What laboratory tests are indicated for diagnosing adrenal insufficiency (Addison's disease)?

From the Guidelines

To diagnose adrenal insufficiency, order the following labs:

• Morning cortisol level and ACTH level to assess the body's natural cortisol peak and differentiate between primary and secondary adrenal insufficiency 1
• Basic metabolic panel, including sodium, potassium, and CO2, to evaluate for signs of adrenal crisis 1
• Renin and aldosterone levels to assess adrenal function 1
• Consider a standard dose ACTH stimulation test for indeterminate results, such as a morning cortisol level between 3-15 mg/dL 1
• Adrenal CT for metastasis or hemorrhage, which are common causes of primary adrenal insufficiency 1 In cases of suspected acute adrenal insufficiency, prioritize drawing a cortisol level and ACTH level before administering any corticosteroids, as these medications can interfere with test results 1. Electrolyte panels, including sodium, potassium, and chloride, can also be useful in evaluating for signs of adrenal crisis, although they are not specifically mentioned in the guidelines, they are a common practice in real-life clinical medicine. The cosyntropin stimulation test is also a valuable tool in diagnosing adrenal insufficiency, particularly in cases where the morning cortisol level is low or borderline, as it can help confirm the diagnosis and assess adrenal reserve 1.

From the FDA Drug Label

2.5 Administration Information • Obtain blood sample for baseline serum cortisol. Obtain blood samples again for assessment of cortisol levels exactly 30 minutes and 60 minutes after administration of cosyntropin for injection. 2.6 Interpretation of Plasma Cortisol Levels after Cosyntropin for Injection • 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 laboratory tests indicated for diagnosing adrenal insufficiency (Addison's disease) include:

• Baseline serum cortisol levels
• Stimulated plasma cortisol levels at 30 and 60 minutes after cosyntropin injection
• Cortisol binding globulin levels, if necessary, to ensure accuracy of interpretation of plasma total cortisol levels 2

From the Research

Laboratory Tests for Diagnosing Adrenal Insufficiency

The following laboratory tests are indicated for diagnosing adrenal insufficiency (Addison's disease):

• Measurement of basal serum cortisol levels, often with a cut-off value of <100 nmol/L or <140 nmol/L 3, 4
• Adrenocorticotropic hormone (ACTH) levels, which are often raised in primary adrenal insufficiency 3, 4
• Cosyntropin (Synacthen®) stimulation test, which is used for confirmatory testing 3, 4, 5, 6
• Insulin tolerance test, which is the gold standard for secondary adrenal insufficiency 3, 5
• Salivary cortisol test, which is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels 4
• 21-hydroxylase antibodies, which are routinely evaluated to rule out autoimmunity 4
• Testing of the hypothalamic-pituitary-adrenal (HPA) axis, imaging, and ruling out systemic causes are necessary for the diagnosis of adrenal insufficiency 4, 5

Special Considerations

• Children and infants require lower doses of cosyntropin for testing 4
• Patients with cancer treatment with immune checkpoint inhibitors (ICI) require close follow-up for adrenal insufficiency 4
• Patients with adrenal insufficiency require education and empowerment to take control of their own medical management 3, 5, 6