Graves' Disease

Definition

Graves' disease is an autoimmune disorder characterized by hyperthyroidism due to circulating thyroid-stimulating immunoglobulins (TSIs) that activate the TSH receptor, leading to increased thyroid hormone production and diffuse thyroid enlargement.

Epidemiology

• Most common cause of hyperthyroidism in adults
• Prevalence: ~0.5–1% of the population
• More common in women (female-to-male ratio 5–10:1)
• Typically occurs between ages 30–50 years

Etiology

• Autoimmune production of TSH receptor antibodies (TRAb/TSI)
• Genetic predisposition: HLA-DR3, CTLA-4, PTPN22 polymorphisms
• Environmental triggers: stress, infection, smoking
• Other risk factors: female sex, pregnancy, iodine excess

Pathophysiology

• TSIs bind TSH receptor → continuous stimulation of thyroid hormone synthesis and release
• Increased thyroid hormone → hypermetabolic state
• Diffuse thyroid enlargement due to hyperplasia of follicular cells
• Extrathyroidal manifestations: orbitopathy, dermopathy due to autoimmune-mediated tissue changes