From the Guidelines
The primary diagnostic test for Addison's disease is the cosyntropin (synacthen or tetracosactide) test, which measures the adrenal glands' response to adrenocorticotropic hormone (ACTH) by producing cortisol. This test is necessary when uncertainty exists about the presence of partial primary adrenal insufficiency (PAI) 1. The standard test requires administration of 0.25 mg cosyntropin intramuscularly or intravenously, followed by measurement of serum cortisol after 30 and/or 60 min, with one of these values needing to exceed 550 nmol L1 to be deemed normal 1.
Key Points to Consider
- The cosyntropin test is useful in patients at risk of developing PAI, such as individuals with 21-hydroxylase autoantibodies (21OH-Ab) without overt PAI, and patients with APS-1 without PAI 1.
- If there is a clinical suspicion of impending acute adrenal crisis, the patient should be given intravenous hydrocortisone (HC) immediately and a physiologic (0.9%) saline infusion, with treatment never being delayed because of the need to carry out diagnostic procedures 1.
- Blood samples for cortisol and ACTH measurement should be secured prior to treatment if possible, as the diagnosis can always be established later, even if treatment has commenced 1.
Additional Diagnostic Tests
- Measuring morning serum cortisol and ACTH levels can be helpful, as patients with Addison's disease typically have low cortisol and elevated ACTH levels.
- Electrolyte panels may show characteristic abnormalities such as hyponatremia (low sodium) and hyperkalemia (high potassium).
- Once adrenal insufficiency is confirmed, further testing may include antibody tests to determine if the cause is autoimmune, and imaging studies such as CT scans of the adrenal glands to look for structural abnormalities.
From the FDA Drug Label
Cosyntropin for injection is a sterile lyophilized powder in single-dose vials containing 0.25 mg of cosyntropin and 10 mg of mannitol. Cosyntropin exhibits the full corticosteroidogenic activity of 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.
The study ordered for diagnosis of Addison’s disease is the Cosyntropin Stimulation Test. This test uses cosyntropin, a synthetic form of adrenocorticotropic hormone (ACTH), to stimulate the adrenal cortex and assess its ability to produce cortisol.
- The test involves administering a dose of cosyntropin and measuring the resulting cortisol levels.
- The cosyntropin stimulation test is used to diagnose adrenal insufficiency, including Addison’s disease 2.
From the Research
Diagnosis of Addison's Disease
To diagnose Addison's disease, a specific study is ordered to confirm the condition. The key study used for this purpose is:
- Cosyntropin stimulation test, which measures the response of cortisol levels to adrenocorticotropic hormone (ACTH) stimulation 3, 4, 5, 6
Details of the Cosyntropin Stimulation Test
The cosyntropin stimulation test involves administering a synthetic form of ACTH, called cosyntropin, and then measuring the cortisol response. The test can be performed with different doses of cosyntropin, including:
- 250 microg cosyntropin stimulation test, which is a commonly used dose 4
- 1 microg cosyntropin stimulation test, which is a lower dose that can also be used to diagnose Addison's disease 4
Interpretation of Test Results
The results of the cosyntropin stimulation test are interpreted based on the cortisol response. A normal response is typically considered to be a cortisol level of ≥18 μg/dL (500 nmol/L) 30 or 60 minutes after cosyntropin administration 5. However, newer specific cortisol assays may have lower thresholds for a normal response, and clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for adrenal insufficiency 5.