What labs are drawn to diagnose adrenal insufficiency?

Laboratory Tests for Diagnosing Adrenal Insufficiency

The essential laboratory tests for diagnosing adrenal insufficiency include morning serum cortisol, ACTH levels, and ACTH stimulation testing, with additional electrolyte measurements to differentiate between primary and secondary forms. 1, 2

Initial Diagnostic Tests

• Morning serum cortisol (approximately 8 AM):

  • <5 μg/dL: Strongly suggestive of adrenal insufficiency
  • 5-10 μg/dL: Intermediate (requires confirmatory testing)

  • 18-20 μg/dL: Typically rules out adrenal insufficiency 1, 2

• Plasma ACTH level (drawn simultaneously with morning cortisol):

  • High ACTH + Low cortisol = Primary adrenal insufficiency
  • Low/normal ACTH + Low cortisol = Secondary adrenal insufficiency 1, 2

• Serum electrolytes:

  • Primary adrenal insufficiency: Hyponatremia, hyperkalemia
  • Secondary adrenal insufficiency: Usually normal electrolytes 1

Confirmatory Testing

• ACTH stimulation test (Cosyntropin/Synacthen test):

  • Administration of 250 μg synthetic ACTH
  • Measure cortisol before and 60 minutes after administration
  • Normal response: Peak cortisol >18-20 μg/dL
  • This is the standard confirmatory test for adrenal insufficiency 1, 2, 3

• Dehydroepiandrosterone sulfate (DHEAS):

  • Low levels in both primary and secondary adrenal insufficiency
  • Can help support diagnosis 2

Additional Testing Based on Type of Adrenal Insufficiency

For Primary Adrenal Insufficiency

• Adrenal autoantibodies (to diagnose autoimmune adrenalitis)
• Aldosterone levels (typically low in primary adrenal insufficiency)
• Plasma renin activity (typically elevated in primary adrenal insufficiency) 1, 4

For Secondary Adrenal Insufficiency

• Insulin tolerance test (gold standard for secondary adrenal insufficiency)
  • Measures entire hypothalamic-pituitary-adrenal axis function
  • Used when ACTH stimulation test results are inconclusive
• Metyrapone test (alternative when insulin tolerance test is contraindicated) 5, 6

Clinical Pearls and Pitfalls

• Morning cortisol alone is insufficient for diagnosis; confirmatory testing is required in most cases 1, 2
• ACTH stimulation test may give false-negative results in recent-onset or mild secondary adrenal insufficiency 6
• In emergency situations with strong clinical suspicion, treatment should be initiated immediately without waiting for test results 5, 3
• Glucocorticoid-induced adrenal insufficiency is the most common form and should be suspected in patients recently tapered off steroid therapy 2
• The pattern of laboratory abnormalities helps distinguish between types:

Parameter	Primary Adrenal Insufficiency	Secondary Adrenal Insufficiency
ACTH	High	Low/Normal
Cortisol	Low	Low
Electrolytes	↓Na, ↑K	Usually normal
Hyperpigmentation	Present	Absent
[1]

• Patients on exogenous steroids may have suppressed cortisol and ACTH levels, making interpretation challenging 2, 5