eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Thyroid Storm

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
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

Updated: Jun 4, 2009

Introduction

Background

Thyroid 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 GI 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.

Pathophysiology

Thyroid 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.¹ 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.

Frequency

United States

The 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/Morbidity

Thyroid 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

• Thyrotoxicosis is 3-5 times more common in females than in males, especially among pubertal children.
• Thyroid storm affects a small percentage of patients with thyrotoxicosis. The incidence is presumed to be higher in females; however, no specific data regarding sex-specific incidence are available.

Age

• Neonatal thyrotoxicosis occurs in 1-2% of neonates born to mothers with Graves disease. Infants younger than 1 year constitute only 1% of childhood thyrotoxicosis.
• More than two thirds of all cases of thyrotoxicosis occur in children aged 10-15 years. Overall, thyrotoxicosis occurs most commonly during the third and fourth decades of life.
• Because childhood thyrotoxicosis is more likely to occur in adolescents, thyroid storm is more common in this age group, although it can occur in patients of all ages.

Clinical

History

Patients 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.²

• General symptoms
  • Fever
  • Profuse sweating
  • Poor feeding and weight loss
  • Respiratory distress
  • Fatigue (more common in older adolescents)
• GI symptoms
  • Nausea and vomiting
  • Diarrhea
  • Abdominal pain
  • Jaundice³
• Neurologic symptoms
  • Anxiety (more common in older adolescents)
  • Altered behavior
  • Seizures, coma

Physical

• Fever
  • Temperature consistently exceeds 38.5°C.
  • Patients may progress to hyperpyrexia.
  • Temperature frequently exceeds 41°C.
• Excessive sweating
• Cardiovascular signs
  • Hypertension with wide pulse pressure
  • Hypotension in later stages with shock
  • Tachycardia disproportionate to fever
  • Signs of high-output heart failure
  • Cardiac arrhythmia (Supraventricular arrhythmias are more common, [eg, atrial flutter and fibrillation], but ventricular tachycardia may also occur.)
• Neurologic signs
  • Agitation and confusion
  • Hyperreflexia and transient pyramidal signs
  • Tremors, seizures
  • Coma
• Signs of thyrotoxicosis
  • Orbital signs
  • Goiter

Causes

• Thyroid storm is precipitated by the following factors in individuals with thyrotoxicosis:
  • Sepsis
  • Surgery
  • Anesthesia induction⁴
  • Radioactive iodine (RAI) therapy⁵
  • Drugs (anticholinergic and adrenergic drugs such as pseudoephedrine; salicylates; nonsteroidal anti-inflammatory drugs [NSAIDs]; chemotherapy⁶ )
  • Excessive thyroid hormone 9TH) ingestion
  • Withdrawal of or noncompliance with antithyroid medications
  • Diabetic ketoacidosis
  • Direct trauma to the thyroid gland
  • Vigorous palpation of an enlarged thyroid
  • Toxemia of pregnancy and labor in older adolescents; molar pregnancy
• Thyroid storm can occur in children with thyrotoxicosis due to any cause but is most commonly associated with Graves disease. Other reported causes of thyrotoxicosis associated with thyroid storm include the following:
  • Transplacental passage of maternal thyroid-stimulating immunoglobulins in neonates
  • McCune-Albright syndrome with autonomous thyroid function⁷
  • Hyperfunctioning thyroid nodule
  • Hyperfunctioning multinodular goiter
  • Thyroid-stimulating hormone (TSH)–secreting tumor
• Graves disease may also occur in children with Down syndrome or Turner syndrome and in association with other autoimmune conditions, including the following:
  • Juvenile rheumatoid arthritis
  • Addison disease
  • Type I diabetes
  • Myasthenia gravis
  • Chronic lymphocytic (Hashimoto) thyroiditis
  • Systemic lupus erythematosus
  • Chronic active hepatitis
  • Nephrotic syndrome
• Although the exact pathogenesis of thyroid storm is not fully understood, the following theories have been proposed:
  • Patients with thyroid storm reportedly have relatively higher levels of free THs than patients with uncomplicated thyrotoxicosis, although total TH levels may not be increased.
  • Adrenergic receptor activation is another hypothesis. Sympathetic nerves innervate the thyroid gland, and catecholamines stimulate TH synthesis. In turn, increased THs increase the density of beta-adrenergic receptors, thereby enhancing the effect of catecholamines. The dramatic response of thyroid storm to beta-blockers and the precipitation of thyroid storm after accidental ingestion of adrenergic drugs such as pseudoephedrine support this theory. This theory also explains normal or low plasma levels and urinary excretion rates of catecholamines. However, it does not explain why beta-blockers fail to decrease TH levels in thyrotoxicosis.
  • Another theory suggests a rapid rise of hormone levels as the pathogenic source. A drop in binding protein levels, which may occur postoperatively, might cause a sudden rise in free hormone levels. In addition, hormone levels may rise rapidly when the gland is manipulated during surgery, during vigorous palpation during examination, or from damaged follicles following RAI therapy.
  • Other proposed theories include alterations in tissue tolerance to THs, the presence of a unique catecholaminelike substance in thyrotoxicosis, and a direct sympathomimetic effect of TH as a result of its structural similarity to catecholamines.

