What are the typical presentation and treatment of Addison's disease?

Presentation and Treatment of Addison's Disease

Addison's disease (primary adrenal insufficiency) typically presents with fatigue, weight loss, hypotension, hyperpigmentation, salt craving, and electrolyte disturbances (hyponatremia and hyperkalemia), and requires lifelong treatment with glucocorticoid and mineralocorticoid replacement therapy. 1, 2, 3

Clinical Presentation

Common Symptoms and Signs

• Insidious onset symptoms:
  • Persistent fatigue and weakness (myasthenia)
  • Unintentional weight loss
  • Anorexia
  • Salt craving
  • Hypotension
  • Hyperpigmentation of skin (especially in areas subjected to friction)
  • Electrolyte disturbances (↓Na, ↑K) 1, 2, 4

Laboratory Findings

• Low cortisol levels (basal and ACTH-stimulated)
• High ACTH levels (in primary adrenal insufficiency)
• Hyponatremia and hyperkalemia
• Presence of autoantibodies against 21-hydroxylase (in autoimmune etiology) 1, 3

Differentiating Primary vs Secondary Adrenal Insufficiency

Type	ACTH Level	Cortisol Level	Electrolytes	Hyperpigmentation
Primary	High	Low	↓Na, ↑K	Present
Secondary	Low	Low	Generally normal	Absent

Etiology

• Primary causes:
  • Autoimmune adrenalitis (most common in industrialized countries)
  • Infectious (e.g., tuberculosis)
  • Hemorrhagic damage
  • Metastatic neoplasms
  • Genetic disorders (e.g., adrenoleukodystrophy)
  • Iatrogenic (medications, adrenalectomy) 2, 5

Treatment

Acute Adrenal Crisis Management

1. Immediate intervention:

   • Hydrocortisone 100 mg IV immediately
   • Fluid resuscitation with normal saline (10-20 ml/kg; maximum 1,000 ml)
   • Followed by hydrocortisone infusion of 200 mg/24h until stabilized 1, 3

2. Weight-based hydrocortisone dosing:

   • Up to 10 kg: 2 mg/kg IV induction, 25 mg/24h maintenance
   • 11-20 kg: 2 mg/kg IV induction, 50 mg/24h maintenance
   • Over 20 kg (prepubertal): 2 mg/kg IV induction, 100 mg/24h maintenance
   • Over 20 kg (pubertal): 2 mg/kg IV induction, 150 mg/24h maintenance 1

Chronic Management

1. Glucocorticoid replacement:

   • Hydrocortisone 10-30 mg daily in divided doses (or equivalent prednisone 5-10 mg daily) 1, 3

2. Mineralocorticoid replacement:

   • Fludrocortisone 0.1 mg daily (range: 0.1 mg three times weekly to 0.2 mg daily)
   • Reduce to 0.05 mg daily if transient hypertension develops 1, 6

3. Combination therapy:

   • Fludrocortisone is preferably administered in conjunction with cortisone (10-37.5 mg daily in divided doses) or hydrocortisone (10-30 mg daily in divided doses) 6

Patient Education and Long-term Management

• Stress dosing instructions
• Emergency injectable hydrocortisone use
• Medical alert bracelet/card
• Recognition of early warning signs of adrenal crisis 1

Monitoring

• Regular assessment for signs indicating dosage adjustment
• Monitoring for side effects: lipodystrophy, hypertension, cardiovascular disease, osteoporosis, and metabolic disorders 1, 6

Important Considerations and Pitfalls

Common Pitfalls

1. Delayed diagnosis due to nonspecific symptoms and insidious onset - maintain high clinical suspicion for patients with fatigue, weight loss, and hyperpigmentation 5, 4

2. Inadequate stress dosing during illness, surgery, or trauma - patients need increased glucocorticoid doses during these periods 1, 5

3. Overlooking mineralocorticoid replacement - essential for patients with primary adrenal insufficiency to maintain electrolyte balance 1, 6

4. Failure to recognize adrenal crisis - a life-threatening emergency requiring immediate treatment without waiting for laboratory confirmation 1, 3

With proper diagnosis and treatment, patients with Addison's disease can resume normal daily activities with a highly functional status, though lifelong treatment and monitoring are required 4.