What are the diagnostic steps and treatment options for Addison's disease?

Diagnostic Steps and Treatment Options for Addison's Disease

The diagnosis of Addison's disease requires measurement of morning cortisol and ACTH levels, followed by an ACTH stimulation test, while treatment consists of lifelong replacement with hydrocortisone (10-30mg daily in divided doses) and fludrocortisone (typically 0.1mg daily), along with comprehensive patient education on stress dosing. 1

Diagnostic Approach

Initial Evaluation

• Look for characteristic symptoms and signs:
  • Fatigue, malaise, anorexia, weight loss
  • Hyperpigmentation (especially on mucosal surfaces, skin folds)
  • Hypotension
  • Electrolyte abnormalities (hyponatremia, hyperkalemia)
  • Hypoglycemia 2

Laboratory Testing

1. First-line tests:

   • Morning serum cortisol and ACTH levels
   • Electrolytes (sodium, potassium)
   • Complete blood count
   • Glucose

2. Confirmatory testing:

   • ACTH stimulation test (gold standard): Measure cortisol levels before and after administration of synthetic ACTH 1
   • Low cortisol with high ACTH indicates primary adrenal insufficiency
   • Low cortisol with low/normal ACTH suggests secondary adrenal insufficiency 1

3. Additional testing:

   • Plasma renin activity and aldosterone levels
   • Adrenal antibodies (to confirm autoimmune etiology)
   • Thyroid function tests (autoimmune thyroid disease often coexists) 3, 2

Imaging

• CT or MRI of abdomen to visualize adrenal glands 1
• If secondary adrenal insufficiency is suspected, pituitary MRI may be indicated 1

Treatment Options

Hormone Replacement

Glucocorticoid Replacement

• Hydrocortisone: 10-30mg daily in divided doses (typically 2-3 doses)
  • Morning dose should be larger to mimic physiological cortisol secretion pattern
  • Usually 15-20mg in morning, 5-10mg in afternoon 1
• Alternative: Cortisone acetate (slightly less effective than hydrocortisone) 4

Mineralocorticoid Replacement

• Fludrocortisone: 0.1mg daily (range 0.05-0.2mg)
  • Dosage may need adjustment based on:
    • Blood pressure
    • Serum electrolytes
    • Plasma renin activity 1, 5
  • If transient hypertension develops, reduce dose to 0.05mg daily 5

Monitoring Treatment

• Regular assessment of:
  • Clinical symptoms
  • Blood pressure (sitting and standing)
  • Electrolytes
  • Plasma renin activity
  • Weight 1

Patient Education and Emergency Management

Critical Education Points

• Stress dosing instructions:
  • Double or triple glucocorticoid dose during illness, fever, or significant stress
  • For severe illness or surgery: 100mg hydrocortisone IV bolus, followed by 100-300mg/day 1
• Emergency injectable hydrocortisone use
• Medical alert bracelet/card
• Recognition of early warning signs of adrenal crisis 1

Adrenal Crisis Management

• Immediate treatment with:
  • 100mg hydrocortisone IV bolus
  • Followed by 100-300mg/day as continuous infusion or divided doses
  • Rapid IV isotonic saline administration 1

Special Considerations

Pregnancy

• Hydrocortisone dose may need to be increased by 2.5-10mg daily in the third trimester
• During delivery: 100mg hydrocortisone bolus, repeated every 6 hours if necessary 1

Exercise

• For intense or prolonged exercise:
  • Increase hydrocortisone and salt intake
  • Take extra 5mg hydrocortisone before marathon-type events 1

Common Pitfalls and Caveats

1. Delayed diagnosis due to nonspecific symptoms

   • Consider Addison's disease in patients with unexplained fatigue, weight loss, hyperpigmentation, and electrolyte abnormalities 6, 2

2. Inadequate stress dosing during illness or procedures

   • Failure to increase glucocorticoid doses during stress can lead to adrenal crisis 1

3. Inappropriate glucocorticoid dosing

   • Underdosing: persistent fatigue, hypotension
   • Overdosing: weight gain, hypertension, impaired glucose tolerance, reduced bone mineral density 1, 4

4. Failure to recognize adrenal crisis

   • Life-threatening emergency requiring immediate treatment
   • Presents with severe hypotension, vomiting, abdominal pain, confusion 2

5. Insufficient patient education

   • Patients must understand the importance of medication adherence and stress dosing 1, 6