Graves disease

Clinic

• Also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid.
• It frequently results in most common cause of hyperthyroidism.
• Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 30% of people with the condition develop eye problems.

The exact cause of the disease is unclear; however, it is believed to involve a combination of genetic and environmental factors. A person is more likely to be affected if they have a family member with the disease. If one twin is affected, a 30% chance exists that the other twin will also have the disease. The onset of disease may be triggered by physical or emotional stress, infection, or giving birth. Those with other autoimmune diseases such as type 1 diabetes and rheumatoid arthritis are more likely to be affected. Smoking increases the risk of disease and may worsen eye problems. The disorder results from an antibody, called thyroid-stimulating immunoglobulin (TSI), that has a similar effect to thyroid stimulating hormone (TSH). These TSI antibodies cause the thyroid gland to produce excess thyroid hormones. The diagnosis may be suspected based on symptoms and confirmed with blood tests and radioiodine uptake. Typically, blood tests show a raised T₃ and T₄, low TSH, increased radioiodine uptake in all areas of the thyroid and TSI antibodies.

The three treatment options are radioiodine therapy, medications, and thyroid surgery. Radioiodine therapy involves taking iodine-131 by mouth, which is then concentrated in the thyroid and destroys it over weeks to months. The resulting hypothyroidism is treated with synthetic thyroid hormones. Medications such as beta blockers may control some of the symptoms, and antithyroid medications such as methimazole may temporarily help people while other treatments are having effect. Surgery to remove the thyroid is another option. Eye problems may require additional treatments.

Graves' disease will develop in about 0.5% of males and 3% of females. It occurs about 7.5 times more often in women than in men. Often, it starts between the ages of 40 and 60 but can begin at any age. It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases). The condition is named after Irish surgeon Robert Graves, who described it in 1835. A number of prior descriptions also exist.

Signs and symptoms

• The signs and symptoms of Graves' disease virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being Graves' ophthalmopathy, goiter, and pretibial myxedema (which are caused by the autoimmune processes of the disease). Symptoms of the resultant hyperthyroidism are mainly insomnia, hand tremor, hyperactivity, hair loss, excessive sweating, oligomenorrhea, itching, heat intolerance, weight loss despite increased appetite, diarrhea, frequent defecation, palpitations, periodic partial muscle weakness or paralysis in those especially of Asian descent, and skin warmth and moistness. Further signs that may be seen on physical examination are most commonly a diffusely enlarged (usually symmetric), nontender thyroid, lid lag, excessive lacrimation due to Graves' ophthalmopathy, arrhythmias of the heart, such as sinus tachycardia, atrial fibrillation, and premature ventricular contractions, and hypertension.

Infectious trigger

• Viral or bacterial infection may trigger antibodies which cross-react with the human TSH receptor, a phenomenon known as antigenic mimicry.
• The bacterium Yersinia enterocolitica bears structural similarity with the human thyrotropin receptor and was hypothesized to contribute to the development of thyroid autoimmunity.
• EBV is another potential trigger.

Pathophysiology[edit]

• Histopathological image of diffuse hyperplasia of the thyroid gland
• Graves' disease is an autoimmune disorder, in which the body produces antibodies that are specific to the receptor for thyroid-stimulating hormone.
• These antibodies bind to TSHr and chronically stimulate it. The TSHr is expressed on the thyroid follicular cells of the thyroid gland and the results is abnormally high production of T3 /T4.
• This causes the clinical symptoms of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter.

Three types of autoantibodies to TSH receptor

1. Thyroid stimulating immunoglobulins: these antibodies (mainly IgG) act as long-acting thyroid stimulants (LATS), activating the cells through a slower and more drawn out process compared to TSH, leading to an elevated production of thyroid hormone.
2. Thyroid growth immunoglobulins: these antibodies bind directly to the TSH receptor and have been implicated in the growth of thyroid follicles.
3. Thyrotrophin binding-inhibiting immunoglobulins: these antibodies inhibit the normal union of TSH with its receptor.

Miasms

HTLV-1

EBV