Diagnostic Approach to Addison's Disease
Initial Laboratory Evaluation
- The diagnosis of Addison's disease requires measurement of serum cortisol and ACTH levels, with confirmation by cosyntropin stimulation testing when necessary, as recommended by the Endocrine Society 1, 2
- Serum cortisol and ACTH are the cornerstone tests for diagnosing Addison's disease, typically showing low or inappropriately normal cortisol and markedly elevated ACTH 3
- Hyponatremia is present in approximately 90% of newly diagnosed cases, and hyperkalemia occurs in about 50% of patients at diagnosis due to aldosterone deficiency 3
- Other common laboratory findings include mild to moderate hypercalcemia, anemia, mild eosinophilia, lymphocytosis, and elevated liver transaminases 3
- Children may present with hypoglycemia, which is rare in adults 3
Confirmatory Testing
- A cosyntropin stimulation test is required when partial adrenal insufficiency is suspected or results are equivocal, involving administration of 0.25 mg cosyntropin intramuscularly or intravenously 1, 4
- Serum cortisol is measured at baseline, 30 minutes, and/or 60 minutes after administration, with a normal response requiring cortisol to exceed 550 nmol/L at either the 30 or 60-minute mark 1
Etiologic Diagnosis
- 21-hydroxylase autoantibodies should be the first test performed to establish an autoimmune cause, which accounts for approximately 85% of cases in Western Europe, according to the European Society of Endocrinology 1, 5
- If 21OH-Ab is negative, further investigation is needed, which may include CT imaging of the adrenals, testing for interferon-ω antibodies, and very long-chain fatty acid measurement 1, 6
Important Caveats
- If clinical suspicion for adrenal crisis exists, treatment should never be delayed for diagnostic testing, as emphasized by the American College of Endocrinology 1, 4
- Blood samples for cortisol and ACTH should be collected before administering hydrocortisone if possible, but immediate treatment takes priority 1
- Exogenous steroid use can confound interpretation of cortisol levels, and screening for other autoimmune conditions is essential in patients with autoimmune Addison's disease, particularly thyroid disease 3, 7, 8