Addison's disease

Addison's disease is a chronic endocrine disorder caused by primary adrenal insufficiency leading to deficient production of glucocorticoids and often mineralocorticoids. It commonly presents with nonspecific systemic features and can progress to life-threatening adrenal crisis if untreated. Management requires hormone replacement, patient education, and often lifelong follow-up with specialists.

Signs and symptoms

Patients typically report progressive fatigue, anorexia, weight loss, and generalized weakness; physical findings may include hyperpigmentation of the skin and mucous membranes, orthostatic hypotension, and salt craving. Additional manifestations include abdominal pain, nausea, vomiting, salt-wasting with hyponatremia, hyperkalemia, and nonspecific neuropsychiatric symptoms that can mimic depressive or cognitive disorders. During physiological stress such as infection, surgery, or trauma, individuals are at high risk of decompensation leading to severe hypotension, shock, and hypoglycemia.

Causes and pathophysiology

The most common cause in developed regions is autoimmune destruction of the adrenal cortex, often associated with other autoimmune conditions such as autoimmune thyroid disease, type 1 diabetes mellitus, and pernicious anemia. Infectious etiologies—historic examples include tuberculosis and more recent concerns include disseminated fungal infections or cytomegalovirus—cause adrenal destruction in endemic or immunocompromised settings. Metastatic infiltration from malignancies (for example lung or breast cancer), bilateral adrenal hemorrhage related to anticoagulation or septicemia (as in Waterhouse–Friderichsen syndrome), and genetic disorders affecting steroidogenesis (including congenital adrenal hyperplasia variants) are other important mechanisms. Loss of cortical tissue reduces cortisol and aldosterone synthesis, leading to decreased gluconeogenesis, impaired vascular responsiveness to catecholamines, and disturbed sodium–potassium balance; pituitary ACTH rises as a compensatory response, accounting for characteristic hyperpigmentation from increased melanocyte-stimulating hormone cleavage.

Diagnosis

Clinical suspicion arises from symptom clusters, electrolyte disturbances, and hemodynamic instability. Initial biochemical evaluation includes morning serum cortisol and plasma ACTH levels; an elevated ACTH with low cortisol supports primary adrenal failure. The standard diagnostic confirmation is an ACTH (cosyntropin) stimulation test demonstrating inadequate cortisol response. Additional tests include plasma renin and aldosterone to assess mineralocorticoid function, adrenal autoantibodies (such as 21-hydroxylase antibodies) to identify autoimmune etiology, and imaging studies—computed tomography or magnetic resonance imaging—of the adrenal glands to detect hemorrhage, infection, or metastases. During adrenal crisis, rapid point-of-care glucose, electrolytes, and arterial blood gas measurements guide urgent care.

Treatment and management

Long-term therapy centers on physiologic hormone replacement: daily oral glucocorticoid replacement (hydrocortisone in divided doses or equivalent such as prednisolone) and mineralocorticoid replacement with fludrocortisone when indicated. Patient education on dose adjustment during intercurrent illness, injury, or surgery (stress dosing), emergency parenteral glucocorticoid use, and carrying medical alert identification or steroid cards is essential. Management also addresses electrolyte abnormalities, volume resuscitation, and treatment of precipitating causes; in adrenal crisis, immediate intravenous hydrocortisone and isotonic saline are cornerstones while awaiting diagnostic confirmation. Coordination with endocrinologists, primary care, pharmacists, and, when relevant, oncologists or infectious disease specialists improves outcomes. Vaccination and prophylactic measures may be considered for patients at risk of infectious precipitants.

Prognosis and complications

With appropriate replacement therapy and education, quality of life and life expectancy approach normal, but risks remain for adrenal crises precipitated by infection, trauma, or nonadherence. Long-term complications include cardiovascular morbidity related to suboptimal replacement, impaired bone density from glucocorticoid exposure, and comorbid autoimmune conditions that may affect multiple organ systems. Periodic reassessment of dosing, monitoring for metabolic effects, and screening for associated autoimmune disorders are recommended to minimize morbidity. Emergency preparedness, including access to injectable glucocorticoids and prompt medical attention during acute illness, substantially reduces mortality.

Category:Endocrine diseases