Aetiology

The most common causes are:

• autoimmune adrenalitis - 80% of cases
  • it can occur as part of autoimmune polyendocrine syndrome
    • autoimmune polyendocrine syndrome type I (APS type 1)
      • around 80% of patients with APS type I develop Addison’s
    • autoimmune polyendocrine syndrome type II (APS type 2) (1)
• historically, tuberculosis but less common today
  • still the most common cause in many developing countries
  • recently a resurgence of tuberculous adrenalitis has been noticed due to an increase in patients with acquired immunodeficiency syndrome (1).
• bilateral adrenalectomy for malignant disease
• cessation of therapeutic corticosteroids or failure to increase dose to cover stress

Less common causes include:

• infections:
  • fungal diseases e.g. histoplasmosis
  • bacterial e.g. Waterhouse-Friedrichson syndrome
  • cytomegalovirus infection in AIDS
    
    
• infiltration:
  • amyloidosis
  • sarcoidosis
  • haemochromatosis
  • metastatic carcinoma (bronchus, breast, malignant melanoma)
    
    
• drugs - rifampicin, etomidate, ketoconazole
  
  
• congenital adrenal hyperplasia
  
  
• congenital adrenal hypoplasia - X linked
  
  
• haemorrhage into the adrenal glands:
  • during breech delivery
  • complication of anticoagulation therapy
    
    
• adrenoleukodystrophy
  
  
• adrenal vein thrombosis after trauma, adrenal venography
  
  
• apparent insufficiency - pseudohypoaldosteronism

Reference:

• (1) Leelarathna L, Powrie JK, Carroll PV. Thomas Addison's disease after 154 years: modern diagnostic perspectives on an old condition. QJM. 2009;102(8):569-73
• (2) Bornstein SR. Predisposing factors for adrenal insufficiency. N Engl J Med. 2009;360(22):2328-39