Thyroid Storm Treatment & Management

The approach to treatment of thyroid storm includes the following:

• Supportive measures
• Antiadrenergic drugs
• Thionamides
• Iodine preparations
• Glucocorticoids
• Bile acid sequestrants
• Treatment of the underlying condition
• Rarely plasmapheresis

Patients with contraindications to thionamides need to be managed with supportive measures, aggressive beta blockade, iodine preparations, glucocorticoids, and bile acid sequestrants for about a week in preparation for a thyroidectomy. Plasmapheresis may be attempted if other measures are not effective. 

Patients with thyroid storm should be treated in an ICU setting for close monitoring of vital signs and for access to invasive monitoring and inotropic support, if necessary. Initial stabilization and management of systemic decompensation is as follows:

• Supportive measures

  • If needed, immediately provide supplemental oxygen, ventilatory support, and intravenous fluids. Dextrose solutions are the preferred intravenous fluids to cope with continuously high metabolic demand.

  • Correct electrolyte abnormalities.

  • Treat cardiac arrhythmia, if necessary.

  • Aggressively control hyperthermia by applying ice packs and cooling blankets and by administering acetaminophen (15 mg/kg orally or rectally every 4 hours).

• Antiadrenergic drugs

  • Promptly administer antiadrenergic drugs (eg, propranolol) to minimize sympathomimetic symptoms. Propranolol is administered orally or via nasogastric tube at a dose of 60-80 mg every 4-6 hours and the dose adjusted based on heart rate and blood pressure. It may also be given intravenously when necessary for rapid onset of action (0.5-1 mg over 10 min followed by 1-2 mg over 10 min every few hours, adjusted based on vital signs). It is important to avoid propranolol in conditions such as asthma, chronic obstructive pulmonary disease, peripheral vascular disease, or decompensated heart failure. Cardioselective beta blockers such as atenolol or metoprolol may be administered in patients with reactive airway disease, and calcium channel blockers may be used when beta blockers are contraindicated. The use of intravenous short acting beta-1 blockers, such as esmolol (loading dose of 250-500 mcg/kg, followed by an infusion of 50-100 mcg/kg per minute), allows quick dose titration with minimization of side effects.

  • Dosing of beta blockers for thyroid storm in a pediatric population:

    • Propranolol: Neonates: 2 mg/kg per day PO/NGT divided every 6-12 hours; Children: 0.5-4 mg/kg per day PO/NGT divided every 6 hours (not to exceed 60 mg per day) or 0.01-0.02 mg/kg IV over 10 minutes (may repeat over 10’ every few hours to a maximum cumulative dose of 5 mg)
    • Esmolol: Loading dose: 250-500 mcg/kg over 1 minute, repeat as needed, maintenance dose: 50-100 mcg/kg per minute IV infusion

• 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. ^[19]

  • 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. ^{[19, 20]}

  • 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. ^[21] 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. ^[22]

• Iodine compounds:

  • Administer iodine compounds (Lugol iodine or potassium iodide) orally or via a nasogastric tube to block the release of THs (at least 1 h after starting antithyroid drug therapy). In adults, SSKI is a given at a dose of 5 drops every 6 hours, or Lugol's iodine at a dose of 10 drops every 8 hours. If available, intravenous radiocontrast dyes such as ipodate and iopanoate can be effective in this regard. These agents are particularly effective at preventing peripheral conversion of T4 to T3.

  • Dosing of iodine compounds for thyroid storm in children:

    • SSKI (50 mg iodide per drop): Neonates: 2 drops PO/NGT every 6-8 hours; Children: 2-5 drops PO/NGT every 6 hours

    • Lugol's iodine (8 mg iodine/drop): 10 drops PO/NGT every 8 hours

• Glucocorticoids

  • Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful in preventing relative adrenal insufficiency due to hyperthyroidism and improving vasomotor symptoms. Hydrocortisone is administered intravenously at a dose of 100 mg every 8 hours or dexamethasone at a dose of 1-2 mg every 6 hours. 

