What are the initial steps for testing and examining a patient suspected of having Addison's disease?

Initial Testing and Examination for Suspected Addison's Disease

The initial diagnostic approach for suspected Addison's disease should include measurement of morning serum cortisol and ACTH levels, followed by a cosyntropin stimulation test if results are inconclusive, and determination of 21-hydroxylase antibodies to establish etiology. 1

Clinical Suspicion and Initial Assessment

When Addison's disease (primary adrenal insufficiency) is suspected, focus on these key clinical manifestations:

• Hyperpigmentation (especially in skin creases, pressure points, and mucous membranes)
• Fatigue and weakness
• Anorexia and weight loss
• Orthostatic hypotension
• Nausea, vomiting, and abdominal pain
• Salt craving
• Hypotension and hyponatremia

Laboratory Evaluation

1. First-line testing:

   • Morning serum cortisol and plasma ACTH levels
   • Serum electrolytes (look for hyponatremia and hyperkalemia)
   • Blood glucose (may show hypoglycemia)

2. Confirmatory testing:

   • Cosyntropin (Synacthen) stimulation test - gold standard for diagnosis
     • Administer 0.25 mg cosyntropin intramuscularly or intravenously
     • Measure serum cortisol at baseline, 30 and/or 60 minutes
     • Normal response: cortisol should exceed 550 nmol/L at one of these time points
     • Failure to reach this threshold confirms adrenal insufficiency 1

Important Caution

If there is clinical suspicion of impending adrenal crisis (shock, hypotension, volume depletion), do not delay treatment to perform diagnostic tests. Immediately administer:

• Intravenous hydrocortisone (100 mg)
• Physiologic (0.9%) saline infusion

Blood samples for cortisol and ACTH should be secured before treatment if possible, but diagnosis can be established later 1.

Determining Etiology

Once primary adrenal insufficiency is confirmed, establish the cause:

1. Autoimmune adrenalitis (85% of cases in Western Europe):

   • Test for 21-hydroxylase antibodies (21OH-Ab) - first-line etiologic test
   • Positive result confirms autoimmune etiology 1

2. If 21OH-Ab negative:

   • Perform CT scan of adrenal glands to identify:
     • Tumors
     • Calcifications (typical of tuberculosis)
     • Hemorrhage
     • Infiltrative disorders

3. In males:

   • Screen for adrenoleukodystrophy by measuring very long-chain fatty acids (VLCFA) in serum 1

4. In young patients with additional symptoms:

   • Consider Autoimmune Polyendocrine Syndrome type-1 (APS-1)
   • Test for interferon omega or IL-22 autoantibodies
   • Consider AIRE gene mutation analysis 1

Additional Testing Based on Clinical Presentation

• If other autoimmune diseases are suspected:

  • Thyroid function tests and TPO antibodies (autoimmune thyroid disease)
  • Vitamin B12 levels (autoimmune gastritis)
  • Blood glucose (diabetes)

• In children and adolescents:

  • Consider genetic causes of adrenal insufficiency
  • Evaluate for congenital adrenal hyperplasia

Common Pitfalls to Avoid

1. Delayed diagnosis due to non-specific early symptoms - maintain high clinical suspicion
2. Misdiagnosis as depression, anorexia, or gastrointestinal disorders
3. Failure to recognize adrenal crisis - a life-threatening emergency requiring immediate treatment
4. Inadequate testing - relying solely on random cortisol levels without confirmatory stimulation testing
5. Missing concomitant autoimmune disorders - up to 50% of patients develop another autoimmune condition

Remember that early detection and appropriate treatment of Addison's disease are crucial to prevent potentially fatal adrenal crisis and improve quality of life for affected individuals.