endocrine and metabolic disorders
Hyperthyroidism
Treatment of Hyperthyroidism
Treatment of hyperthyroidism depends on cause ( Treatment references ) but may include Radioactive iodine Methimazoleorpropylthiouracil Beta-blockers Iodine Surgery In the United States, iodine-131 is the most common treatment for hyperthyroidism. Radioiodine is often recommended as the treatment of choice for Graves disease and toxic nodular goiter in all patients, including children. Dosage of iodine-131 is difficult to adjust because the response of the gland cannot be predicted; some physicians give a standard dose of 8 to 15 millicurie. Others adjust the dose based on estimated thyroid size and the 24-hour uptake to provide a dose of 80 to 120 microcurie/g thyroid tissue. When sufficient iodine-131 is given to cause euthyroidism, about 25 to 50%of patients become hypothyroid 1 year later, and the incidence continues to increase yearly. Thus, most patients eventually become hypothyroid. However, if smaller doses are used, incidence of recurrence is higher. Larger doses, such as 10 to 20 millicurie, often cause hypothyroidism within 6 months, and thus ablative therapy (ie, iodine-131) has become the preferred approach. Radioactive iodine is not used during lactation because it can enter breast milk and cause hypothyroidism in the infant. It is not used during pregnancy because it crosses the placenta and can cause severe fetal hypothyroidism. There is no proof that radioiodine increases the incidence of tumors, leukemia, thyroid cancer, or birth defects in children born to previously hyperthyroid women who become pregnant later in life. These antithyroid drugs block thyroid peroxidase, decreasing the organification of iodide, and impair the coupling reaction.Propylthiouracilin high doses also inhibits the peripheral conversion of T4 to T3. Methimazoleis the preferred drug. The usual starting dosage ofmethimazoleis 5 to 20 mg orally 2 or 3 times a day. Normalization of TSH lags normalization of T4 and T3 levels by one or more weeks. Therefore, when T4 and T3 levels normalize, the dosage is decreased to the lowest effective amount, usuallymethimazole2.5 to 10 mg once a day in order to avoid inducing hypothyroidism. Control generally is achieved in 2 to 3 months. Maintenance doses ofmethimazolemay be continued for one or many years depending on the clinical circumstances. Carbimazole, which is used widely in Europe but is unavailable in the US, is rapidly converted tomethimazole. The usual starting dose is similar to that ofmethimazole; maintenance dosage is 2.5 to 10 mg orally once a day or 2.5 to 5 mg twice a day. Because of severe liver failure in some patients<age 40, especially children,propylthiouracilis recommended only in special situations (eg, in the 1st trimester of pregnancy, in thyroid storm). The usual starting dose ofpropylthiouracilis 100 to 150 mg orally every 8 hours. Rapid control can be achieved by increasing the dosage ofpropylthiouracilto 150 to 200 mg every 8 hours. Such dosages or higher ones (up to 400 mg every 8 hours) are generally reserved for severely ill patients, including those with thyroid storm, to block the conversion of T4 to T3. Maintenance dosing withpropylthiouracilis 50 mg twice a day or 3 times a day About 20 to 50%of patients with Graves disease remain in remission after a 1- to 2-year course of either drug. The return to normal or a marked decrease in gland size, the restoration of a normal serum TSH level, and less severe hyperthyroidism before therapy are good prognostic signs of long-term remission. The concomitant use of antithyroid drug therapy andlevothyroxinedoes not improve the remission rate in patients with Graves disease. Because toxic nodular goiter rarely goes into remission, antithyroid drug therapy is given only in preparation for surgical treatment or iodine-131 therapy. Adverse effects include rash, allergic reactions, abnormal liver function (including hepatic failure withpropylthiouracil), and, in about 0.1%of patients, reversible agranulocytosis. Patients allergic to one drug can be switched to the other, but cross-sensitivity may occur. If agranulocytosis occurs, the patient cannot be switched to the other drug; other therapy (eg, radioiodine, surgery) should be used. If agranulocytosis occurs with one of the antithyroid peroxidase drugs (methimazoleorpropylthiouracil), avoid using another drug in the same class; use another therapy (eg, radioiodine, surgery) instead. Potential adverse effects or other characteristics vary between the two drugs and guide the indications for each.Methimazoleneed only be given once a day, which improves adherence. Furthermore, whenmethimazoleis used in dosages of<20 mg a day, agranulocytosis is less common; withpropylthiouracil, agranulocytosis may occur at any dosage. Methimazolehas been used