Guideline sources The following summarized guidelines for the evaluation and management of hyperthyroidism are prepared by our editorial team based on guidelines from the Endocrine Society (ES 2020) and the American Thyroid Association (ATA 2016). 1 2 3 4 4 5 6 7 Definition Hyperthyroidism is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormone. 3 Epidemiology Causes of hyperthyroidism include increased synthesis of thyroid hormones (e.g. Grave's disease), release of preformed thyroid hormones due to destruction of thyroid tissue (e.g. thyroiditis), and exogenous thyroid hormone intake. 5 Pathophysiology https://web.pathway.md/diseases/recDEwiYN0ZUgdOP7 1/7 6/24/23, 12:45 PM Hyperthyroidism Pathway In the United States, the prevalence of hyperthyroidism is estimated at 13000 per 100,000 population. In Europe, the prevalence of hyperthyroidism is estimated at 800 per 100,000 population. 4 4 Disease course Hyperthyroidism leads to a higher incidence of AF and atrial flutter, and, at least partly by that mechanism, a higher risk of cerebral arterial thrombosis. Hyperthyroidism additionally leads to increased bone turnover and a negative bone balance. 6 7 Guidelines 1. Diagnostic investigations Initial evaluation: Determine the etiology of thyrotoxicosis. If the diagnosis is not apparent based on the clinical presentation and initial biochemical evaluation, perform diagnostic testing including: measurement of thyrotropin receptor antibodies determination of the radioactive iodine uptake, or measurement of thyroidal blood flow on ultrasound. B Obtain a 123I or 99mTc pertechnetate scan when the clinical presentation suggests a toxic adenoma or a toxic multinodular goiter. B Thyroid antibodies: measure TSH receptor antibody levels when the etiology of hyperthyroidism in pregnancy is uncertain. B Lipid profile: re-evaluate lipid panel in patients with hyperthyroidism after reaching euthyroid state. A 2. Medical management Antithyroid drugs (general principles): consider a baseline CBC, including WBC count with differential, and a liver profile including bilirubin and transaminases prior to initiating anti-thyroid drug therapy for Graves' disease. C Antithyroid drugs (pregnant patients): avoid treating transient hCG-mediated TSH suppression in early pregnancy with antithyroid drug therapy. D Beta-adrenergic blockers: administer -adrenergic blockade in all patients with symptomatic thyrotoxicosis, especially elderly patients and thyrotoxic patients with resting HRs in excess of 90 bpm or coexistent CVD. B Potassium iodide: insufficient evidence to recommend potassium iodide for the treatment of hyperthyroidism; potassium iodide may be of benefit in select patients with hyperthyroidism due to Graves' disease, those who have adverse reactions to antithyroid drugs, and those who have a https://web.pathway.md/diseases/recDEwiYN0ZUgdOP7 2/7 6/24/23, 12:45 PM Hyperthyroidism Pathway contraindication or aversion to radioactive iodine therapy or aversion to repeat radioactive iodine therapy, or surgery. I Antihistamine therapy: manage minor cutaneous reactions with concurrent antihistamine therapy without stopping the antithyroid drug. Manage the persistent symptomatic minor side effects of antithyroid medication by cessation of the medication and changing to radioactive iodine or surgery, or switching to the other antithyroid drug when radioactive iodine or surgery are not options. In the case of a serious allergic reaction, avoid prescribing the alternative drug. B Management of Graves' disease: treat patients with overt Graves' hyperthyroidism with any of the following modalities: radioactive iodine therapy, antithyroid drugs, or thyroidectomy. B Management of toxic multinodular goiter: consider treating patients with overtly toxic multinodular goiter or toxic adenoma with radioactive iodine therapy or thyroidectomy. On occasion, long-term, low-dose treatment with methimazole may be appropriate. C Management of subclinical hyperthyroidism: Treat subclinical hyperthyroidism when TSH is persistently < 0.1 mU/L in the following clinical settings: patients 65 years of age patients with cardiac risk factors, heart disease or osteoporosis postmenopausal women who are not on estrogens or bisphosphonates patients with symptoms. B Management of thyroid nodules: evaluate and manage according to recently published guidelines regarding thyroid nodules in euthyroid individuals if a thyroid nodule is discovered in a