How is an Adrenocorticotropic Hormone (ACTH) stimulation test interpreted?

Interpretation of ACTH Stimulation Test

The ACTH stimulation test should be interpreted using a cortisol value exceeding 18 μg/dL (550 nmol/L) at either 30 or 60 minutes as the threshold for normal adrenal function. 1

Standard Testing Protocol

The standard ACTH stimulation test involves the following steps:

• Administer 250 μg (high-dose) cosyntropin intravenously or intramuscularly 2, 3
• Obtain baseline serum cortisol level before administration
• Measure serum cortisol levels at 30 minutes and 60 minutes after administration 3
• A normal response is defined as cortisol level >18 μg/dL (550 nmol/L) at either 30 or 60 minutes 1, 3

Key Interpretation Criteria

Normal Adrenal Function

• Peak cortisol >18 μg/dL (550 nmol/L) at either 30 or 60 minutes indicates adequate adrenal function 1, 3
• Both 30 and 60-minute measurements should be obtained as some patients may reach peak levels at different timepoints 4
• No further testing is required if the response is normal 1

Adrenal Insufficiency

• Stimulated cortisol levels <18 μg/dL at both 30 and 60 minutes suggest adrenal insufficiency 3
• In critically ill patients, alternative criteria for relative adrenal insufficiency include:
  • Delta cortisol <9 μg/dL (250 nmol/L) after ACTH administration
  • Random cortisol <10 μg/dL (276 nmol/L) 2, 1

Important Considerations

Assay-Specific Cutoffs

• Different cortisol assays may require different cutoff values:
  • Traditional polyclonal antibody assays: 18 μg/dL
  • Newer monoclonal antibody-based assays (e.g., Abbott Architect): 14.6 μg/dL at 60 minutes 5
• Using assay-specific cutoffs is essential to avoid misclassification and overtreatment 5

Timing Considerations

• Measuring cortisol at both 30 and 60 minutes is important as:
  • 54% of patients may reach peak cortisol levels at 60 minutes
  • 11% of patients who fail at 30 minutes may pass at 60 minutes 4
• 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 4

Special Populations

• In critically ill patients with altered binding proteins:
  • Use delta cortisol <9 μg/dL as diagnostic criterion 2
  • Consider free cortisol measurements when available 2, 1

Potential Pitfalls

1. Medication Interference:

   • Stop glucocorticoids and spironolactone on the day of testing
   • Discontinue estrogen-containing drugs 4-6 weeks before testing 3
   • Long-acting glucocorticoids may require longer washout periods 3

2. Technical Factors:

   • Time of day may affect baseline cortisol levels 6
   • Different assay methods yield different results 6, 5
   • Improper sample handling can affect results 6

3. Clinical Context:

   • Consider pre-test probability of adrenal insufficiency 6
   • In suspected acute adrenal crisis, treat immediately without waiting for test results 1
   • Never delay treatment for diagnostic testing in emergency situations 1

4. Reproducibility:

   • Day-to-day and diurnal variations can affect test results 7
   • Morning cortisol levels tend to be higher than afternoon levels in healthy individuals 7

High-Dose vs. Low-Dose Testing

The high-dose (250 μg) ACTH test is preferred over the low-dose (1 μg) test for several reasons:

• Similar diagnostic accuracy for adrenal insufficiency 2
• Easier to perform with less preparation required 2
• More practical and feasible in clinical settings 2
• Better standardization across institutions 2

The high-dose test is also recommended over using hemodynamic response to hydrocortisone for diagnosis of critical illness-related corticosteroid insufficiency (CIRCI) 2.

By following these interpretation guidelines and being aware of potential confounding factors, clinicians can accurately diagnose adrenal insufficiency using the ACTH stimulation test.