What is the role of thionamides in thyroid storm treatment?

Updated: Mar 16, 2020
  • Author: Madhusmita Misra, MD, MPH; Chief Editor: Robert P Hoffman, MD  more...
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Answer

Thionamides: Correct the hyperthyroid state. Administer antithyroid medications to block further synthesis of thyroid hormones (THs).

  • High-dose propylthiouracil (PTU) or methimazole may be used for treatment of thyroid storm. PTU has a theoretical advantage in severe thyroid storm because of its early onset of action and capacity to inhibit peripheral conversion of T4 to T3. However, a study by the taskforce committee of the Japan Thyroid Association (JTA) and the Japan Endocrine Society (JES) found evidence that in severe thyroid storm, T4-to-T3 conversion may already be reduced. The taskforce also found that disease severity and mortality did not significantly differ between thyroid storm patients in the study who were managed with methimazole or PTU. [17]

  • Dosing for thyroid storm in adults is as follows: PTU 200 mg every 4 hours or methimazole 20 mg orally every 4-6 hours; these drugs may need to be administered through a nasogastric tube. Guidelines released in 2016 by the JTA/JES recommended the use of intravenous methimazole in severe cases of thyroid storm; however, intravenous methimazole is not currently available in the United States. [17, 18]

  • Dosing for thyroid storm in children is as follows: PTU in neonates: 5-10 mg/kg per day PO/NGT divided every 6-8 hours; PTU in children: 15-20 mg/kg per day PO/NGT divided every 6-8 hours (up to 40 mg/kg per day has been used; not to exceed 1200 mg per day); recommendations for methimazole dosing are variable (a reasonable starting dose is about one tenth of the PTU dose given every 6-8 hours).

  • Of note, the US Food and Drug Administration (FDA) has 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 those who cannot tolerate other treatments such as methimazole, radioactive iodine, or surgery.

    • The decision to include a boxed warning was based on the FDA's review of postmarketing safety reports and 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. Among adults, 12 deaths and 5 liver transplants occurred; 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 now considered as a second-line drug therapy for treatment of hyperthyroidism in general (though not thyroid storm), except in patients who are allergic or intolerant to methimazole, or women who are in the first trimester of pregnancy. Rare cases of embryopathy, including aplasia cutis, have been reported with methimazole during pregnancy. For more information, see the FDA Safety Alert. [19] The FDA recommends the following criteria be considered for prescribing PTU.

    • Reserve PTU use for during first trimester of pregnancy or for patients who are allergic to or intolerant of methimazole.
    • Closely monitor patients undergoing 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 and evaluate 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.
  • If the patient is given PTU during treatment of thyroid storm, this should be switched to methimazole at the time of discharge unless methimazole is contraindicated. If methimazole is contraindicated, alternative methods to treat hyperthyroidism should be considered after discharge, such as radioactive iodine or surgery.

  • One retrospective review found no difference in mortality rates in patients with thyroid storm treated with PTU vs. methimazole. [20]


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