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Graves' disease

Graves' disease is a syndrome that can include hyperthyroidism, goiter, eye disease, and skin disease


Introduction
Graves's disease is an autoimmune disease syndrome which is characterized and driven by antibodies directed against the TSH receptor. These antibodies are called Thyroid Stimulating Immunoglobulins (TSI's). Graves' disease is not necessarily the same as hyperthyroidism. Some patients may only have certain manifestations of this syndrome and not even have hyperthyroidism. Graves's is only one of many causes of hyperthyroidism, and is one of few causes of persistent high-uptake-hyperthyroidism.  The condition is named after Dr. Robert James Graves who described the condition in 1835. 

The Causes

The thyroid gland is usually enlarged in patients with this condition. The gland is full of enlarged thyroid cells, colloid , and patchy lymphocytic infiltration. There are a number of antibodies which activate the TSH receptor, which stimulates thyroid hormone (T4, T3) synthesis and growth of the thyroid gland itself. There are a number of possible immune mechanisms involved in the pathogenesis of Graves' hyperthyroidism: Molecular mimicry, thyroid cell expression of HLA molecules, and bystander activation of local T cells. 

Predisposing Factors

A few factors are associated with patients that are predisposed to Graves' hyperthyroidism. There is a genetic susceptibility with disease clusters in families and more common in women. The concordance rate in monozygotic twins is up to 40%. The sibling recurrence rate is >10%. In animal models autoimmune hyperthyroid disease can be induced with certain viral infections, but there has been no direct evidence of this occurring in humans.  As compared to patients without the disease, patients with Grave's hyperthyroidism more often give a history of some type of psychological stress. Smoking is a risk factor for Graves' and is a strong risk factor for Graves' eye disease. Certain medications like amiodarone and alpha interferon can precipitate a recurrence of Graves.

Treatment

The treatment for Graves' hyperthyroidism is the same as for any high uptake thyroid condition. If hyperthyroidism is not present then each aspect of the syndrome (eye disease, skin disease) would need to be treated independently.


1. Sonino N, Girelli ME, Boscaro M, Fallo F, Busnardo B, Fava GA.  Life events in the pathogenesis of Graves' disease. A controlled study. Acta Endocrinol (Copenh). 1993;128(4):293
2.Prummel MF, Wiersinga WM. Smoking and risk of Graves' disease.  JAMA. 1993;269(4):479
3. Stenszky V, Kozma L, Balázs C, Rochlitz S, Bear JC, Farid NR. The genetics of Graves' disease: HLA and disease susceptibility. J Clin Endocrinol Metab. 1985;61(4):735.
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