patient with Graves' disease. B 3. Nonpharmacologic interventions Smoking cessation: advise smoking cessation in patients with Graves' disease and refer them to a structured smoking cessation program. Identify patients exposed to secondhand smoke and advise of its negative impact, as both firsthand and secondhand smoking increase Graves' orbitopathy risk. B 4. Therapeutic procedures Radioactive iodine ablation (Graves' disease): optimize the treatment of comorbidities prior to radioactive iodine therapy. B Radioactive iodide ablation (toxic goiter and adenoma): administer sufficient activity of radioactive iodine in a single application to alleviate hyperthyroidism in patients with toxic multinodular goiter. B Radioactive iodine ablatiom (pediatric patients): consider pretreatment with methimazole and -adrenergic blockade until total T4 and/or free T4 normalize before proceeding with radioactive https://web.pathway.md/diseases/recDEwiYN0ZUgdOP7 3/7 6/24/23, 12:45 PM Hyperthyroidism Pathway iodine treatment in children with Graves' disease having total T4 levels of > 20 g/dL or free T4 > 5 ng/dL who are to receive radioactive iodine therapy. C Ethanol and radiofrequency ablation: insufficient evidence to assess benefits and risks of alternative therapies such as ethanol or radiofrequency ablation of toxic adenoma and toxic multinodular goiter; these therapies can be considered in select patients in whom radioactive iodine, surgery, and long-term antithyroid drug are inappropriate, contraindicated, or refused, and expertise in these procedures is available. I 5. Perioperative care Pre-RAI corticosteroid coverage: insufficient evidence to recommend for or against the use of prophylactic corticosteroids in smokers who receive radioactive iodine and have no evidence of Graves' ophtalmopathy. I Pre-thyroidectomy care (Graves' disease): render patients euthyroid prior to the procedure with antithyroid drug pretreatment, with or without -adrenergic blockade if surgery is chosen as treatment for Graves' disease. Give a potassium iodide-containing preparation in the immediate preoperative period. B Post-thyroidectomy care in Graves disease: consider undertaking alternative strategies for management of calcium levels: serum calcium with or without intact PTH levels can be measured, and oral calcium and calcitriol supplementation administered based on these results, or prophylactic calcium with or without calcitriol prescribed empirically, following thyroidectomy for Graves' disease. C Post-thyroidectomy care (toxic multinodular goitre): measure serum calcium with or without intact PTH levels, and administer oral calcium and calcitriol supplementation based on the results, following thyroidectomy for toxic multinodular goiter. B 6. Surgical interventions Thyroidectomy for Graves' disease: perform near-total or total thyroidectomy as the procedure of choice if surgery is chosen as the primary therapy for Graves' disease. B Thyroidectomy for toxic multinodular goitre: render patients with overt hyperthyroidism euthyroid prior to the procedure with methimazole pretreatment, with or without -adrenergic blockade if surgery is chosen as treatment for toxic multinodular goiter or toxic adenoma. Avoid using preoperative iodine in this setting. B Thyroidectomy in pediatric patients: render children with Graves' disease undergoing thyroidectomy euthyroid with the use of methimazole. Give a potassium iodide-containing preparation in the immediate preoperative period. B Thyroidectomy for pregnant patients: use thyroidectomy only when medical management has been unsuccessful or antithyroid drugs cannot be used because pregnancy is a relative contraindication to thyroidectomy. B https://web.pathway.md/diseases/recDEwiYN0ZUgdOP7 4/7 6/24/23, 12:45 PM Hyperthyroidism Pathway Thyroidectomy for amiodarone-induced thyrotoxicosis: perform thyroidectomy in patients with amiodarone-induced thyrotoxicosis who are unresponsive to aggressive medical therapy with methimazole and corticosteroids. B 7. Specific circumstances Pregnant patients: diagnose hyperthyroidism in pregnancy using serum TSH values, and either total thyroxine and T3 with total thyroxine and T3 reference ranges increasing to 1.5 times above the nonpregnant range by the second and third trimester or free thyroxine and total T3 estimations with trimester-specific normal reference ranges. B Show 2 more Pediatric patients: treat children with Graves' disease with