Which medications in the drug class Antithyroid agents are used in the treatment of Graves Disease?

Updated: Apr 17, 2020
  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Antithyroid agents

Thioamides function as antithyroid agents mainly by inhibiting iodide organification and coupling processes, thereby preventing synthesis of thyroid hormones. Half-life of T4 is 7 d in persons who are euthyroid and somewhat shorter in patients who are thyrotoxic. This accounts for a several-week delay in onset of clinical improvement in most patients. Agents have been reported to alter intrathyroidal immunoregulatory mechanisms. Only oral preparations are available, but they have been used as retention enemas in patients in whom oral intake is not possible or is contraindicated.

Although these agents fall under pregnancy category D, they have been used safely in many pregnant patients. Retrospective study indicates rate of major congenital malformations with PTU (3%) or methimazole (2.7%) was not significantly different from normal background rate (2-5%). Duration of treatment ranged from 0-23 wk, with doses ranging from 100-600 mg/d of PTU or 10-60 mg/d of methimazole.

Concentrations of methimazole are higher in breast milk; therefore, PTU is preferred in this patient population.

Risk of agranulocytosis is similar (0.2-0.5%) in members of this class. In general, PTU is associated with transaminase elevation in susceptible individuals, while methimazole may cause a cholestatic effect. [88]

The US Food and Drug Administration (FDA) added a boxed warning, the strongest warning issued by the FDA, to the prescribing information for PTU. The boxed warning emphasizes the risk for severe liver injury and acute liver failure, some of which have been fatal. The boxed warning also states that PTU should be reserved for use in patients who cannot tolerate other treatments, such as methimazole, radioactive iodine, or surgery.

Medically treated Graves disease has a significant risk of relapse (23% within 6 months of discontinuation of antithyroid medication and 42% within 5 years). The presence of goiter is associated with an increased risk of relapse after medical therapy. [89]

The decision to include a boxed warning was based on the FDA's review of postmarketing safety reports and on meetings held with the American Thyroid Association, the National Institute of Child Health and Human Development, and the pediatric endocrine clinical community.

The FDA has identified 32 cases (22 adult and 10 pediatric) of serious liver injury associated with PTU. Of the adults, 12 deaths and 5 liver transplants occurred, and among the pediatric patients, 1 death and 6 liver transplants occurred. PTU is indicated for hyperthyroidism due to Graves disease. These reports suggest an increased risk for liver toxicity with PTU compared with methimazole. Serious liver injury has been identified with methimazole in 5 cases (3 resulting in death).

PTU is considered to be a second-line drug therapy, except in patients who are allergic to or intolerant of methimazole, or in women who are in the first trimester of pregnancy. Rare cases of embryopathy, including aplasia cutis, have been reported with methimazole during pregnancy. The FDA recommends the following criteria be considered for prescribing PTU (for more information, see the FDA Safety Alert):

- Reserve PTU use during first trimester of pregnancy, or in patients who are allergic to or intolerant of methimazole.

- Closely monitor PTU therapy for signs and symptoms of liver injury, especially during the first 6 months after initiation of therapy.

- For suspected liver injury, promptly discontinue PTU therapy, evaluate the patient for evidence of liver injury, and provide supportive care.

- PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of methimazole and no other treatment options are available.

- Counsel patients to promptly contact their health care provider for the following signs or symptoms: fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising, or yellowing of the eyes or skin.


Derivative of thiourea that inhibits organification of iodine by thyroid gland. Blocks oxidation of iodine in thyroid gland, thereby inhibiting thyroid hormone synthesis; inhibits T4-to-T3 conversion by blocking type I deiodinase (advantage over other agents). Usual course/duration of therapy is 1-2 y; sustained remission more likely after 1-2 y vs 3-6 mo of therapy.

Methimazole (Tapazole)

Inhibits thyroid hormone by blocking oxidation of iodine in thyroid gland; however, not known to inhibit peripheral conversion of thyroid hormone. Considerable debate surrounds optimal dosage/duration.

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