What is the role of the cosyntropin stimulation test in assessing adrenal function?

Role of Cosyntropin Stimulation Test in Assessing Adrenal Function

The high-dose (250-μg) ACTH stimulation test is the preferred diagnostic test for assessing adrenal function due to its reliability, standardization, and ease of performance compared to alternative methods. 1, 2

Test Procedure and Administration

The cosyntropin stimulation test involves:

• Administration of 0.25 mg (250 μg) cosyntropin intravenously or intramuscularly 3
• Collection of blood samples for cortisol measurement:
  • Baseline (before administration)
  • 30 minutes after administration
  • 60 minutes after administration 2

Important Pre-Test Considerations

• Discontinue glucocorticoids and spironolactone on the day of testing
• Stop estrogen-containing medications 4-6 weeks before testing
• Long-acting glucocorticoids may need to be stopped for a longer period 3

Interpretation of Results

A normal response is defined as:

• Cortisol level >18 μg/dL at either 30 or 60 minutes after cosyntropin administration 2

However, interpretation must consider:

• Assay-specific cutoffs (newer assays may require different thresholds)
• Recent data suggests lower cutoffs may be appropriate with newer assays (as low as 15.7 μg/dL at 30 minutes with the Roche Elecsys Cortisol II assay) 4
• Measuring cortisol at both 30 and 60 minutes is important as 54% of patients may reach peak levels at 60 minutes 2
• 11% of patients who fail at 30 minutes may pass at 60 minutes 2

Alternative Criteria for Special Populations

For patients with altered binding proteins (cirrhosis, critical illness):

• Delta cortisol <9 μg/dL after ACTH administration
• Random cortisol <10 μg/dL 2

High-Dose vs. Low-Dose Testing

The Society of Critical Care Medicine and European Society of Intensive Care Medicine recommend the high-dose (250-μg) over the low-dose (1-μg) test because:

• Both tests have similar diagnostic accuracy
• The high-dose test is easier to perform and better standardized
• The high-dose test doesn't require bedside preparation (commercial ampoules contain 250 μg) 1

A meta-analysis of 30 studies found that for secondary adrenal insufficiency, both tests had comparable diagnostic accuracy, with likelihood ratios of positive tests at 9.1 and 5.9 for high and low-dose tests, respectively 1.

Clinical Applications

The cosyntropin test is particularly valuable in:

1. Screening for adrenocortical insufficiency in adults and children 3
2. Diagnosing critical illness-related corticosteroid insufficiency (CIRCI) 1
3. Evaluating secondary adrenal insufficiency in patients with hypothalamic-pituitary disease 5

Important Caveats

• Never delay treatment with hydrocortisone in suspected acute adrenal crisis for diagnostic testing 2
• Cortisol binding protein alterations (seen in critical illness, liver disease, etc.) can affect total cortisol measurements
• Weight status may affect timing of peak response (overweight individuals tend to peak at 30 minutes, normal/underweight at 60 minutes) 2
• Various medications and clinical conditions can affect test results 6

Advantages Over Alternative Tests

The cosyntropin test is preferred over:

• Salivary cortisol measurement (limited evidence of benefit, practical challenges) 1
• Hemodynamic response to hydrocortisone (less standardized, limited evidence) 1
• Corticotropin level measurement (not recommended for routine diagnosis) 1

The cosyntropin stimulation test provides a standardized, reliable, and clinically validated approach to assessing adrenal function, making it the cornerstone diagnostic test in evaluating suspected adrenal insufficiency.