What labs are used to diagnose Addison's disease?

Diagnostic Laboratory Tests for Addison's Disease

The diagnosis of Addison's disease (primary adrenal insufficiency) requires measurement of serum cortisol and ACTH levels, with confirmation by cosyntropin stimulation testing when necessary. 1

Initial Laboratory Evaluation

• Serum cortisol and ACTH are the cornerstone tests for diagnosing Addison's disease. Typically, cortisol is low or inappropriately normal while ACTH is markedly elevated 1
• Hyponatremia is present in approximately 90% of newly diagnosed cases, though sodium levels may be only marginally reduced 1
• Hyperkalemia occurs in about 50% of patients at diagnosis due to aldosterone deficiency 1
• Other common laboratory findings include mild to moderate hypercalcemia (10-20% of patients), anemia, mild eosinophilia, lymphocytosis, and elevated liver transaminases 1
• Children may present with hypoglycemia, which is rare in adults 1

Confirmatory Testing

• When partial adrenal insufficiency is suspected or results are equivocal, a cosyntropin (synacthen) stimulation test is required 1
• The standard test involves administration of 0.25 mg cosyntropin intramuscularly or intravenously 1
• Serum cortisol is measured at baseline, 30 minutes, and/or 60 minutes after administration 1
• A normal response requires cortisol to exceed 550 nmol/L at either the 30 or 60-minute mark 1
• Importantly, approximately 10% of patients with Addison's disease may present with normal cortisol concentrations despite having the condition 2

Etiologic Diagnosis

Once primary adrenal insufficiency is confirmed, determining the etiology is mandatory 1:

• 21-hydroxylase autoantibodies (21OH-Ab) should be the first test performed to establish an autoimmune cause, which accounts for approximately 85% of cases in Western Europe 1
• If 21OH-Ab is negative, further investigation is needed, which may include 1:
  • CT imaging of the adrenals (for bleeding, tumors, tuberculosis)
  • Testing for interferon-ω antibodies (for APS-1)
  • Very long-chain fatty acid (VLCFA) measurement (for adrenoleukodystrophy)

Important Caveats

• If clinical suspicion for adrenal crisis exists, treatment should never be delayed for diagnostic testing 1
• Blood samples for cortisol and ACTH should be collected before administering hydrocortisone if possible, but immediate treatment takes priority 1
• The diagnosis can be established later even after treatment has commenced 1
• Exogenous steroid use (including inhaled steroids like fluticasone) can confound interpretation of cortisol levels 1
• In patients with autoimmune Addison's disease, screening for other autoimmune conditions is essential, particularly thyroid disease 1

Additional Testing During Follow-up

• Annual monitoring should include 1:
  • Serum sodium and potassium
  • Thyroid function tests (TSH, FT4, TPO-Ab)
  • Plasma glucose and HbA1c
  • Complete blood count
  • Vitamin B12 levels
• For patients with symptoms suggesting under- or over-replacement of glucocorticoids, a salivary cortisol day curve may help optimize treatment 3

By following this systematic approach to laboratory testing, Addison's disease can be diagnosed accurately, allowing for prompt initiation of life-saving hormone replacement therapy 4.