From the Guidelines
Normal results of an ACTH stimulation test show an appropriate cortisol response to synthetic ACTH (cosyntropin) administration, with a peak serum cortisol level of at least 18-20 mcg/dL (500-550 nmol/L) at either 30 or 60 minutes after ACTH administration, as confirmed by the Endocrine Society guidelines 1.
Key Diagnostic Features
- The baseline cortisol level is typically between 5-25 mcg/dL in the morning, but the key diagnostic feature is the rise in cortisol after stimulation, not just the absolute value.
- For the low-dose 1 mcg test, similar cutoff values apply, as suggested by the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017 guidelines 1.
- These results indicate normal adrenal function and the ability of the adrenal glands to respond appropriately to stress by increasing cortisol production.
Important Considerations
- Normal results effectively rule out primary adrenal insufficiency (Addison's disease) and most cases of secondary adrenal insufficiency.
- Recent glucocorticoid use can affect test results, so medications should be disclosed before testing, as emphasized by the SCCM and ESICM guidelines 1.
- The test should ideally be performed in the morning when cortisol levels are naturally higher, to ensure accurate results.
Diagnostic Criteria
- The 2008 guidelines suggested that the diagnosis of CIRCI is best made by a delta total serum cortisol of <9 μg/dl after i.v. cosyntropin (250 μg) administration or a random total cortisol of <10 μg/dl, but these criteria have not been widely adopted in clinical practice 1.
- The latest Surviving Sepsis Campaign guidelines suggest not using the ACTH stimulation test to select patients with septic shock that may be treated with hydrocortisone, highlighting the need for careful consideration of test results in clinical decision-making 1.
From the FDA Drug Label
The pharmacologic profile of cosyntropin is similar to that of purified natural ACTH. It has been established that 0. 25 mg of cosyntropin will stimulate the adrenal cortex maximally and to the same extent as 25 units of natural ACTH. This dose of cosyntropin will produce maximal secretion of 17-OH corticosteroids, 17-ketosteroids and/or 17-ketogenic steroids.
The normal results of the Adrenocorticotropic hormone (ACTH) stimulation test are maximal secretion of 17-OH corticosteroids, 17-ketosteroids, and/or 17-ketogenic steroids in response to stimulation by cosyntropin.
- Key points:
From the Research
Normal Results of the Adrenocorticotropic Hormone (ACTH) Stimulation Test
The normal results of the ACTH stimulation test are defined as a peak cortisol response to pharmacologic stimulation with cosyntropin of ≥18 μg/dL 3, 4. However, newer specific cortisol assays may have lower thresholds for a normal response, with suggested cutoffs ranging from 14 to 15 μg/dL 4.
Cortisol Response Thresholds
- The traditional threshold for a normal cortisol response is ≥18 μg/dL 3, 4
- Newer assays may have lower thresholds, such as:
Diagnostic Accuracy
The diagnostic accuracy of the ACTH stimulation test can be influenced by various factors, including the assay used and the patient's underlying condition 4, 5, 6, 7. Basal cortisol levels can also be used to predict adrenal insufficiency, with levels ≥450 nmol/L having a high negative predictive value and levels ≤100 nmol/L having a high positive predictive value 5.
Interpretation of Test Results
It is essential to interpret the results of the ACTH stimulation test in the context of the patient's clinical presentation and medical history 6, 7. A normal response to the test does not necessarily rule out adrenal insufficiency, and further evaluation may be necessary in some cases 6. Morning serum cortisol can be used as a screening test for adrenal insufficiency, with a cutoff value of 234.2 mmol/L having a sensitivity of 83.3% and a specificity of 89.1% 7.