Hyperthyroidism, thyroid storm, and Graves disease are conditions of excess thyroid hormone. The elevated level of thyroid hormones can result in clinical manifestations ranging from mild to severely toxic with resultant morbidity and mortality for affected patients.
Hyperthyroidism
Hyperthyroidism presents as a constellation of symptoms due to elevated levels of circulating thyroid hormones. Because of the many actions of thyroid hormone on various organ systems in the body, the spectrum of clinical signs produced by the condition is broad. The presenting symptoms can be subtle and nonspecific, making hyperthyroidism difficult to diagnose in its early stages without the aid of laboratory data.
The term hyperthyroidism refers to inappropriately elevated thyroid function. Though often used interchangeably, the term thyrotoxicosis, which refers to an excessive amount of circulating thyroid hormone, is not synonymous with hyperthyroidism. Increased levels of hormone can occur despite otherwise normal thyroid function, such as in instances of inappropriate exogenous thyroid hormone or excessive release of stored hormone from an inflamed thyroid gland.
Graves disease
Graves disease (diffuse toxic goiter), the most common form of overt hyperthyroidism, is an autoimmune condition in which autoantibodies are directed against the thyroid-stimulating hormone (TSH) receptor. As a result, the thyroid gland is inappropriately stimulated with ensuing gland enlargement and increase of thyroid hormone production. Risk factors for Graves disease include family history of hyperthyroidism or various other autoimmune disorders, high iodine intake, stress, use of sex steroids, and smoking. The disease is classically characterized by the triad of goiter, exophthalmos, and pretibial myxedema.
Thyroid storm
Thyroid storm is a rare and potentially fatal complication of hyperthyroidism.[1] It typically occurs in patients with untreated or partially treated thyrotoxicosis who experience a precipitating event such as surgery, infection, or trauma. Thyroid storm must be recognized and treated on clinical grounds alone, as laboratory confirmation often cannot be obtained in a timely manner. Patients typically appear markedly hypermetabolic with high fevers, tachycardia, nausea and vomiting, tremulousness, agitation, and psychosis. Late in the progression of disease, patients may become stuporous or comatose with hypotension.
For more information, see Medscape's Thyroid Disease Resource Center.
In healthy patients, the hypothalamus produces thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary gland to secrete thyroid-stimulating hormone (TSH); this in turn triggers the thyroid gland to synthesize thyroid hormone.
Thyroid hormone concentration is regulated by negative feedback by circulating free hormone primarily on the anterior pituitary gland and to a lesser extent on the hypothalamus. The secretion of TRH is also partially regulated by higher cortical centers.
The thyroid gland produces the prohormone thyroxine (T4), which is deiodinated primarily by the liver and kidneys to its active form, triiodothyronine (T3). The thyroid gland also produces a small amount of T3 directly. T4 and T3 exist in 2 forms: a free, unbound portion that is biologically active and a portion that is protein bound to thyroid-binding globulin (TBG). Despite consisting of less than 0.5% of total circulating hormone, free or unbound T4 and T3 levels best correlate with the patient's clinical status.
The overall incidence of hyperthyroidism is estimated between 0.05% and 1.3%, with the majority consisting of subclinical disease. A population-based study in the United Kingdom and Ireland found an incidence of 0.9 cases per 100,000 children younger than 15 years, showing that the disease incidence increases with age.[2] The prevalence of hyperthyroidism is approximately 5-10 times less than hypothyroidism.
Thyroid storm is a rare disorder. Approximately 1-2% of patients with hyperthyroidism progress to thyroid storm. In Japan, the estimated incidence of thyroid storm in hospitalized patients is 0.20 per 100,000 annually, according to a study by Akamizu, with the rate being 0.22% of all thyrotoxic patients.[3]
Mortality/Morbidity
Thyroid storm, if unrecognized and untreated, is often fatal. Adult mortality rate from thyroid storm is approximately 10-20%, but it has been reported to be as high as 75% in hospitalized populations. Underlying precipitating illness may contribute to high mortality.
