What are the diagnostic criteria for adrenal insufficiency (Addison's disease)?

From the Guidelines

The diagnosis of adrenal insufficiency should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, and should be confirmed by paired measurement of serum cortisol and plasma ACTH, with a synacthen stimulated peak serum cortisol <500 nmol L-1 being diagnostic of primary adrenal insufficiency. The diagnostic criteria for adrenal insufficiency, also known as Addison's disease, involve a combination of clinical assessment and laboratory testing. According to the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1, the initial evaluation should include morning serum cortisol and ACTH levels.

Key Diagnostic Criteria

• The diagnosis of primary adrenal insufficiency (PAI) should be considered in patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea.
• Hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia increase clinical suspicion of PAI.
• Paired measurement of serum cortisol and plasma ACTH is the diagnostic test for primary PAI.
• A synacthen (tetracosactide) stimulated peak serum cortisol <500 nmol L-1 is diagnostic of PAI.
• In cases of suspected acute adrenal insufficiency, treatment should not be delayed by diagnostic procedures.

Laboratory Testing

• Morning serum cortisol and ACTH levels should be measured.
• A corticotropin stimulation test (also called ACTH stimulation test or cosyntropin test) may be necessary to confirm the diagnosis.
• A peak cortisol level below a certain threshold (e.g., <500 nmol L-1) indicates adrenal insufficiency.

Clinical Symptoms

• Fatigue, weakness, weight loss, hyperpigmentation (in primary insufficiency), hypotension, and electrolyte abnormalities such as hyponatremia and hyperkalemia support the diagnosis.
• Early morning testing is crucial as cortisol follows a diurnal rhythm with peak levels in the morning. It is essential to note that the diagnosis of adrenal insufficiency requires a comprehensive approach, considering both clinical presentation and laboratory results, as outlined in the guidelines 1. Additionally, the Endocrine Society confirmed that the high-dose (250-μg) ACTH stimulation test is superior to other existing diagnostic tests to establish the diagnosis of primary adrenal insufficiency 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 diagnostic criteria for adrenal insufficiency (Addison's disease) using cosyntropin for injection include:

• Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection. Note that cutoff values for exclusion of adrenocortical insufficiency may vary according to the assay used 2.

From the Research

Diagnostic Criteria for Adrenal Insufficiency

The diagnostic criteria for adrenal insufficiency, also known as Addison's disease, involve a combination of clinical presentation, laboratory tests, and stimulation tests. The following are some of the key diagnostic criteria:

• Basal cortisol level: A basal cortisol level of <85 nmol/L can indicate adrenal insufficiency, while a level of >350 nmol/L can rule out the condition 3
• ACTH stimulation test: This test is considered the gold standard for diagnosing adrenal insufficiency. A peak cortisol response to pharmacologic stimulation with cosyntropin of ≥18 μg/dL is considered normal, while a response of <500 nmol/L at 30 or 60 minutes after stimulation is indicative of adrenal insufficiency 3, 4
• Salivary cortisone level: Home waking salivary cortisone level can be used to screen for adrenal insufficiency, with a cutoff value that can provide a negative predictive value of 96% and a positive predictive value of 95% to exclude and confirm adrenal insufficiency, respectively 5
• Clinical presentation: Patients with adrenal insufficiency may present with non-specific symptoms such as nausea, emesis, chills, and diaphoresis, and a high index of suspicion is required to diagnose the condition 6

Interpretation of Test Results

The interpretation of test results for adrenal insufficiency requires careful consideration of the clinical presentation, laboratory results, and stimulation test results. The following are some key points to consider:

• Time of day: The time of day when the test is performed can affect the results, with morning cortisol levels typically being higher than evening levels 7
• Type of assay: The type of assay used to measure cortisol levels can affect the results, and clinicians should be aware of the limitations of different assays 7
• Sample source: The source of the sample (e.g. serum, saliva) can affect the results, and clinicians should be aware of the differences between different sample sources 5
• Clinical context: The clinical context in which the test is performed is crucial, and clinicians should consider the patient's symptoms, medical history, and other laboratory results when interpreting the test results 6, 7