From the Guidelines
The workup of adrenal insufficiency should begin with evaluating morning levels of ACTH and cortisol, as well as basic metabolic panels, renin, and aldosterone, according to the most recent guidelines 1. The initial evaluation of adrenal insufficiency involves assessing morning cortisol and ACTH levels, with specific thresholds guiding further testing.
- For morning cortisol levels below 3 mg/dL, adrenal insufficiency is likely, and further testing, such as an ACTH stimulation test, may be necessary to confirm the diagnosis.
- Basic metabolic panels, including sodium, potassium, CO2, and glucose, should also be evaluated to assess for electrolyte imbalances and other metabolic disturbances.
- Renin and aldosterone levels should be checked to evaluate the mineralocorticoid axis, which is crucial in primary adrenal insufficiency.
- An adrenal CT scan may be considered to evaluate for metastasis or hemorrhage, which are common causes of primary adrenal insufficiency, as recommended by the guidelines 1. Key considerations in the workup of adrenal insufficiency include:
- Evaluating for precipitating causes of crisis, such as infection
- Considering the use of a standard dose ACTH stimulation test for indeterminate results
- Assessing the need for emergent therapy, such as dexamethasone, in suspected cases of adrenal insufficiency, as suggested by previous guidelines 1. The most recent and highest-quality study 1 provides the basis for these recommendations, prioritizing morbidity, mortality, and quality of life as outcomes.
From the Research
Diagnosis of Adrenal Insufficiency
The diagnosis of adrenal insufficiency is based on clinical assessment and biochemical tests, including basal hormone level measurements and stimulation tests 2. The following are key points to consider in the workup of adrenal insufficiency:
- Clinical presentation and likelihood of adrenal insufficiency before testing should be taken into consideration when interpreting the results of the ACTH stimulation test 3
- Technical aspects such as time of day, type of assay, and sample source used for cortisol measurement can affect the clinical value of the ACTH stimulation test 3
- A short corticotropin test (250 μg) is recommended as the "gold standard" diagnostic tool to establish the diagnosis of primary adrenal insufficiency 4
- Measurement of morning plasma ACTH and cortisol levels can be used as an initial screening procedure if a short corticotropin test is not possible 4
Biochemical Tests
The following biochemical tests are used in the diagnosis of adrenal insufficiency:
- Basal hormone level measurements, including cortisol and ACTH levels 2, 5
- ACTH stimulation tests, including high- and low-dose tests 3, 4, 6
- Autoantibody assays, such as 21-hydroxylase autoantibodies, to diagnose underlying causes of primary adrenal insufficiency 4
Interpretation of Test Results
The interpretation of test results should take into account the following factors:
- Pre-analytical and analytical phases of testing, including assay methodology and sample handling 2, 5
- Clinical presentation and likelihood of adrenal insufficiency before testing 3
- Cut-off values for diagnosis, which may vary depending on the assay and laboratory 5, 6
- The use of likelihood ratios to interpret the results of ACTH stimulation tests, with a positive test result having a reasonable likelihood ratio but a negative test result having a suboptimal likelihood ratio 6