Causes of Graves’ disease

The exact cause of Grave’s Disease seems to be unclear. Graves’ disease is speculated to be an autoimmune condition that leads to overactivity of the thyroid gland or hyperthyroidism. (1-6)

What is the thyroid gland and what does it do?

The thyroid is a small butterfly shaped organ that lies in front of the neck in front of the voice box and secretes hormones like thyroxine (T4) and triiodothyronine (T3). These hormones help regulate the metabolism, brain development, heart rate, energy levels, calories burnt by the body and various other important functions of the body.

Thus overall the thyroid hormones maintain a delicate balance in regulating mood, weight, and mental and physical energy levels.

When there is an excess of these hormones, the condition is called hyperthyroidism and when there is a paucity of this hormones, it is termed hypothyroidism.

What is an autoimmune condition?

Autoimmune conditions are those in which the body’s immune cells, that are supposed to fight foreign microbes or other organisms, turn back on the body’s own tissues. These cells produce antibodies against the targeted tissues that may lead to destruction or disease of the target tissues.

Causes of Graves’ disease

In Graves’ disease the body starts to make antibodies that cause the thyroid gland to make more hormone than normal. Graves’ disease is the most common cause of hyperthyroidism.

Here the B and T lymphocytes begin to make antibodies against the thyroid gland termed - thyroid-stimulating immunoglobulins (TSIs). These antibodies target 4 different proteins within the thyroid. These include:

• Thyroglobulin
• Thyroid peroxidase
• Sodium-iodide symporter
• Thyroid stimulating hormone (TSH) receptor

In normal conditions the Thyroid stimulating hormone (TSH) acts on tiny receptors over the thyroid gland and makes the thyroid produce the T3 and T4 hormones. The primary antibody that leads to Grave’s disease is the one directed against the TSH receptor.

The antibodies behave like TSH and bind to the TSH receptor on the thyroid cell causing the thyroid gland to grow in size leading to goitre or swelling of the thyroid gland. In addition, these antibodies also stimulate the thyroid follicles to produce more thyroid hormone. This gives rise to the features of hyperthyroidism.

The three other antibodies have less of a role in the pathophysiology of Graves' disease but may be assessed to look at the disease progression. In addition, around 5% of those with anti-thyroid peroxidase antibodies and TSI may become hypothyroid with time. This means their thyroid gland secretes less hormone than necessary. Some patients produce antibodies which block rather than stimulate the TSH receptors and this may also lead to hypothyroidism.

Who does Graves’ disease affect?

Women are more susceptible to autoimmune conditions. Graves is up to eight times more common in women than men. In addition, those suffering from or with a family member who suffers from other autoimmune conditions such as insulin-dependent diabetes, rheumatoid arthritis, vitiligo and pernicious anaemia are at a greater risk of getting Graves’ disease.

The disease commonly affects persons between ages 20 and 40. However Graves’ disease may affect men and people of other ages as well.

Genes and Graves’ disease

Genes may also play a role is the risk of Graves’ disease. Some families have more than one case and the condition seem to run in the families.

Some genes that have been suspected to carry the condition from parents to offspring include genes that code for CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22. Specific gene loci have been identified. These may vary among different racial and ethnic groups.

Graves’ disease and environmental factors

In addition, some bacteria like Yersinia enterocolitica, Escherichia coliand other Gram-negative organisms, have been found to have TSH binding sites. These may also lead to thyroid problems.

Other environmental factors that lead to thyroid conditions like Graves’ disease include:

• smoking
• stress
• pollution
• pregnancy
• iodine therapy
• selenium intake
• injury or surgery of the thyroid gland
• injection of certain medications like ethanol, interferon beta-1b or interleukin-4 therapy etc. (4)

Sources

1. http://www.royalberkshire.nhs.uk/pdf/Graves_jan11.pdf
2. www.bbc.co.uk/health/physical_health/conditions/gravesdisease.shtml
3. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001398/
4. http://www.patient.co.uk/doctor/Graves'-Disease.htm
5. http://www.endocrine.niddk.nih.gov/pubs/graves/graves.pdf
6. www.thyroid.org/.../Graves_brochure.pdf