What is the purpose of the Cosyntropin (Adrenocorticotropic hormone, ACTH) stimulation test?

From the Guidelines

The high-dose (250-μg) cosyntropin test is the recommended diagnostic test for adrenal insufficiency due to its ease of use, safety, and comparable accuracy to the low-dose test. The cosyntropin test is a diagnostic procedure used to evaluate adrenal gland function by measuring how well the adrenal glands respond to adrenocorticotropic hormone (ACTH) 1. The test involves administering synthetic ACTH (cosyntropin) and measuring cortisol levels before and after administration. Typically, 250 mcg of cosyntropin is given intravenously or intramuscularly, with blood samples collected at baseline (0 minutes) and at 30 and 60 minutes after injection. A normal response shows cortisol levels rising to at least 18-20 mcg/dL (500-550 nmol/L) at the 30 or 60-minute mark. Some key points to consider when using the cosyntropin test include:

• The test helps diagnose adrenal insufficiency, including primary adrenal insufficiency (Addison's disease) and secondary adrenal insufficiency due to pituitary dysfunction 1.
• Patients should discontinue glucocorticoids before testing if possible, as they can interfere with results.
• The test is generally safe with minimal side effects, though patients with known allergies to cosyntropin should inform their healthcare provider.
• A recent meta-analysis found that the high-dose ACTH test had similar diagnostic accuracy to the low-dose test for secondary adrenal insufficiency, with a likelihood ratio of a positive test of 9.1 for adults and 43.5 for children 1.
• The high-dose ACTH test is easier to perform and requires less preparation at the bedside compared to the low-dose test, making it a more practical choice for diagnosis 1.

From the FDA Drug Label

Cosyntropin for injection is an adrenocorticotropin hormone 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 samples for serum cortisol level at baseline and exactly 30 and 60 minutes after cosyntropin for injection administration.

The Cosyntropin test is used to diagnose adrenocortical insufficiency in adults and pediatric patients.

• The test involves administering 0.25 mg of cosyntropin by intravenous or intramuscular injection to adults, and 0.125 mg for patients birth to less than 2 years of age, and 0.25 mg for patients 2 to 17 years of age.
• Blood samples for serum cortisol level are obtained at baseline, and exactly 30 and 60 minutes after cosyntropin administration 2.

From the Research

Cosyntropin Test Overview

• The cosyntropin test is used to diagnose adrenal insufficiency, a condition where the adrenal glands do not produce enough cortisol 3, 4.
• The test involves administering a synthetic form of adrenocorticotropic hormone (ACTH), called cosyntropin, and measuring the response of the adrenal glands by checking the level of cortisol in the blood 5.

Diagnostic Cutoffs

• The diagnostic cutoffs for the cosyntropin test vary depending on the assay used to measure cortisol levels 6, 7.
• Studies have shown that the traditional cutoff of 18 μg/dL may not be suitable for newer, more specific cortisol assays, and lower cutoffs may be more appropriate 6, 7.
• For example, a study using the Abbott Architect immunoassay found that a cutoff of 14.6 μg/dL at 60 minutes after stimulation had a sensitivity of 92% and a specificity of 96% 6.
• Another study found that new cutoffs of 14-15 μg/dL, depending on the assay used, may be more suitable for reducing false-positive results 7.

Test Interpretation

• The interpretation of the cosyntropin test results should take into account the clinical presentation of the patient and the likelihood of adrenal insufficiency before testing 5.
• Clinicians should be aware of the technical aspects of the test, such as the time of day the test is performed and the type of assay used, which can affect cortisol values and diagnostic accuracy 5.
• The test should be performed in patients suspected of having adrenal insufficiency when basal serum cortisol levels are inconclusive 4.

Comparison of Low-Dose and High-Dose Cosyntropin Tests

• Studies have compared the low-dose (1 μg) and high-dose (250 μg) cosyntropin tests for diagnosing adrenal insufficiency 3, 4.
• The low-dose test is more sensitive for diagnosing secondary adrenal insufficiency in non-stressed patients, while the high-dose test is more sensitive for diagnosing primary adrenal insufficiency 3.
• The operating characteristics of the low-dose and high-dose tests are similar for diagnosing secondary adrenal insufficiency 4.