Thyrotoxic Storm Following Thyroidectomy 

Updated: Aug 06, 2020
Author: Peter F Czako, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA 

Overview

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 precipitated by the stress of surgery, anesthesia, or thyroid manipulation and may be prevented by pretreatment with antithyroid drugs (ATDs).[1] Improved preoperative management has markedly decreased the incidence of this complication.[2] Today, thyroid storm occurs more commonly as a medical crisis rather than a surgical crisis.

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.

Diagnosis is primarily clinical, and no specific laboratory tests are available. Patients with a Burch–Wartofsky Point Scale (BWPS) of ≥45 or Japanese Thyroid Association (JTA) categories of thyroid storm 1 (TS1) or thyroid storm 2 (TS2) with evidence of systemic decompensation require aggressive therapy. The decision to use aggressive therapy in patients with a BWPS of 25–44 is based on clinical judgment.[1]

According to the guidelines of the American Thyroid Association (ATA), a multimodality treatment approach should be individualized to the patient and includes β-adrenergic blockade, ATD therapy, inorganic iodide, corticosteroid therapy, cooling with acetaminophen and cooling blankets, volume resuscitation, nutritional support, respiratory care, and monitoring in an intensive care unit.[1]

ATA guidelines also recommend that patients undergoing thyroidectomy be rendered euthyroid with methimazole preoperatively and that potassium iodide (KI) be given in the immediate preoperative period. The recommendation to render patients euthyroid with antithyroid medication is an effort to reduce the risk of thyroid storm that the stress of surgery could precipitate. KI is recommended to reduce thyroid gland vascularity with the goal of improving operative visualization and reducing operative complications.[1]

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 thyroid hormones (THs) due to increased release (with or without increased synthesis) or, rarely, increased intake of TH.[3]

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.

Etiology

A precipitating factor usually is found with thyroid storm. Presently, the most common cause of thyroid storm is intercurrent illness or infection.[4, 5]

Some causes of rapidly increased thyroid hormone levels include the following:

  • Surgery, thyroidal or nonthyroidal

  • Radioiodine therapy

  • Withdrawal of antithyroid drug therapy

  • Vigorous thyroid palpation

  • Iodinated contrast dye

  • Thyroid hormone ingestion

Other common precipitants include the following:

  • Infection

  • Emotional stress

  • Tooth extraction

  • Diabetic ketoacidosis

  • Hypoglycemia

  • Trauma

  • Bowel infarction

  • Parturition

  • Toxemia of pregnancy

  • Pulmonary embolism

  • Cerebrovascular accident

  • Gestational trophoblastic disease

Although it can develop in toxic adenoma or multinodular toxic goiter, thyroid storm is more commonly seen in toxicity secondary to Graves disease. See the image below.

Pathophysiologic mechanisms of Graves disease rela Pathophysiologic mechanisms of Graves disease relating thyroid-stimulating immunoglobulins to hyperthyroidism and ophthalmopathy. T4 is levothyroxine. T3 is triiodothyronine.

Epidemiology

United States statistics

Among 121,384 hospital discharges with thyrotoxicosis identified between 2004 and 2013, 19,723 (16.2%) were diagnosed with thyroid storm.[6] The incidence of thyroid storm is approximately 0.65 cases per 100,000 persons per year and 5.2 per 100,000 hospitalized patients per year.[6]

International statistics

In Japan, thyroid storm is a rare disorder occurring in approximately 1–5% of patients hospitalized for thyrotoxicosis.[4, 7]

Age- and sex-related demographics

Age and sex predilection depends on the etiology of thyrotoxicity. Graves disease more frequently develops in females (ie, male-to-female ratio ranges from 1:7 to 1:10); multinodular goiter more often manifests in the elderly population. In one study, the majority of patients with thyrotoxicosis were middle aged and white, and about 76% were female.[6]

Prognosis

Thyroid storm (TS) is an acute, life-threatening emergency. If untreated, thyroid storm is almost invariably fatal in adults (90% mortality rate). Death from thyroid storm may be a consequence of cardiac arrhythmia, congestive heart failure, hyperthermia, multiple organ failure or other factors, though the precipitating factor is often the cause of death.

