From the Guidelines
The most appropriate diagnostic test for adrenal insufficiency (Addison's disease) is a paired measurement of serum cortisol and plasma ACTH, followed by a synacthen (tetracosactide) stimulated test if results are equivocal, as recommended by the 2014 consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1.
Diagnostic Approach
To evaluate adrenal insufficiency, the following steps should be taken:
- Measure serum cortisol and plasma ACTH levels to assess adrenal function 1.
- If results are equivocal, perform a synacthen (tetracosactide) stimulated test, which involves administering 0.25 mg of synacthen intramuscularly or intravenously and measuring serum cortisol levels after 30 and/or 60 minutes 1.
- A peak serum cortisol level <500 nmol/L is diagnostic of primary adrenal insufficiency 1.
Considerations
- Treatment should never be delayed by diagnostic procedures, especially in cases of suspected acute adrenal crisis 1.
- Blood samples for cortisol and ACTH measurement should be collected prior to treatment if possible 1.
- The diagnostic approach may vary depending on the clinical context and suspected underlying cause of adrenal insufficiency 1.
Additional Tests
- Measuring ACTH levels can help differentiate between primary and secondary adrenal insufficiency 1.
- Additional tests, such as an insulin tolerance test or metyrapone test, may be necessary in certain cases, but are not routinely recommended 1.
Recent Guidelines
- The 2017 guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) suggest using the high-dose (250-μg) ACTH stimulation test for diagnosis, but note that the low-dose (1-μg) test may be equally accurate 1.
From the FDA Drug Label
Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in adult and pediatric patients. Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test
The diagnostic test to evaluate adrenal insufficiency (Addison's disease) is the metyrapone test, which should be used in combination with other diagnostic tests. Additionally, the ability of the adrenals to respond to exogenous ACTH should be demonstrated before metyrapone is employed as a test 2.
From the Research
Diagnostic Tests for Adrenal Insufficiency
To evaluate adrenal insufficiency, also known as Addison's disease, several diagnostic tests can be performed. The choice of test depends on the clinical presentation and suspicion of the disease.
- Morning Serum Cortisol: This is a cost-effective screening test that can be used to predict the results of the adrenocorticotropic hormone (ACTH) stimulation test 3, 4. A morning serum cortisol level of ≥300 nmol/L can exclude the possibility of adrenal insufficiency, while a level of <110 nmol/L suggests adrenal insufficiency 3.
- ACTH Stimulation Test: This test is commonly performed in patients suspected of having adrenal insufficiency when the basal serum cortisol levels are inconclusive 5. The test involves administering synthetic ACTH (cosyntropin) and measuring the cortisol response. A peak cortisol response of ≥18 μg/dL is considered normal 6.
- Insulin Tolerance Test: This test is considered the gold standard for diagnosing secondary adrenal insufficiency 7. It involves administering insulin to induce hypoglycemia and measuring the cortisol response.
- Cosyntropin Stimulation Test: This test is similar to the ACTH stimulation test and is used to diagnose adrenal insufficiency 7.
Interpretation of Test Results
The interpretation of test results should take into account the clinical presentation and the likelihood of adrenal insufficiency before testing 5. The results of the morning serum cortisol test can be used to predict the results of the ACTH stimulation test, and a normal result can exclude the possibility of adrenal insufficiency 3, 4. The ACTH stimulation test and insulin tolerance test can be used to confirm the diagnosis of adrenal insufficiency 5, 7.
Algorithm for Diagnostic Testing
An algorithm can be developed to reduce laboratory utilization in ACTH stimulation testing 6. This algorithm can involve analyzing cortisol levels at 0 and 60 minutes after cosyntropin administration, and only analyzing the 30-minute sample if the 60-minute cortisol level is subnormal. This approach can reduce unnecessary laboratory utilization and align practice with recommendations from professional societies 6.