What is the basic workup for Addison's disease?

Basic Workup for Addison's Disease

The basic workup for Addison's disease should include measurement of morning serum cortisol and ACTH levels, followed by a cosyntropin stimulation test to confirm the diagnosis, and 21-hydroxylase antibody testing to determine etiology. 1

Initial Diagnostic Steps

Clinical Suspicion

• Look for characteristic symptoms:
  • Fatigue and weakness
  • Hyperpigmentation (especially on mucosal surfaces, skin creases)
  • Orthostatic hypotension
  • Weight loss
  • Salt craving
  • Nausea, vomiting, abdominal pain
  • Muscle and joint pain

Laboratory Testing

1. First-line tests:

   • Morning serum cortisol (8 AM)
   • Plasma ACTH level (elevated in primary adrenal insufficiency)
   • Serum electrolytes (look for hyponatremia, hyperkalemia)
   • Blood glucose (may show hypoglycemia)

2. Confirmatory testing:

   • Cosyntropin (ACTH) stimulation test: The standard test requires administration of 0.25 mg cosyntropin intramuscularly or intravenously, followed by measurement of serum cortisol after 30 and/or 60 minutes. A normal response should exceed 550 nmol/L (approximately 20 μg/dL). 1

Etiologic Diagnosis

Once primary adrenal insufficiency (PAI) is confirmed, determine the cause:

1. 21-hydroxylase antibodies (21OH-Ab): The first test to establish etiology, as autoimmune adrenalitis accounts for approximately 85% of cases in Western countries 1

   • If positive → Autoimmune Addison's disease
   • If negative → Further investigation needed

2. If 21OH-Ab negative:

   • CT scan of adrenals to evaluate for:
     • Hemorrhage
     • Tuberculosis
     • Tumors
     • Infiltrative diseases
   • Consider testing for:
     • Very long chain fatty acids (VLCFA) for adrenoleukodystrophy
     • Interferon-omega antibodies for APS-1 (Autoimmune Polyendocrine Syndrome type 1)

Additional Testing

• Thyroid function tests: TSH, free T4, and thyroid peroxidase antibodies (TPO-Ab) to screen for autoimmune thyroid disease
• Complete blood count: To screen for anemia
• Vitamin B12 levels: To screen for pernicious anemia
• Plasma glucose and HbA1c: To screen for diabetes
• Tissue transglutaminase antibodies and total IgA: In patients with GI symptoms to screen for celiac disease

Important Clinical Considerations

• Never delay treatment if adrenal crisis is suspected. If clinical suspicion of impending adrenal crisis exists, immediately administer intravenous hydrocortisone (100 mg) and 0.9% saline infusion before completing diagnostic workup. Blood samples for cortisol and ACTH should be secured prior to treatment if possible. 1

• Watch for concomitant autoimmune disorders: Up to 50% of patients with autoimmune Addison's disease develop another autoimmune disorder during their lifetime. 2

• Consider special populations: In patients with end-stage renal disease, diagnosis can be challenging as many symptoms overlap with those of renal failure. 3

Follow-up After Diagnosis

After diagnosis and initiation of treatment with glucocorticoids (hydrocortisone) and mineralocorticoids (fludrocortisone), patients should be monitored regularly:

• Annual assessment of health and well-being
• Measurement of weight and blood pressure
• Serum electrolyte monitoring
• Screening for development of new autoimmune disorders
• Bone mineral density assessment every 3-5 years 1

The diagnostic algorithm should be systematic and thorough to ensure proper identification and management of this potentially life-threatening condition.