From the Guidelines
To order a cosyntropin stimulation test, administer 250 mcg of synthetic ACTH (cosyntropin) intravenously or intramuscularly after obtaining baseline cortisol and ACTH blood samples from the patient in the morning. The high-dose cosyntropin stimulation test is the recommended method for diagnosing adrenal insufficiency, as suggested by the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017 guidelines 1. The procedure involves the following steps:
- Obtain baseline cortisol and ACTH blood samples from the patient in the morning (around 8 AM)
- Administer 250 mcg of synthetic ACTH (cosyntropin) intravenously or intramuscularly
- Collect additional cortisol blood samples at 30 and 60 minutes after cosyntropin administration
- The patient should be fasting and at rest during the test
- Prior to testing, discontinue exogenous steroids if possible, as they can interfere with results
- Inform the laboratory that you're performing a stimulation test so they can process the samples appropriately This test evaluates adrenal function by measuring the adrenal glands' response to ACTH stimulation, and in healthy individuals, cortisol levels should rise significantly after cosyntropin administration 1. The high-dose ACTH test is easy to perform and safe, and it has comparable accuracy to the low-dose ACTH test for diagnosing adrenal insufficiency, as shown in a recent meta-analysis of 30 studies involving 1209 adults and 228 children 1. Inadequate cortisol response suggests adrenal insufficiency, which could be primary (adrenal gland dysfunction) or secondary (pituitary dysfunction), and the test is useful for diagnosing conditions like Addison's disease and hypopituitarism.
From the FDA Drug Label
2.1 Important Information Before Conducting Cosyntropin for Injection Testing • In general, stop glucocorticoids and spironolactone on the day of cosyntropin for injection testing. However, long-acting glucocorticoids may need to be stopped for a longer period before cosyntropin for injection testing [seeWarnings and Precautions (5. 2), Drug Interactions (7)]. • Stop estrogen-containing drugs four to six weeks before cosyntropin for injection testing [see Warnings andPrecautions (5.2), Drug Interactions (7)]. 2.2 Recommended Dose for Adults • The recommended dose of cosyntropin for injection in adults is 0.25 mg to be administered by intravenous or intramuscular injection. 2.5 Administration Information • Cosyntropin for injection may be administered by intramuscular or intravenous injection. • 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.
To order a cosyntropin stimulation test, stop glucocorticoids and spironolactone on the day of testing, and stop estrogen-containing drugs four to six weeks before testing. The recommended dose for adults is 0.25 mg administered by intravenous or intramuscular injection.
- Obtain a baseline blood sample for serum cortisol.
- Administer 0.25 mg of cosyntropin.
- Obtain additional blood samples exactly 30 minutes and 60 minutes after administration of cosyntropin for assessment of cortisol levels 2.
From the Research
Cosyntropin Stim Test Procedure
To order a cosyntropin stimulation test, the following steps can be taken:
- The test is typically ordered by a healthcare provider to assess adrenal insufficiency, and the provider will determine the appropriate dosage and timing of the test 3, 4, 5, 6.
- The test involves administering a synthetic form of adrenocorticotropic hormone (ACTH), known as cosyntropin, to stimulate the adrenal glands to produce cortisol 3, 4, 5, 6.
- The most commonly used dosages are 1 μg, 25 μg, and 250 μg, with the 1 μg dose being considered a low-dose test and the 250 μg dose being considered a high-dose test 3, 4, 5, 6.
Test Interpretation
The results of the cosyntropin stimulation test are interpreted based on the cortisol levels measured at specific time points after administration of the cosyntropin:
- A cortisol level of 18-20 μg/dL or higher at 30 minutes after stimulation is generally considered a normal response 3, 5.
- A cortisol level of less than 18-20 μg/dL at 30 minutes after stimulation may indicate adrenal insufficiency 3, 5.
- The use of a cortisol cut-off value of 550 nmol/L or more for the 30-minute cortisol level has been shown to have high sensitivity and specificity for diagnosing secondary adrenal insufficiency 5.
- The utility of measuring cortisol levels at 30 and 60 minutes after high-dose synthetic ACTH-1-24 injection has been compared, and the results suggest that the 60-minute sample may be sufficient for diagnosis 7.
Dosage Comparison
Studies have compared the diagnostic accuracy of different cosyntropin dosages:
- The 1 μg dose has been shown to be more sensitive than the 250 μg dose for diagnosing secondary adrenal insufficiency in non-stressed patients 3, 4.
- The 10 μg dose has been compared to the 250 μg dose, and the results suggest that the lower dose may be more sensitive for detecting adrenocortical dysfunction 4.
- A study comparing the 1 μg, 25 μg, and 250 μg doses found that all three doses had excellent correlations with the insulin tolerance test, but the 1 μg dose may be the most convenient and sensitive method for screening abnormalities of the hypothalamic-pituitary-adrenocortical axis 6.