Graves Disease



Autoimmune disease in which thyroid-stimulating hormone receptor (TSHR) 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 (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
  • Graves disease accounts for 60–80% of all cases of hyperthyroidism
  • Synonym(s): von 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.


  • Higher risk with personal or family history of any autoimmune disease, especially Hashimoto thyroiditis
  • Twin studies show concordance rate as high as 20%.

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

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