With adequate thyroid-suppressive therapy and sympathetic blockade, clinical improvement should occur within 24 hours. Adequate therapy should resolve the crisis within a week. With treatment, mortality has been reported as 8-25%.[5, 8] In one retrospective study from Japan of 1324 patients who were diagnosed with thyroid storm, the following factors were associated with increased mortality risk in thyroid storm[9] :

  • Age 60 years or older

  • Central nervous system (CNS) dysfunction at admission

  • Lack of antithyroid drug and beta-blockade use

  • Need for mechanical ventilation and plasma exchange along with hemodialysis

In addition, CNS dysfunction of greater than mild severity appears to be a risk factor for mortality.[5, 8]

Complications

Cardiogenic shock (CS) is a rare complication of thyroid storm, which occurs more commonly in male patients with preexisting structural and atherosclerotic heart disease, and carries a very poor prognosis. In review of 41,835 patients with thyroid storm between 2003-2011, there was an increase in incidence of CS from 0.5% in 2003 to 3% in 2011 but a decrease in mortality from 60.5% in 2003 to 20.9% in 2011. The researches theorized that the decreased mortality rates were due to improved intensive care and increasing use of mechanical circulatory devices such as the intra-aortic balloon pump (IABP) and extra corporeal mechanical ventilation (ECMO).[10]

Patient Education

For patient education resources, see the Thyroid and Metabolism Center as well as Thyroid Problems, Thyroid Storm, and Graves Disease.

 

Presentation

History

Clinical features form the hallmark in diagnosing thyroid storm. Patients with a known history of thyrotoxicosis present with a classic triad of hyperthermia, tachycardia and altered mental status. Most patients have goiter, and many of those with Graves disease have concurrent ophthalmopathy. 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.

Physical Examination

An accentuation of signs and symptoms is seen in uncomplicated thyrotoxicosis. The point of transition from uncomplicated thyrotoxicosis to thyroid storm is difficult to ascertain. Very few criteria define the change. However, certain clinical features (eg, high-grade fever, mental obtundation, decompensation of one or more organ systems secondary to the severe state of hypermetabolism) herald its onset.

The table below presents some changes in the symptoms and signs of thyroid storm when compared with uncomplicated thyrotoxicosis. Importantly, some findings of thyroid storm (eg, atrial dysrhythmia) may also prevail in uncomplicated thyrotoxicosis. Therefore, the table represents only guidelines, not specific criteria to define thyroid storm.

Table. Symptoms and Signs of Thyroid Storm When Compared with Uncomplicated Thyrotoxicosis (Open Table in a new window)

Uncomplicated Thyrotoxicosis

Thyroid Storm

1. Heat intolerance, diaphoresis

1. Hyperpyrexia, temperature in excess of 38°C, dehydration

2. Sinus tachycardia, heart rate 100-140

2. Heart rate faster than 140 beats/min, hypotension, atrial dysrhythmias, congestive heart failure

3. Diarrhea, increased appetite with loss of weight

3. Nausea, vomiting, severe diarrhea, abdominal pain, hepatocellular dysfunction-jaundice

4. Anxiety, restlessness

4. Confusion, agitation, delirium, frank psychosis, seizures, stupor, or coma

Certain unusual presentations include chest pain, acute abdomen, status epilepticus, stroke, acute renal failure due to rhabdomyolysis, and apathetic thyroidism. Apathetic thyroidism is more frequently seen in elderly patients but has been described in all ages. Patients in this variant group present without goiter, ophthalmopathy, or prominent symptoms of hyperthyroidism. These patients have a low pulse rate and a propensity to develop thyroid storm due to delay in diagnosis.

 

DDx

Diagnostic Considerations

Postoperative complications (eg, sepsis, hemorrhage, septicemia, transfusion drug reactions) mimic the thyrotoxic state. Previous history of hyperthyroidism, precipitating factors, increased T3 and T4 levels, and decreased thyroid stimulating hormone (TSH) levels help to establish the diagnosis of thyroid storm.

