What is the recommended testing protocol for suspected adrenal insufficiency?

Testing Protocol for Suspected Adrenal Insufficiency

The recommended diagnostic approach for suspected adrenal insufficiency should begin with morning serum cortisol and ACTH measurements, followed by ACTH stimulation testing when results are indeterminate. 1

Initial Diagnostic Evaluation

First-line Testing

• Morning cortisol and ACTH levels (drawn between 7-9 AM)
  • Morning cortisol >13 μg/dL (>375 nmol/L): Adrenal insufficiency unlikely 2
  • Morning cortisol <5 μg/dL with elevated ACTH: Diagnostic of primary adrenal insufficiency 3
  • Morning cortisol <5 μg/dL with low/normal ACTH: Suggests secondary adrenal insufficiency 3
  • Intermediate cortisol (5-13 μg/dL): Requires further testing 3, 4

Additional Basic Laboratory Tests

• Basic metabolic panel (sodium, potassium, CO2, glucose) 1
• Complete blood count 1

ACTH Stimulation Testing (Confirmatory Test)

Standard Protocol (250 μg Cosyntropin Test)

1. Collect baseline blood sample for cortisol measurement
2. Administer 250 μg cosyntropin (synthetic ACTH) intramuscularly or intravenously 5
3. Collect second blood sample exactly 30 minutes after administration 5
4. Normal response criteria:
   • Baseline cortisol should exceed 5 μg/dL 5
   • 30-minute cortisol should show increment of at least 7 μg/dL above baseline 5
   • 30-minute cortisol >18-20 μg/dL in non-stressed patients 6
   • 30-minute cortisol >25 μg/dL in critically ill patients 6

Low-dose Protocol (1 μg Cosyntropin Test)

• More sensitive for detecting secondary adrenal insufficiency 6
• Requires dilution of standard cosyntropin dose 4
• Same timing protocol as standard test
• Normal response: 30-minute cortisol >18-20 μg/dL 6

Interpretation of Results

Primary Adrenal Insufficiency

• Low cortisol with high ACTH
• Positive 21-hydroxylase (anti-adrenal) autoantibodies confirm autoimmune etiology 1
• If antibodies negative, consider adrenal CT imaging 1
• In males with negative antibodies, test very long-chain fatty acids to check for adrenoleukodystrophy 1

Secondary Adrenal Insufficiency

• Low cortisol with low or inappropriately normal ACTH
• Consider MRI of pituitary/brain with contrast in patients with multiple endocrine abnormalities or new severe headaches 1

Important Clinical Considerations

Special Testing Situations

• Patients on exogenous steroids: Should omit pre-test doses on testing day 5
• Women taking estrogen-containing medications: May exhibit abnormally high basal cortisol levels 5
• Patients on spironolactone: May have elevated baseline cortisol 5

Critical Pitfalls to Avoid

1. Never delay treatment when adrenal crisis is suspected - diagnosis can be established after treatment is initiated 1
2. Time of day matters - cortisol levels should be drawn in the morning when levels are highest 7
3. Assay variability - different cortisol assays may yield different results 7
4. Stress effects - acute illness can affect cortisol levels and test interpretation 7
5. Medication interference - certain medications can affect test results 5

Emergency Situations

• If adrenal crisis is suspected, immediate treatment with IV hydrocortisone 100 mg should be given before diagnostic testing 1
• Dexamethasone 4 mg can be used instead if diagnosis is unclear and stimulation testing will be needed later 1

By following this structured approach to testing for adrenal insufficiency, clinicians can achieve accurate diagnosis while ensuring patient safety, particularly in emergency situations where treatment should never be delayed for diagnostic procedures.