Autoimmune disease in which thyroid-stimulating hormone (TSH) receptor activation by thyrotropin receptor antibodies (TRAb) cause increased thyroid hormone secretion; most common cause of hyperthyroidism; classic findings are thyrotoxicosis, diffuse goiter, ophthalmopathy (orbitopathy), and occasionally localized dermopathy (pretibial myxedema).
- Annual incidence of 20 to 50 cases per 100,000 persons
- Peaks between 30 and 50 years of age
- Occurs in 0.2% of pregnancies, of which 95% is due to Graves disease
- Graves disease accounts for 60–80% of all cases of hyperthyroidism.
Etiology and Pathophysiology
- Excessive production of 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.
- Higher risk with personal or family history of any autoimmune disease, especially Hashimoto thyroiditis
- Twin studies show concordance rate as high as 20%.
- 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 therapy (HAART); rarely, immune-modulating medications (e.g., interferon therapy)
- Smoking (higher risk of developing ophthalmopathy)
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
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