Graves Disease

BASICS

DESCRIPTION

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).

EPIDEMIOLOGY

Incidence

  • 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.

Prevalence

Has been reported to affect 1–1.5% of the world population

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.

Genetics

  • 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, selenium, amiodarone, lithium, highly active antiretroviral (HAART); rarely, immune-modulating medications (e.g., interferon therapy)
  • Smoking (higher risk of developing ophthalmopathy)
  • Low vitamin D levels
  • Bacterial/viral infections

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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