What is Addison's disease?

What is Addison's Disease

Addison's disease is chronic primary adrenal insufficiency resulting from damage to the adrenal cortex, leading to inadequate production of cortisol and aldosterone, which can be life-threatening if untreated. 1

Definition and Epidemiology

• Addison's disease occurs when the adrenal cortex is damaged and cannot produce sufficient cortisol and aldosterone, regardless of the underlying cause. 1
• The prevalence is approximately 10-15 per 100,000 population, making it a rare condition. 1
• In Europe and developed countries, autoimmunity accounts for approximately 85% of cases, having surpassed tuberculosis as the primary cause. 1, 2
• Other causes include tuberculosis (still significant in some populations), adrenal hemorrhage, malignant disorders, genetic conditions like adrenoleukodystrophy, and certain medications. 2, 3

Pathophysiology

• The disease disrupts the hypothalamic-pituitary-adrenal (HPA) axis, resulting in cortisol deficiency which is critical for regulating metabolism, immune function, and stress responses. 3
• Aldosterone deficiency leads to dysregulation of sodium and potassium homeostasis, causing hypotension and dehydration. 3
• Symptoms typically do not occur until most of the adrenal gland (often >90%) has been destroyed. 4

Clinical Presentation

• Symptoms develop insidiously over months to years and are often nonspecific, including persistent fatigue, myasthenia (muscle weakness), unintentional weight loss, malaise, anorexia, and nausea. 3, 4
• Salt craving is a characteristic symptom. 1, 5
• Hyperpigmentation of the skin, especially in areas subjected to friction, is a classic finding due to elevated ACTH levels. 3, 2
• Hypotension and features consistent with orthostatic hypotension are common. 5
• Gastrointestinal complaints including nausea, vomiting, and abdominal pain may occur. 5
• Neuropsychiatric manifestations including depression and psychosis can occur. 3

Laboratory Findings

• Hyponatremia is present in approximately 90% of newly diagnosed cases. 1, 6
• Hyperkalemia occurs in approximately 50% of cases at diagnosis due to aldosterone deficiency. 1, 6
• Low serum cortisol with markedly elevated plasma ACTH levels are characteristic. 1, 6
• Other findings may include mild to moderate hypercalcemia, anemia, mild eosinophilia, lymphocytosis, and elevated liver transaminases. 6
• Children may present with hypoglycemia, which is rare in adults. 6

Associated Autoimmune Conditions

• Approximately half of patients with autoimmune Addison's disease have other co-existing autoimmune diseases. 1
• Autoimmune polyendocrine syndrome type-1 (APS-1) includes PAI, hypoparathyroidism, and chronic mucocutaneous candidiasis. 1
• Autoimmune polyendocrine syndrome type-2 (APS-2) includes PAI with primary hypothyroidism and other autoimmune conditions. 1

Critical Complication: Adrenal Crisis

• Following an acute stressor such as a gastrointestinal infection or trauma, patients may experience an adrenal crisis, which can cause sudden death. 5, 7
• Adrenal crisis is a life-threatening emergency requiring immediate treatment with hydrocortisone 100 mg IV or IM, followed by 100 mg every 6-8 hours until recovery. 1
• Rapid infusion of isotonic (0.9%) sodium chloride solution, initially at 1 L/hour until hemodynamic improvement, is essential. 1

Prognosis and Mortality

• Even with established glucocorticoid and mineralocorticoid replacement therapy, mortality in patients with Addison's disease remains increased. 7
• Health-related quality of life is often reduced despite treatment. 7
• Premature death from adrenal crises remains a significant risk, emphasizing the importance of patient education and emergency preparedness. 1, 7