What is the workup for suspected adrenal insufficiency based on random cortisol level?

Workup for Adrenal Insufficiency Based on Random Cortisol Level

For suspected adrenal insufficiency, a random plasma cortisol level <10 μg/dL is suggestive of adrenal insufficiency, but confirmation with ACTH stimulation testing is recommended for definitive diagnosis. 1

Initial Assessment with Random Cortisol

Random cortisol levels can provide valuable initial information:

• <5 μg/dL: Highly suggestive of adrenal insufficiency, particularly primary adrenal insufficiency 2
• 5-10 μg/dL: Intermediate zone requiring further testing 2
• >10 μg/dL: Less likely to have adrenal insufficiency, but doesn't completely rule it out
• >18 μg/dL: Adrenal insufficiency unlikely in a stressed patient 3

Confirmatory Testing

ACTH Stimulation Testing

The standard confirmatory test is the ACTH (cosyntropin) stimulation test:

• Standard dose: 250 μg IV cosyntropin with cortisol measurement at baseline and 60 minutes 1, 2
• Low-dose option: 1 μg cosyntropin may be more sensitive for secondary adrenal insufficiency 3
• Normal response: Peak cortisol ≥18 μg/dL and/or increment ≥9 μg/dL from baseline 1, 2
• Intramuscular alternative: When IV access is difficult, 25 units of ACTH can be administered intramuscularly with cortisol measurement at 60 minutes 4

Additional Laboratory Tests

• Morning cortisol with ACTH level: Helps distinguish primary from secondary adrenal insufficiency 1, 2
  • Primary: Low cortisol + high ACTH
  • Secondary: Low cortisol + low/normal ACTH
• DHEAS levels: Typically low in adrenal insufficiency 2
• Electrolytes: Hyponatremia and hyperkalemia suggest primary adrenal insufficiency 1

Diagnostic Algorithm

1. Measure random cortisol level:

   • If <5 μg/dL: Highly suspicious for adrenal insufficiency
   • If 5-10 μg/dL: Proceed with ACTH stimulation test
   • If >10 μg/dL but clinical suspicion remains high: Proceed with ACTH stimulation test

2. Perform ACTH stimulation test:

   • Normal response: Peak cortisol ≥18 μg/dL and/or increment ≥9 μg/dL
   • Abnormal response: Peak cortisol <18 μg/dL and increment <9 μg/dL

3. Determine type of adrenal insufficiency:

   • Measure ACTH level
   • Check electrolytes (Na+, K+)
   • Consider additional testing based on suspected etiology

Important Considerations

• Assay variability: Newer monoclonal antibody cortisol assays may yield lower values than older polyclonal assays, potentially increasing false positive diagnoses if traditional cutoffs are used 5

• Timing matters: Morning cortisol samples (around 8 AM) are preferred for initial assessment 2

• Medication effects: Recent etomidate use for intubation can suppress the hypothalamic-pituitary-adrenal axis 3

• Clinical context: In patients with shock, an inappropriately low random cortisol (<18 μg/dL) may indicate relative adrenal insufficiency requiring steroid therapy 3

• Low sensitivity of basal cortisol: A study showed basal cortisol has only 60% sensitivity to detect adrenal insufficiency compared to ACTH stimulation testing 4

Urgent Management

If adrenal crisis is suspected during workup (hypotension, shock, altered mental status):

• Administer hydrocortisone 100 mg IV immediately 1
• Provide fluid resuscitation with isotonic saline 1
• Do not delay treatment to complete diagnostic testing