What labs are used to diagnose Addison's disease?

Diagnostic Laboratory Tests for Addison's Disease

The diagnosis of Addison's disease requires measurement of serum cortisol and ACTH levels as cornerstone tests, with confirmation by cosyntropin stimulation testing when necessary. 1

Initial Laboratory Evaluation

• Serum cortisol and ACTH are the primary tests for diagnosing Addison's disease, typically showing low or inappropriately normal cortisol with markedly elevated ACTH levels 1
• Common electrolyte abnormalities include hyponatremia (present in approximately 90% of newly diagnosed cases) and hyperkalemia (occurs in about 50% of patients) due to aldosterone deficiency 1, 2
• Other laboratory findings often include mild to moderate hypercalcemia, anemia, mild eosinophilia, lymphocytosis, and elevated liver transaminases 1
• Hypoglycemia may be present, particularly in children 1

Confirmatory Testing

• A cosyntropin (synacthen or tetracosactide) stimulation test is required when partial adrenal insufficiency is suspected or results are equivocal 3, 1
• The standard protocol involves:
  • Administration of 0.25 mg cosyntropin intramuscularly or intravenously 3, 2
  • Measurement of serum cortisol at baseline, 30 minutes, and/or 60 minutes after administration 3, 2
  • A normal response requires cortisol to exceed 550 nmol/L (or 500 nmol/L, depending on the laboratory reference) at either the 30 or 60-minute mark 3, 1, 2
• Basal cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 2
• Basal cortisol <400 nmol/L with elevated ACTH in acute illness raises strong suspicion of adrenal insufficiency 2

Etiologic Diagnosis

• Once primary adrenal insufficiency (PAI) is confirmed, determine the etiology as it affects treatment decisions and follow-up 3
• 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 3, 1
• If 21OH-Ab is positive, further etiologic evaluation is generally unnecessary 3
• If 21OH-Ab is negative, further investigation is needed: 3
  • CT imaging of the adrenal glands to detect tumors, calcifications (typical of tuberculosis), or evidence of bleeding 3
  • In males, screening for adrenoleukodystrophy by measuring very long-chain fatty acids 3
  • Additional testing based on clinical suspicion (e.g., tuberculosis testing, genetic testing) 3

Important Clinical Considerations

• If clinical suspicion for adrenal crisis exists, treatment should never be delayed for diagnostic testing 3, 1, 2
• Blood samples for cortisol and ACTH should be collected before administering hydrocortisone if possible, but immediate treatment takes priority 3, 1
• Early adrenal insufficiency may present with normal morning cortisol but significantly elevated ACTH levels, indicating the need to include ACTH measurement in initial testing 4
• The large interindividual variation in ACTH levels indicates varying sensitivity to cortisol, which may necessitate individualized treatment approaches 5
• Subjects with adrenal autoantibodies should be monitored over time for early signs of adrenal dysfunction 6

Pitfalls and Caveats

• Exogenous steroid use (including inhaled steroids) can confound interpretation of cortisol levels 2
• Early Addison's disease may be missed if only cortisol levels are measured without ACTH, as cortisol can remain normal while ACTH is already elevated 4
• Addison's disease can present with a clinical picture nearly identical to SIADH (Syndrome of Inappropriate ADH secretion), making it essential to rule out adrenal insufficiency in cases of hyponatremia 2
• Annual monitoring should include serum sodium and potassium, thyroid function tests, plasma glucose and HbA1c, complete blood count, and vitamin B12 levels 1
• Screening for other autoimmune conditions is essential in patients with autoimmune Addison's disease, particularly thyroid disease 1