What is the protocol for the short synacthen (adrenocorticotropic hormone stimulation) test in diagnosing adrenal insufficiency?

Short Synacthen Test Protocol

The standard short Synacthen test requires administration of 0.25 mg (250 μg) cosyntropin (tetracosactide) intramuscularly or intravenously, with serum cortisol measured at baseline and at 30 and/or 60 minutes post-administration, where a peak cortisol value >550 nmol/L (>18-20 μg/dL) is considered normal. 1

Test Administration

• Administer 0.25 mg (250 μg) cosyntropin either intramuscularly or intravenously 1
• The test can be performed at any time of day, though morning testing is preferred but not strictly necessary 2
• Obtain a basal blood sample for serum cortisol and ACTH measurement before Synacthen administration 2
• Draw additional serum cortisol samples at 30 minutes and/or 60 minutes after administration 1

Interpretation Criteria

• A peak cortisol value >550 nmol/L (>18-20 μg/dL) at either 30 or 60 minutes is considered a normal response 1, 2
• A peak cortisol <500-550 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 2, 3
• The test is useful for diagnosing both primary and secondary adrenal insufficiency 3

Critical Pre-Test Considerations

• If there is clinical suspicion of impending adrenal crisis, immediately administer IV hydrocortisone 100 mg and 0.9% saline infusion—never delay treatment for diagnostic testing 1, 2
• Secure blood samples for cortisol and ACTH measurement before treatment if possible, but do not delay emergency treatment 1
• Exogenous steroids (prednisolone, inhaled fluticasone) can suppress the HPA axis and confound test results 2
• If you need to treat suspected adrenal crisis but still want to perform diagnostic testing later, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 2

When to Order the Test

• The test is indicated when uncertainty exists about whether partial adrenal insufficiency is present 1
• Useful in patients at risk of developing primary adrenal insufficiency, such as individuals with 21-hydroxylase autoantibodies without overt disease 1
• Essential for distinguishing adrenal insufficiency from SIADH in patients with hypo-osmolar hyponatremia, as both conditions present with similar laboratory findings 2
• A baseline cortisol <420 nmol/L warrants proceeding with the full Synacthen test, as this threshold has 100% sensitivity for identifying patients who will fail the test 4

Common Pitfalls to Avoid

• Do not rely solely on electrolyte abnormalities for diagnosis—hyperkalemia is present in only ~50% of primary adrenal insufficiency cases, and hyponatremia may be only marginally reduced 2
• Never delay emergency treatment of suspected adrenal crisis to perform diagnostic procedures 1, 2, 3
• The high-dose (250 μg) test is preferred over the low-dose (1 μg) test due to easier practical administration, comparable diagnostic accuracy, and FDA approval 2
• The low-dose test requires dilution of the commercial preparation at bedside, making it less practical for routine clinical use 2