Non-cancerous growths of the thyroid gland or pituitary gland
Tumors of the testes or ovaries
Inflammation (irritation and swelling) of the thyroid due to viral infections or other causes
Ingestion (taking in through the mouth, such as in eating) of large amounts of thyroid hormone
Ingestion of excessive iodine
Graves disease accounts for 85% of all cases of hyperthyroidism
Frequent bowel movements
Menstrual irregularities in women
Goiter (visibly enlarged thyroid) may be present
Additional symptoms that may be associated with this disease:
Skin blushing or flushing
Nausea and vomiting
Lack of menstruation
Itching - overall
Breast development in men
High blood pressure
Protruding eyes (exophthalmos
Physical examination may reveal thyroid enlargement or goiter. Vital signs (temperature, pulse, rate of breathing, blood pressure) show increased heart rate. Systolic blood pressure (the first number in a blood pressure reading) may be high.
Laboratory tests that evaluate thyroid function:
Serum TSH is usually low
T3 and free T4 are usually high
This disease may also alter the results of the following tests:
Radioactive iodine uptake
Graves' disease is the most common cause of hyperthyroidism, accounting for 60 to 80 percent of all cases.8 It is an autoimmune disease caused by an antibody, active against the thyroid-stimulating hormone (TSH) receptor, which stimulates the gland to synthesize and secrete excess thyroid hormone. It can be familial and associated with other autoimmune diseases. An infiltrative ophthalmopathy accompanies Graves' disease in about 50 percent of patients.
toxic multinodular goiter
Toxic multinodular goiter causes 5 percent of the cases of hyperthyroidism in the United States and can be 10 times more common in iodine-deficient areas. It typically occurs in patients older than 40 years with a long-standing goiter, and has a more insidious onset than Graves' disease
Toxic adenomas are autonomously functioning nodules that are found most commonly in younger patients and in iodine-deficient areas.10
Subacute. Subacute thyroiditis produces an abrupt onset of thyrotoxic symptoms as hormone leaks from an inflamed gland. It often follows a viral illness. Symptoms usually resolve within eight months. This condition can be recurrent in some patients.11
Lymphocytic and Postpartum. Lymphocytic thyroiditis and postpartum (subacute lymphocytic) thyroiditis are transient inflammatory causes of hyperthyroidism that, in the acute stage, may be clinically indistinguishable from Graves' disease. Postpartum thyroiditis can occur in up to 5 to 10 percent of women in the first three to six months after delivery. A transient hypothyroidism often occurs before resolution
Time course of changes in thyroid function tests in patients with thyroiditis. (T4 = thyroxine; T3 = triiodothyronine; TSH = thyroid-stimulating hormone.)
. Iodine-induced hyperthyroidism can occur after intake of excess iodine in the diet, exposure to radiographic contrast media, or medications. Excess iodine increases the synthesis and release of thyroid hormone in iodine-deficient patients and in older patients with preexisting multinodular goiters.5
Amiodarone-induced. Amiodarone- (Cordarone-) induced
hyperthyroidism can be found in up to 12 percent of treated patients, especially those in iodine-deficient areas, and occurs by two mechanisms. Because amiodarone contains 37 percent iodine, type I is an iodine-induced hyperthyroidism (see above). Amiodarone is the most common source of iodine excess in the United States. Type II is a thyroiditis that occurs in patients with normal thyroid glands. Medications such as interferon and interleukin-2 (aldesleukin) also can cause type II.5
Factitial hyperthyroidism is caused by the intentional or accidental ingestion of excess amounts of thyroid hormone. Some patients may take thyroid preparations to achieve weight loss.