 

Workup

Approach Considerations

The difference between severe thyrotoxicosis and thyroid storm is clinical diagnosis. Two assessment systems exist: The Burch–Wartofsky Point Scale (BWPS) and the Japanese Thyroid Association (JTA) diagnostic criteria for thyroid storm.

The BWPS is based on dysfunction in various systems (thermoregulatory, central nervous, gastrointestinal, and cardiovascular). A score of 45 or greater is highly suggestive of thyroid storm; a score of 25–44 is suggestive of impending storm, and a score below 25 is unlikely to represent thyroid storm.​[1, 11]

The JTA criteria is based on the presence of thyrotoxicosis with elevated levels of free triiodothyronine (FT3) or free thyroxine (FT4) with the following combinations of features[12] :

  • TS1 (definitive thyroid storm): At least one CNS manifestation and fever, tachycardia, CHF, or GI/ hepatic manifestations OR at least three combinations of fever, tachycardia, CHF, or GI/ hepatic manifestations

  • TS2 (suspected thyroid storm): Two of the following: fever, tachycardia, CHF, or GI/hepatic manifestations OR& TS1 criteria is met but serum FT3 or FT4 level are not available

Laboratory Studies

Laboratory findings in thyroid storm are consistent with those of thyrotoxicosis and include the following:

  • Elevated T3 and T4 levels

  • Elevated T3 uptake

  • Suppressed TSH levels

  • Elevated 24-hour radioiodine uptake

Elevated T4 and decreased TSH are the only abnormal findings needed for conformation of thyrotoxicosis. Treatment should not be withheld for any laboratory confirmation of hyperthyroidism when thyroid storm is suspected clinically. A 2-hour radioiodine uptake is advisable if thyroid storm is suspected and no past history of hyperthyroidism exists.

Other abnormal laboratory values that point toward decompensation of homeostasis include the following:

  • Increased BUN and creatinine kinase

  • Electrolyte imbalance from dehydration, anemia, thrombocytopenia, and leukocytosis

  • Hepatocellular dysfunction as shown by elevated levels of transaminases, lactate dehydrogenase, alkaline phosphatase, and bilirubin

  • Elevated calcium levels

  • Hyperglycemia

 

Treatment

Approach Considerations

Goals of treatment are lowering of thyroid hormone synthesis and secretion, reduction of circulating thyroid hormones, control of the peripheral effects of thyroid hormone, resolution of systemic manifestation, and treatment of precipitating illness.[7] The criteria established by Burch and Wartofsky help in early recognition of impending storm. In thyroid storm, intensive management as described below improves the chance of survival.[11]

Medical Care

Management of thyroid storm is a multistep process. Blocking the synthesis, secretion, and peripheral action of the thyroid hormone is the ideal therapy. Aggressive supportive therapy then is used to stabilize homeostasis and reverse multiorgan decompensation.[13] Additional measures are taken to identify and treat the precipitating factor, followed by definitive treatment to avoid recurrence. Thyroid storm is a fulminating crisis that demands an intensive level of care, continuous monitoring, and vigilance.

Blocking thyroid hormone synthesis

Antithyroid compounds propylthiouracil (PTU) and methimazole (MMI) are used to block the synthesis of the thyroid hormone. PTU also blocks peripheral conversion of T4 to T3 and hence is preferred in thyroid storm over MMI. MMI is the common agent used in hyperthyroidism. PTU and MMI block the incorporation of iodine into thyroglobulin within 1 hour of ingestion. A history of hepatotoxicity or agranulocytosis from previous thioamide therapy precludes use of PTU and MMI.

The US Food and Drug Administration (FDA) had added a boxed warning, the strongest warning issued by the FDA, to the prescribing information for propylthiouracil. The boxed warning emphasizes the risk for severe liver injury and acute liver failure, which have been fatal in some cases. The boxed warning also states that propylthiouracil 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 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 a 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.

  • 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.

Blocking thyroid hormone secretion

After initiation of antithyroid therapy, hormone release can be inhibited by large doses of iodine, which reduce thyroidal iodine uptake. Lugol solution or saturated solution of potassium iodide can be used.

