Hyperthyroidism, Thyroid Storm, and Graves Disease: Treatment and Medication
Treatment
Emergency Department Care:
- 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. Only in the setting of subacute thyroiditis is aspirin indicated.
- 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.
- 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.
- 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.
Consultations:
- 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.
Medication
The goals of medical therapy are blockade of peripheral effects, inhibition of hormone synthesis, blockade of hormone release, and prevention of peripheral conversion of T4 to T3. Restoration of a clinical euthyroid state may take up to 8 weeks.
Blocking agents such as beta-blockers reduce sympathetic hyperactivity and decrease peripheral conversion of T4 to T3.
Guanethidine and reserpine have been used to provide sympathetic blockade and may be effective agents if beta-blockers are contraindicated or not tolerated.
Iodides and lithium work to block release of preformed thyroid hormone.
Thionamides prevent synthesis of new thyroid hormone.
Drug Category: Inhibitors of hormone synthesis -- Thionamides (eg, propylthiouracil, methimazole) prevent hormone synthesis by inhibiting both the organification of iodine to tyrosine residues and the coupling of iodotyrosines. The drug must be given orally or via a nasogastric tube. PTU has the added benefit of inhibiting peripheral conversion of T4 to T3.
| Propylthiouracil (PTU) -- DOC; effects may be seen soon after drug is started, but therapy may need to be continued for 4-12 wk. Laboratory monitoring of T4 and T3 levels may be required to adjust therapy. Although classified as pregnancy category D, recommended as DOC for women who are pregnant or breastfeeding. | |||||||||||
| Adult Dose | Mild-to-moderate thyrotoxicosis: 150-450 mg/d PO or via nasogastric tube Thyroid storm: 600-1200 mg loading dose followed by 200-250 mg PO q4-6h Pediatric Dose | <6 years: Not established | 6-10 years: 50-150 mg/d PO >10 years: 150-300 mg/d PO Contraindications | Documented hypersensitivity; breastfeeding mothers | Interactions | Has antivitamin K activity; may potentiate activity of oral anticoagulants | Pregnancy |
D - Unsafe in pregnancy
| Precautions | Rashes are common; agranulocytosis may occur; rarely associated with hepatitis, hepatic necrosis, and liver failure; monitor prothrombin time during treatment; once symptoms of hyperthyroidism have resolved, lower maintenance dose if serum TSH levels elevated | |
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| Methimazole (Tapazole) -- An effective inhibitor of thyroid synthesis; however, it does not inhibit peripheral conversion of thyroid hormone | |||||||||||
| Adult Dose | Mild-to-moderate thyrotoxicosis: 15-30 mg/d PO divided q8h Thyroid storm: 20 mg PO q4h Pediatric Dose | 0.4-0.7 mg/kg/d PO divided q8h; maintenance dose is usually one half of initial | Contraindications | Documented hypersensitivity; breastfeeding mothers | Interactions | Has antivitamin K activity; may potentiate activity of oral anticoagulants | Pregnancy |
D - Unsafe in pregnancy
| Precautions | Rashes are common; agranulocytosis may occur; rarely associated with hepatitis, hepatic necrosis, and liver failure; monitor prothrombin time during treatment; once symptoms of hyperthyroidism have resolved, lower maintenance dose if serum TSH levels elevated | |
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Drug Category: Blockade of hormone release -- Iodides and lithium are used effectively to block the release of thyroid hormone. Effects are exerted directly on the thyroid gland. Lithium is used only as a secondary agent due to difficulty in titrating to an effective dose and its narrow therapeutic window. These agents should be administered at least 1 hour after PTU is given to ensure the advance blockade of thyroid hormone formation; otherwise, administering iodides could worsen symptoms. Iodide preparations are known to cause serum sickness–type reactions. Iodides should not be used for long-term therapy in thyrotoxicosis. Preparations include saturated solution of potassium iodide (SSKI), iopanoic acid, and Lugol iodine.
| Iopanoic acid -- Absorption from GI tract is rapid and complete. Iodine equilibrates in extracellular fluids and is concentrated specifically by thyroid gland. For treatment of thyrotoxicosis, parenteral iodine may be used. | |||||||||
| Adult Dose | 1 g via slow IV drip q8h for first 24 h then 500 mg bid | ||||||||
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| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults Contraindications | Documented hypersensitivity to iodinated compounds; burn patients | Interactions | Increases lithium toxicity by producing additive hypothyroid effects; decreased anticoagulant effectiveness of warfarin | Pregnancy |
D - Unsafe in pregnancy
| Precautions | Avoid infusion in phlebitis; do not give undiluted into peripheral vein by direct injection | |
| Saturated solution of potassium iodide (SSKI, PIMA) -- Inhibits thyroid hormone secretion. Solution contains 50 mg of iodide per drop and may be mixed with juice or water. | |||||||||
| Adult Dose | 1-5 gtt PO tid until stable | ||||||||
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| Pediatric Dose | Infants: 150-250 mg (3-6 gtt) PO tid Children: Administer as in adults Contraindications | Documented hypersensitivity; pulmonary edema; severe bronchitis; renal disorders; tuberculosis; hyperkalemia | Interactions | Increases lithium toxicity by producing additive hypothyroid effects; decreased anticoagulant effectiveness of warfarin | Pregnancy |
D - Unsafe in pregnancy
| Precautions | Prolonged use may result in hypothyroidism; caution in renal failure and GI obstruction; iododerma, coryza, cough, nausea, rhinorrhea, and parotiditis may occur | |
| Lugol solution -- Inhibits thyroid hormone secretion. Contains 8 mg of iodide per drop. May be mixed with juice or water for intake. | |
| Adult Dose | 5-10 gtt PO tid until stable |
|---|---|
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; pulmonary edema; bronchitis; tuberculosis; hyperkalemia |
| Interactions | Increases lithium toxicity by producing additive hypothyroid effects; decreased anticoagulant effectiveness of warfarin |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Prolonged use may result in hypothyroidism; caution in renal failure or GI obstruction |
Drug Category: Beta-adrenergic blockers -- Beta-blockade is mainstay of symptomatic therapy; antiadrenergic effects block effects of excess thyroid hormone. Beta-blockade also plays a role in the prevention of peripheral conversion of T4 to T3. Propranolol is the best studied in this class, but other beta-blockers have similar effects in hyperthyroidism.
Effects are relatively dramatic, and results may be seen within 10 minutes after administration.
Use of beta-blockers improves heart failure that is due to thyrotoxic tachycardia or thyrotoxic myocardial depression but may worsen heart failure that is due to other causes. When in doubt, therapy may be begun with a short-acting titratable agent, such as esmolol.
Reserpine and guanethidine are effective autonomic blockers that may be used if beta-blockers are contraindicated.
| Propranolol (Inderal) -- DOC; can control cardiac and psychomotor manifestations within minutes. | |||||||||||
| Adult Dose | 20-80 mg PO q4h 1-2 mg IV q10-15min or until symptoms controlled Pediatric Dose | 2 mg/kg/d PO divided q6h | 0.05-0.15 mg/kg IV; administer half of desired dose and observe for effect; remainder may be given in 2 min, if required Contraindications | Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities; bronchospasm | Interactions | Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; may increase toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines | Pregnancy |
C - Safety for use during pregnancy has not been established.
| Precautions | Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely | |
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Drug Category: Corticosteroids -- These agents play a role in the prevention of peripheral conversion of T4 to T3
| Dexamethasone (Decadron) -- Blocks conversion of T4 to T3 and does not interfere with cortisol stimulation testing. | |
| Adult Dose | 2 mg PO/IV q6h |
|---|---|
| Pediatric Dose | Loading dose: 0.15 mg/kg/dose PO/IV q6h |
| Contraindications | Documented hypersensitivity; active bacterial or fungal infection |
| Interactions | Barbiturates, phenytoin, and rifampin decrease effects; decreases effects of salicylates and vaccines used for immunization |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Increases risk of multiple complications, including severe infections; monitor for adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications |
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Synonyms And Related Keywords
thyroid hormone, thyroxine, T4, triiodothyronine, T3, elevated levels of thyroid hormone, diffuse toxic goiter, goiter, exophthalmos, pretibial myxedema, thyrotoxicosis, toxic multinodular goiter, congestive heart failure, thyromegaly, atrial fibrillation, myopathy, periodic paralysis, thyroid bruit, infrequent blinking, lid lag, pulmonary infection, diabetic ketoacidosis, hyperosmolar coma, insulin-induced hypoglycemia, withdrawal of antithyroid medication, vigorous palpation of thyroid gland, thyroid hormone overdose, toxemia of pregnancy
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