What blood tests are used to diagnose adrenal insufficiency?

Blood Tests for Diagnosing Adrenal Insufficiency

The diagnostic test for adrenal insufficiency should be paired measurement of serum cortisol and plasma ACTH, with the cosyntropin stimulation test used in equivocal cases. 1

Initial Diagnostic Tests

• Morning (8 AM) serum cortisol and plasma ACTH measurements are the first-line tests for diagnosing adrenal insufficiency 1, 2
• A morning serum cortisol >13 mcg/dL (>300 nmol/L) reliably rules out adrenal insufficiency 3, 4
• Morning cortisol <5 μg/dL with elevated ACTH levels is diagnostic of primary adrenal insufficiency 2
• Serum cortisol <250 nmol/L with increased ACTH in acute illness is diagnostic of primary adrenal insufficiency 1
• Serum cortisol <400 nmol/L with increased ACTH in acute illness raises strong suspicion of adrenal insufficiency 1

Cosyntropin (Synacthen) Stimulation Test

• The cosyntropin stimulation test is indicated when morning cortisol results are equivocal 1, 5
• The test involves:
  • Administration of 0.25 mg cosyntropin (tetracosactide) intravenously or intramuscularly 6
  • Measurement of serum cortisol at baseline, 30 minutes, and 60 minutes after administration 5, 6
  • A peak cortisol value <500 nmol/L (18 μg/dL) is diagnostic of adrenal insufficiency 1, 6

Distinguishing Primary from Secondary Adrenal Insufficiency

• Primary adrenal insufficiency: Low cortisol with high ACTH levels 5, 2
• Secondary adrenal insufficiency: Low cortisol with low or inappropriately normal ACTH levels 5, 2
• In secondary adrenal insufficiency, the cosyntropin test may give false normal results; insulin hypoglycemia test or metyrapone test may be needed 7

Additional Laboratory Findings

• Basic metabolic panel to check for hyponatremia and hyperkalemia, which are common in primary adrenal insufficiency 1
• Plasma renin activity (PRA) is typically increased in primary adrenal insufficiency 1
• Serum aldosterone and dehydroepiandrosterone sulfate (DHEAS) levels are typically low in primary adrenal insufficiency 1, 2
• TSH may be mildly elevated (4-10 IU/L) in primary adrenal insufficiency due to lack of cortisol's inhibitory effect 1

Important Considerations

• Treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 1, 5
• Exogenous steroid use (oral prednisolone, dexamethasone) and inhaled steroids (fluticasone) may confound interpretation of cortisol levels 1, 6
• Estrogen-containing drugs should be stopped 4-6 weeks before testing as they increase cortisol binding globulin levels 5, 6
• Glucocorticoids and spironolactone should be stopped on the day of testing 5, 6
• Long-acting glucocorticoids may need to be stopped for a longer period before testing 6

Pitfalls to Avoid

• Do not rely solely on electrolyte abnormalities for diagnosis, as hyponatremia may be only marginally reduced and hyperkalemia is present in only about 50% of cases 5
• Do not confuse adrenal insufficiency with SIADH, as both can present with similar laboratory findings of hyponatremia 5
• Do not delay treatment if adrenal crisis is suspected; blood samples for cortisol and ACTH should be obtained before treatment if possible, but treatment should not be delayed 5, 8