Iodine therapy should be administered after approximately 1 hour following administration of PTU or MMI; iodine used alone helps to increase thyroid hormone stores and may increase the thyrotoxic state.

The iodinated x-ray contrast agent, sodium ipodate, can be administered instead of iodine and also inhibits peripheral conversion of T4 to T3. Potassium iodide (KI) decreases thyroidal blood flow and hence is used preoperatively in thyrotoxicosis.

Patients intolerant to iodine can be treated with lithium, which also impairs thyroid hormone release. Patients unable to take PTU or MMI also can be treated with lithium, as use of iodine alone is debatable. Unlike iodine, lithium is not subject to the escape phenomenon; lithium blocks the release of thyroid hormone throughout its administration.

Plasmapheresis, plasma exchange, peritoneal dialysis exchange transfusion, and charcoal plasma perfusion are other techniques used to remove excess circulating hormone. Presently, these techniques are reserved for patients who do not respond to the initial line of management.[14]

The intravenous preparation of sodium iodide (given as 1 g slow infusion q8-12h) has been taken off of the market.

Blocking peripheral action of thyroid hormone

Propranolol is the drug of choice to counter peripheral action of thyroid hormone. Propranolol blocks beta-adrenergic receptors and prevents conversion of T4 to T3. It produces dramatic improvement in clinical status and greatly ameliorates symptoms. Propranolol produces the desired clinical response in thyroid storm only after large doses. Intravenous administration of propranolol requires continuous monitoring of cardiac rhythm.

Presently, esmolol is the ultra-short-acting beta-blocking agent used successfully in thyrotoxicosis and thyroid storm.

Noncardioselective beta-blockers (eg, propranolol, esmolol) cannot be used in patients with congestive cardiac failure, bronchospasm, or history of asthma. Guanethidine or reserpine can be used instead in these cases.[15]

Successful treatment with reserpine in cases of thyroid storm resistant to large doses of propranolol has been documented. However, guanethidine and reserpine cannot be used in the presence of cardiovascular collapse or shock.

Supportive measures

Aggressive fluid and electrolyte therapy is needed for dehydration and hypotension. This excessive hypermetabolic state, with increased intestinal transit and tachypnea, leads to immense fluid loss. Fluid requirements may increase to 3-5 L/day. Therefore, invasive monitoring is advisable in elderly patients and in those with congestive cardiac failure.

  • Pressor agents can be used when hypotension persists following adequate fluid replacement.

  • Add glucose to IV fluids for nutritional support.

Multivitamins, especially vitamin B-1, are added to prevent Wernicke encephalopathy.

Hyperthermia is treated through central cooling and peripheral heat dissipation.

Acetaminophen is the drug of choice, as aspirin may displace thyroid hormone from binding sites and increase severity of thyroid storm.

Cooling blankets, ice packs, and alcohol sponges encourage dissipation of heat. Use of a cooled humidified oxygen tent is advised.

Use of glucocorticoids in thyroid storm is associated with improved survival rates. Initially, glucocorticoids were used to treat potential relative insufficiency due to accelerated production and degradation owing to the hypermetabolic state. However, the patient may have type 2 autoimmune deficiency, in which Graves disease coexists with absolute adrenal insufficiency.

Glucocorticoids reduce iodine uptake and antibody titers of thyroid-stimulating antibodies with stabilization of the vascular bed. In addition, dexamethasone and hydrocortisone have an inhibitory effect on conversion of T4 to T3. Therefore, a stress dose of glucocorticoid (eg, hydrocortisone, dexamethasone) now is routine.

Cardiac decompensation, although seen more frequently in elderly patients, may appear in younger patients and in patients without underlying cardiac disease.

Digitalization is required to control the ventricular rate in patients with atrial fibrillation.

Anticoagulation drugs may be needed for atrial fibrillation and can be administered in the absence of contraindications.[16] Digoxin may be used in larger doses than those normally used in other conditions. Closely monitor digoxin levels to prevent toxicity. As the patient improves, reduce digoxin dose.

