How to diagnose adrenal insufficiency?

Diagnosis of Adrenal Insufficiency

The diagnosis of adrenal insufficiency requires paired measurement of morning serum cortisol and plasma ACTH, with ACTH stimulation testing in equivocal cases. 1, 2

Initial Diagnostic Approach

• Consider adrenal insufficiency in patients with unexplained collapse, hypotension, vomiting, diarrhea, hyperpigmentation, hyponatremia, hyperkalemia, acidosis, or hypoglycemia 2, 1
• Initial laboratory evaluation should include:
  • Morning (8 AM) serum cortisol and plasma ACTH 2
  • Basic metabolic panel to assess electrolytes (sodium, potassium, glucose) 2, 1
• Treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 2, 1

Diagnostic Criteria

• In acute illness, cortisol <250 nmol/L (9 μg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency 2
• Cortisol <400 nmol/L (14.5 μg/dL) with elevated ACTH in acute illness raises strong suspicion of primary adrenal insufficiency 2
• Low cortisol with low or normal ACTH suggests secondary adrenal insufficiency 2, 3

Confirmatory Testing

• ACTH stimulation test (Synacthen/cosyntropin test) is the standard confirmatory test 2, 4:
  • Administer 0.25 mg cosyntropin intravenously or intramuscularly 4
  • Measure cortisol at baseline, 30 minutes, and 60 minutes after administration 4
  • Peak cortisol <500 nmol/L (18 μg/dL) confirms adrenal insufficiency 2, 4
• For pediatric patients, dosing is age-dependent:
  • Birth to <2 years: 0.125 mg 4
  • 2-17 years: 0.25 mg 4

Determining Etiology

• For primary adrenal insufficiency:
  • Measure 21-hydroxylase (anti-adrenal) autoantibodies 2, 1
  • If antibodies are negative, obtain adrenal CT imaging to evaluate for hemorrhage, tumor, or infection 2
  • In male patients, measure very long-chain fatty acids to check for adrenoleukodystrophy 2, 1
• For secondary adrenal insufficiency:
  • MRI of the brain with pituitary/sellar cuts in patients with multiple endocrine abnormalities or new severe headaches 2
  • Evaluate other pituitary hormones (TSH, FT4, LH, FSH, testosterone/estradiol) 2, 3

Special Considerations

• Certain medications can affect test results:
  • Glucocorticoids and spironolactone may falsely elevate cortisol levels 4
  • Estrogen-containing drugs increase cortisol binding globulin levels 4
  • Stop these medications before testing when possible 4
• In patients with suspected secondary adrenal insufficiency where the ACTH stimulation test may be falsely normal, consider:
  • Insulin tolerance test (gold standard for secondary adrenal insufficiency) 5
  • Metyrapone test (30 mg/kg at midnight) 6, 7

Common Pitfalls to Avoid

• Delaying treatment in suspected acute adrenal crisis while waiting for test results 2, 1
• Failing to recognize adrenal insufficiency due to non-specific symptoms 3, 8
• Not considering adrenal insufficiency in patients who have recently tapered or discontinued glucocorticoids 3, 7
• Misinterpreting results in patients taking medications that affect cortisol or cortisol binding globulin levels 4

Management of Acute Adrenal Crisis During Evaluation

• Administer IV or IM hydrocortisone 100 mg immediately, followed by 100 mg every 6-8 hours until recovered 2, 1
• Provide isotonic (0.9%) sodium chloride solution at an initial rate of 1 L/hour until hemodynamic improvement 2, 1
• Identify and treat the underlying precipitant of adrenal crisis (e.g., infection) 2, 1

By following this diagnostic algorithm, clinicians can effectively diagnose adrenal insufficiency and initiate appropriate treatment to prevent potentially life-threatening adrenal crisis.