A study by Ono et al of 1324 patients indicated that the following factors are associated with increased mortality risk in thyroid storm[4] :
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, a study by Swee et al of 28 patients with thyroid storm reported that CNS dysfunction of greater than mild severity appeared to be a risk factor for mortality.[5]
A study by Mohananey et al found that among patients hospitalized in the United States with thyroid storm, the incidence of cardiogenic shock increased from 0.5% in 2003 to 3% in 2011. However, the mortality rate among the cardiogenic shock patients fell from 60.5% in 2003 to 20.9% in 2011. The investigators also reported that a history of atrial fibrillation, alcohol abuse, preexisting congestive heart failure, coagulopathy, drug use, liver disease, pulmonary circulatory disease, valvular disease, weight loss, renal failure, and fluid and electrolyte disease was more likely in thyroid storm patients with cardiogenic shock than in other thyroid storm patients.[6]
Race
See the list below:
White and Hispanic populations in the United States have a slightly higher prevalence of hyperthyroidism in comparison with black populations.
Sex
See the list below:
A slight predominance of hyperthyroidism exists among females.
Age
See the list below:
Thyroid storm may occur at any age but is most common in those in their third through sixth decades of life.
Graves disease predominantly affects those aged 20-40 years.
The prevalence of toxic multinodular goiter increases with age and becomes the primary cause of hyperthyroidism in elderly persons.
The clinical presentation of hyperthyroidism ranges from an array of nonspecific historical features to an acute life-threatening event. Historical features common to hyperthyroidism and thyroid storm are numerous and represent a hypermetabolic state with increased beta-adrenergic activity.
Weight loss
Patients typically report an average loss of approximately 15% of their prior weight.
Basal metabolic rate is increased with a stimulation of lipolysis and lipogenesis.
Palpitations
Chest pain - Often occurs in the absence of cardiovascular disease
Psychosis
Menstrual irregularity
Disorientation
Tremor
Nervousness, anxiety, or emotional lability
Heat intolerance
Increased perspiration
Fatigue
Weakness - Typically affects proximal muscle groups
Hyperthyroidism results from numerous etiologies, including autoimmune, drug-induced, infectious, idiopathic, iatrogenic, and malignancy.
Autoimmune
Graves disease
Chronic thyroiditis (Hashimoto thyroiditis) - Although the primary cause of hypothyroidism, the disease process occasionally presents initially with thyrotoxicosis
Postpartum thyroiditis - Presents similarly to subacute thyroiditis 2-6 months postpartum but typically painless with mild symptoms
Drug-induced
Iodine-induced - Occurs after administration of either supplemental iodine to those with prior iodine deficiency or pharmacologic doses of iodine (contrast media, medications) in those with underlying nodular goiter
Amiodarone - Its high iodine content is primarily responsible for producing a hyperthyroid state, though the medication may itself induce autoimmune thyroid disease.
Antineoplastic agents - Agents may cause thyroid dysfunction in 20-50% of patients. Symptoms of thyrotoxicosis may be mistaken for sepsis or an adverse drug effect, so monitoring of thyroid function must be considered.[7]
Infectious
Suppurative thyroiditis - Often bacterial, results in a painful gland commonly in those with underlying thyroid disease or in immunocompromised individuals
Postviral thyroiditis
Idiopathic
Toxic multinodular goiter - The second most common cause of hyperthyroidism, characterized by functionally autonomous nodules, typically after age 50 years
Iatrogenic
Thyrotoxicosis factitia - A psychiatric condition in which high quantities of exogenous thyroid hormone are consumed
Surgery - Now uncommon secondary to preventative measures, manipulation of the thyroid gland during thyroidectomy historically caused a flood of hormone release, often resulting in highly toxic blood levels
Miscellaneous
Toxic adenoma - A single, hyperfunctioning nodule within a normally functioning thyroid gland commonly among patients in their 30s and 40s
Thyrotropin-producing pituitary tumors
Struma ovarii - Ovarian teratoma with ectopic thyroid tissue
Thyroid storm can be triggered by many different events, classically in patients with underlying Graves disease or toxic multinodular goiter.
Infection
Surgery
Cardiovascular events
Toxemia of pregnancy
Diabetic ketoacidosis, hyperosmolar coma, and insulin-induced hypoglycemia
Thyroidectomy
Discontinuation of antithyroid medication
Radioactive iodine
Vigorous palpation of the thyroid gland in hyperthyroid patients
Thyroid function studies confirm the diagnosis in the appropriate clinical setting.