Congestive cardiac failure is seen as a result of impaired myocardial contractility and may require Swan-Ganz catheter monitoring.

Surgical Care

After improvement of thyroid function, which generally occurs within 24 hours, iodine can be gradually discontinued and glucocorticoids tapered and discontinued. ATD and β blockers should be titrated according to thyroid function. Definitive therapy with thyroidectomy or radioactive iodine is suggested.[7]

Prior to radioiodine therapy or surgery, a patient should be made euthyroid with antithyroid drugs and propranolol. Antithyroid drugs are administered for 12-24 months, during which, a remission may occur. Antithyroid drugs are continued until a normal metabolic state is reached. If in remission, the patient should be closely monitored for 6 months, as relapse is more common during this period after discontinuation of therapy. Iodine is progressively withdrawn. Serially monitor patients until the thyroid gland is sufficiently depleted of its hormone to allow radioiodine therapy. Delaying radioiodine ablation for several months may be necessary because of the large doses of iodine used in management of thyroid storm. Some surgeons may reintroduce iodine for 10 days prior to surgery if subtotal thyroidectomy is planned. Follow patients for up to 5 years.

Although medical management with antithyroid medications is the standard of care to re-establish a euthyroid state before more definitive treatment options are undertaken, circumstances may arise that require alternative treatment options. Emergent thyroidectomy has been shown to be safe for treating TS without obtaining euthyroid status prior to the procedure. In a series of 24 patients with iodine-induced hyperthyroidism who underwent surgical thyroidectomy after medical therapy failed, all but one patient survived.[17]

Prevention

American Thyroid Association guidelines recommend that patients undergoing thyroidectomy be rendered euthyroid with methimazole preoperatively and that potassium iodide (KI) be given in the immediate preoperative period. The recommendation to render patients euthyroid with antithyroid medication is an effort to reduce the risk of thyroid storm that the stress of surgery could precipitate. KI is recommended to reduce thyroid gland vascularity with the goal of improving operative visualization and reducing operative complications.[1]

 

Guidelines

Guidelines Summary

American Thyroid Association

In 2016, the American Thyroid Association (ATA) updated the 2011 hyperthyroidism/thyrotoxicosis guidelines it had codeveloped with the American Association of Clinical Endocrinologists. The following are a sampling of the recommendations for the diagnosis and management of thyroid storm[1] :

  • The diagnosis of thyroid storm should be made clinically in a severely thyrotoxic patient with evidence of systemic decompensation

  • Aggressive therapy is indicated in patients with a Burch–Wartofsky Point Scale (BWPS) score of ≥45 or Japanese Thyroid Association (JTA) categories of thyroid storm 1 (TS1) or thyroid storm 2 (TS2) with evidence of systemic decompensation

  • Patients with a BWPS score of 25–44 should be observed closely for signs of deterioration; clinical judgment guides the decision to use aggressive therapy, bearing in mind the risk of drug toxicity

  • A multimodality treatment approach should be used, including β-adrenergic blockade, antithyroid therapy, inorganic iodide, corticosteroid therapy, cooling with acetaminophen and cooling blankets, volume resuscitation, nutritional support, and respiratory care and monitoring in an intensive care unit, as appropriate for an individual patient

  • For prevention of thyroid storm, patients undergoing thyroidectomy should be rendered euthyroid with methimazole preoperatively and potassium iodide (KI) should be given in the immediate preoperative period

Japan Thyroid Association and Japan Endocrine Society

In 2016, the Japan Thyroid Association and Japan Endocrine Society released guidelines for the management of thyroid storm. Recommendations include the following[12] :

  • A multimodality approach with antithyroid drugs, inorganic iodide, corticosteroids, beta-adrenergic receptor antagonists, and antipyretic agents should be used to ameliorate thyrotoxicosis and its adverse effects on multiple organ systems

  • Antithyroid drugs, either methimazole or propylthiouracil, should be administered for the treatment of hyperthyroidism in thyroid storm

