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.
Special patient groups
Graves disease in children
- Epidemiology: most common cause of hyperthyroidism in children
- Features of hyperthyroidism: See “Clinical features” in “ .”
- Most children develop a goiter, which can be large and cause compressive symptoms (See “Symptoms/clinical findings” in )
- Younger children often show a growth spurt
- Graves ophthalmopathy, if present, is often mild. However, lid lag causing apparent proptosis is often seen.
- Graves dermopathy rarely occurs in children.
- Best initial treatment
- Methimazole is the drug of choice
- Most children go into remission within 2 years of treatment.
- Symptom control with β blockers: atenolol, propranolol
Radioactive iodine (RAI) ablation
- In children > 10 years/adolescents without large goiters: potential first-line treatment option
- In children who relapse after long-term therapy with antithyroid drugs: as a second-line treatment
- In children > 5 years: lower dose is recommended
- Contraindicated in children < 5 years
- Nearly half the children treated with radioiodine ablation become hypothyroid (thyroid hormone replacement is necessary)
- Risk of thyroid cancer is not elevated with therapeutic/diagnostic doses of radioactive iodine.
- Surgery (near-total thyroidectomy) is indicated in:
- Lifelong monitoring of thyroid function
- Antithyroid drugs
Graves disease in the elderly
- Epidemiology: the second most common cause of hyperthyroidism in elderly individuals, after toxic multinodular goiter
- Classic signs of thyrotoxicosis are often absent/minimal in elderly individuals
- Treatment of other co-existing diseases may mask the symptoms of hyperthyroidism (e.g., β blockers for hypertension/angina may mask tachycardia and tremors).
- Monosymptomatic hyperthyroidism: Elderly patients may present with only one symptom of hyperthyroidism, myopathy being the most common.
- Apathetic hyperthyroidism: A common presentation of Graves in the elderly
- Diagnostics: The diagnosis of thyrotoxicosis in the elderly is often made during laboratory workup for unexplained weight loss or worsening cardiovascular disease (see “Diagnostics” above).