  • Dosing of glucocorticoids for thyroid storm in children:

    • Hydrocortisone: 5 mg/kg (up to 100 mg) intravenously every 6-8 hours

    • Dexamethasone: 0.1-0.2 mg/kg per day divided every 6-8 hours

• Bile acid sequestrants prevent reabsorption of free THs in the gut (released from conjugated TH metabolites secreted into bile through the enterohepatic circulation). A recommended dose is 4 g of cholestyramine every 6 hours via a nasogastric tube. Another option is 20-30 g/day of Colestipol-HCl. ^[11]

• Treat the underlying condition, if any, that precipitated thyroid storm and exclude comorbidities such as diabetic ketoacidosis and adrenal insufficiency. Infection should be treated with antibiotics.

• Rarely, as a life-saving measure, plasmapheresis has been used to treat thyroid storm in adults. ^[23]

Iodine preparations should be discontinued once the acute phase resolves and the patient becomes afebrile with normalization of cardiac and neurological status. Glucocorticoids should be weaned and stopped and the dose of thioamides adjusted to maintain thyroid function in the normal range. Beta-blockers may be discontinued once thyroid function normalizes.

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 there is a contraindication for the use of methimazole, alternative methods to treat hyperthyroidism should be considered after discharge, such as radioactive iodine or surgery.

Patients with contraindications to thionamides need to be managed with supportive measures, aggressive beta blockade, iodine preparations, glucocorticoids and bile acid sequestrants for about a week in preparation for a thyroidectomy. Plasmapheresis may be attempted if other measures are not effective. 

Patients with Graves disease who need urgent treatment of hyperthyroidism but have absolute contraindications to thioamides may be treated acutely with beta-blockers, iodine preparations, glucocorticoids, and bile acid sequestrants as described. Plasmapheresis is sometimes used as a last resort if other measures are not effective. Subsequently, thyroidectomy may be performed after about 7 days of iodine administration. Iodine reduces the vascularity of the gland and the risk for thyroid storm.

In rare patients with hyperthyroidism, thyroid artery embolization has been used as adjuntive therapy ^{[24, 25, 26]} .  In one case series, this strategy caused an increase in thyroid hormone levels over the first three days following embolization followed by a subsequent reduction in levels (with normalization in nine out of twelve patients by 12 weeks), but the majority did not achieve permanent remission ^[26] .  In one reported case of a 64 year old man in whom thyroid hormone levels remained elevated and the patient remained unstable despite steroids, a thionamide, beta blockers and plasmapheresis, thyroid artery embolization was performed as the patient had contraindications to radioactive iodine and surgery ^[25] . Thyroid hormone levels increased over the first 2-3 days, but decreased from baseline after a week of the procedure. The goal of embolization in this patient was to cause atrophy, but not acute necrosis of the gland given the risk of thyroid storm with the latter. Subsequently, the patient's clinical condition improved and he was able to undergo a thyroidectomy.

The following consultations are indicated:

• Endocrinologist

• Intensivist

Promptly and appropriately treat thyrotoxicosis after diagnosis. Perform surgery in thyrotoxic patients only after appropriate thyroid and/or beta-adrenergic blockade.

Thyroid storm following radioactive iodine (RAI) therapy for hyperthyroidism may be related to (1) withdrawal of antithyroid medications for RAI administration (usually withdrawn 5-7 d before administration of RAI and held until 5-7 d after RAI therapy), (2) release of large amounts of thyroid hormone from damaged follicles, and (3) RAI itself. Because TH levels are often higher immediately before RAI treatment than they are afterward, many endocrinologists believe that withdrawal of antithyroid drugs is the cause of thyroid storm. One option is to stop antithyroid drugs (including methimazole) only 3 days (rather than 5-7 d) before RAI therapy and to restart antithyroid drugs 3 days after RAI administration. Early institution of antithyroid drugs after RAI therapy may decrease the efficacy of treatment, requiring a second dose.

Consider testing thyroid function before operative procedures in children at high risk for hyperthyroidism (eg, patients with McCune-Albright syndrome).