Differential Diagnoses

Anxiety Disorder: Panic Disorder
Heart Failure, Congestive
Hypertension
Hyperthyroidism
Pheochromocytoma
Supraventricular Tachycardia, Atrial Ectopic Tachycardia

Other Problems to Be Considered

Anticholinergic or adrenergic drug intoxication
CNS infections
Hypertensive encephalopathy
Malignant hyperthermia
Septic shock

Workup

Laboratory Studies

Thyroid storm diagnosis is based on clinical features, not on laboratory test findings. If the patient's clinical picture is consistent with thyroid storm, do not delay treatment pending laboratory confirmation of thyrotoxicosis.

• Thyroid studies
  • Results of thyroid studies are usually consistent with hyperthyroidism and are useful only if the patient has not been previously diagnosed.
  • Test results may not come back quickly and are usually unhelpful for immediate management.
  • Usual findings include elevated triiodothyronine (T3), thyroxine (T4) and free T4 levels; increased T3 resin uptake; suppressed thyroid-stimulating hormone (TSH) levels; and an elevated 24-hour iodine uptake. TSH levels are not suppressed in the rare instances of excess TSH secretion.
• CBC count: CBC count reveals mild leukocytosis, with a shift to the left.
• Liver function tests (LFTs): LFTs commonly reveal nonspecific abnormalities such as elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatinine kinase, alkaline phosphatase, and serum bilirubin.
• ABG and urinalysis: Measurement of blood gas and electrolyte levels and urinalysis testing may be performed to assess and monitor short-term management.

Imaging Studies

• Chest radiography
  • Chest radiography may reveal cardiac enlargement due to congestive heart failure.
  • Radiography may also reveal pulmonary edema caused by heart failure and/or evidence of pulmonary infection.
• CT scanning: Head CT scanning may be necessary to exclude other neurologic conditions if diagnosis is uncertain after the initial stabilization of a patient who presents with altered mental status.

Other Tests

• ECG is useful in monitoring for cardiac arrhythmias. Atrial fibrillation is the most common cardiac arrhythmia associated with thyroid storm. Other arrhythmias such as atrial flutter and, less commonly, ventricular tachycardia may also occur.

Treatment

Medical Care

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:

• 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 h).
• Promptly administer antiadrenergic drugs (eg, propranolol) to minimize sympathomimetic symptoms.
• Correct the hyperthyroid state. Administer antithyroid medications to block further synthesis of thyroid hormones (THs). High-dose propylthiouracil is preferred because of its early onset of action and capacity to inhibit peripheral conversion of T4 to T3 (June 3, 2009: see new FDA warning discussion listed below).
• The US Food and Drug Administration (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 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. 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.⁸
  • 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.
• 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). 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.
• Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful in preventing relative adrenal insufficiency due to hyperthyroidism.
• 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.⁹

Consultations

• Endocrinologist
• Intensivist

Medication

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.

Antithyroids

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.

Dosing

Adult

Not first-line agent
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

Not first-line agent
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-third to two-thirds of initial dose q8-12h

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)

Contraindications

Documented hypersensitivity; liver impairment; pediatric patients (unless allergic or intolerant to methimazole and no other treatment is an option)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

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; risk of serious liver injury, including liver failure and death, has been reported in adults and children by the FDA (carefully consider drug therapy, and if PTU initiated, monitor for symptoms and signs of liver injury, especially during first 6 mo of therapy)

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. Comatose patients may require administration via NG tube because agent is available solely as PO preparation.

Dosing

Adult

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

Initial dose: 0.5–1 mg/kg/d PO/NG divided q8h
Hyperthyroidism without thyroid storm: 0.5-0.7 mg/kg/d PO divided q8-24h
Maintenance dose: One-third to one-half of initial daily dose divided in 1-3 doses; not to exceed 30 mg/d

Interactions

Concurrent use with lithium or potassium iodide may cause hypothyroidism; concurrent use with anticoagulants (eg, warfarin) may cause bleeding diathesis

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

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 LFT results persist; administer with food to minimize adverse GI effects; infants born to mothers receiving methimazole have suffered from aplasia cutis

Iodides

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)

Used to inhibit TH release from thyroid gland. 1 mL 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.

