What are the best laboratory tests to assess for adrenal insufficiency?

Best Laboratory Tests for Assessing Adrenal Insufficiency

The most effective diagnostic approach for adrenal insufficiency is to measure morning ACTH and cortisol levels, followed by an ACTH stimulation test (cosyntropin/Synacthen test) for indeterminate results. 1

Initial Diagnostic Workup

• Morning serum cortisol and plasma ACTH measurements should be the first-line laboratory tests for suspected adrenal insufficiency 1
• Basic metabolic panel (sodium, potassium, CO2, glucose) should be obtained to assess for electrolyte abnormalities commonly seen in adrenal insufficiency 1
• Hyponatremia and hyperkalemia are often present in primary adrenal insufficiency due to aldosterone deficiency 1, 2

Interpreting Initial Results

• Basal cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1, 2
• Basal cortisol <400 nmol/L with elevated ACTH in acute illness raises strong suspicion of adrenal insufficiency 1, 2
• Primary adrenal insufficiency is characterized by low cortisol with high ACTH levels 1, 2
• Secondary adrenal insufficiency is characterized by low cortisol with low or inappropriately normal ACTH levels 2

ACTH Stimulation Test (Cosyntropin/Synacthen Test)

• The ACTH stimulation test is the gold standard for confirming adrenal insufficiency when initial results are indeterminate 1, 3
• Administer 0.25 mg cosyntropin (tetracosactide) intravenously or intramuscularly 3
• Obtain baseline cortisol measurement before administration, then measure cortisol levels at 30 and 60 minutes after administration 3
• A peak cortisol <500 nmol/L (18 μg/dL) is diagnostic of adrenal insufficiency 1, 3

Important Considerations and Pitfalls

• Treatment of suspected acute adrenal insufficiency should never be delayed for diagnostic procedures 1, 2
• Exogenous steroid use (oral prednisolone, dexamethasone, inhaled fluticasone) may confound interpretation of cortisol levels 1, 3
• Stop glucocorticoids and spironolactone on the day of cosyntropin testing; long-acting glucocorticoids may need to be stopped for a longer period 3
• Estrogen-containing drugs should be stopped 4-6 weeks before testing as they increase cortisol binding globulin levels 3
• Morning cortisol values >300 nmol/L generally exclude adrenal insufficiency, while values <110 nmol/L strongly suggest it 4, 5

Additional Testing for Specific Situations

• For suspected primary adrenal insufficiency with positive biochemical findings, measure 21-hydroxylase (anti-adrenal) autoantibodies to identify autoimmune etiology 1, 2
• If autoantibodies are negative, adrenal CT imaging is recommended to evaluate for other causes 1
• In male patients with primary adrenal insufficiency, very long-chain fatty acids should be measured to check for adrenoleukodystrophy 1
• For suspected secondary adrenal insufficiency, additional pituitary hormone testing may be necessary 2

Special Considerations in Hyponatremia

• Adrenal insufficiency must be excluded before diagnosing SIADH, as both conditions can present with similar laboratory findings including hyponatremia 2
• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases and can be indistinguishable from SIADH if adrenal function is not specifically assessed 2