What is Addison's disease?

What is Addison's Disease

Addison's disease is primary adrenal insufficiency resulting from damage to the adrenal cortex, causing inadequate production of cortisol and aldosterone hormones, regardless of the underlying cause. 1

Epidemiology and Prevalence

• The disease affects approximately 10-15 per 100,000 population, making it a rare condition. 1
• In Western Europe, autoimmunity accounts for approximately 85% of cases after excluding congenital adrenal hyperplasia. 1
• Tuberculosis, adrenal hemorrhage, and genetic disorders comprise the remaining causes. 1

Pathophysiology

• The condition results from destruction of the adrenal cortex, the region responsible for hormone synthesis. 2
• This disrupts the hypothalamic-pituitary-adrenal (HPA) axis, leading to cortisol deficiency which is critical for regulating metabolism, immune function, and stress responses. 2
• Aldosterone deficiency causes dysregulation of sodium and potassium homeostasis, resulting in hypotension and dehydration. 2
• Patients also lose adrenal androgen production (DHEA, androstenedione), which is particularly significant in women as the adrenal glands are their primary androgen source. 3

Clinical Presentation

• Symptoms develop insidiously over months to years and are often nonspecific. 1, 4
• Common manifestations include persistent fatigue, muscle weakness (myasthenia), unintentional weight loss, hypotension, and salt craving. 5, 2
• Hyperpigmentation of the skin occurs, especially in areas subjected to friction, due to elevated ACTH levels. 2, 6
• Additional symptoms include malaise, anorexia, and nausea. 7
• Symptoms typically do not appear until most of the adrenal gland has been destroyed. 7

Laboratory Findings

• Hyponatremia is present in 90% of newly diagnosed cases. 1, 5
• Hyperkalaemia occurs in approximately 50% of cases. 5
• Low serum cortisol and elevated plasma ACTH levels are characteristic. 5
• The classical combination of hyponatremia and hyperkalaemia is not always reliable for diagnosis. 1

Associated Autoimmune Conditions

• Approximately 50% of patients with autoimmune Addison's disease have other co-existing autoimmune diseases. 1, 5
• Common associations include autoimmune thyroid disease, autoimmune gastritis with vitamin B12 deficiency, type 1 diabetes mellitus, premature ovarian insufficiency, vitiligo, and coeliac disease. 1
• Autoimmune polyendocrine syndrome type-1 (APS-1) is defined by the combination of two of three components: primary adrenal insufficiency, hypoparathyroidism, and chronic mucocutaneous candidiasis. 1, 5
• Autoimmune polyendocrine syndrome type-2 (APS-2) most commonly involves primary adrenal insufficiency with primary hypothyroidism, but can include Graves' disease, autoimmune gastritis, and type 1 diabetes. 1, 5

Historical Context and Prognosis

• Prior to the 1940s, Addison's disease was always fatal. 1
• The synthesis of corticosteroids by Kendall and Reichstein made life-saving treatments possible and transformed it into a fully treatable chronic condition. 1
• With proper treatment, Addison's disease is now a manageable chronic condition. 5
• However, premature death from adrenal crises remains a risk, and patients face therapy-related complications including osteoporosis and cardiovascular disease. 1, 5
• Quality of life and ability to work is reduced in many patients. 1