The treatment of Graves' hyperthyroidism is directed toward lowering the serum concentrations of thyroid hormones to reestablish a eumetabolic state. There are currently three available modalities of treatment, all of which are effective. These include antithyroid drugs (ATDs), radioactive iodine (131I), and thyroid surgery.
The patient should have a clear understanding of the indications and implications of all forms of therapy, including risks, benefits, and side effects, and should be an active participant in the decision-making process regarding type of therapy. Because therapy is frequently ablative, the participation of an endocrinologist in the patient's treatment may be beneficial in those cases in which the primary care physician does not have experience with the disorder. In patients with hyperthyroidism and a low radioactive iodine uptake, none of these therapies are indicated, since low-uptake hyperthyroidism usually implies thyroiditis, which generally resolves spontaneously. Therapy with beta-blocking agents is usually sufficient to control the symptoms of hyperthyroidism in these individuals.
Antithyroid Drugs.[ref. 2]--The ATDs, methimazole and propylthiouracil, inhibit thyroid hormone biosynthesis. They are useful either as a primary form of therapy or to lower thyroid hormone levels before (and in some cases after) radioactive iodine therapy or surgery. Long-term ATD therapy may lead to remission in some patients with Graves' disease. Initial daily doses of methimazole generally range from 10 to 40 mg, and for propylthiouracil, 100 to 600 mg. There is no clear-cut standard for duration of therapy with ATDs, but when used as primary therapy, they are usually given for 6 months to 2 years, although a longer period of administration is acceptable. Some physicians prefer a regimen of combined ATD and thyroid hormone to avoid frequent adjustments of ATD doses.
Adverse reactions to both methimazole and propylthiouracil occur, including rash, itching, and less commonly, arthralgias or hepatic abnormalities. Hepatic necrosis caused by propylthiouracil and cholestatic jaundice caused by methimazole are sufficiently rare enough that routine monitoring of liver function tests is unnecessary. The most serious reaction to either drug is agranulocytosis, which occurs in about 0.3% of patients. Patients should be cautioned about the side effects of ATD prior to the initiation of therapy. Some clinicians obtain white blood cell (WBC) counts prior to initiating ATD, since mild leukopenia is common in Graves' disease. A baseline WBC may therefore be useful for comparison if subsequent WBC counts are obtained.
Patients developing fever, rash, jaundice, arthralgia, or oropharyngitis should promptly discontinue their medication, contact their physician, and have appropriate laboratory studies including a complete blood cell count with WBC differential.
Lithium carbonate or stable iodine has been used to block release of thyroid hormone from the thyroid gland in patients who are intolerant to ATDs, although their use is infrequent.
Radioactive Iodine Therapy.[ref. 3]--Radioactive iodine (131I) is the most commonly used form of treatment in the United States. It is safe, the principal side effect being the early or late development of hypothyroidism, necessitating life-long thyroid hormone replacement following 131I treatment. Treatment with 131I does not cause a reduction in fertility and does not cause cancer, nor has it been shown to produce ill effects in offspring of those so treated prior to pregnancy. It is contraindicated during pregnancy. Its use in individuals under the age 20 years, while controversial, is common. Pregnancy needs to be excluded before 131I is administered to young women and should be deferred for a few months following therapy. Therapy with 131I is also contraindicated in women who are breast-feeding. Elderly patients or individuals at risk for developing cardiac complications may be pretreated with ATDs prior to 131I therapy, especially if hyperthyroidism is severe, to deplete the gland of stored hormone, thereby minimizing the risk of exacerbation of hyperthyroidism due to 131I-induced thyroiditis. In some patients, ATDs may be required for control for several months following radioiodine therapy. A radioactive iodine uptake test is usually performed just prior to the administration of 131I to determine the appropriate dose.
Surgery.[ref. 4]--Thyroidectomy is infrequently recommended for patients with Graves' disease. Specific indications include patients with very large goiters who may be relatively resistant to 131I, those who have coincidental thyroid nodules, pregnant patients allergic to ATDs, and patients who are allergic to ATDs and/or do not wish 131I therapy. The procedure should be performed only by an experienced surgeon and only after careful medical preparation. Patients must be cautioned about potential complications of surgery, including hypoparathyroidism and injury to the recurrent laryngeal nerve. Hyperthyroidism may persist or recur if insufficient thyroid tissue is removed, whereas hypothyroidism usually develops after near-total thyroidectomy.
Adjunctive Therapy.--The most useful adjuncts are beta-adrenergic blockers such as propranolol or nadolol, which can provide symptomatic improvement until the euthyroid state has been achieved. Patients who cannot tolerate beta-blockers may be treated with calcium channel blockers such as diltiazem.