Can Addison's disease occur in anyone or is a prior medical history required?

Addison's Disease Can Occur in Anyone Without Prior Medical History

Addison's disease (primary adrenal insufficiency) can develop in anyone without requiring a prior medical history, as it is most commonly caused by autoimmune destruction of the adrenal cortex. 1, 2

Causes and Risk Factors

Addison's disease can develop through several pathways:

• Autoimmune adrenalitis: The predominant cause in Western countries (85% of cases), resulting from immune-mediated destruction of the adrenal cortex 1
• Infections: Including tuberculosis, fungal infections, and viral infections 1
• Hemorrhage: Can occur with anticoagulant therapy, antiphospholipid syndrome, or trauma 1
• Genetic disorders: Including adrenoleukodystrophy, congenital adrenal hyperplasia, and mitochondrial disorders 1
• Infiltrative conditions: Such as amyloidosis, hemochromatosis, and metastatic cancer 1
• Medication-induced: From drugs like ketoconazole, etomidate, and mitotane 1

Diagnostic Approach

When Addison's disease is suspected, diagnosis follows a two-step process:

1. Confirm adrenal insufficiency:

   • Measure morning cortisol and ACTH levels
   • Perform ACTH stimulation test (gold standard): administering 250 μg synthetic ACTH with cortisol measurement at 0,30, and 60 minutes 2
   • Peak cortisol <500 nmol/L confirms adrenal insufficiency 2

2. Determine etiology:

   • Test for 21-hydroxylase antibodies (21OH-Ab) - positive in autoimmune cases 1
   • CT scan of adrenal glands if 21OH-Ab negative 1
   • Very long-chain fatty acid testing in males to rule out adrenoleukodystrophy 1
   • Additional testing based on clinical presentation 1

Clinical Presentation

Addison's disease often presents with subtle symptoms that develop gradually:

• Fatigue and weakness
• Weight loss and decreased appetite
• Hyperpigmentation (especially in skin creases, mucous membranes)
• Salt craving
• Hypotension and orthostatic symptoms
• Gastrointestinal symptoms (nausea, vomiting, abdominal pain)
• Laboratory findings: hyponatremia (90% of cases), hyperkalemia (50% of cases) 1, 3

Treatment Approach

Treatment requires lifelong hormone replacement:

• Glucocorticoid replacement: Hydrocortisone 15-25 mg daily in divided doses 2
• Mineralocorticoid replacement: Fludrocortisone 50-200 μg daily 2, 4
• Stress dosing: Critical for preventing adrenal crisis
  • Minor illness: Double or triple usual daily dose
  • Moderate stress: Hydrocortisone 50-75 mg/day in divided doses
  • Severe stress/adrenal crisis: Hydrocortisone 100 mg IV immediately, followed by 100 mg every 6-8 hours 2

Important Considerations

• No prior medical history required: Addison's disease can be the first manifestation of autoimmune disease in a previously healthy individual 3
• Associated conditions: Up to 50% of patients with autoimmune Addison's disease develop other autoimmune disorders during their lifetime 3
• Common associations: Autoimmune thyroid disease, autoimmune gastritis with vitamin B12 deficiency, type 1 diabetes, premature ovarian insufficiency, vitiligo, and celiac disease 1
• Polyendocrine syndromes: Addison's disease can be part of autoimmune polyendocrine syndromes (APS-1 or APS-2) 1

Patient Education and Monitoring

• All patients should wear medical alert identification and carry a steroid emergency card 2
• Regular monitoring of clinical status, weight, blood pressure, and electrolytes 2
• Annual screening for associated autoimmune conditions 2
• Education on recognizing and managing adrenal crisis is essential 2

Addison's disease requires high clinical suspicion for diagnosis, as symptoms can be subtle until an adrenal crisis develops. The condition can affect anyone regardless of prior medical history, with autoimmunity being the most common cause in developed countries.