methimazole, radioactive iodine therapy, or thyroidectomy. Avoid radioactive iodine therapy in very young children < 5 years of age. Radioactive iodine therapy in children is acceptable if the activity is > 150 Ci/g (5.55 MBq/g) of thyroid tissue, and for children between 5 and 10 years of age if the calculated radioactive iodine administered activity is < 10 mCi (< 370 MBq). Choose thyroidectomy when definitive therapy is required, the child is too young for radioactive iodine, and surgery can be performed by a high-volume thyroid surgeon. B Patients with iodine-induced thyrotoxicosis: avoid routine administration of antithyroid drugs before iodinated contrast media exposure for all patients. D Patients with postpartum thyroiditis: perform selective diagnostic studies to distinguish postpartum destructive thyroiditis from postpartum Graves' disease in women developing thyrotoxicosis after delivery. B Patients with Graves' opthalmopathy: consider radioactive iodine therapy, antithyroid drugs, and thyroidectomy as equally acceptable therapeutic options in patients with Graves' hyperthyroidism who have mild active ophthalmopathy and no risk factors for deterioration of their eye disease. B Patients with amiodarone-induced thyrotoxicosis: consider monitoring thyroid function tests before and within the first 3 months following the initiation of amiodarone therapy, and at 3- to 6- month intervals thereafter. C Patients with thyrotoxicosis due to destructive thyroiditis: treat patients with mild symptomatic subacute thyroiditis initially with -adrenergic-blocking drugs and nonsteroidal anti-inflammatory agents. Use corticosteroids instead of NSAIDs when patients fail to respond or present initially with moderate-to-severe pain and/or thyrotoxic symptoms. B Patients with other causes of thyrotoxicosis: monitor patients taking medications known to cause thyrotoxicosis, including interferon-a, IL-2, TKIs, and lithium, clinically and biochemically at 6-month intervals for the development of thyroid dysfunction. Evaluate patients who develop thyrotoxicosis to determine etiology and treat accordingly. B https://web.pathway.md/diseases/recDEwiYN0ZUgdOP7 5/7 6/24/23, 12:45 PM Hyperthyroidism Pathway 8. Patient education Counseling for radioactive iodide ablation: provide written advice concerning radiation safety precautions following treatment when administering radioactive iodine, and select an alternative therapy if the precautions cannot be followed. B 9. Follow-up and surveillance Monitoring of patients on antithyroid drugs: obtain a differential WBC count during febrile illness and at the onset of pharyngitis in all patients taking antithyroid medication to exclude agranulocytosis. B References 1. Ross DS, Burch HB, Cooper DS et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26 10 1343 1421. Open 2. Connie B Newman, Michael J Blaha, Jeffrey B Boord et al. Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2020 Dec 1;105 12):dgaa674. Open 3. David S Cooper. Hyperthyroidism. 2003 Aug 9;362 9382 459 68.2003 Aug 9;362 9382 459 68. Open 4. De Leo S, Lee SY, Braverman LE . Hyperthyroidism. Lancet. 2016 Aug 27;388 10047 906 918. Open 5. Lea Slahor. CME Thyrotoxicosis and Thyroiditis]. 2018;107 22 1187 1192.2018;107 22 1187 1192. Open 6. Laura P B Elbers, Alessandro Squizzato, Victor E A Gerdes. Thyroid Disorders and Hemostasis. 2018 Oct;44 7 676 682.2018 Oct;44 7 676 682. Open 7. Medea Amashukeli, Maka Korinteli, Tamar Zerekidze et al. The negative correlation between thyrotropin receptor-stimulating antibodies and bone mineral density in postmenopausal patients with Graves' disease. 2013 Jun;61 5 842 7.2013 Jun;61 5 842 7. Open 8. Erik K Alexander, Elizabeth N Pearce, Gregory A Brent et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017 Mar;27 3 315 389. Open 9. LeFevre ML, U.S. Preventive Services Task Force. Screening for thyroid dysfunction: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015 May 5;162 9 641 50. Open 10. Simone De Leo, Sun Y Lee, Lewis E Braverman. Hyperthyroidism. Lancet. 2016 Aug 27;388 10047 906 918. Open 11. Mark P J Vanderpump. The epidemiology of thyroid disease. Br Med Bull. 2011;99 39 51. Open 12. Douglas S Ross, Henry B Burch, David S Cooper et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 https://web.pathway.md/diseases/recDEwiYN0ZUgdOP7 6/7 6/24/23, 12:45 PM Hyperthyroidism Pathway Oct;26 10 1343 1421. Open https://web.pathway.md/diseases/recDEwiYN0ZUgdOP7 7/7