successfully in pregnant and nursing women without fetal or infant complications, but rarelymethimazolehas been associated with scalp and gastrointestinal defects in neonates and with a rare embryopathy. Because of these complications,propylthiouracilis used in the 1st trimester of pregnancy. Propylthiouracilis preferred for the treatment of thyroid storm, because the high dosages used (over 800 mg a day) partially block the peripheral conversion of T4 to T3 in addition to decreasing production in the thyroid. The combination of high-dosepropylthiouracilanddexamethasone, also a potent inhibitor of T4 to T3 conversion, can relieve symptoms of severe hyperthyroidism as seen in patients with thyroid storm and restore the serum T3 level to normal within a week. Symptoms and signs of hyperthyroidism due to adrenergic stimulation may respond to beta-blockers;propranololhas had the greatest use, butatenololormetoprololmay be preferable. Other manifestations typically do not respond. Manifestations typically responding to beta-blockers: Tachycardia, tremor, mental symptoms, eyelid lag; occasionally heat intolerance and sweating, diarrhea, proximal myopathy Manifestations typically not responding to beta-blockers: goiter, exophthalmos, weight loss, bruit, increased oxygen consumption, and increased circulating thyroxine levels is indicated in thyroid storm (see table Treatment of Thyroid Storm ). It rapidly decreases heart rate, usually within 2 to 3 hours when given orally and within minutes when given intravenously. Iodine in pharmacologic doses inhibits the release of T3 and T4 within hours and inhibits the organification of iodine, a transitory effect lasting from a few days to a week, after which inhibition usually ceases. Iodine is used for emergency management of thyroid storm, for hyperthyroid patients undergoing emergency nonthyroid surgery, and (because it also decreases the vascularity of the thyroid) for preoperative preparation of hyperthyroid patients undergoing thyroidectomy. Iodine generally is not used for routine treatment of hyperthyroidism. The usual dosage is 2 to 3 drops (100 to 150 mg) of a saturatedpotassium iodidesolution orally 3 times a day or 4 times a day orsodium iodidein 1 L 0.9% saline solution 0.5 to 1 g IV given slowly once a day. Complications of iodine therapy include inflammation of the salivary glands, conjunctivitis, and rash. Surgery is indicated for patients with Graves disease whose hyperthyroidism has recurred after courses of antithyroid drugs and who refuse iodine-131 therapy, patients who cannot tolerate antithyroid drugs, patients with very large goiters, and in some younger patients with toxic adenoma and multinodular goiter. Surgery may be done in older patients with giant nodular goiters. Surgery usually restores normal function. Postoperative recurrences vary between 2 and 16%; risk of hypothyroidism is directly related to the extent of surgery. Vocal cord paralysis and hypoparathyroidism are uncommon complications. Saturated solution ofpotassium iodide3 drops (about 100 to 150 mg) orally 3 times a day should be given for 10 days before surgery to reduce the vascularity of the gland.Methimazolemust be given first because the patient should be euthyroid before iodide is given.Dexamethasonecan be added to rapidly restore euthyroidism. Surgical procedures on the anterior neck are more difficult in patients who previously underwent thyroidectomy or radioiodine therapy. A treatment regimen for thyroid storm is shown in the table Treatment of Thyroid Storm . The precipitating cause should also be addressed. In infiltrative dermopathy (in Graves disease), topical corticosteroids or corticosteroid injections into the lesions may decrease the dermopathy. Dermopathy sometimes remits spontaneously after months or years. -like growth factor 1 (IGF-1) receptor inhibitor, is very effective therapy for moderately severe ophthalmopathy ( Treatment references ). Radioiodine therapy may accelerate progression of ophthalmopathy when ophthalmopathy is active, and is thus contraindicated in this active phase. In patients with subclinical hyperthyroidism who are takinglevothyroxine, reduction of the dose is the most appropriate management unless therapy is aimed at maintaining suppressed TSH levels in patients with thyroid cancer. Therapy is indicated for patients with endogenous subclinical hyperthyroidism (serum TSH<0.1 mU/L), especially those with atrial fibrillation or reduced bone mineral density. The usual treatment is iodine-131, but low doses ofmethimazoleare also effective. 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.Thyroid26(10):1343–1421, 2016. doi: 10.1089/thy.2016.0229 2.Douglas RS, Kahaly GJ, Patel A, et al:Teprotumumabfor the treatment of active thyroid eye disease.N Engl J Med382(4):341–352. 2020. doi: 10.1056/NEJMoa1910434 