Description

Autoimmune disease in which thyroid-stimulating antibodies cause increased thyroid function; most common cause of hyperthyroidism. Classic findings are goiter, ophthalmopathy (orbitopathy), and occasionally dermopathy (pretibial or localized myxedema).

Epidemiology

• Annual incidence of 20 to 50 cases per 100,000 persons (1)
• Peaks between 30 and 50 years of age, but people can be affected at any age
• Occurs in 0.2% of pregnancies, of which 95% is due to Graves disease

• Overall prevalence of hyperthyroidism in United States: ~2% for women and 0.2% for men
• More common in white and Hispanic populations in comparison to the black population
• Graves disease accounts for 60–80% of all cases of hyperthyroidism
• Synonym(s): Basedow disease

Etiology and Pathophysiology

• Excessive production of thyroid-stimulating hormone (TSH) receptor antibodies from B cells primarily within the thyroid, likely due to genetic clonal lack of suppressor T cells
• Binding of these antibodies to TSH receptors in the thyroid activates the receptor, stimulating thyroid hormone synthesis and secretion as well as thyroid growth (leading to goiter).
• Binding to similar antigen in retro-orbital connective tissue causes ocular symptoms.

Genetics
Higher risk with personal or family history of any autoimmune disease, especially Hashimoto thyroiditis

Risk Factors

• Female gender (5 to 10 times more than men)
• Postpartum period
• Family history (15% of patients with Graves disease have an affected relative)
• Medications: iodine, amiodarone, lithium, highly active antiretroviral (HAART); rarely, immune-modulating medications (e.g., interferon therapy)
• Smoking (higher risk of developing ophthalmopathy)

General Prevention

Screening TSH in asymptomatic patients is not recommended.

Commonly Associated Conditions

• Mitral valve prolapse
• Type 1 diabetes mellitus
• Addison disease, hypokalemic periodic paralysis
• Vitiligo, alopecia areata
• Other autoimmune disorders (myasthenia gravis, celiac disease)