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Management of Graves Disease A Review

Henry B. Burch, MD1,2; David S. Cooper, MD3
[+] Author Affiliations
1Endocrinology Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland
2Uniformed Services University of Health Sciences, Bethesda, Maryland
3The Johns Hopkins University School of Medicine, Baltimore, Maryland
JAMA. 2015;314(23):. doi:10.1001/jama.2015.16535.
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Importance  Graves disease is the most common cause of persistent hyperthyroidism in adults. Approximately 3% of women and 0.5% of men will develop Graves disease during their lifetime.

Observations  We searched PubMed and the Cochrane database for English-language studies published from June 2000 through October 5, 2015. Thirteen randomized clinical trials, 5 systematic reviews and meta-analyses, and 52 observational studies were included in this review. Patients with Graves disease may be treated with antithyroid drugs, radioactive iodine (RAI), or surgery (near-total thyroidectomy). The optimal approach depends on patient preference, geography, and clinical factors. A 12- to 18-month course of antithyroid drugs may lead to a remission in approximately 50% of patients but can cause potentially significant (albeit rare) adverse reactions, including agranulocytosis and hepatotoxicity. Adverse reactions typically occur within the first 90 days of therapy. Treating Graves disease with RAI and surgery result in gland destruction or removal, necessitating life-long levothyroxine replacement. Use of RAI has also been associated with the development or worsening of thyroid eye disease in approximately 15% to 20% of patients. Surgery is favored in patients with concomitant suspicious or malignant thyroid nodules, coexisting hyperparathyroidism, and in patients with large goiters or moderate to severe thyroid eye disease who cannot be treated using antithyroid drugs. However, surgery is associated with potential complications such as hypoparathyroidism and vocal cord paralysis in a small proportion of patients. In pregnancy, antithyroid drugs are the primary therapy, but some women with Graves disease opt to receive definitive therapy with RAI or surgery prior to becoming pregnant to avoid potential teratogenic effects of antithyroid drugs during pregnancy.

Conclusions and Relevance  Management of Graves disease includes treatment with antithyroid drugs, RAI, or thyroidectomy. The optimal approach depends on patient preference and specific patient clinical features such as age, history of arrhythmia or ischemic heart disease, size of goiter, and severity of thyrotoxicosis. Physicians should be familiar with the advantages and disadvantages of each therapy to best counsel their patients.

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Summary of the Biosynthesis of Thyroid Hormone and Overview of the Management of Graves Disease

A, Thyroid hormone synthesis begins with iodide uptake by thyroid follicular cells followed by oxidation of iodide by thyroid peroxidase (TPO) using endogenously generated H2O2. TPO catalyzes the subsequent steps of thyroid hormone synthesis—iodination of tyrosine residues in thyroglobulin to form iodotyrosines and coupling of 2 iodotyrosines to form the iodothyronines bound to thyroglobulin. The iodothyronines are stored in the follicular lumen as colloid then ingested by thyroid follicular cells. Within the follicular cells, thyroid hormones thyroxine (T4)and triiodothyronine (T3) are released from thyroglobulin and enter the bloodstream.

B, Options for the management of Graves disease include antithyroid drug therapy such as methimazole, radioactive iodine (RAI) treatment, and surgery. Left, Antithyroid drug (ATD) therapy interferes with new thyroid hormone synthesis and reduces serum levels of T4 and T3 until they are normal. Most patients also have normalization of TSH-receptor antibody (TRAb) levels.12 ATD therapy is generally continued for 12 to 18 months before the possibility of remission is assessed by measuring TRAb levels. ATD therapy is stopped if the TRAb level is normal. Center, Radioactive iodine (RAI, 131I) is taken up by thyroid follicular cells and incorporated into thyroid hormone. Ionizing radiation damages thyroid follicular cell DNA and gradually destroys the gland. T4 and T3 levels decline resulting in hypothyroidism, which is treated by replacement with levothyroxine. Levels of TRAb generally increase following RAI treatment and may remain elevated for prolonged periods of time.12 Right, Surgery (total thyroidectomy) is performed when thyroid function has normalized following 1 to 3 months of pretreatment with methimazole. Thyroid hormone replacement therapy is started after surgery prior to discharge from the hospital. DIT indicates diiodotyrosine; MIT, monoiodotyrosine.

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