Rare causes of hyperthyroidism include metastatic thyroid cancer, ovarian tumors that produce thyroid hormone (struma ovarii), trophoblastic tumors that produce human chorionic gonadotrophin and activate highly sensitive TSH receptors, and TSH-secreting pituitary tumor
Beta blockers offer prompt relief of the adrenergic symptoms of hyperthyroidism such as tremor, palpitations, heat intolerance, and nervousness. Propranolol (Inderal) has been used most widely, but other beta blockers can be used. Nonselective beta blockers such as propranolol, are preferred because they have a more direct effect on hypermetabolism.25 Therapy with propranolol should be initiated at 10 to 20 mg every six hours. The dose should be increased progressively until symptoms are controlled. In most cases, a dosage of 80 to 320 mg per day is sufficient.5 Calcium channel blockers such as diltiazem (Cardizem) can be used to reduce heart rate in patients who cannot tolerate beta blockers.17
Iodides block the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and inhibit hormone release. Iodides also are used as adjunctive therapy before emergency nonthyroid surgery, if beta blockers are unable to control the hyperthyroidism, and to reduce gland vascularity before surgery for Graves' disease.9 Iodides are not used in the routine treatment of hyperthyroidism because of paradoxical increases in hormone release that can occur with prolonged use. Organic iodide radiographic contrast agents (e.g., iopanoic acid or ipodate sodium) are used more commonly than the inorganic iodides (e.g., potassium iodide). The dosage of either agent is 1 g per day for up to 12 weeks.26
Antithyroid drugs act principally by interfering with the organification of iodine, thereby suppressing thyroid hormone levels. Methimazole (Tapazole) and propylthiouracil (PTU) are the two agents available in the United States. Remission rates vary with the length of treatment, but rates of 60 percent have been reported when therapy is continued for two years.15 Relapse can occur in up to 50 percent of patients who respond initially, regardless of the regimen used. A recent randomized trial27 indicated that relapse was more likely in patients who smoked, had large goiters, or had elevated thyroid-stimulating antibody levels at the end of therapy.
Methimazole usually is the drug of choice in nonpregnant patients because of its lower cost, longer half-life, and lower incidence of hematologic side effects. The starting dosage is 15 to 30 mg per day, and it can be given in conjunction with a beta blocker.28 The beta blockade can be tapered after four to eight weeks and the methimazole adjusted, according to clinical status and monthly free T4 or free T3 levels, toward an eventual euthyroid (i.e., normal T3 and T4 levels) maintenance dosage of 5 to 10 mg per day.9,17 TSH levels may remain undetectable for months after the patient becomes euthyroid and should not be used to monitor the effects of therapy. At one year, if the patient is clinically and biochemically euthyroid and a thyroid-stimulating antibody level is not detectable, therapy can be discontinued. If the thyroid-stimulating antibody level is elevated, continuation of therapy for another year should be considered. Once antithyroid drug therapy is discontinued, the patient should be monitored every three months for the first year, because relapse is more likely to occur during this time, and then annually, because relapse can occur years later. If relapse occurs, radioactive iodine or surgery generally is recommended, although antithyroid drug therapy can be restarted.9
PTU is preferred for pregnant women because methimazole has been associated with rare congenital abnormalities. The starting dosage of PTU is 100 mg three times per day with a maintenance dosage of 100 to 200 mg daily.28 The goal is to keep the free T4 level at the upper level of normal.9
Complications. Agranulocytosis is the most serious complication of antithyroid drug therapy and is estimated to occur in 0.1 to 0.5 percent of patients treated with these drugs.28 The risk is higher in the first several months of therapy and may be higher with PTU than methimazole.5,9,15 It is extremely rare in patients taking less than 30 mg per day of methimazole.9 The onset of agranulocytosis is sometimes abrupt, so patients should be warned to stop taking the drug immediately if they develop a sudden fever or sore throat. Routine monitoring of white cell counts remains controversial, but results of one study29 showed that close monitoring of white cell counts allowed for earlier detection of agranulocytosis. In this study, patients had white cell counts every two weeks for the first two months, then monthly. In most cases, agranulocytosis is reversible with supportive treatment.15,25 Minor side effects (e.g., rash, fever, gastrointestinal symptoms) sometimes can be treated symptomatically without discontinuation of the antithyroid drug; however, if symptoms of arthralgia occur, antithyroid drugs should be discontinued because arthralgia can be a precursor of a more serious polyarthritis syndrome.28