Dosing

Adult

2-5 drops (approximately 100-250 mg) PO/NG q6h

Pediatric

Neonates: 100 mg PO/NG q6-8h
Children: Administer as in adults

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

Contraindications

Documented hypersensitivity; hyperkalemia; pregnant adolescents; impaired renal function, Addison disease

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

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

Strong iodine (Lugol Solution)

Contains 100 mg potassium iodide and 50 mg iodine; provided 8 mg iodide/drop.

Dosing

Adult

10 drops PO tid mixed in water or juice

Pediatric

Administer as in adults

Interactions

Increases lithium toxicity by producing additive hypothyroid effects; decreased anticoagulant effectiveness of warfarin

Contraindications

Documented hypersensitivity; pulmonary edema; bronchitis; tuberculosis; hyperkalemia

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Prolonged use may result in hypothyroidism; caution in renal failure or GI obstruction

Beta- blockers

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.

Dosing

Adult

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

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

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

Contraindications

Documented hypersensitivity; uncompensated CHF; cardiogenic shock; bradycardia; heart block; pulmonary edema; severe hyperactive airway disease; chronic obstructive pulmonary disease; Raynaud disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

Esmolol (Brevibloc)

Beta 1–specific antagonist with a short duration of action.

Dosing

Adult

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

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

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

Contraindications

Documented hypersensitivity; uncompensated CHF; cardiogenic shock; bradycardia; heart block; Raynaud disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

Glucocorticoids

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 succinate (Solu-Cortef)

Provides mineralocorticoid activity and glucocorticoid effects.

Dosing

Adult

100-200 mg IV q6-8h

Pediatric

5 mg/kg IV q6-8h

Interactions

Barbiturates or rifampin may decrease effect; potassium-depleting agents (eg, diuretics) may increase risk of hypokalemia; may increase digitalis toxicity secondary to hypokalemia

Contraindications

Documented hypersensitivity; serious infections (excluding meningitis, septic shock); fungal infections; varicella infections.

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

Dexamethasone (Decadron)

Elicits glucocorticoid effects.

Dosing

Adult

2 mg PO/IV q6h

Pediatric

0.1-0.2 mg/kg/d PO divided q6-8h

Interactions

Concurrent use of barbiturates, phenytoin, or rifampin can decrease effects; conversely, dexamethasone decreases effect of salicylates and immunization vaccines

Contraindications

Documented hypersensitivity; serious infections (excluding meningitis, septic shock); fungal infections; varicella infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

Follow-up

Further Inpatient Care

• A pediatric ICU is the recommended inpatient care setting.
• Continue supportive treatment.
• Appropriately manage the precipitating event.
• Follow up with laboratory tests to confirm thyrotoxicosis diagnosis, if previously undiagnosed.

Inpatient & Outpatient Medications

• Patients may require propranolol and iodides administration for 1 week.

Deterrence/Prevention

• 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).

Prognosis

• If untreated, thyroid storm is almost invariably fatal in adults and is likely to cause a similarly severe outcome in children, although the condition is so rare in children that these data are not available.
• With adequate thyroid-suppressive therapy and sympathetic blockade, clinical improvement should occur within 24 hours.
• Adequate therapy should resolve the crisis within a week.
• Treatment for adults has reduced mortality to less than 20%.
• In adult patients, the precipitating factor is often the cause of death.

Patient Education

• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education articles Thyroid Problems and Thyroid Storm.

Miscellaneous

Medicolegal Pitfalls

• Diagnosis may be missed because of variable presentation and because thyroid storm is rare in children.
• In younger children and neonates, thyroid storm is most likely to be confused with sepsis and septic shock in the absence of a previous thyrotoxicosis diagnosis.

References

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8. FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). US Food and Drug Administration. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm. Accessed June 3, 2009.

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Keywords

thyroid storm, thyrotoxic crisis, thyrotoxicosis, thyroid hormones, TH, hypertension, congestive heart failure, hypotension, shock, heat intolerance, tachycardia, delirium, seizures, diarrhea, jaundice, vomiting, abdominal pain, Graves disease, respiratory distress, fatigue, atrial flutter, atrial fibrillation, goiter, McCune-Albright syndrome, juvenile rheumatoid arthritis, Addison disease, type I diabetes, myasthenia gravis, chronic lymphocytic thyroiditis, Hashimoto thyroiditis, systemic lupus erythematosus, chronic active hepatitis, nephrotic syndrome

Contributor Information and Disclosures

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, MD is a member of the following medical societies: Endocrine Society and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Tercica Grant/research funds Principal investigator; Ipsen Consulting fee Review panel membership

Coauthor(s)

Abhay Singhal, MD, Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Indiana University School of Medicine
Abhay Singhal, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

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
Deborah E Campbell, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Medical Association, National Perinatal Association, New York Academy of Medicine, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School
Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds PI, also occasional consultant

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

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