From the Guidelines
The latest cutoffs for diagnosing adrenal insufficiency after ACTH stimulation testing are a peak cortisol level below 18 μg/dl at either 30 or 60 minutes after administration of 250 μg of synthetic ACTH (cosyntropin). This threshold applies when using modern cortisol assays, as confirmed by a recent guideline from the Endocrine Society 1. For patients taking oral estrogen or using certain newer cortisol assays, a lower cutoff of 13.5-15 μg/dL may be more appropriate.
Key Points to Consider
- The high-dose (250-μg) ACTH stimulation test is superior to other existing diagnostic tests to establish the diagnosis of primary adrenal insufficiency 1.
- Some centers are now using lower-dose ACTH stimulation tests (1 μg) which may be more sensitive for detecting secondary adrenal insufficiency, though the 250 μg test remains the standard in most clinical settings.
- The test involves measuring baseline cortisol, administering synthetic ACTH, and then measuring cortisol levels again at 30 and 60 minutes post-administration.
- A normal response shows a significant rise in cortisol levels above the threshold, while failure to reach these levels suggests adrenal insufficiency.
Clinical Application
The diagnosis of adrenal insufficiency is critical in certain clinical contexts, such as septic shock, where the ability of the adrenal glands to respond to stress with adequate cortisol production can significantly impact patient outcomes. The use of the ACTH stimulation test, with the cutoffs as mentioned, helps in identifying patients who may benefit from corticosteroid therapy. However, it's crucial to interpret these results in the context of the patient's overall clinical picture, as suggested by the latest guidelines from the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 1.
From the FDA Drug Label
Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection are suggestive of adrenocortical insufficiency. The latest cutoffs for diagnosis of adrenal insufficiency after ACTH stimulation are less than 18 mcg/dL at 30 or 60 minutes post cosyntropin for injection 2.
- Key points:
- Cutoff values for exclusion of adrenocortical insufficiency may vary according to the assay used.
- Test results can be affected by concomitant medications and certain medical conditions. Note that these values are based on the information provided in the drug label for cosyntropin (IV) 2.
From the Research
Latest Cut Offs for Diagnosis of Adrenal Insufficiency
The latest cut offs for diagnosis of adrenal insufficiency after ACTH stimulation are as follows:
- A threshold of 14.6 μg/dL for the level of cortisol at 60 minutes after ACTH stimulation for the Abbott assay 3
- A threshold of 13.2 μg/dL at 30 minutes after stimulation for the Abbott assay 3
- New cortisol cutoffs of 14.6 μg/dL for Elecsys II, 14.8 μg/dL for Access, and 14.5 μg/dL for LC-MS/MS at 30-minute values 4
- A diagnostic threshold for adrenal insufficiency of 350nmol/L with a sensitivity of 91% and specificity 97% using the Roche Cortisol II assay 5
Assay-Specific Cut Offs
Different assays have different cut offs for diagnosis of adrenal insufficiency, including:
- Abbott Architect immunoassay: 14.6 μg/dL at 60 minutes and 13.2 μg/dL at 30 minutes after stimulation 3
- Elecsys II immunoassay: 14.6 μg/dL at 30-minute values 4
- Access immunoassay: 14.8 μg/dL at 30-minute values 4
- LC-MS/MS: 14.5 μg/dL at 30-minute values 4
- Roche Cortisol II assay: 350nmol/L 5
Importance of Assay-Specific Cut Offs
Using assay-specific cut offs is essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency 3, 4, 5