In the United States, radioactive iodine is the treatment of choice for most patients with Graves' disease and toxic nodular goiter. It is inexpensive, highly effective, easy to administer, and safe. There has been reluctance to use radioactive iodine in women of childbearing years because of the theoretical risk of cancer of the thyroid, leukemia, or genetic damage in future offspring. Long-term follow-up of patients has not validated these concerns.14,15 The treatment of hyperthyroidism in children remains controversial, but radioactive iodine is becoming more acceptable in this group.30
Dosage. The treatment dosage of radioactive iodine has been a topic of much debate. A gland-specific dosage based on the estimated weight of the gland and the 24-hour uptake may allow a lower dosage and result in a lower incidence of hypothyroidism but may have a higher recurrence rate.15 Higher-dose ablative therapy increases the chance of successful treatment and allows the early hypothyroidism that results from this regimen to be diagnosed and treated while the patient is undergoing close monitoring. Some studies 8,18 have shown that the eventual incidence of hypothyroidism is similar regardless of the radioactive iodine dosage. The high-dose regimen is clearly favored in older patients, those with cardiac disease, and other groups who need prompt control of hyperthyroidism to avoid complications. Patients with toxic nodular goiter or toxic adenomas are more radio resistant and generally need high-dose therapy to achieve remission. They have a lower incidence of eventual hypothyroidism because the rest of the gland has been suppressed by the toxic nodules and protected from the effects of radioactive iodine.18,30
Graves' Disease. In 15 percent of patients, Graves' ophthalmopathy can develop or be worsened by the use of radioactive iodine.17,19 The use of prednisone, 40 to 80 mg per day tapered over at least three months, can prevent or improve severe eye disease in two thirds of patients.19 Lower-dose radioactive iodine sometimes is used in patients with ophthalmopathy because posttreatment hypothyroidism may be associated with exacerbation of eye disease. Cigarette smoking is a risk factor for the development and progression of Graves' ophthalmopathy.14,19
Use with Other Treatments. Using antithyroid drugs to achieve a euthyroid state before treatment with radioactive iodine is not recommended for most patients, but it may improve safety for patients with severe or complicated hyperthyroidism. Limited evidence supports this approach.8,14,17 It is unclear whether antithyroid drugs increase radioactive iodine failure rates.20,31,32 If used, they should be withdrawn at least three days before radioactive iodine and can be restarted two to three days later. The antithyroid drug is continued for three months after radioactive iodine, then tapered. Beta blockers are used to control symptoms before radioactive iodine and can be continued throughout treatment if needed. Iodine-containing medications need to be discontinued several weeks before therapy.21
Safety Precautions. Most of the radioactive iodine is eliminated from the body in urine, saliva, and feces within 48 hours; however, double flushing of the toilet and frequent hand washing are recommended for several weeks. Close contact with others, especially children and pregnant women, should be avoided for 24 to 72 hours.21 Additional treatments with radioactive iodine can be initiated as early as three months, if indicated.33
Gradually, radioactive iodine has replaced surgery for the treatment of hyperthyroidism, but it still may be indicated in some patients and is considered underused by some researchers. A subtotal thyroidectomy is performed most commonly. This surgery preserves some of the thyroid tissue and reduces the incidence of hypothyroidism to 25 percent, but persistent or recurrent hyperthyroidism occurs in 8 percent of patients.22 Total thyroidectomy is reserved for patients with severe disease or large goiters in whom recurrences would be highly problematic, but carries an increased risk of hyperparathyroidism and laryngeal nerve damage.22,23
Newer treatment options under investigation include endoscopic subtotal thyroidectomy,34 embolization of the thyroid arteries,35 plasmapheresis,36 and percutaneous ethanol injection of toxic thyroid nodules.37 Autotransplantation of cryopreserved thyroid tissue may become a treatment option for postoperative hypothyroidism.38 Nutritional supplementation with L-carnitine39 has been shown to have a beneficial effect on the symptoms of hyperthyroidism, and L-carnitine may help prevent bone demineralization caused by the disease.
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