What causes Graves’ disease is not yet firmly established, but the underlying root cause is believed to be an autoimmune disorder. Additionally, there are trigger factors that make you more prone to this disease.
What happens is that the autoimmune system of the body mistakenly attacks the thyroid gland tissue and puts it into overdrive.
This speeds up the production and secretion of the thyroid hormones, which rise to excessive levels and lead to hyperthyroidism throwing your body into a hypermetabolic state.
We all know that our body protects itself from external pathogens and provides resistance to infection and toxins. This is done by the immune system of the body.
At times, the immune system makes a mistake and attacks normal healthy tissues within the body causing health problems. These problems are labeled as autoimmune diseases.
There are various reasons why you can develop hyperthyroidism, but Graves’ disease remains the most common cause accounting for 70% of the cases.
Research still has to identify the main reason why some people develop autoimmune diseases and some do not. There could possibly be a genetic cause combined with some external triggers such as an infection.
Pathophysiology
An autoimmune reaction is basically a reaction between an external invading agent (called the antigen) and the antibodies that the immune system produces to fight the antigen.
In Graves’ disease, the B and T lymphocytes of the immune system make antibodies, mainly IgG against the thyroid gland. These antibodies are called thyroid-stimulating immunoglobulins (TSIs).
These antibodies target four different proteins (antigens) that are present in the thyroid. These include:
Thyroglobulin
Thyroid peroxidase
Sodium-iodide symporter
Thyroid-stimulating hormone (TSH) receptor
Antibodies to the thyroid hormones T3 and T4 are also produced.
In the normal course, when the levels of thyroid hormones drop in the body, the pituitary releases the hormone, Thyroid Stimulating Hormone (TSH). This hormone stimulates the thyroid gland to produce more thyroid hormones to keep up their hormone levels in the blood.
In Graves’ disease, what happens is that TSI binds to and stimulates TSH. It acts as a long-acting stimulant making the thyroid produce more of its hormones in spite of their levels being optimal. This leads to excessive amounts of T3 and T4 in the body resulting in the onset of hyperthyroidism and goiter (enlargement of the thyroid gland).
The cause of the symptom of exophthalmos (protruding eyes) often seen in Graves’ disease is explained by the fact that the thyroid gland and the eye muscles invite the same antigen. This results in the release of antibodies that attack the thyroid and the eye muscles causing them both to enlarge. That is why you see the protruding eyes in Graves’.
The “orange peel” appearance of the skin seen in Graves’ dermopathy is due to the infiltration of antibodies beneath the skin resulting in an antigen-antibody reaction causing inflammation and fibrous plaques on the skin.
Causes and risk factors
If you are associated with any of the following factors, you are at an increased risk. These are the conditions that can cause you to develop Graves’ disease and its symptoms.
The following are the common causes of Graves’ disease and which also increase your risk.
Autoimmune predisposition
People with an autoimmune predisposition are more likely to contract this disease. For example, those who have been affected by other autoimmune diseases such as rheumatoid arthritis, lupus, and vitiligo are at a higher risk.
Gender and ethnicity
Again, if you are a woman, your risk of contracting Graves’ disease increases tenfold. However, men present with a more severe form of hyperthyroidism and have a lower remission rate than women after a course of antithyroid medication.
Women, particularly of African-American, Hispanic-American, and Native-American women origin are at a higher risk for some of these autoimmune disorders.
Infection
It is suspected that a viral or bacterial infection can trigger off the onset of this disease. Some bacteria such as Yersinia enterocolitica, Escherichia coli, and some other Gram-negative bacteria have been found to contain TSH binding sites.
Genetic trait
People with a particular genetic makeup are more prone to develop Graves’. Therefore, if you have a family history of an autoimmune disease, it makes you more liable.
Genes that are suspected to carry Graves disease from parents to their children include genes that code for CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22.
Autoimmune diseases tend to run in families. You do find families where more than one member suffers from Graves’ disease and it tends to affect the following generations.
Cigarette smoking
Cigarette smoking is a major factor, which can double your risk of developing Graves’ disease. The more you smoke, the higher the risk. Heavy smokers who smoked more than 25 cigarettes a day tripled their risk.
If you have quit smoking, the risk dramatically reduces after 10 to 15 years. But, your risk still stays higher than a nonsmoker.
Smoking has an adverse effect on your immune system, which can go rogue and attack your thyroid. It also increases the risk of developing severe ophthalmopathy.
Age
Though Graves’ can strike at any age, it peaks between the age of 20 and 40 years, which makes you more prone during those years.
Pregnancy
Graves’ disease is also seen to occur during pregnancy and childbirth because of the stressed-out immune system. It again is the most common cause of hyperthyroidism during pregnancy seen in 1 out of 1500 pregnancies.
Additionally, women with Graves’ disease who become pregnant are at a higher risk of developing severe hyperthyroidism, which can lead to a thyroid storm.
Graves’ disease usually improves during the third trimester of pregnancy but can rebound after childbirth.
Stress
Mental stress or physical stress makes you more susceptible to Graves’. Acute stress, such as trauma, surgery, heart attack, childbirth, or infection, usually can trigger this thyroid problem and precipitate it.
At times like these, the immune system is under considerable stress and can mistakenly attack the thyroid gland.
In an untreated Graves’ disease, stress-like situations can even trigger a thyroid storm, which can be life-threatening.
Environmental causes
Besides the genetic and immune causes, certain environmental factors increase the risk in susceptible individuals. They include:
smoking
stress
pollution
infections
radiation exposure
increased iodine therapy
selenium intake
injury or surgery of the thyroid gland
injection of certain medications like Ethanol, Interferon Beta-1b or Interleukin-4 Therapy
pregnancy
Obesity and alcohol
According to WebMD, obesity and alcohol were not associated with an increased risk of Graves’ disease, as believed by some.
Aggravating factors
The following factors can aggravate an existing Graves’ disease and cause it to flare up:
