- Author: Stephanie L Lee, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
Drug therapy includes medications that reduce the symptoms of thyrotoxicosis and decrease the synthesis and release of thyroid hormone. In the United States, the most common definitive therapy for hyperthyroidism is ablation of the hyperactive thyroid with an oral dose of radioactive iodine (131I).
In some cases the patient is treated with antithyroid medication to return thyroid hormone levels to normal. When that is accomplished, some patients (eg, those with a toxic multinodular goiter or toxic adenoma) are treated immediately with radioactive iodine, while patients with autoimmune Graves disease may be treated for 12-18 months with antithyroid medications because of the possibility that the patient will go into remission.
Patients with other forms of hyperthyroidism, including toxic multinodular goiter and toxic adenoma, continue to be thyrotoxic indefinitely. Remissions with antithyroid medications are not expected.
Antithyroid agents inhibit the synthesis of thyroxine (T4) and triiodothyronine (T3).
With few exceptions, methimazole should be used in every patient who needs antithyroid drug therapy for hyperthyroidism. The exceptions are women in the first trimester of pregnancy, patients in thyroid storm, and patients with methimazole allergy or intolerance. Methimazole is avoided in early pregnancy because of increased placental transfer and risk of a rare fetal condition (cutis aplasia). Compared with propylthiouracil, it has a higher transfer rate into the milk of lactating women.
Methimazole inhibits thyroid hormone by blocking oxidation of iodine in the thyroid gland. However, it is not known to inhibit peripheral conversion of thyroid hormone. The drug is available as 5-mg or 10-mg tablets. It is readily absorbed and has a serum half-life of 6-8 hours. Methimazole is less protein-bound than propylthiouracil is.
Methimazole's duration of action is longer than its half-life, and the drug should be dosed every 12-24 hours. Studies have shown that rectal suppositories or retention enemas can be used at the same dose as orally administered methimazole for patients who cannot take oral medications. Usually, after thyroid function improves, the dose must be decreased or the patient will become hypothyroid.
Propylthiouracil is a derivative of thiourea that inhibits organification of iodine by the thyroid gland. It blocks oxidation of iodine in the thyroid gland, thereby inhibiting thyroid hormone synthesis; the drug inhibits T4 -to-T3 conversion (and thus has an advantage over other agents).
Propylthiouracil remains the drug of choice in uncommon situations of life-threatening severe thyrotoxicosis. It may be preferable during and before the first trimester of pregnancy.
In 2010, the US Food and Drug Administration (FDA) added a boxed warning to the prescribing information for propylthiouracil, emphasizing the risk for severe liver injury and acute liver failure, some cases of which have been fatal.
Propylthiouracil is available as a 50-mg tablet. It is readily absorbed and has a serum half-life of 1-2 hours. It is highly protein-bound in the serum. The drug's duration of action is longer than its half-life, and propylthiouracil generally should be dosed every 6-8 hours (though it can also be administered twice daily). If patient compliance is an issue, methimazole may be a better choice because it can be given as a single daily dose in many cases.
Thyroid hormone levels (thyroid-stimulating hormone [TSH], T4, free thyroxine index [FTI] or free T4, and T3) should be reassessed in 4-6 weeks after starting propylthiouracil. The dosage is increased if thyroid hormone levels have not significantly fallen or decreased if thyroid hormone levels have fallen by 50% or more (even if the patient is still thyrotoxic).
Usually, after thyroid function improves, the dosage should be gradually decreased to 50-150 mg/day in divided doses. Otherwise, the patient will become hypothyroid.
Potassium iodide inhibits thyroid hormone secretion. Iodide therapy is primarily used for the treatment of thyroid storm or given preoperatively, 10-14 days before surgical procedures (including thyroidectomy).
Until high levels of iodine build up in the thyroid follicular cell, however, administration of iodine can increase thyroid hormone synthesis and lead to higher serum levels of thyroid hormone. Thus, it is usually recommended that iodine not be started until after antithyroid drug therapy has been initiated. In thyroid storm, iodine should be administered at least 1 hour after methimazole or propylthiouracil.
Potassium iodide and iodine (Lugol's solution)
Lugol's solution is primarily administered for 10 days before thyroidectomy or during thyrotoxic crisis because high levels of iodine in the follicular thyroid cell temporarily inhibit thyroid hormone synthesis and secretion. T4 and T3 concentrations can be reduced for several weeks.
Until high levels of iodine build up in the thyroid follicular cell, however, administration of iodine can increase thyroid hormone synthesis and lead to higher serum levels of thyroid hormone. Thus, it is usually recommended that iodine not be started until after antithyroid drug therapy has been initiated.
Radioactive iodine is approved by the FDA for treatment of hyperthyroidism in adults. It can also be used with a radioactive uptake test to evaluate thyroid function. The agent is quickly absorbed and taken up by the thyroid. No other tissue or organ in the body is capable of retaining radioactive iodine; therefore, few adverse effects develop.
Beta Blockers, Nonselective
Nonselective beta blockers reduce many of the symptoms of thyrotoxicosis, including tachycardia, tremor, and anxiety. Usually, propranolol is recommended because of central nervous system (CNS) penetration, but some patients prefer longer-acting beta blockers. Patients note an immediate improvement in tachycardia, anxiety, heat intolerance, and tremor. Calcium channel blockers for tachycardia are sometimes used when beta blockers are contraindicated or not tolerated.
Propranolol is the drug of choice for treating cardiac arrhythmias resulting from hyperthyroidism. It controls cardiac and psychomotor manifestations within minutes.
Beta Blockers, Beta1-Selective
Beta blockers diminish hyperthyroid symptoms, such as tachycardia, tremor, and anxiety. Beta1 -selective drugs may be tolerated better in patients who have relative beta-blockade contraindications.
Atenolol selectively blocks beta1 receptors, with little or no effect on beta2 types. It is a longer-acting drug that can be more useful than propranolol for intraoperative and postoperative control.
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|Common Forms (85-90% of Cases)||24-Hour RAIU Over Neck*|
|Diffuse toxic goiter (Graves disease)||Increased (moderate to high: 40-100%)|
|Toxic multinodular goiter (Plummer disease)||Increased (mild to moderate: 25-60%)|
|Thyrotoxic phase of subacute thyroiditis||Decreased (very low: < 2%)|
|Toxic adenoma||Increased (mild to moderate: 25-60%)|
|Less Common Forms|
|Iodide-induced thyrotoxicosis||Variable but usually low (< 25%)|
|Thyrotoxicosis factitia||Decreased (very low: < 2%)|
|Pituitary tumors producing TSH||Increased (mild to moderate: 25-60%)|
|Excess human chorionic gonadotropin (molar pregnancy/choriocarcinoma)||Increased (variable: 25-100%)|
|Pituitary resistance to thyroid hormone||Increased (mild to moderate: 25-60%)|
|Metastatic thyroid carcinoma||Decreased|
|Struma ovarii with thyrotoxicosis||Decreased|
|RAIU = radioactive iodine uptake; TSH = thyroid-stimulating hormone.
* A normal 6-hour RAIU is approximately 2-16%; a 24-hour RAIU is about 8-25% but is modified according to the iodine content of the patient’s diet. RAIU or scanning should not be performed in a woman who is pregnant (with the exception of a molar pregnancy) or breastfeeding.