Epidemiology

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

Etiology

Genetic predisposition

50% of patients with Graves disease have a family history of autoimmune disorders (e.g., type 1 diabetes
mellitus, Hashimoto disease, pernicious anemia, myasthenia gravis)

Associated with HLA-DR3 and HLA-B8 alleles

Autoimmunity: B and T lymphocyte-mediated disorder

Triggers

Infectious agents: Yersinia enterocolitica and Borrelia burgdorferi have been shown to trigger antigen
mimicry for homologies between their protein constituents and thyroid autoantigens.

Stress

Physical: surgery, trauma

Psychological

Pregnancy [2]

Environmental factors: smoke, irradiations, drugs, endocrine disruptors

Stress causes cortisol-mediated immune suppression, which is often followed by rebound immunologic
hyperactivity and can trigger Graves disease in genetically susceptible individuals.

Thyroid overstimulation by high levels of hCG and TRAb during the first trimester increases the risk of
Graves disease in the first trimester of pregnancy. In the second trimester, the risk decreases due to
progesterone-induced immunosuppression. The risk of Graves disease increases postpartum in
susceptible patients due to a drop in progesterone level which leads to the rebound of the immune
system that can trigger autoimmunity.

Clinical features

Symptoms of hyperthyroidism

Triad of Graves disease

Diffuse goiter

Smooth, uniformly enlarged goiter

Bruit may be heard at the superior poles of the lobes

Ophthalmopathy (see Graves ophthalmopathy)

Exophthalmos

Ocular motility disturbances

Lid retraction and conjunctival conditions

Dermopathy (pretibial myxedema): non-pitting edema and firm plaques on the anterior/lateral aspects
of both legs

Hyperthyroidism

A condition of increased thyroid gland function (e.g., synthesis and secretion of thyroid hormones).
Etiologies include Graves disease and toxic multinodular goiter. Manifestations include heat intolerance,
weight loss, diarrhea, tachycardia, fine tremor, and muscle weakness.

Risk factors

Although anyone can develop Graves' disease, many factors can increase the risk of disease, including:
Family history. Because a family history of Graves' disease is a known risk factor, there is likely a gene or
genes that can make a person more susceptible to the disorder.

Sex. Women are much more likely to develop Graves' disease than are men.

Age. Graves' disease usually develops in people before age 40.

Other autoimmune disorders. People with other disorders of the immune system, such as type 1
diabetes or rheumatoid arthritis, have an increased risk.

Emotional or physical stress. Stressful life events or illness may act as a trigger for the onset of Graves'
disease among people who have genes that increase their risk.

Pregnancy. Pregnancy or recent childbirth may increase the risk of the disorder, particularly among
women who have genes that increase their risk.

Smoking. Cigarette smoking, which can affect the immune system, increases the risk of Graves' disease.
Smokers who have Graves' disease are also at increased risk of developing Graves' ophthalmopathy.