What is the initial step in screening for Addison's disease?

Screening for Addison's Disease

The initial step in screening for Addison's disease is measuring morning serum cortisol and ACTH levels, followed by a high-dose (250-μg) ACTH stimulation test, which is considered the gold standard for diagnosis. 1

Initial Diagnostic Approach

Laboratory Tests

• Morning serum cortisol and ACTH measurement:

  • Primary adrenal insufficiency: Low cortisol with high ACTH
  • Secondary adrenal insufficiency: Low cortisol with low ACTH 1

• Basic metabolic panel:

  • Check for characteristic electrolyte abnormalities:
    • Hyponatremia (low sodium)
    • Hyperkalemia (high potassium) 1, 2

Confirmatory Testing

• High-dose (250-μg) ACTH stimulation test:

  • Gold standard for diagnosing adrenal insufficiency
  • Normal response: Cortisol exceeding 550 nmol/L (18-20 μg/dL) at either 30 or 60 minutes 1
  • Blunted response indicates adrenal insufficiency

• Low-dose (1-μg) ACTH stimulation test:

  • May be more sensitive in early or mild cases of adrenal insufficiency
  • Particularly useful when standard high-dose test results are equivocal 3

Clinical Features to Evaluate

• Skin examination: Look for hyperpigmentation, especially in:

  • Oral mucosa
  • Tongue
  • Fingernails
  • Skin creases 4, 2

• Vital signs: Check for:

  • Hypotension
  • Orthostatic changes 4

• Common symptoms to inquire about:

  • Fatigue and weakness
  • Weight loss
  • Salt craving
  • Gastrointestinal complaints (nausea, vomiting, abdominal pain)
  • Dizziness upon standing 4, 2

Additional Testing

• 21-hydroxylase antibody testing:

  • Determines if autoimmune etiology (accounts for ~85% of cases in Western countries)
  • Positive result indicates autoimmune Addison's disease 1

• Screening for associated autoimmune conditions:

  • Thyroid function tests
  • Plasma glucose and HbA1c
  • Complete blood count
  • Vitamin B12 levels 1

Important Clinical Considerations

• Diagnostic pitfalls:

  • Symptoms are often nonspecific and insidious, leading to delayed diagnosis
  • Diagnosis may be missed until an adrenal crisis occurs, which can be fatal 4, 2
  • In patients with end-stage renal disease, symptoms may be attributed to renal failure rather than adrenal insufficiency 5

• When to suspect Addison's disease:

  • Unexplained fatigue, weight loss, and GI symptoms
  • Hyperpigmentation (a distinctive feature)
  • Unexplained hyponatremia and/or hyperkalemia
  • Hypotension unresponsive to fluid resuscitation 4, 2

• Urgent management:

  • If adrenal crisis is suspected, immediate treatment with intravenous hydrocortisone is essential before completing diagnostic workup 1

Following this diagnostic approach will help identify Addison's disease early, preventing potentially life-threatening adrenal crises and allowing for appropriate hormone replacement therapy.