Methimazole is used in patients with Graves' disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option. The drug also is used to ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy.
Some clinicians state that methimazole should be used in virtually every patient who chooses antithyroid drug therapy for the treatment of Graves' disease, except during the first trimester of pregnancy when propylthiouracil is preferred
(see Pregnancy under Cautions: Pregnancy and Lactation), in the treatment of thyroid storm (see Thyrotoxic Crisis under Uses: Hyperthyroidism), and in patients with minor adverse reactions to methimazole who refuse radioactive iodine therapy or surgery.
Because of postmarketing reports of severe liver injury in pediatric patients receiving propylthiouracil, methimazole is the preferred agent when an antithyroid drug is required for a pediatric patient.
(See Cautions: Pediatric Precautions.)
Thioamide antithyroid agents (e.g., methimazole, propylthiouracil) are used to control the symptoms of hyperthyroidism associated with Graves' disease and maintain the patient in a euthyroid state for a period of several years (generally 1-2 years) until a spontaneous remission occurs. Thioamide antithyroid agents do not affect the underlying cause of hyperthyroidism. Spontaneous remission does not occur in all patients receiving therapy with thioamide antithyroid agents, and most patients eventually require ablative therapy (i.e., surgery, radioactive iodine). The minimum duration of thioamide therapy necessary before assessing whether spontaneous remission has occurred is not clearly established. However, some clinicians state that if methimazole is chosen as the primary therapy for Graves' disease, the drug should be continued for approximately 12-18 months in adults or 1-2 years in children, then tapered or discontinued if thyrotropin (thyroid stimulating hormone, TSH) concentrations return to normal at that time. If adults or children with Graves' disease remain hyperthyroid after completing a course of methimazole, treatment with radioactive iodine or thyroidectomy should be considered. Some clinicians state that treatment with low-dose methimazole for longer than 12-18 months in adults may be considered in patients not in remission who prefer this pharmacologic approach. Methimazole therapy also may be continued in children until the child is considered old enough for radioactive iodine therapy or surgery.
Methimazole is used to return the hyperthyroid patient to a normal metabolic state prior to thyroidectomy and to control the thyrotoxic crisis that may accompany thyroidectomy.
(See Thyrotoxic Crisis under Uses: Hyperthyroidism.)Some clinicians recommend that, whenever possible, adults or children with Graves' disease undergoing thyroidectomy or adults with toxic adenoma or toxic multinodular goiter undergoing surgery be rendered euthyroid with methimazole prior to the procedure.
Methimazole is used as an adjunct to radioactive iodine therapy in patients who require control of symptoms of hyperthyroidism prior to and after administration of radioactive iodine until the ablative effects of the iodine occur. However, the beneficial and detrimental effects and optimal sequencing of antithyroid drugs before or after radioactive iodine therapy have not been clearly established. Some clinicians recommend that pretreatment with methimazole prior to radioactive iodine therapy for Graves' disease, toxic adenoma, or toxic multinodular goiter be considered in adults who are at increased risk for complications due to worsening of hyperthyroidism (e.g., geriatric patients, patients with severe hyperthyroidism [e.g., extremely symptomatic, free thyroxine (T4) estimates 2-3 times the upper limit of normal] or substantial comorbidities [e.g., cardiovascular disease]). However, conflicting opinions exist, and other clinicians state that pretreatment with methimazole prior to radioactive iodine therapy is not necessary because there is insufficient evidence to indicate that radioactive iodine worsens the clinical or biochemical aspects of hyperthyroidism, and that pretreatment with methimazole will only delay treatment with radioactive iodine. In addition, some evidence indicates that pretreatment with methimazole may reduce the efficacy of subsequent radioactive iodine therapy. In children with Graves' disease having total T4 concentrations exceeding 20 mcg/dL or free T4 estimates exceeding 5 ng/dL who are to receive radioactive iodine therapy, some clinicians suggest pretreatment with methimazole and β-adrenergic blockade until total T4 and/or free T4 estimates normalize before proceeding with radioactive iodine.
Antithyroid agents do not induce remission in patients with nodular thyroid disease (i.e., toxic adenoma, toxic multinodular goiter), and discontinuance of therapy results in relapse. Therefore, some clinicians suggest that adults with overt toxic adenoma or toxic multinodular goiter be treated with either radioactive iodine therapy or thyroidectomy, and that long-term methimazole therapy be avoided. However, these clinicians state that long-term (life-long) antithyroid drug therapy may be the best choice for some geriatric or otherwise ill patients with limited longevity and increased surgical risk who can be monitored regularly (e.g., residents of nursing homes or other care facilities where compliance with radiation safety regulations may be difficult) or for patients who prefer this pharmacologic approach.
In the management of thyrotoxic crisis, thioamide antithyroid agents are used to inhibit thyroid hormone synthesis. Because propylthiouracil also blocks the peripheral conversion of thyroxine to triiodothyronine, it theoretically may be more useful than methimazole or carbimazole (not commercially available in the US) in the management of thyrotoxic crisis. Iodides (e.g., potassium iodide, strong iodine solution) are given to inhibit the release of thyroid hormone from the gland but may subsequently be used as a substrate for thyroid hormone synthesis; therefore, treatment with a thioamide antithyroid agent is usually initiated before iodide therapy. A β-adrenergic blocking agent (e.g., propranolol) is also usually given concomitantly to manage peripheral signs and symptoms of hyperthyroidism, particularly cardiovascular effects (e.g., tachycardia).