What is the appropriate dose of Acton Prolongatum (tetracosactide) for the ACTH stimulation test?

ACTH Stimulation Test Dosing with Acton Prolongatum (Tetracosactide)

Use 250 μg (0.25 mg) of tetracosactide (Acton Prolongatum/Synacthen) administered intramuscularly or intravenously for the ACTH stimulation test to diagnose adrenal insufficiency. 1

Standard Dosing Protocol

The high-dose ACTH stimulation test is the recommended approach:

• Dose: 250 μg of synthetic ACTH (tetracosactide/cosyntropin) 1
• Route: Intramuscular (IM) or intravenous (IV) administration 1
• Timing: Measure serum cortisol at baseline, 30 minutes, and 60 minutes post-injection 1
• Diagnostic threshold: Peak cortisol <500 nmol/L (<18 μg/dL) at 30 or 60 minutes indicates adrenal insufficiency 1

Rationale for High-Dose (250 μg) Over Low-Dose (1 μg)

The 2017 SCCM/ESICM guidelines specifically recommend the high-dose test over the low-dose alternative, despite the supraphysiologic nature of 250 μg 1. The reasoning includes:

• Comparable diagnostic accuracy: Meta-analysis of 30 studies involving 1,209 adults and 228 children found similar diagnostic accuracy between high- and low-dose tests for secondary adrenal insufficiency 1
• Practical advantages: The 250 μg dose is easier to perform and safe, whereas the 1 μg dose requires bedside preparation and dilution from commercial 250 μg ampoules 1
• Established validation: The Endocrine Society confirmed that the 250 μg test is superior to other existing diagnostic tests for establishing primary adrenal insufficiency 1

Alternative Formulation: Porcine ACTH (Acton Prolongatum)

In regions where synthetic tetracosactide is unavailable, long-acting porcine ACTH (Acton Prolongatum) provides an accurate alternative:

• Dose: 30 units intramuscularly 2, 3
• Timing: Measure cortisol at 60 and 120 minutes post-injection 2, 3
• Diagnostic threshold: Cortisol ≥19.5 μg/dL at 120 minutes indicates adrenal sufficiency (sensitivity 100%, specificity 88%) 2
• Validation: Area under the curve of 0.986 compared to standard Synacthen test 2

Critical Interpretation Points

For acute illness/suspected adrenal crisis 1:

• Serum cortisol <250 nmol/L with elevated ACTH is diagnostic of primary adrenal insufficiency
• Serum cortisol <400 nmol/L with elevated ACTH raises strong suspicion

For CIRCI diagnosis in critically ill patients 1:

• Delta cortisol (change from baseline) <9 μg/dL at 60 minutes after 250 μg cosyntropin may indicate CIRCI
• However, current guidelines make no strong recommendation for using ACTH stimulation testing to guide corticosteroid therapy in septic shock 1

Common Pitfalls

• Never delay treatment: In suspected acute adrenal insufficiency, treatment should never be delayed for diagnostic testing 1
• Avoid low-dose testing: Despite theoretical advantages for detecting secondary adrenal insufficiency, the low-dose test offers no practical benefit and adds complexity 1
• Assay-dependent thresholds: Peak cortisol cutoffs may vary by laboratory assay; the 500 nmol/L (18 μg/dL) threshold is assay-dependent 1