  • Intravenous administration of methimazole is recommended in severely ill patients with consciousness disturbances or impaired gastrointestinal tract function

  • Inorganic iodide should be administered simultaneously with antithyroid drugs to patients with thyroid storm caused by thyrotoxic diseases associated with hyperthyroidism

  • Corticosteroids (300 mg/day hydrocortisone or 8 mg/day dexamethasone) should be administered to patients with thyroid storm regardless of its origin

  • Aggressive cooling with acetaminophen and mechanical cooling with cooling blankets or ice packs should be performed for thyroid storm patients with high fever

  • The focus of infection should be investigated in patients with high fever and accompanying infection should be treated

  • In addition to prompt treatment of thyrotoxicosis, differential diagnosis and treatment of acute disturbances of consciousness, psychosis, and convulsion in thyroid storm should be performed based on established guidelines in consultation with a psychiatrist or neurologist

  • Since thyrotoxicosis and dysfunction of multiple organs such as the liver and kidney can affect pharmacokinetics in thyroid storm patients, the condition of each patient should be considered individually when selecting and adjusting doses of psychotropic medications

  • Beta1-selective adrenergic receptor antagonists (landiolol, esmolol [intravenous], or bisoprolol [oral]) should be selected as the first choice of treatment for tachycardia in thyroid storm; other beta1-selective oral drugs are also recommended; although the nonselective beta-adrenergic receptor antagonist propranolol is not contraindicated, it is not recommended for the treatment of tachycardia in thyroid storm

  • When atrial fibrillation occurs, digitalis is used in patients without severe renal dysfunction (it is given intravenously at an initial dose of 0.125 to 0.25 mg, followed by an appropriate maintenance dose with careful monitoring for signs and symptoms of digitalis toxicity); when hemodynamics are impaired rapidly because of atrial fibrillation, cardioversion is recommended when left atrial thrombus has been ruled out; class Ia and Ic antiarrhythmics are recommended to maintain sinus rhythm after cardioversion (amiodarone may be considered for patients with impaired left ventricular systolic function)

  • Anticoagulation should be used for persistent atrial fibrillation based on the CHADS2 (congestive heart failure, hypertension, age ≥75, diabetes mellitus, stroke [doubled]) score, which has been used to evaluate the risk of stroke onset

  • Gastrointestinal symptoms, including diarrhea, nausea, and vomiting, are associated with thyrotoxicosis, heart failure, neurologic disorders, and gastrointestinal infection; treatment for gastrointestinal infection should be performed in parallel with that for thyrotoxicosis to improve gastrointestinal symptoms

  • Administration of large doses of corticosteroids, coagulopathy associated with thyroid storm, and intensive care unit (ICU) stay with prolonged mechanical ventilation may be risk factors for gastrointestinal hemorrhage and mortality; acid-suppressive drugs such as proton pump inhibitors or histamine-2 receptor antagonists are recommended for patients in these instances

  • Hepatotoxicity with or without jaundice in thyroid storm can be caused by hepatocyte damage due to thyrotoxicosis, heart failure, precipitating hepatic-biliary infection, or drug-induced liver damage; nationwide surveys showed that patient prognosis is worse when total bilirubin levels are ≥3.0 mg/dL; differential diagnosis for the origin of hepatic dysfunction and appropriate treatment based on its origin should be performed, including therapeutic plasmapheresis for acute hepatic failure

  • ICU admission should be recommended for all thyroid storm patients; patients with potentially fatal conditions such as shock, disseminated intravascular coagulation (DIC), and multiple organ failure should immediately be admitted to the ICU
  • Based on nationwide survey analyses, it is strongly recommended that patients with APACHE II (Acute Physiologic Assessment and Chronic Health Evaluation II) scores above 9 be admitted to the ICU

  • DIC, which is often complicated with thyroid storm, should be intensively treated because DIC was shown to be associated with high mortality in the Japan Thyroid Association nationwide surveys

  • The APACHE II score or Sequential Organ Failure Assessment score can be used for the prognostic prediction of thyroid storm

  • Care should be taken to prevent thyroid storm in patients with poor adherence who are undergoing antithyroid drug treatment

  • Definitive treatment of Graves disease, either by radioiodine treatment or thyroidectomy, should be considered to prevent recurrent thyroid storm in patients successfully managed during the acute stage of thyroid storm

  • When patients with high fever (≥38°C), marked tachycardia (≥130 bpm), and symptoms originating from multiple organ systems such as the central nervous system, cardiovascular system, and gastrointestinal tract present, it is important to consider the possibility of thyroid storm

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antithyroid agents

Class Summary

These agents block thyroid hormone synthesis.

