GRAVES’ DISEASE DEFINITION
Graves’ disease is named for the doctor who first described it in Ireland—Robert J. Graves. He noticed it in a patient in 1835. The disease is also referred to as Basedow’s disease—named after a German, Karl Adolph van Basedow, who described the disease in 1840. He didn’t know that Graves had described the same disease just a few years earlier. The term Basedow’s disease is more commonly used in continental Europe; in the United States, it’s called Graves’ disease.
Graves’ disease is a type of autoimmune problem that causes the thyroid gland to produce too much thyroid hormone, which is called hyperthyroidism. Graves’ disease is often the underlying cause of hyperthyroidism.
GRAVES’ DISEASE CAUSES
Graves’ disease is caused by a malfunction in the body’s disease-fighting immune system, although the exact reason why this happens is still unknown.
One normal immune system response is the production of antibodies designed to target a specific virus, bacterium or other foreign substance. In Graves’ disease — for reasons that aren’t well understood — the body produces an antibody to one part of the cells in the thyroid gland, a hormone-producing gland in the neck.
Normally, thyroid function is regulated by a hormone released by a tiny gland at the base of the brain (pituitary gland). The antibody associated with Graves’ disease — thyrotropin receptor antibody (TRAb) — acts like the regulatory pituitary hormone. That means that TRAb overrides the normal regulation of the thyroid, causing an overproduction of thyroid hormones (hyperthyroidism).
GRAVES’ DISEASE PATHOPHYSIOLOGY
Graves’ disease (antibodies to the TSH receptor) is part of the spectrum of autoimmune thyroid disease that also includes Hashimoto’s thyroiditis (lymphocytic infiltration and destruction of thyroid tissue with secondary antibodies to thyroid peroxidase, thyroglobulin, and other thyroid antigens), painless thyroiditis (subacute destruction of thyroid follicles with release of preformed hormone), and hypothyroidism due to TSH receptor-blocking antibodies. Many patients have overlapping autoimmunity; hence the majority of Graves’ patients also have anti-thyroid peroxidase (TPO) antibodies.
Thyroid follicular cells, in response to interferon gamma produced by infiltrating T cells, express HLA class II molecules. This allows presentation of TSH receptor to activated T cells and initiation of the autoimmune cascade. Anti-TSH receptor antibodies cause thyroid hormone hyperproduction as well as thyroid hypertrophy and hyperplasia of thyroid follicular cells.
The TSH receptor antibody in the serum is measurable by a bioassay utilising cyclic AMP generation in a thyroid cell line (commonly referred to as thyroid stimulating immunoglobulin [TSI] in the US) or by a radioreceptor assay (referred to either as thyrotropin-binding inhibitory immunoglobulin [TBII] or generically as thyrotropin receptor antibody [TRAb]). Activity is correlated with severity of the autoimmune process. Presence of blocking antibodies and co-existing thyroid tissue damage as a component of autoimmune thyroiditis may modify the hyperthyroid state. Some patients have Graves’ ophthalmopathy, dermopathy, and/or acropachy and are euthyroid or even hypothyroid, despite very high levels of TSH receptor antibodies. Five percent of hyperthyroid Graves’ patients do not have detectable TSH receptor antibodies, which may be due to insensitivity of the assay.
The pathogenesis of extrathyroidal manifestations, such as ophthalmopathy, dermopathy, and acropachy, is less clear. Most probably, the antigen involved in these manifestations is TSH receptor expressed in fibroblasts of retro-orbital and dermal tissues. Fibroblasts are stimulated and produce glycosaminoglycans and differentiate into fat cells. Cytokines produced by T cells also play a major role. The clinical manifestations of ophthalmopathy (such as proptosis, chemosis, and restrictive ophthalmoplegia) are the consequences of increased orbital soft tissue and extra-ocular muscle volume. Orbital tissues, including muscles, are infiltrated by inflammatory cells, including lymphocytes, mast cells, and macrophages, potentially causing impaired venous return and, in extreme cases, pressure on the optic nerve, and corneal exposure and ulcers.
GRAVES’ DISEASE SYMPTOMS
Symptoms of Graves’ disease include goiter, problems conceiving a child, lighter menstrual flow and less frequent periods, weight loss, frequent bowel movements, heartpalpitations, thinning of hair, brittle hair, hand tremors, problems sleeping, heat insensitivity, increased sweating, eye changes (exophthalmos), and reddening and thickening of the skin on the shins and top of thefeet (pretibial myxedema).
GRAVES’ DISEASE DIAGNOSIS
The diagnosis of Graves’ disease is usually easily made. The combination of eye signs, goiter, and any of the characteristic symptoms and signs of hyperthyroidism forms a picture that can hardly escape recognition. It is only in the atypical cases, or with coexisting disease, or in mild or early disease, that the diagnosis may be in doubt. The symptoms and signs have been described in detail in the section on manifestations of Graves’ disease. These occur with sufficient regularity that clinical diagnosis can be reasonably accurate. Scoring the presence or absence and severity of particular symptoms and signs can provide a clinical diagnostic index almost as reliable a diagnostic measure as laboratory tests.
GRAVES’ DISEASE TREATMENT
With proper treatment, you can minimize the effects of Graves’ disease. The goal of treatment is to control over-production of thyroid hormones (hyperthyroidism). There are three treatment options for Graves’ disease. Your doctor or endocrinologist will recommend the best treatment for you and your particular case of Graves’ disease.
These drugs help prevent the thyroid from producing hormones. Methimazole and propylthiouracil (PTU) are generic medications that interfere with the thyroid gland’s ability to produce hormones. While effective in relieving symptoms within a few weeks, hyperthyroidism may return after the drug is stopped.
Possible side effects that may mean you have an allergy to this type of medicine include skin rash, itching, and hives. Other more common side effects that are usually temporary include nausea, vomiting, heartburn, headache, joint or muscle aches, loss of taste, and a metallic taste.
Be sure to ask your doctor to explain serious side effects you may experience and what to do should a side effect develop. One serious side effect with antithyroid medications is agranulocytosis, which causes you to not have enough white blood cells. That makes you more susceptible to infection, but agranulocytosis is rare. However, if you develop a fever or sore throat while on antithyroid medications, definitely call your doctor; it may be agranulocytosis.
If you have hyperthyroidism and become pregnant, your doctor will carefully monitor your thyroid hormone levels and adjust your medication as necessary—so that you and your baby stay healthy. In pregnant women, PTU is more commonly used than methimazole.