Graves disease is the most common cause of hyperthyroidism and often affects women. It is an autoimmune condition that is associated with circulating TSH receptor autoantibodies leading to overstimulation of the thyroid gland with excess thyroid hormone production. The classic clinical triad of Graves disease involves a diffuse vascular goiter, ophthalmopathy, and pretibial myxedema, although not all features may be present in a patient. The clinical diagnosis of Graves disease is confirmed via assessment of TSH and T3/T4 levels as well as through detection of thyroid antibodies (TRAb, TPOAb, TgAb). In addition, a diffuse uptake of 123I may be seen on thyroid scintigraphy. Treatment includes beta blockers to quickly alleviate symptoms, antithyroid drugs to achieve euthyroid status, and radioiodine ablation or, less commonly, near-total thyroidectomy for definitive control of the disease.
- Most common cause of hyperthyroidism in the United States
- Incidence: ∼ 30 cases per 100,000 people per year
- Sex: ♀ > ♂ (8:1)
- Typical age range: 20–40 years
Epidemiological data refers to the US, unless otherwise specified.
- Genetic predisposition
- Autoimmunity: B and T lymphocyte-mediated disorder
- Infectious agents: Yersinia enterocolitica and Borrelia burgdorferi have been shown to trigger antigen mimicry for homologies between their protein constituents and thyroid autoantigens.
- Physical: surgery, trauma
- Pregnancy 
- Environmental factors: smoke, irradiations, drugs, endocrine disruptors
- General mechanism: B and T cell-mediated autoimmunity → production of stimulating immunoglobulin G (IgG) against TSH-receptor (TRAb; type II hypersensitivity reaction) → ↑ thyroid function and growth → hyperthyroidism and diffuse goiter
- Thyroid-associated ophthalmopathy: activated B and T cells infiltrate retro-orbital space targeting orbital fibroblasts → cytokine release (e.g. TNF-α, IFN-γ) → local inflammatory response → fibroblast proliferation and differentiation to adipocytes → production of hyaluronic acid and GAGs and increased amount of adipocytes → increase in the volume of intraorbital fat and muscle tissues → exophthalmos, lid retraction, disturbances in ocular motility (causing diplopia)
- Pretibial myxedema: dermal fibroblast stimulation and deposition of glycosaminoglycans in connective tissue
- Symptoms of
Triad of Graves disease
- Diffuse goiter
- Ophthalmopathy (see )
- Dermopathy (pretibial myxedema): non-pitting edema and firm plaques on the anterior/lateral aspects of both legs
- Best initial test: ↓/undetectable TSH and ↑ T3/T4 (see “Diagnostics” in )
- Measure thyroid antibodies
- Thyroid scintigraphy
- Thyroid ultrasound (with color Doppler)
- Diffuse, uniform gland enlargement
- Cut surfaces show beefy red appearance
- Microscopic: histological features of an overactive gland
- β-blockers: rapid control of hyperthyroidism symptoms
- : thionamides (e.g., methimazole, propylthiouracil)
- Surgery: near-total thyroidectomy is rarely done in Graves disease
- Complications of therapy
- See “Therapy” in h for more information.
- Also see orbital disorders for the treatment of Graves ophthalmopathy.