From the Guidelines
The interpretation and treatment approach following an adrenocorticotropic hormone (ACTH) stimulation test is to use the high-dose (250-μg) ACTH stimulation test as the most popular diagnostic test for adrenal insufficiency, with a delta total serum cortisol of <9 μg/dl or a random total cortisol of <10 μg/dl indicating adrenal insufficiency 1.
Key Points
- The high-dose ACTH test is easy to perform and safe, but may result in significant stimulation of the adrenocortical cells in patients with proven adrenal insufficiency 1.
- The low-dose (1-μg) ACTH test requires some preparation at the bedside and has similar diagnostic accuracy to the high-dose test for secondary adrenal insufficiency, but both tests have low sensitivity 1.
- A delta cortisol <9 μg/dl after the low-dose ACTH stimulation test is associated with poorer outcomes, including higher-dose and prolonged treatment with catecholamines, a higher amount of fluid, and higher mortality rate 1.
Treatment Approach
- Hydrocortisone may be considered for treatment of patients with septic shock and suspected adrenal insufficiency, but the ACTH stimulation test should not be used to select patients for treatment 1.
- The treatment approach should be tailored to the individual patient's circumstances, taking into account their values and preferences, and should involve a multidisciplinary team to ensure adequate deliberation about management options 1.
- The high-dose ACTH test is recommended over the low-dose test due to its ease of use and comparable accuracy 1.
From the FDA Drug Label
Indication and Usage CORTROSYN™ (cosyntropin) for Injection is intended for use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency Because of its rapid effect on the adrenal cortex it may be utilized to perform a 30-minute test of adrenal function (plasma cortisol response) as an office or outpatient procedure, using only 2 venipunctures Severe hypofunction of the pituitary - adrenal axis is usually associated with subnormal plasma cortisol values but a low basal level is not per se evidence of adrenal insufficiency and does not suffice to make the diagnosis. Many patients with proven insufficiency will have normal basal levels and will develop signs of insufficiency only when stressed For this reason a criterion which should be used in establishing the diagnosis is the failure to respond to adequate corticotropin stimulation. When presumptive adrenal insufficiency is diagnosed by a subnormal CORTROSYN™ test, further studies are indicated to determine if it is primary or secondary. The differentiation of both types is based on the premise that a primarily defective gland cannot be stimulated by ACTH whereas a secondarily defective gland is potentially functional and will respond to adequate stimulation with ACTH. Patients selected for further study as the result of a subnormal CORTROSYN test should be given a 3 or 4 day course of treatment with Repository Corticotropin Injection USP and then retested.
The interpretation of an adrenocorticotropic hormone (ACTH) stimulation test using cosyntropin involves assessing the plasma cortisol response to stimulation.
- A normal response is denoted by the following criteria:
- The control plasma cortisol level should exceed 5 micrograms/100 mL.
- The 30-minute level should show an increment of at least 7 micrograms/100 mL above the basal level.
- The 30-minute level should exceed 18 micrograms/100 mL.
- If the test results are subnormal, further studies are indicated to determine if the adrenal insufficiency is primary or secondary.
- Treatment approach: Patients with primary adrenal insufficiency (Addison's disease) will not respond to ACTH stimulation, while those with secondary adrenal insufficiency may respond to adequate stimulation with ACTH.
- Patients with a subnormal CORTROSYN test result may be given a 3 or 4 day course of treatment with Repository Corticotropin Injection USP and then retested to differentiate between primary and secondary adrenal insufficiency 2.
- The test may be performed at any time during the day, but the 30-minute plasma cortisol level remains unchanged throughout the day, so only this single criterion should be used 2.
From the Research
Interpretation of ACTH Stimulation Test
The interpretation of the adrenocorticotropic hormone (ACTH) stimulation test requires method- and assay-specific cutoffs of the level of cortisol 3. The test is commonly performed in patients suspected of having adrenal insufficiency when the basal serum cortisol levels are inconclusive 4.
- The optimized threshold for cortisol using the Abbott assay was 14.6 μg/dL at 60 minutes after stimulation (sensitivity, 92%; specificity, 96%) and 13.2 μg/dL at 30 minutes after stimulation (sensitivity, 100%; specificity, 89%) 3.
- A normal response to the rapid ACTH test can be dangerously misleading, particularly in incomplete ACTH deficiency states 5.
- The cortisol level cutoffs obtained from patients who underwent ACTH stimulation tests showed wide variability for its utility in adrenal insufficiency diagnosis 6.
Treatment Approach
The treatment approach following an ACTH stimulation test depends on the interpretation of the results.
- Patients with adrenal insufficiency may require glucocorticoid replacement therapy 5, 6.
- The use of assay-specific cutoffs will be essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency 3.
- Basal cortisol levels ≤100 and ≥450 nmol/L were found in almost half of patients tested for possible adrenal insufficiency and had high diagnostic accuracy, abolishing the need for formal ACTH testing 7.
Factors Affecting Test Results
Several factors can affect the results of the ACTH stimulation test, including: