You are in: eMedicine Specialties > Pediatrics: General Medicine > Endocrinology Thyroid StormArticle Last Updated: Aug 22, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Madhusmita Misra, MD, Assistant in Pediatrics, Mass General Hospital for Children, Harvard Medical School; Assistant Professor of Pediatrics, Fellowship Program Director, Department of Pediatric Endocrinology, Massachusetts General Hospital Madhusmita Misra is a member of the following medical societies: Endocrine Society and Lawson-Wilkins Pediatric Endocrine Society Coauthor(s): Abhay Singhal, MD, Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Indiana University School of Medicine; Deborah E Campbell, MD, Professor of Clinical Pediatrics, Albert Einstein College of Medicine; Director, Department of Pediatrics, Division of Neonatology, Weiler Hospital Division of Montefiore Medical Center Editors: Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School; Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences; George P Chrousos, MD, FAAP, MACP, MACE, Professor and Chair, Department of Pediatrics, Athens University Medical School Author and Editor Disclosure Synonyms and related keywords: thyroid storm, thyrotoxic crisis, thyrotoxicosis INTRODUCTIONSection 2 of 10
  BackgroundThyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis. Thyroid storm may be the initial presentation of thyrotoxicosis in undiagnosed children, particularly in neonates. The clinical presentation includes fever, tachycardia, hypertension, and neurological and gastrointestinal abnormalities. Hypertension may be followed by congestive heart failure that is associated with hypotension and shock. Because thyroid storm is almost invariably fatal if left untreated, rapid diagnosis and aggressive treatment are critical. Fortunately, this condition is extremely rare in children. Diagnosis is primarily clinical, and no specific laboratory tests are available. Several factors may precipitate the progression of thyrotoxicosis to thyroid storm. In the past, thyroid storm was commonly observed during thyroid surgery, especially in older children and adults, but improved preoperative management has markedly decreased the incidence of this complication. Today, thyroid storm occurs more commonly as a medical crisis rather than a surgical crisis. PathophysiologyThyroid storm is a decompensated state of thyroid hormone–induced, severe hypermetabolism involving multiple systems and is the most extreme state of thyrotoxicosis. The clinical picture relates to severely exaggerated effects of THs due to increased release (with or without increased synthesis) or, rarely, increased intake of TH. Heat intolerance and diaphoresis are common in simple thyrotoxicosis but manifest as hyperpyrexia in thyroid storm. Extremely high metabolism also increases oxygen and energy consumption. Cardiac findings of mild-to-moderate sinus tachycardia in thyrotoxicosis intensify to accelerated tachycardia, hypertension, high-output cardiac failure, and a propensity to develop cardiac arrhythmias. Similarly, irritability and restlessness in thyrotoxicosis progress to severe agitation, delirium, seizures, and coma. GI manifestations of thyroid storm include diarrhea, vomiting, jaundice, and abdominal pain, in contrast to only mild elevations of transaminases and simple enhancement of intestinal transport in thyrotoxicosis. FrequencyUnited StatesThe true frequency of thyrotoxicosis and thyroid storm in children is unknown. The incidence of thyrotoxicosis increases with age. Thyrotoxicosis may affect as many as 2% of older women. Children constitute less than 5% of all thyrotoxicosis cases. Graves disease is the most common cause of childhood thyrotoxicosis and, in a possibly high estimate, reportedly affects 0.2-0.4% of the pediatric and adolescent population. About 1-2% of neonates born to mothers with Graves disease manifest thyrotoxicosis. Mortality/MorbidityThyroid storm is an acute, life-threatening emergency. The adult mortality rate is extremely high (90%) if early diagnosis is not made and the patient is left untreated. With better control of thyrotoxicosis and early management of thyroid storm, adult mortality rates have declined to less than 20%. Sex
Age
CLINICALSection 3 of 10
HistoryPatients may have a known history of thyrotoxicosis. In the absence of previously diagnosed thyrotoxicosis, the history may include symptoms such as irritability, agitation, emotional lability, a voracious appetite with poor weight gain, excessive sweating and heat intolerance, and poor school performance caused by decreased attention span. Burch and Wartofsky have published precise criteria and a scoring system for the diagnosis of thyroid storm based on clinical features.
Physical
Causes
DIFFERENTIALSSection 4 of 10
Anxiety Disorder: Panic Disorder Heart Failure, Congestive Hypertension Hyperthyroidism Pheochromocytoma Supraventricular Tachycardia, Atrial Ectopic Tachycardia
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| Drug Name | Propylthiouracil (PTU, Propyl-Thyracil) |
|---|---|
| Description | 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. |
| Adult Dose | Initial: 200-400 mg PO/NG q4-8h Hyperthyroidism without thyroid storm: 150-450 mg/d PO divided q8h initially Maintenance: 100-150 mg/d PO divided q8-12h |
| Pediatric Dose | Neonate dose: 5-10 mg/kg/d PO/NG divided q6-8h Children: 15-20 mg/kg/d PO/NG divided q6-8h initially; higher doses of up to 30-40 mg/kg/d have been successfully used; not to exceed 1200 mg/d Hyperthyroidism without thyroid storm: 5-7 mg/kg/d PO divided q6-8h initially Children, maintenance dose: one to two thirds of initial dose q8-12h |
| Contraindications | Documented hypersensitivity |
| Interactions | Concurrent use with other drugs known to cause bone marrow suppression may cause agranulocytosis; may cause hypothyroidism if used with lithium or potassium iodide; may cause bleeding diathesis if used with anticoagulants (eg, warfarin) |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Adverse effects higher in children; aplastic anemia has been described, but leukopenia more often observed; dermatitis, especially urticarial rash; arthritis; arthralgia; lupuslike syndrome; idiosyncratic reactions (eg, hepatitis, hepatic failure) may occur; discontinue upon neutropenia or abnormal LFT results; administer with food to minimize adverse GI effects |
| Drug Name | Methimazole (Tapazole) |
|---|---|
| Description | 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. Comatose patients may require administration via NG tube because agent is available solely as PO preparation. |
| Adult Dose | Initial dose: 60-120 mg/d PO/NG divided q6-8h Hyperthyroidism without thyroid storm: 15-60 mg/d PO divided q8-24h initially Maintenance dose: 10-20 mg/d PO divided q8-24h |
| Pediatric Dose | Initial dose: 0.5–1.0 mg/kg/d PO/NG divided q8h Hyperthyroidism without thyroid storm: 0.5-0.7 mg/kg/d PO divided q8-24h Maintenance dose: 1/2 to 1/3 of initial daily dose divided in 1-3 doses; not to exceed 30 mg/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Concurrent use with lithium or potassium iodide may cause hypothyroidism; concurrent use with anticoagulants (eg, warfarin) may cause bleeding diathesis |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Adverse effects higher in children; aplastic anemia has been described, but leukopenia observed more often; dermatitis, especially urticarial rash; arthritis; arthralgias; lupuslike syndrome; idiosyncratic reactions (eg, cholestatic jaundice) may occur; liver failure has not been identified; discontinue if neutropenia occurs and if abnormal LFTs persist; administer with food to minimize adverse GI effects; infants born to mothers receiving methimazole have suffered from aplasia cutis |
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.
| Drug Name | Potassium iodide, saturated solution (Pima, SSKI, Thyro-Block) |
|---|---|
| Description | Used to inhibit TH release from thyroid gland. One milliliter of SSKI contains 1 g of potassium iodide (ie, approximately 50 mg/drop). In adults, sodium iodide 0.25 g IV q6h or 0.5 g IV q12h has also been used successfully. |
| Adult Dose | 2-5 drops PO/NG q6h |
| Pediatric Dose | Neonates: 100 mg PO/NG q6-8h Children: Administer as in adults |
| Contraindications | Documented hypersensitivity; hyperkalemia; pregnant adolescents; impaired renal function, Addison disease |
| Interactions | Use with other potassium-containing agents, potassium-sparing diuretics, and ACE inhibitors may result in hyperkalemia; use with lithium or potassium iodide may precipitate hypothyroidism; administer propylthiouracil before iodides in thyroid storm so that the effect of the propylthiouracil is fully manifested; iodides may inhibit the action of the thiourea drugs because iodine uptake may be initially increased |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Hypersensitivity reactions; arrhythmias; GI bleeding; angioedema; administer PO after meals with food or milk or dilute with large quantity of juice, water, or milk |
| Drug Name | Strong iodine (Lugol Solution) |
|---|---|
| Description | Contains 100 mg potassium iodide and 50 mg iodine; provided 8 mg iodide/drop. |
| Adult Dose | 10 drops PO tid mixed in water or juice |
| 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 |
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.
| Drug Name | Propranolol (Inderal) |
|---|---|
| Description | 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. |
| Adult Dose | 20-80 mg/dose PO/NG q4-6h 1-2 mg/dose slow IVP as a single dose; not to exceed administration rate of 1 mg/min; may repeat q10-15min or until symptoms are controlled |
| Pediatric Dose | Neonates: 2 mg/kg/d PO/NG divided q6-12h Children: 0.5-4 mg/kg/d PO/NG divided q6h; not to exceed 60 mg/d 0.025-0.15 mg/kg IV over 10 min; may be repeated q10min until hyperdynamic cardiovascular state is improved; not to exceed cumulative dose of 5 mg |
| Contraindications | Documented hypersensitivity; uncompensated CHF; cardiogenic shock; bradycardia; heart block; pulmonary edema; severe hyperactive airway disease; chronic obstructive pulmonary disease; Raynaud disease |
| Interactions | Barbiturates, indomethacin, and rifampin may increase propranolol metabolism, lowering serum levels, whereas cimetidine, hydralazine, verapamil, and chlorpromazine may increase serum levels; bioavailability may be increased in Down syndrome, so lower doses may be required in these children; coadministration with catecholamine-depleting drugs such as reserpine may lead to hypotension, bradycardia, and vertigo; may decrease the clearance of theophylline, antipyrine, and lidocaine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Most common adverse drug reactions include hypotension, CHF, bradycardia, heart block, CNS depression; nausea, vomiting, constipation, hypoglycemia agranulocytosis; do not administer IV dose faster than 1 mg/min with continuous monitoring; gradually taper dose over 1-2 wk when discontinuing; administer at same time each day; advise patient to inform physician if using concurrently with other adrenergic agonists |
| Drug Name | Esmolol (Brevibloc) |
|---|---|
| Description | Beta 1–specific antagonist with a short duration of action. |
| Adult Dose | 500 mcg/kg/min IV infused over 1 min, then 50-100 mcg/kg/min for 4 min; repeat until desired effect; not to exceed 200 mcg/kg/min |
| Pediatric Dose | Loading dose: 250-500 mcg/kg IV infused over 1 minute; may repeat frequently until desired effect Maintenance dose: 50-100 mcg/kg/min IV infusion |
| Contraindications | Documented hypersensitivity; uncompensated CHF; cardiogenic shock; bradycardia; heart block; Raynaud disease |
| Interactions | Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, digoxin, or flecainide; toxicity increases when administered concurrently with acetaminophen, clonidine, epinephrine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Common adverse cardiovascular reactions include hypotension, CHF, bradycardia, and heart block; use with caution in patients with diabetes, as drug can cause hypoglycemia and mask signs and symptoms; bronchospasm; infusion site reactions (eg, phlebitis, skin necrosis) upon extravasation |
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.
| Drug Name | Hydrocortisone succinate (Solu-Cortef) |
|---|---|
| Description | Provides mineralocorticoid activity and glucocorticoid effects. |
| Adult Dose | 100-200 mg IV q6-8h |
| Pediatric Dose | 5 mg/kg IV q6-8h |
| Contraindications | Documented hypersensitivity; serious infections (excluding meningitis, septic shock); fungal infections; varicella infections. |
| Interactions | Barbiturates or rifampin may decrease effect; potassium-depleting agents (eg, diuretics) may increase risk of hypokalemia; may increase digitalis toxicity secondary to hypokalemia |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May suppress immune function, but benefits outweigh risks in serious conditions such as thyroid storm; if PO, administer with meals to decrease GI upset; early-onset adverse effects include glucose intolerance, hypertension, agitation, and indigestion; late-onset adverse effects include immune suppression, increased susceptibility to sepsis, adrenal suppression, hypertension, urinary calcium loss, osteopenia, and gastric irritation and bleeding |
| Drug Name | Dexamethasone (Decadron) |
|---|---|
| Description | Elicits glucocorticoid effects. |
| Adult Dose | 2 mg PO/IV q6h |
| Pediatric Dose | 0.1-0.2 mg/kg/d PO divided q6-8h |
| Contraindications | Documented hypersensitivity; serious infections (excluding meningitis, septic shock); fungal infections; varicella infections |
| Interactions | Concurrent use of barbiturates, phenytoin, or rifampin can decrease effects; conversely, dexamethasone decreases effect of salicylates and immunization vaccines |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May suppress immune function, but benefits outweigh risks in serious conditions such as thyroid storm; administer with meals to decrease GI upset; early-onset adverse effects include glucose intolerance, hypertension, agitation, and indigestion; late-onset adverse effects include immune suppression, increased susceptibility to sepsis, adrenal suppression, hypertension, urinary calcium loss, osteopenia, and gastric irritation and bleeding |
Article Last Updated: Aug 22, 2006
