What is a simple way to interpret the short synacthen (adrenocorticotropic hormone stimulation) test?

Interpreting the Short Synacthen Test

The short synacthen (ACTH stimulation) test is best interpreted by considering a cortisol value exceeding 550 nmol/L (18 μg/dL) at either 30 or 60 minutes as a normal response, ruling out adrenal insufficiency. 1, 2

Test Protocol and Interpretation

Standard Protocol:

• Administration of 0.25 mg cosyntropin (synacthen/tetracosactide) intramuscularly or intravenously
• Measurement of serum cortisol at baseline, 30 minutes, and 60 minutes after administration
• Normal response: cortisol value >550 nmol/L (18 μg/dL) at either 30 or 60 minutes

Key Interpretation Points:

1. Pass/Fail Criteria: A peak cortisol >550 nmol/L at any time point indicates adequate adrenal function 1
2. Late Responders: Approximately 5% of patients show insufficient response at 30 minutes but adequate response at 60 minutes 3
3. False Negatives: No cases have been reported where patients pass at 30 minutes but fail at 60 minutes 3

Special Considerations

Cirrhosis Patients:

• Standard interpretation may be flawed due to reduced serum levels of cortisol binding globulin (CBG) and albumin
• Consider these alternative criteria for relative adrenal insufficiency (RAI):
  • Delta total serum cortisol <250 nmol/L (9 μg/dL) after ACTH administration
  • Random total cortisol <276 nmol/L (10 μg/dL) in critically ill patients 1

Free Cortisol Assessment:

• More accurate in patients with altered binding proteins (cirrhosis, critical illness)
• Serum-free cortisol levels <50 nmol/L at baseline or <86 nmol/L after ACTH suggest RAI
• Salivary cortisol (correlates with free cortisol): baseline <1.8 ng/ml or increment <3 ng/ml suggests RAI 1

Clinical Applications

Screening Thresholds:

• A baseline cortisol <420 nmol/L has 100% sensitivity for identifying those who will fail the test
• A baseline cortisol <142 nmol/L has 100% specificity for adrenal insufficiency 4
• Using these thresholds can reduce unnecessary testing by up to 44% 4

Long-term Safety:

• The standard SST is safe for excluding clinically significant adrenal insufficiency
• Patients with borderline responses (510-550 nmol/L) rarely develop adrenal insufficiency during follow-up 5

Potential Modifications

Simplified Testing:

• Recent evidence suggests the 30-minute sample may be omitted, with a single 60-minute measurement providing sufficient diagnostic information 3
• This simplification saves resources without compromising diagnostic accuracy

Low-Dose Alternative:

• The 1 μg low-dose short synacthen test (LDSST) may be more sensitive
• Using a cortisol cut-off of 600 nmol/L with LDSST produces no falsely reassuring results 6

Common Pitfalls to Avoid

1. Failing to consider protein binding abnormalities in critically ill patients or those with liver disease
2. Misinterpreting borderline results without clinical context
3. Repeating normal tests unnecessarily
4. Attributing non-specific symptoms to adrenal dysfunction without clear diagnostic evidence 2

Remember that in suspected acute adrenal crisis, treatment should never be delayed for diagnostic testing. Administer intravenous hydrocortisone immediately and obtain blood samples for cortisol and ACTH measurement prior to treatment if possible 1.