What is the proper administration protocol for Cosyntropin (synthetic ACTH)?

Cosyntropin Administration Protocol

Administer 250 μg of cosyntropin as an intravenous or intramuscular bolus injection, measure baseline cortisol, then obtain cortisol levels at exactly 30 and 60 minutes post-injection. 1, 2

Dosing

Adults

• Standard dose: 250 μg IV or IM 2
• The 250 μg dose is the gold standard with the highest degree of validation 1
• Low-dose protocols (1 μg) offer no superior diagnostic accuracy for primary adrenal insufficiency 1

Pediatric Patients

• Birth to <2 years: 0.125 mg (125 μg) 2
• 2 to 17 years: 0.25 mg (250 μg) 2

Reconstitution

• Reconstitute lyophilized powder with 1 mL of 0.9% sodium chloride 2
• Final concentration: 0.25 mg/mL
• Solution must be clear, colorless, and free of particulates
• Discard if not used immediately 2

Administration Timing

1. Obtain baseline cortisol sample
2. Administer cosyntropin as IV or IM bolus (not infusion—bolus injection is equally effective) 3
3. Collect cortisol at exactly 30 minutes post-injection
4. Collect cortisol at exactly 60 minutes post-injection 2

Key Timing Considerations

• The test can be performed at any time of day—diurnal variation does not significantly affect results 1
• Both 30 and 60-minute samples are necessary per FDA labeling, though evidence suggests 60-minute sampling may be more reliable 4
• Peak cortisol typically occurs at 60 minutes with the 250 μg dose 1

Pre-Test Medication Management

Must Stop Before Testing

• Glucocorticoids and spironolactone: Stop on the day of testing 2
• Long-acting glucocorticoids: Stop for longer period (specific duration depends on half-life) 2
• Estrogen-containing drugs: Stop 4-6 weeks before testing to allow cortisol-binding globulin levels to normalize 2

Critical Exception

In patients with severe adrenal insufficiency symptoms or adrenal crisis, immediately administer IV hydrocortisone at stress doses before awaiting test results 1. Draw baseline ACTH and cortisol before giving hydrocortisone if possible, but never delay treatment for testing 1.

Interpretation

• Stimulated cortisol <18 mcg/dL (<500 nmol/L) at 30 or 60 minutes suggests adrenocortical insufficiency 2
• Cutoff values may vary by assay 2
• Interpretation is based on peak stimulated cortisol concentration 1

Common Pitfalls

False Elevations

• Glucocorticoids and spironolactone artificially elevate cortisol levels 2
• Elevated cortisol-binding globulin (from estrogens, pregnancy) increases total cortisol without reflecting true adrenal function 2

False Reductions

• Low cortisol-binding globulin (cirrhosis, nephrotic syndrome) decreases total cortisol 2
• Consider measuring cortisol-binding globulin levels when interpretation is uncertain 2

Route Considerations

IV and IM routes are equivalent in diagnostic accuracy 1. Choose based on clinical convenience—IV provides more precise timing control, while IM may be easier in outpatient settings.