Hyperthyroidism, Thyroid Storm, and Graves Disease Guidelines

ATA and AACE (2011)

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 ^[17] :

• 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 ^[18] :

• 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 ^[19] :

• 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 ^[20] :

• 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