Elevation of free T4 and low to undetectable TSH levels are diagnostic of thyrotoxicosis; in earlier stages, T3 rise precedes T4 rise.
Excessive TSH levels in the setting of elevated free T4 indicate hyperthyroidism of pituitary origin.
There is little utility in obtaining total T4 levels, as variations in serum thyroid-binding proteins alter the ability to interpret results.
Particularly in thyroid storm, the diagnosis must be made on the basis of the clinical examination as rapid assays are not universally available.
Thyroid function studies do not distinguish thyrotoxicosis from thyroid storm; however, several laboratory abnormalities may be encountered in thyroid storm.
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.
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, although this effect is minimal and not usually clinically significant.
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.
Antithyroid medications appear to also have an immunosuppressive effect, evidenced by decreased serum concentrations of antithyrotropin-receptor antibodies.
Primary antithyroid treatment (as an alternative to surgery) is often suggested for Graves disease, as remission after cessation of medical management is possible. In those with toxic multinodular goiters and solitary autonomous nodules, first-line treatment with antithyroid drugs is not recommended since spontaneous remission is rare.
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, some of which have been fatal. 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.[8] 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.[9]
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.
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.
Charcoal hemoperfusion has been shown to be effective in treatment of iatrogenic or intentional ingestion of excessive doses of levothyroxine.[10]
Plasmapheresis has been used successfully in medication-induced thyroid storm[11] and in conditions in which oral/conventional therapy is not possible.[12]
In 2011, a task force of expert clinicians assembled by the American Thyroid Association and the American Association of Clinical Endocrinologists released a set of 100 evidence-based recommendations on the management of thyrotoxicosis. These guidelines addressed the following[13] :
The initial assessment and treatment of thyrotoxicosis
The use of radioactive iodine, antithyroid drugs, or surgery to treat Graves hyperthyroidism
The use of radioactive iodine or surgery to treat toxic multinodular goiter or toxic adenoma
The treatment of other causes of thyrotoxicosis
Graves disease occurring in children or adolescents or during pregnancy
Subclinical hyperthyroidism
Hyperthyroidism in Graves ophthalmopathy patients
ATA (2016)
In 2016, the American Thyroid Association updated the 2011 guidelines. The following are a sampling of the 124 evidence-based recommendations included in the guideline update[14] :
Beta-adrenergic blockade is recommended in all patients with symptomatic thyrotoxicosis, especially elderly patients and thyrotoxic patients with resting heart rates in excess of 90 beats per minute or coexistent cardiovascular disease
Patients with overt Graves hyperthyroidism should be treated with any of the following modalities: radioactive iodine therapy, antithyroid drugs, or thyroidectomy
If methimazole is chosen as the primary therapy for Graves disease, the medication should be continued for approximately 12-18 months and then discontinued if the serum thyrotropin and thyrotropin receptor antibody levels are normal at that time
If surgery is chosen as the primary therapy for Graves disease, near-total or total thyroidectomy is the procedure of choice
If surgery is chosen as treatment for toxic multinodular goiter, near-total or total thyroidectomy should be performed
If surgery is chosen as the treatment for toxic adenoma, a thyroid sonogram should be done to evaluate the entire thyroid gland; an ipsilateral thyroid lobectomy (or isthmusectomy, if the adenoma is in the thyroid isthmus), should be performed for isolated toxic adenomas
Children with Graves disease should be treated with methimazole, radioactive iodine therapy, or thyroidectomy; radioactive iodine therapy should be avoided in very young children (< 5 years); radioactive iodine therapy in children is acceptable if the activity is over 150 μCi/g (5.55 MBq/g) of thyroid tissue and for children between ages 5 and 10 years if the calculated radioactive iodine administered activity is under 10 mCi (< 473 MBq); thyroidectomy should be chosen when definitive therapy is required, the child is too young for radioactive iodine, and surgery can be performed by a high-volume thyroid surgeon
If methimazole is chosen as the first-line treatment for Graves disease in children, it may be tapered in those children requiring low doses after 1-2 years to determine if a spontaneous remission has occurred, or it may be continued until the child and caretakers are ready to consider definitive therapy, if needed
If surgery is chosen as therapy for Graves disease in children, total or near-total thyroidectomy should be performed
