Medication Summary
Therapy is aimed at (1) ameliorating hyperadrenergic effects of thyroid hormone (TH) on peripheral tissues with use of beta-blockers (eg, propranolol, labetalol); (2) decreasing further synthesis of THs with antithyroid medications (eg, propylthiouracil [PTU], methimazole); (3) decreasing hormonal release from the thyroid, using iodides; and (4) preventing further TH secretion and peripheral conversion of T4 to T3, using glucocorticoids or iodinated radiocontrast dyes when available.
Based on evidence and frequency estimates, Rivkees and Mattison have raised significant concerns regarding the potential for severe liver disease in children due to PTU. [27] This side effect is not seen with methimazole, and current recommendations (endorsed by the Endocrine Society) are to preferentially use methimazole in the pediatric population for treatment of Graves disease. The use of PTU in conditions of thyroid storm was not specifically addressed; however, the use of PTU may be preferred in this setting because of the ability of this drug to inhibit conversion of T4 to T3.
Of note, one retrospective chart review from Japan has reported a higher risk of mortality in patients receiving non-selective bea-blockers compared with selective beta-blockers [22] .
Antithyroids
Class Summary
These agents belong to the thioureylene (thionamide) class and inhibit synthesis of THs within 1-2 hours. They have no effect on decreasing the release of preformed THs.
Propylthiouracil (PTU, Propyl-Thyracil)
DOC that inhibits synthesis of TH by preventing organification and trapping of iodide to iodine and by inhibiting coupling of iodotyrosines; also inhibits peripheral conversion of T4 to T3, an important component of management.
Comatose patients may require administration via NG tube because the agent is available solely as PO preparation; has been successfully administered PR as an enema or suppository. Very rarely, in patients who cannot take the medication PO, via NG, or PR, IV administration has been described. The IV preparation should be made by the hospital pharmacy by dissolving tablets in normal saline rendered alkaline by adding sodium hydroxide to obtain a pH of 9.25; it is essential to ensure sterility.
Methimazole (Tapazole)
Inhibits synthesis of TH by preventing organification of iodide to iodine and coupling of iodotyrosines. Although at least 10 times more potent than PTU on a weight basis, it does not inhibit peripheral conversion of T4 to T3. May be used instead of PTU in thyroid storm if iodinated radiocontrast agents are used in conjunction to prevent the conversion of T4 to T3 or if the condition is not life-threatening.
Comatose patients may require administration via NG tube because agent is available only as a PO preparation. In rare instances, it may be necessary to administer methimazole PR as an enema or suppository or IV after dissolving tablets in normal saline at a neutral pH and filtering the solution through a fine filter. PR and IV preparations should be made by the hospital pharmacy; it is essential to ensure sterility of IV preparations.
Iodides
Class Summary
Iodides inhibit the release of TH from the thyroid gland. Precede iodide administration with thionamides by at least 1 hour to prevent increased intrathyroidal TH synthesis. Iodinated radiographic contrast dyes that contain ipodate (Oragrafin) or iopanoic acid (Telepaque) have also been used and effectively prevent conversion of T4 to T3. However, their utility in childhood thyroid storm is untested. Another benefit of these radiocontrast agents is the once-daily dosing regimen, as opposed to 3-4 daily doses with iodine-containing oral solutions. Currently, these radiocontrast agents are no longer available in the United States. Lithium carbonate may be used if the patient is hypersensitive to iodine.
Potassium iodide, saturated solution (Pima, SSKI, Thyro-Block)
This agent is used to inhibit TH release from the thyroid gland. One mL of SSKI contains 1 g of potassium iodide or 750 mg of iodide (ie, approximately 50 mg iodide/drop and 15 drops per mL). Because of the viscosity, SSKI comes as 15 drops per mL rather than the usual 20 drops per mL.
Strong iodine (Lugol Solution)
Contains 100 mg potassium iodide and 50 mg iodine; provided 8 mg iodide/drop, 20 drops per ml.
Beta- blockers
Class Summary
These agents are used as the mainstay therapy to control autonomic effects of TH. Beta-blockers also block peripheral conversion of T4 to T3. Esmolol, a short-acting selective beta 1-antagonist, has been used successfully in children, as has labetalol in adults. Beta-blockers should be used with caution in congestive cardiac failure and thyrotoxic cardiomyopathy. In the latter case, they have been known to precipitate cardiac arrest.
Propranolol (Inderal)
DOC most widely used in this group; is a nonselective beta–adrenergic antagonist. Decreases heart rate, myocardial contractility, BP, and myocardial oxygen demand. Often the only adjunctive drug needed to control thyroid storm symptoms.
Esmolol (Brevibloc)
Beta 1–specific antagonist with a short duration of action.
Glucocorticoids
Class Summary
These agents block conversion of T4 to T3. The use of corticosteroids has been associated with improved survival. Stress doses are required to replace accelerated production and degradation of cortisol induced by TH. If corticosteroids are not administered, acute glucocorticoid deficiency hypothetically could occur because demand may outpace production.
Hydrocortisone (Solu-Cortef)
Hydrocortisone provides mineralocorticoid activity and glucocorticoid effects and may help ameliorate decreased adrenal reserve. It reduces the conversion of T4 to T3.
Dexamethasone (Decadron)
Dexamethasone elicits glucocorticoid effects; however, hydrocortisone is preferred in thyroid storm.
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Pathophysiologic mechanisms of Graves disease relating thyroid-stimulating immunoglobulins to hyperthyroidism and ophthalmopathy. T4 is levothyroxine. T3 is triiodothyronine.
