From the Guidelines
To diagnose adrenal insufficiency, the most appropriate diagnostic test is the ACTH stimulation test, also known as the cosyntropin or Synacthen test, which involves administering 250 mcg of synthetic ACTH and measuring cortisol levels at 30 and 60 minutes after administration, with a normal response being a cortisol level above 18-20 μg/dL (500-550 nmol/L) at any time point. This test is recommended as it has comparable accuracy to the low-dose ACTH test, but is easier to perform and safer, as suggested by the Society of Critical Care Medicine and European Society of Intensive Care Medicine in their 2017 guidelines 1. The ACTH stimulation test is a crucial diagnostic tool for adrenal insufficiency, as it can help distinguish between primary and secondary adrenal insufficiency, and guide appropriate hormone replacement therapy.
Some key points to consider when performing the ACTH stimulation test include:
- Measuring baseline cortisol levels before administering synthetic ACTH
- Administering 250 mcg of synthetic ACTH intravenously or intramuscularly
- Measuring cortisol levels at 30 and 60 minutes after administration
- Interpreting the results, with a normal response being a cortisol level above 18-20 μg/dL (500-550 nmol/L) at any time point
- Considering the clinical context and potential need for immediate treatment with intravenous hydrocortisone and physiologic saline infusion if there is a suspicion of impending acute adrenal crisis, as emphasized in the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 2.
It is also important to note that the ACTH stimulation test should be performed in the morning when cortisol levels are naturally highest, and patients should temporarily discontinue exogenous steroids if possible. Additionally, measuring the ACTH level can help distinguish between primary and secondary adrenal insufficiency, with elevated ACTH indicating primary adrenal insufficiency (Addison's disease) and normal or low ACTH suggesting secondary adrenal insufficiency (pituitary or hypothalamic dysfunction).
From the FDA Drug Label
Cosyntropin for injection is indicated, in combination with other diagnostic tests, for use as a diagnostic agent in the screening of adrenocortical insufficiency in adults and pediatric patients. Obtain blood sample for baseline serum cortisol. Obtain blood samples again for assessment of cortisol levels exactly 30 minutes and 60 minutes after administration of cosyntropin for injection. Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection are suggestive of adrenocortical insufficiency.
The diagnostic test used to evaluate adrenal insufficiency (Addison's disease) is the cosyntropin stimulation test, which measures plasma cortisol levels before and after administration of cosyntropin 3, 4, 5.
- The test involves administering cosyntropin via intravenous or intramuscular injection.
- Blood samples are taken at baseline, 30 minutes, and 60 minutes after cosyntropin administration to assess cortisol levels.
- A stimulated plasma cortisol level of less than 18 mcg/dL at 30 or 60 minutes post cosyntropin injection is suggestive of adrenocortical insufficiency.
From the Research
Diagnostic Tests for Adrenal Insufficiency
The diagnostic tests used to evaluate adrenal insufficiency (Addison's disease) include:
- Cosyntropin stimulation test (CST) 6, 7, 8, 9, 10
- Measurement of basal serum cortisol levels 8, 10
- Adrenocorticotrophin (ACTH) test 10
- Salivary cortisol test 10
Cosyntropin Stimulation Test (CST)
The CST is a commonly used test to diagnose adrenal insufficiency 6, 7, 8, 9. The test involves administering cosyntropin (a synthetic form of ACTH) and measuring the response of cortisol levels in the blood. There are two types of CST:
Interpretation of Test Results
The interpretation of test results depends on various factors, including the clinical presentation of the patient, the time of day the test is performed, and the type of assay used to measure cortisol levels 6. A morning serum cortisol level >13 mcg/dL can reliably rule out adrenal insufficiency, while a level ≤13 mcg/dL requires further evaluation with the CST 8.
Special Considerations
Special considerations are needed when testing children and infants, who require lower doses of cosyntropin 10. Additionally, newer highly specific cortisol assays have reduced the cut-off points for cortisol in the diagnosis of adrenal insufficiency 10.