Euthyroidism should be expeditiously achieved and maintained in hyperthyroid patients with Graves orbitopathy or risk factors for the development of orbitopathy
In patients with Graves hyperthyroidism who have mild active ophthalmopathy and no risk factors for deterioration of their eye disease, radioactive iodine therapy, antithyroid drugs, and thyroidectomy should be considered equally acceptable therapeutic options
In Graves disease patients with mild Graves orbitopathy who are treated with radioactive iodine, steroid coverage is recommended if there are concomitant risk factors for Graves orbitopathy deterioration
Japanese guidelines (2016)
Also in 2016, the Japan Thyroid Association and Japan Endocrine Society released guidelines for the management of thyroid storm. Recommendations include the following[15] :
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
ATA (2017)
In 2017, the American Thyroid Association released guidelines pertaining to the diagnosis and management of thyroid disease in women during pregnancy and the postpartum period, as well as prior to conception. Recommendations regarding Graves disease and hyperthyroidism in pregnancy included the following[16] :
Excessive doses of iodine exposure during pregnancy should be avoided, except in preparation for the surgical treatment of Graves disease; clinicians should carefully weigh the risks and benefits when ordering medications or diagnostic tests that will result in high iodine exposure
Women with Graves disease seeking future pregnancy should be counseled regarding the complexity of disease management during future gestation, including the association of birth defects with antithyroid drug use; preconception counseling should review the risks and benefits of all treatment options and the patient’s desired timeline to conception
In the setting of a patient with Graves disease undergoing urgent, nonthyroid surgery, if the patient is well controlled on antithyroid medication, no other preparation is needed; beta blockade should also be utilized if needed
If the patient has a past history of Graves disease treated with ablation (radioiodine or surgical), a maternal serum determination of thyroid-stimulating antibody (TSab) is recommended at initial thyroid function testing during early pregnancy
If maternal TSab concentration is elevated in early pregnancy, repeat testing should occur at weeks 18-22
If the patient requires treatment with antithyroid drugs for Graves disease through midpregnancy, a repeat determination of TSab is again recommended at weeks 18-22
If elevated TSab is detected at weeks 18-22 or the mother is taking antithyroid medication in the third trimester, a TSab measurement should again be performed in late pregnancy (weeks 30-34) to evaluate the need for neonatal and postnatal monitoring
Fetal surveillance should be performed in women who have uncontrolled hyperthyroidism in the second half of pregnancy and in women with high TSab levels detected at any time during pregnancy (greater than 3 times the upper limit of normal); a consultation with an experienced obstetrician or maternal-fetal medicine specialist is recommended; monitoring may include ultrasonography to assess heart rate, growth, amniotic fluid volume, and the presence of fetal goiter
If antithyroid drug therapy is given for hyperthyroidism caused by autonomous nodules, the fetus should be carefully monitored for goiter and signs of hypothyroidism during the second half of pregnancy; a low dose of antithyroid medication should be administered with the goal of maternal free thyroxine (FT4) or total T4 concentration at the upper limit or moderately above the reference range
Excepting treatment decisions specifically made on the grounds of improving lactation, the decision to treat hyperthyroidism in lactating women should be guided by the same principles applied to nonlactating women
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. A study by Tun et al indicated that in patients with Graves disease receiving thionamide therapy, high thyrotropin receptor–stimulating antibody (TRab) levels at diagnosis of the disease and/or high TRab levels at treatment cessation are risk factors for relapse, particularly within the first two years. The study included 266 patients.[17]
A retrospective study by Rabon et al indicated that in children with Graves disease, antithyroid drugs usually do not induce remission, although most children who do achieve remission through these agents do not relapse. Of 268 children who were started on an antithyroid drug, 57 (21%) experienced remission, with 16 of them (28%) relapsing.[18]
Clinical Context:
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.
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.
Clinical Context:
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.
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.
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.
Patients with mild-to-moderate hyperthyroidism or Graves disease should follow up with their primary care physician or endocrinologist after a period of ED monitoring.
