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| ==Medical Management==
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| Hyperthyroidism caused by toxic adenoma rarely remits spontaneously. The mainstay of treatment for most patients with toxic adenoma includes radioiodine, anti thyroid drugs or surgery.
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| ===RADIOACTIVE IODINE===
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| In United States radioactive iodine is the preferred choice of treatment for patients with toxic adenoma.
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| ====Indications====
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| Radioactive iodine is generally preferred over surgery when there is
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| *No suspicion of coexisting thyroid malignancy
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| *No large goiter threatening local compressive symptoms
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| *No other reason for neck surgery (e.g., primary hyperparathyroidism)
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| *No imperative for immediate cure, and whenever the patient’s general health makes him or her a poor candidate for surgery. <Ref>
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| ===Contraindications===
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| *Pregnant women
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| *Children and adolescents(associated with risk of thyroid cancer)<ref>
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| It is controversial whether the administered 131 I dose should be determined by some form of simplified dosimetry or an arbitrary dosage used in all patients.
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| *Typical dosimetric schemes consider gland size, its fractional uptake of a preceding tracer dose, and a standard administered dose constant (e.g., 0.16 mCi/g of estimated hyperfunctioning tissue). However, controlled studies have failed to show that calculated administered doses of radioiodine are superior to an empirically chosen constant dose for all patients (e.g., 15 mCi). 113 114 115 This is probably due to the result of imprecision in the estimated mass and heterogeneous radioisotope distribution within and lack of data about 131 I retention time in the functioning thyroid tissue. Although radioiodine is largely cleared from the patient within 14 days, resolution of hyperthyroidism typically requires 4 to 8 weeks. Consequently, it may be prudent to use temporary antithyroid drug treatment to achieve euthyroidism, discontinue it for several days before and after 131 I administration, and then resume therapy to maintain normal thyroid function while waiting for the effect of the radioiodine, particularly in older patients and those with cardiac disease. Because propylthiouracil (PTU) has been shown to induce relative resistance to radioiodine in those with Graves’ disease and methimazole has not, the latter is the antithyroid drug of choice for such adjunctive therapy. 116 117 118 119 120 121 122 123 One randomized controlled trial has also confirmed this effect of PTU in toxic multinodular goiter. 124 With typical administered radioiodine doses, such as 10 to 30 mCi of 131 I, hyperthyroidism is cured in 62% to 98% of patients with toxic adenoma or toxic nodular goiter. 125 126 127 128 129 130 The remainder almost invariably respond to a second radioiodine dose, which is typically given no sooner than 4 to 6 months later. Predictors of relative resistance to radioiodine therapy include large goiters and those with a higher fractional thyroid uptake of radioiodine. 131
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| ====Complications====
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| Potential adverse effects of 131 I therapy for toxic nodular goiter include
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| *Radiation thyroiditis
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| *Postablative hypothyroidism.
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| ====Radiation thyroiditis =====
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| *Radiation thyroiditis presents with anterior neck pain in the week after therapy and exacerbation of thyrotoxicosis because of the release of preformed thyroid hormone from the gland, which typically occurs 2 to 8 weeks after treatment.
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| *Pretreatment with an antithyroid drug has been shown to decrease the severity of thyrotoxicosis caused by radiation thyroiditis in Graves’ disease, 132 133 134 135 but this has not been established for toxic nodular goiter.
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| *Thyroiditis-related gland swelling with potential worsening of compressive symptoms is a concern that has not actually been realized in studies of radioiodine therapy for nodular goiter. 136 137
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| *Long term, thyroid volume typically decreases by about 40% after 131 I treatment. 138 139
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| ====Postablative hypothyroidism====
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| *The incidence of postablative hypothyroidism after radioiodine therapy has been reported to be 25% to 50%, which is lower than that encountered after treatment of patients with Graves’ disease.
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| *This is presumably because suppressed extranodular thyroid tissue does not take up radioiodine.
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| *Radioisotopic distribution within functioning tissue can also be heterogeneous.
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| *Postablative hypothyroidism is more common when higher doses of radioactive iodine are administered.
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| ===RECOMBINANT THYROID-STIMULATING HORMONE–STIMULATED 131 I Therapy===
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| The relatively low fractional uptake of radioiodine by nodular goiters can limit the effectiveness of 131 I therapy and increase the administered dose requirement. Consequently, in recent years, recombinant TSH (thyrotropin alfa, rTSH, Thyrogen) has been investigated as an off-label approach to increasing thyroidal radioiodine uptake for the treatment of hyperthyroidism and goiter size in patients with toxic nodular goiter. rTSH has also been used to facilitate goiter shrinkage with 131 I in patients with nontoxic nodular goiter, in whom rTSH permits a 50% to 60% reduction in the administered 131 I dose 143 144 while producing a more substantial decrease in goiter volume. Studies in nontoxic nodular goiter patients have demonstrated the importance of using a rTSH dose less than that used for thyroid cancer testing (e.g., a single 0.01- to 0.45-mg rTSH dose). 144 145 146 Larger rTSH doses have been reported to induce severe thyrotoxicosis or gland swelling with increased obstructive symptoms. rTSH-stimulated 131 I therapy has also been used for older patients with clinical or subclinical hyperthyroidism caused by large multinodular goiters. In such patients, the relatively low fractional uptake of radioiodine by the thyroid reduces the cure rate after 131 I. In one study of 41 patients with clinical or subclinical hyperthyroidism caused by large multinodular goiter, patients who were randomly assigned to receive 0.45 mg rTSH before 131 I had a greater reduction in goiter volume at 1 year, 58% versus 40%. However, rTSH pre-treated patients also had a higher rate of postradioiodine hypothyroidism, 65% versus 21%, 147 probably because rTSH enhanced uptake in previously suppressed regions of the gland. Because of its risk of exacerbating hyperthyroidism, rTSH is generally inadvisable when administering a larger 131 I dose is an option, especially in older patients and those with underlying heart disease.
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| ===ANTITHYROID DRUGS===
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| *The thionamide antithyroid drugs—methimazole and propylthiouracil in the United States and carbimazole in Europe and Asia—have limited roles in the management of patients with nontoxic nodular goiter.
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| *Unlike hyperthyroid Graves’ disease, thyroid autonomy in toxic nodular goiter rarely remits unless it has been provoked by an iodine load.
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| *Furthermore, because of the substantial store of previously synthesized thyroid hormone that can be present in the large gland of a patient with toxic nodular goiter, thionamide therapy alone may not control hyperthyroidism completely for weeks or months.
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| *Nonetheless, there remain certain indications for short-term antithyroid drug therapy. First, thionamides can be useful for the initial control of hyperthyroidism that is severe or complicates cardiac or other conditions in a fragile patient. By restoring euthyroidism, such thionamide pretreatment can then make subsequent surgery or radioiodine therapy safer. Second, PTU is the immediate treatment of choice for pregnant patients with hyperthyroidism, although toxic nodular goiter is rare in this population. Third, a time-limited course of antithyroid drugs can sometimes be useful to evaluate the clinical status of patients with subclinical hyperthyroidism who have nonspecific symptoms, such as nervousness or insomnia, that may or may not improve with definitive treatment of mild hyperthyroidism. If a patient experiences an improvement in symptoms or sense of well-being when thyroid function has been restored to normal on thionamide therapy, then the case for radioiodine therapy or surgery is stronger.
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| The specific mechanisms of action, doses, and side effects of the thionamide antithyroid drugs have been extensively reviewed.
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