From the Guidelines
To order an ACTH stimulation test, the high-dose (250-μg) test is recommended due to its ease of performance, safety, and comparable accuracy to the low-dose test, as suggested by recent guidelines 1. When ordering the test, it is essential to consult with an endocrinologist or laboratory service to ensure the proper protocol is followed. The standard test involves:
- Measuring baseline cortisol levels
- Administering synthetic ACTH (cosyntropin/Synacthen) at a dose of 250 mcg intravenously or intramuscularly
- Measuring cortisol levels at 30 and 60 minutes post-administration The patient should arrive fasting in the morning (typically between 8-9 AM) when cortisol levels are naturally highest. Certain medications, particularly exogenous glucocorticoids, should be discontinued before testing if possible (usually 24-48 hours for short-acting steroids, longer for long-acting ones) as they can interfere with results 1. The laboratory requisition should clearly specify "ACTH stimulation test" with orders for baseline, 30-minute, and 60-minute cortisol samples. This test evaluates adrenal function by assessing the adrenal glands' ability to respond to ACTH stimulation, which is crucial for diagnosing conditions like adrenal insufficiency. A normal response shows cortisol rising to >18-20 μg/dL (>500 nmol/L) at either the 30 or 60-minute mark, while lower values suggest adrenal insufficiency requiring further investigation 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Ordering an ACTH Stimulation Test
To order an ACTH stimulation test, the following steps can be considered:
- The test is used to diagnose adrenal insufficiency (AI) and evaluate the hypothalamo-pituitary-adrenal (HPA) axis 2, 3, 4, 5
- The test involves administering synthetic adrenocorticotropic hormone (ACTH) and measuring the cortisol response 6, 4
- The dosage of ACTH can vary, with low-dose ACTH stimulation tests being a sensitive and safe alternative to insulin tolerance tests (ITT) 4
- The test can be performed at different time intervals, with 30-minute and 60-minute cortisol levels being commonly measured 2, 3, 5
- The interpretation of the test results requires method- and assay-specific cutoffs for cortisol levels 2, 3
Key Considerations
- The choice of assay for measuring cortisol levels can affect the interpretation of the test results 2, 3
- The use of assay-specific cutoffs is essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency 2, 3
- The test can be repeated to evaluate the repeatability of the results 4
- Other dynamic stimulation tests, such as the glucagon stimulation test (GST) and ITT, can also be used to evaluate the HPA axis and GH-IGF-1 axis 4
Cutoff Levels for Adrenal Insufficiency Diagnosis
- Proposed cutoff levels for 30-minute delta cortisol include Δ < 1.8 µg/dL for both low-dose and high-dose tests, and Δ > 11.8 µg/dL for low-dose tests and Δ > 10.5 µg/dL for high-dose tests 5
- These cutoff levels can provide diagnostic performance for AI equal to that of the 60-minute test, with high sensitivity and specificity > 90% 5