Overall rate of mortality due to thyroid storm is approximately 10-20% but has been reported as high as 75%; the precipitating factor or underlying illness is often the cause of death.
With early diagnosis and adequate treatment, the prognosis is good.
What is hyperthyroidism?What is Graves disease?What is thyroid storm?What are conditions of excess thyroid hormone?What is the pathophysiology of conditions of excess thyroid hormone?What is the incidence of hyperthyroidism?What is the incidence of thyroid storm?What is the mortality risk from thyroid storm?What is the racial predilections of hyperthyroidism?How does the incidence of hyperthyroidism vary by sex?How does the incidence of hyperthyroidism, thyroid storm, and Graves disease vary by age?What are the signs and symptoms of hyperthyroidism and thyroid storm?Which physical findings are characteristic of hyperthyroidism?What are autoimmune etiologies of hyperthyroidism?What are drug-induced etiologies of hyperthyroidism?What are infectious etiologies of hyperthyroidism?What is the role of toxic multinodular goiter in the etiology of hyperthyroidism?What are iatrogenic etiologies of hyperthyroidism?What is the role of tumors in the etiology of hyperthyroidism?What are events that may trigger thyroid storm?What are the differential diagnoses for Hyperthyroidism, Thyroid Storm, and Graves Disease?What is the role of thyroid function studies in the workup of hyperthyroidism, thyroid storm, and Graves disease?Which lab studies are performed in the workup of hyperthyroidism, thyroid storm, and Graves disease?What is the role of imaging studies in the workup of hyperthyroidism, thyroid storm, and Graves disease?Which findings on electrocardiogram suggest hyperthyroidism, thyroid storm, and Graves disease?What is included in emergency department (ED) care of hyperthyroidism, thyroid storm, and Graves disease?Which medications are used in the emergency department (ED) treatment of hyperthyroidism, thyroid storm, and Graves disease?What are the FDA warnings for the use of propylthiouracil (PTU) in the treatment of hyperthyroidism, and Graves disease?What is the role of propylthiouracil (PTU) in the emergency department (ED) treatment of hyperthyroidism, and Graves disease?How is thyrotoxicosis managed in the emergency department (ED)?What are treatment options for medication-induced thyroid storm?Which specialists should be consulted for the treatment of hyperthyroidism, thyroid storm, and Graves disease?What are the key recommendations of the Japanese guidelines (2016) on the management of thyroid storm?What do the ATA and AACE (2011) treatment guidelines for thyrotoxicosis cover?What are the key recommendations of the ATA (2016) treatment guidelines for hyperthyroidism, thyroid storm, and Graves disease?What are the ATA (2017) recommendations on the management of hyperthyroidism, thyroid storm, and Graves disease during pregnancy?What are the goals of medical therapy for hyperthyroidism, thyroid storm, and Graves disease?Which medications are used in the treatment of hyperthyroidism, thyroid storm, and Graves disease?Which medications in the drug class Corticosteroids are used in the treatment of Hyperthyroidism, Thyroid Storm, and Graves Disease?Which medications in the drug class Beta-adrenergic blockers are used in the treatment of Hyperthyroidism, Thyroid Storm, and Graves Disease?Which medications in the drug class Blockade of hormone release are used in the treatment of Hyperthyroidism, Thyroid Storm, and Graves Disease?Which medications in the drug class Inhibitors of hormone synthesis are used in the treatment of Hyperthyroidism, Thyroid Storm, and Graves Disease?What outpatient followup is needed for hyperthyroidism, thyroid storm, and Graves disease?What is included in inpatient care of hyperthyroidism, thyroid storm, and Graves disease?When is transfer indicated for patients with hyperthyroidism, thyroid storm, and Graves disease?What are the complications of hyperthyroidism, thyroid storm, and Graves disease?What is the prognosis of hyperthyroidism, thyroid storm, and Graves disease?What is included in patient education about hyperthyroidism, thyroid storm, and Graves disease?
Erik D Schraga, MD, Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Howard A Bessen, MD, Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Romesh Khardori, MD, PhD, FACP, Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School
Disclosure: Nothing to disclose.
Additional Contributors
Robin R Hemphill, MD, MPH, Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University School of Medicine
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.
