What is the protocol for the short synacthen (cosyntropin) test in diagnosing adrenal insufficiency?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: September 23, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Short Synacthen Test Protocol for Diagnosing Adrenal Insufficiency

The standard short synacthen (cosyntropin) test protocol requires administration of 0.25 mg cosyntropin intramuscularly or intravenously, followed by measurement of serum cortisol at baseline and at 30 and 60 minutes post-administration, with a normal response defined as cortisol exceeding 550 nmol/L at either time point. 1

Preparation and Administration

  1. Pre-test preparation:

    • Stop glucocorticoids and spironolactone on the day of testing 2
    • For long-acting glucocorticoids, stop for a longer period before testing 2
    • Stop estrogen-containing medications 4-6 weeks before testing 2
  2. Dosing:

    • Adults: 0.25 mg IV or IM 2
    • Pediatric patients: 2
      • 0.125 mg for patients from birth to less than 2 years
      • 0.25 mg for patients 2 to 17 years
  3. Sample collection:

    • Obtain blood samples for serum cortisol at:
      • Baseline (before cosyntropin administration)
      • 30 minutes post-administration
      • 60 minutes post-administration 2

Interpretation of Results

  • Normal response: Cortisol level exceeding 550 nmol/L at either 30 or 60 minutes 1
  • Abnormal response: Failure to reach cortisol level of 550 nmol/L at both time points

Clinical Considerations

Importance of the 60-minute Sample

Recent evidence suggests that approximately 5% of patients may have a late response (normal at 60 minutes but insufficient at 30 minutes) 3. This indicates that omitting the 60-minute sample could lead to inappropriate diagnosis of adrenal insufficiency and unnecessary long-term steroid treatment.

Predictive Value of Test Results

Cortisol levels across the SST can predict recovery of adrenal insufficiency:

  • Patients with 30-minute cortisol levels >350 nmol/L have a 99% chance of recovering adrenal function within 4 years 4
  • Patients with 30-minute cortisol levels <350 nmol/L have only a 49% chance of recovery within the same period 4

Common Pitfalls to Avoid

  1. Medication interference:

    • Glucocorticoids and spironolactone may falsely elevate cortisol levels 2
    • Estrogen can elevate total cortisol levels 2
    • Any condition that affects cortisol binding globulin levels can impact test results 2
  2. Timing considerations:

    • Ensure precise timing of sample collection at exactly 30 and 60 minutes 2
    • Both 30 and 60-minute samples are necessary for accurate diagnosis 3
  3. Emergency situations:

    • If there is clinical suspicion of impending adrenal crisis, immediate treatment with IV hydrocortisone and 0.9% saline should not be delayed for diagnostic testing 1
    • Blood samples for cortisol and ACTH should be secured prior to treatment if possible 1

Follow-up Testing

After confirming adrenal insufficiency, further testing should be conducted to determine etiology:

  • Measure 21-hydroxylase antibodies (21OH-Ab) to identify autoimmune causes 1
  • If 21OH-Ab negative, consider additional investigations based on clinical presentation 1

The short synacthen test is a reliable and widely used diagnostic tool for adrenal insufficiency when performed correctly with appropriate interpretation of results.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.