical Considerations

The test loses sensitivity when performed outside morning hours. For afternoon samples (12 PM-6 PM), a lower threshold of <250 nmol/L is required to maintain 96.1% sensitivity for detecting adrenal insufficiency. 3

Assay variability matters. Different immunoassays may cross-react with synthetic corticosteroids or be affected by cortisol-binding globulin alterations. 1, 4 LC-MS/MS methods offer superior specificity but are not universally available. 4

False Results

Conditions causing low cortisol-binding globulin (critical illness, cirrhosis, nephrotic syndrome) may produce falsely low total cortisol despite adequate free cortisol levels. 1 In these situations, free cortisol or salivary cortisol may be considered, though guidelines suggest against routine use of these alternatives. 1

Drugs affecting cortisol metabolism (thyroid hormones, certain psychotropic agents) can create discrepancies between total and free cortisol measurements. 5

Clinical Algorithm for AM Cortisol Use

1. Suspect adrenal insufficiency based on symptoms (fatigue, weight loss, hypotension, hyponatremia, hyperkalemia) 1
2. Obtain AM cortisol (8 AM-12 PM) with simultaneous ACTH 1
3. Interpret results:
   • If ≥300 nmol/L: Adrenal insufficiency excluded 2, 3
   • If <110 nmol/L: Adrenal insufficiency likely, initiate treatment 2
   • If 110-300 nmol/L: Perform ACTH stimulation test 2, 3
4. Use ACTH level to localize defect (high = primary, low = secondary) 1
5. In patients on corticosteroids, defer testing until steroids can be appropriately withdrawn 1

For immune checkpoint inhibitor-related endocrinopathies, AM cortisol with ACTH is essential for diagnosing both primary adrenal insufficiency and hypophysitis, which are common immune-related adverse events requiring prompt recognition and treatment. 1