Propylthiouracil (PTU)

Thiourea agent that blocks production of thyroid hormones. In addition, inhibits peripheral deiodination of T4 to T3. Preferred over MMI in thyroid storm.

Methimazole (Tapazole)

Active moiety of parent compound carbimazole. Blocks incorporation of iodine into thyroglobulin within 1 h of ingestion.

Methimazole was initially thought to be associated with neonatal aplasia cutis (ie, defect in the neonatal scalp) and was thought to be more likely to cross the placenta than PTU. However, recent studies by Wing et al concluded that PTU and MMI are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Lithium (Eskalith, Lithotabs)

Used in patients intolerant to iodine; impairs thyroid hormone release.

Potassium Iodide (Thyro-Block, Pima)

Inhibits thyroid hormone secretion. Contains 8 mg of iodide per drop. May be mixed with juice or water for intake.

Iodide treatment is reserved for the treatment of thyroid storm. It is also used for 10-14 d prior to surgical procedure, including thyroidectomy. Can be used with Graves thyrotoxicosis but exacerbates thyrotoxicosis from toxic multinodular goiter and toxic adenoma.

Sodium ipodate (Oragrafin)

One of the most effective inhibitors of deiodinase, which converts T4 to the more biologically active T3. Reduction in conversion of T4 to T3 can greatly reduce T3 levels and thyrotoxic symptoms.

Glucocorticoids

Class Summary

These agents reduce iodine uptake and antibody titers of thyroid-stimulating antibodies with stabilization of the vascular bed.

Dexamethasone (Decadron, Dexone)

Has many pharmacologic benefits but significant adverse effects. Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, IFN-gamma). The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. Suppresses lymphocyte proliferation through direct cytolysis and inhibits mitosis. Breaks down granulocyte aggregates and improves pulmonary microcirculation. Has inhibitory effect on conversion of T4 to T3.

Adverse effects include hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.

Readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Lacks salt-retaining property of hydrocortisone.

Patients can be switched from an IV to PO regimen in a 1:1 ratio.

Hydrocortisone (Cortef, Solu-Cortef)

Elicits anti-inflammatory properties and causes profound and varied metabolic effects. Modifies the body's immune response to diverse stimuli.

Analgesics

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties.

Acetaminophen (Feverall, Panadol)

Inhibits action of endogenous pyrogens on heat-regulating centers; reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increases the dissipation of body heat via sweating and vasodilation.

Beta-adrenergic blockers

Class Summary

These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.

Propranolol (Inderal, Betachron E-R)

DOC to counter peripheral action of thyroid hormone; blocks beta-adrenergic receptors; prevents conversion of T4 to T3.

Esmolol (Brevibloc)

Ultra–short-acting agent that selectively blocks beta1-receptors with little or no effect on beta2-receptor types. Particularly useful in patients with elevated arterial pressure, especially if surgery is planned. Shown to reduce episodes of chest pain and clinical cardiac events compared with placebo. Used successfully in thyrotoxicosis and thyroid storm. Can be discontinued abruptly if necessary.

Useful in patients at risk for experiencing complications from beta-blockade; particularly those with reactive airway disease, mild-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.

Antihypertensive agents

Class Summary

These agents reduce blood pressure.

Guanethidine (Ismelin)

For use in patients with congestive cardiac failure, bronchospasm, or history of asthma.

Reserpine

For use in patients with congestive cardiac failure, bronchospasm, or history of asthma; successful treatment has been documented in cases of thyroid storm resistant to large doses of propranolol.