Hyperthyroidism, Thyroid Storm, and Graves Disease Treatment & Management

See the list below:

• Do not delay treatment once thyroid storm is suspected.

• Patients with severe thyrotoxicosis must be placed on a cardiac monitor. The patient should be intubated if profoundly altered. Supplemental oxygen may be required. Aggressive fluid resuscitation may be indicated.

• Fevers are treated with cooling measures and antipyretics. However, aspirin should be avoided to prevent decreased protein binding and subsequent increases in free T3 and T4 levels.

• Aggressive hydration of up to 3-5 L/d of crystalloid compensates for potentially profound GI and insensible losses.

• Appropriate electrolyte replacement should be directed by laboratory values.

• Atrial fibrillation due to thyroid storm may be refractory to rate control, and conversion to sinus rhythm may be impossible until after antithyroid therapy has been initiated.

• Intravenous glucocorticoids are indicated if adrenal insufficiency is suspected. Large doses of dexamethasone (2 mg q6h) inhibit hormone production and decrease peripheral conversion from T4 to T3.

• Antithyroid medications such as propylthiouracil (PTU) and methimazole (MMI) oppose synthesis of T4 by inhibiting the organification of tyrosine residues.

  • PTU also inhibits the conversion of T4 to active T3, although this effect is minimal and not usually clinically significant.

  • Clinical effects may be seen as soon as 1 hour after administration. Both agents are administered orally or via a nasogastric tube.

  • PTU and MMI inhibit the synthesis of new thyroid hormone but are ineffective in blocking the release of preformed thyroid hormone. Iodide administration serves this purpose well; however, it should be delayed until 1 hour after the loading dose of antithyroid medication to prevent the utilization of iodine in the synthesis of new thyroid hormone. Lithium may be used as an alternative in those with iodine allergy.

  • Antithyroid medications appear to also have an immunosuppressive effect, evidenced by decreased serum concentrations of antithyrotropin-receptor antibodies.

  • Primary antithyroid treatment (as an alternative to surgery) is often suggested for Graves disease, as remission after cessation of medical management is possible. In those with toxic multinodular goiters and solitary autonomous nodules, first-line treatment with antithyroid drugs is not recommended since spontaneous remission is rare.

• The US Food and Drug Administration (FDA) added a boxed warning, the strongest warning issued by the FDA, to the prescribing information for propylthiouracil. The warning emphasizes the risk for severe liver injury and acute liver failure, some episodes of which have been fatal. The warning also states that propylthiouracil 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 propylthiouracil (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 as a second-line drug therapy, except in patients who are allergic or intolerant to methimazole, or for women who are in the first trimester of pregnancy. ^[14] 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. ^[15]

    • 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 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.

• Beta-adrenergic blocking agents are the mainstays of symptomatic therapy for thyrotoxicosis. Propranolol has been used with the greatest success due to the additional benefit of inhibition of peripheral conversion of T4 to T3.

• Charcoal hemoperfusion has been shown to be effective in treatment of iatrogenic or intentional ingestion of excessive doses of levothyroxine. ^[16]

• Plasmapheresis has been used successfully in medication-induced thyroid storm ^[3] and in conditions in which oral/conventional therapy is not possible. ^[4]

See the list below:

• An intensivist should be consulted for admission to an ICU when thyroid storm is the presumptive diagnosis.

• An endocrinologist or internist may be helpful in confirming the diagnosis and in assisting in patient management.