Causes and Risk Factors of Graves’ Disease

Graves’ disease is the most common cause of an overactive thyroid gland (hyperthyroidism). The condition is thought to be caused by genetic, environmental, and other factors. 

Learn more about the causes and risk factors of Graves’ disease.

Common Causes

Graves’ disease is an autoimmune disease that occurs when the body’s immune system mistakenly attacks the thyroid gland. When a person has Graves’ disease, the immune system produces an abnormal antibody known as thyroid-stimulating immunoglobulin (TSI).

TSI stimulates the thyroid gland by mimicking the thyroid-stimulating hormone (TSH) produced in the pituitary gland. The thyroid gland then produces excess thyroid hormone, leading to hyperthyroidism.

A combination of genetic and environmental risk factors is believed to cause Graves’ disease. Certain lifestyle habits also contribute to the development of the disease.

Genetics 

Anyone can develop Graves’ disease, but having a family member with the condition can increase your risk of developing it. Research shows that hereditary factors account for 75% to 80% of a person’s risk of developing Graves’ disease.

Family and twin studies show that a single gene does not cause Graves’ disease—multiple genes and genetic variants contribute to its heritability.

Some of the genes responsible for developing Graves’ disease include:

Immunomodulators: Genes responsible for regulating the immune system have been linked to Graves’ disease. These include HLA, CD25, CD40, CTLA-4, and FOXP3.

Thyroid function genes: Genes responsible for thyroid function, such as the thyroid stimulating hormone receptor (TSHR) and thyroglobulin (Tg), are also associated with Graves’ disease.

Modifier genes: Genes that affect how other genes are expressed—known as modifier genes—may also play a role in developing Graves’ disease.

Not everyone genetically predisposed to Graves’ disease will be affected by the condition. Research suggests that certain environmental factors—such as infection, stress, or pregnancy—activate these genes and contribute to the development of Graves’ disease.

Environmental

Certain environmental factors trigger the body’s autoimmune response and subsequent attack on the thyroid gland, leading to the overproduction of thyroid hormones. Environmental factors associated with the onset of Graves’ disease include:

• Viral infections
• Exposure to radiation
• Exposure to harmful toxins (e.g., the herbicide Agent Orange, heavy metals)

Lifestyle Risk Factors

There are several risk factors associated with Graves' disease, including: 

• Sex: Women are 7 to 8 times more likely to develop Graves' disease than men.
• Age: Graves' disease is more likely in people under age 40.
• Autoimmune history: If you have another autoimmune disease, such as type 1 diabetes or rheumatoid arthritis, you have a higher chance of developing Graves' disease.
• Smoking: Cigarette smoking is associated with an increased risk of Graves' disease.
• Pregnancy: Graves' disease may appear during pregnancy, and the risk of developing the disease is 7 times higher a year after giving birth.
• Increased iodine intake: Eating foods rich in iodine, such as seaweed and seafood, can be harmful and potentially trigger Graves' disease in susceptible people.
• Vitamin D deficiency: Low levels of vitamin D in the bloodstream is associated with Graves' disease.
• Stress: Some research suggests that emotional stress and stressful life events may contribute to some people's onset of Graves' disease.

Summary

Graves’ disease is an autoimmune disorder that causes an overactive thyroid (hyperthyroidism). It occurs when the immune system mistakenly attacks healthy thyroid tissue, which triggers the thyroid gland to overproduce thyroid hormones. 

A combination of genetic and environmental factors contributes to the development of Graves’ disease. Research suggests that a family history of Graves’ disease accounts for 79% of the risk. This means having a family member with Graves’ disease can make you more susceptible to developing the disorder.

Environmental factors account for 21% of the risk. Smoking, vitamin D deficiency, increased iodine intake, exposure to radiation, and viral infections are known to increase a person’s risk of developing Graves’ disease, particularly if they have a genetic predisposition to the disorder. 

A Word From Verywell 

No matter the cause, Graves’ disease is treatable, and most people with the condition can live full, active lives. Talk to your healthcare provider if you have symptoms of Graves’ disease or have a family history and are concerned about your risks.