From the Guidelines
Testing for adrenal insufficiency should involve a paired measurement of serum cortisol and plasma ACTH, with a synacthen stimulated peak serum cortisol <500 nmol/L being diagnostic of primary adrenal insufficiency. According to the most recent and highest quality study 1, the workup and evaluation of primary adrenal insufficiency (AI) should include measuring morning (AM) levels of ACTH and cortisol, as well as a basic metabolic panel.
Key Diagnostic Steps
- Evaluate AM levels of ACTH (if > 23 ULN) and cortisol level (if < 3 mg/dL) 1
- Perform a standard dose ACTH stimulation test for indeterminate results (AM cortisol > 3 mg/dL and < 15 mg/dL) 1
- Measure renin and aldosterone levels 1
- Consider adrenal CT for metastasis or hemorrhage (most common causes of primary AI) 1
Interpretation of Test Results
- A peak cortisol level < 500 nmol/L after synacthen stimulation is diagnostic of primary adrenal insufficiency 1
- Morning cortisol levels < 250 nmol/L and increased ACTH in the presence of acute illness are diagnostic of primary PAI, while levels < 400 nmol/L and increased ACTH raise a strong suspicion of PAI 1 It is essential to note that treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 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.
Test for Adrenal Insufficiency:
- Cosyntropin is used as a diagnostic agent in the screening of adrenocortical insufficiency.
- The test involves administering cosyntropin via intravenous or intramuscular injection and measuring serum cortisol levels at baseline, 30 minutes, and 60 minutes after administration.
- The results of the test may be affected by certain medications, such as glucocorticoids and estrogen, which should be stopped before testing 2.
From the Research
Adrenal Insufficiency Diagnosis
The diagnosis of adrenal insufficiency can be challenging due to its rarity and limitations in biochemical assessment of cortisol status 3.
Tests for Adrenal Insufficiency
- The adrenocorticotropic hormone (ACTH) stimulation test is commonly used to diagnose adrenal insufficiency 4, 5, 3, 6, 7.
- The low-dose ACTH stimulation test has been shown to be more sensitive and specific than the high-dose test, but the high-dose test is preferred since the low-dose test has not been validated 4.
- Recent studies have evaluated the impact of technical aspects such as time of day, type of assay, and sample source used for cortisol measurement on the clinical value of the ACTH stimulation test 3.
Interpretation of Test Results
- The interpretation of the ACTH stimulation test requires method- and assay-specific cutoffs of cortisol levels 7.
- 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 and Δ > 10.5 µg/dL for high-dose tests 6.
- Assay-specific cutoffs are essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency 7.
Diagnostic Cutoffs
- New diagnostic cutoffs for adrenal insufficiency after cosyntropin stimulation using the Abbott Architect cortisol immunoassay have been established, with a threshold of 14.6 μg/dL at 60 minutes after stimulation and 13.2 μg/dL at 30 minutes after stimulation 7.
- These cutoffs may significantly decrease false-positive results due to ACTH stimulation testing compared to historical thresholds 7.