How is a cosyntropin (adrenocorticotropic hormone, ACTH) stimulation test performed?

How to Perform a Cosyntropin Stimulation Test

The cosyntropin stimulation test is performed by administering 0.25 mg of cosyntropin intramuscularly or intravenously, followed by measurement of serum cortisol at baseline and at 30 and 60 minutes after administration. 1, 2, 3

Preparation and Administration

Test Preparation

• Patients taking cortisone, hydrocortisone, or spironolactone should omit their pre-test doses on the day of testing 2, 3
• Women taking estrogen-containing medications may exhibit abnormally high basal cortisol levels 2, 3
• Collect a control (baseline) blood sample of 6-7 mL in a heparinized tube 2, 3

Administration Options

1. Intramuscular injection (most common method):

   • Reconstitute 0.25 mg cosyntropin with 1 mL of 0.9% sodium chloride 2, 3
   • Inject intramuscularly

2. Intravenous injection:

   • Reconstitute 0.25 mg cosyntropin
   • Inject intravenously in 2-5 mL of saline over a 2-minute period 2, 3

3. Intravenous infusion (for greater adrenal stimulation):

   • Add 0.25 mg cosyntropin to glucose or saline solution
   • Administer at approximately 40 micrograms per hour over a 6-hour period 2, 3
   • Do not add to blood or plasma (may be inactivated by enzymes) 2, 3

Pediatric Dosing

• For children aged 2 years or less, a dose of 0.125 mg is often sufficient 2, 3

Sample Collection and Processing

• Collect a second blood sample exactly 30 minutes after cosyntropin administration 2, 3
• The Endocrine Society recommends collecting samples at both 30 and 60 minutes, as 54% of patients may reach peak cortisol levels at 60 minutes 1
• Refrigerate blood samples until laboratory analysis 2, 3
• If samples cannot be processed within 12 hours, separate plasma and refrigerate or freeze 2, 3

Interpretation of Results

Normal Response Criteria

A normal response meets all of the following criteria:

1. Baseline (control) plasma cortisol level should exceed 5 μg/dL 2, 3
2. 30-minute level should show an increment of at least 7 μg/dL above baseline 2, 3
3. 30-minute level should exceed 18 μg/dL 2

Important Considerations

• Plasma cortisol levels typically peak 45-60 minutes after cosyntropin injection 2
• Measuring cortisol at both 30 and 60 minutes is important as 11% of patients who fail at 30 minutes may pass at 60 minutes 1
• The high-dose (250 μg) test is preferred over low-dose (1 μg) tests due to similar diagnostic accuracy, ease of performance, and better standardization 1

Special Considerations

Medication Effects

• Etomidate can cause adrenal suppression by inhibiting 11β-hydroxylase 1
• Valproate has no significant effects on ACTH/cortisol circadian rhythmicity 1

Patient-Specific Factors

• Weight status may affect timing of peak response:
  • Overweight/obese individuals tend to peak at 30 minutes
  • Normal/underweight individuals tend to peak at 60 minutes 1

Emergency Situations

• In suspected acute adrenal crisis, treatment with intravenous hydrocortisone should never be delayed for diagnostic testing 1
• Blood samples for cortisol and ACTH measurement should be obtained prior to treatment if possible 1

Common Pitfalls to Avoid

• Failing to collect samples at both 30 and 60 minutes, potentially missing peak cortisol response
• Not adjusting interpretation based on assay-specific cutoffs
• Attributing non-specific symptoms to adrenal dysfunction without clear diagnostic evidence
• Overlooking other endocrine disorders that may present similarly
• Premature treatment without diagnostic confirmation, leading to unnecessary side effects

By following this standardized protocol, the cosyntropin stimulation test provides a reliable assessment of adrenal function for diagnosing adrenal insufficiency.