What are the guidelines for radioactive iodine therapy in the treatment of Graves disease?

Updated: Apr 17, 2020
  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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The most commonly used therapy for Graves disease is radioactive iodine. Indications for radioactive iodine over antithyroid agents include a large thyroid gland, multiple symptoms of thyrotoxicosis, high levels of thyroxine, and high titers of TSI. Information and guidelines are as follows:

  • Many physicians in the United States prefer to use radioactive iodine as first-line therapy, especially in younger patients, because of the high relapse rate (>50%) associated with antithyroid therapy.

  • Radioiodine treatment can be performed in an outpatient setting.

  • The usual dose ranges from 5-15 mCi, determined either by using various formulas that take into account the estimated thyroid weight and radioiodine uptake or by using fixed dosages of iodine I 131; detailed kinetic studies of131 I are not essential and do not lead to better treatment results. A fixed dose of 7 mCi has been advocated by some researchers as the first empirical dose in the treatment of hyperthyroidism. In general, higher dosages are required for patients who have large goiters, have low radioiodine uptake, or who have been pretreated with antithyroid drugs.

  • Patients currently taking antithyroid drugs must discontinue the medication at least 2 days prior to taking the radiopharmaceutical. [45] In one study, withholding antithyroid drugs for just over 2 weeks before radioiodine treatment resulted in the lowest failure rate. Pretreatment with thioamides reduces the cure rate of radioiodine therapy in hyperthyroid diseases. [46]

  • Thyroid function test results generally improve within 6-8 weeks of therapy, but this can be highly variable.

  • With radioactive iodine, the desired result is hypothyroidism due to destruction of the gland, which usually occurs 2-3 months after administration.

  • Following up with the patient and monitoring thyroid function monthly or as the clinical condition dictates is important.

  • When patients become hypothyroid, they require lifelong replacement with thyroid hormone.

  • The possibility exists that radioactive iodine can precipitate thyroid storm by releasing thyroid hormones. This risk is higher in elderly and debilitated patients. This problem can be addressed by pretherapy administration with antithyroidal medication such as propylthiouracil (PTU) or methimazole, but antithyroid medication also may decrease the effectiveness of radioiodine, as discussed above.

  • If thyroid function does not normalize within 6-12 months of treatment, a second course at a similar or higher dose can be given. Third courses are rarely needed.

  • Hypothyroidism may ensue in the first year in up to 90% of patients given higher doses of radioiodine.

  • Approximately one third of patients develop transient hypothyroidism. Unless a patient is highly symptomatic, thyroxine replacement may be withheld if hypothyroidism occurs within the first 2 months of therapy. If it persists for longer than 2 months, permanent hypothyroidism is likely and replacement with T4 should be initiated.

  • Radiation thyroiditis is rare, but it may occur and exacerbate thyrotoxicosis.

  • Long-term follow-up is mandatory for all patients.

  • One concern with the use of radioiodine in persons with Graves disease is its controversial potential for exacerbating existing Graves ophthalmopathy. However, the presence of ophthalmopathy should not influence the choice of therapy for hyperthyroidism. If possible in patients with mild progressive ophthalmopathy, institute a course of steroids (prednisone up to 1 mg/kg) for 2-3 months, tapering a few days before radioiodine therapy. For those with no obvious ophthalmopathy, the chances of exacerbation are much lower. In patients with severe Graves ophthalmopathy, treatment of hyperthyroidism and ophthalmopathy should proceed concurrently and independently of each other.

  • The absolute contraindication for radioiodine is pregnancy. No evidence of germ-line mutations has been demonstrated from gonadal exposure. The incidence of birth defects or abnormal pregnancies has not increased after radioiodine treatments. [47] After radioiodine therapy, germinal epithelium and Leydig cell function may change marginally, which may have some clinical significance in male patients with preexisting fertility impairment. [48]

  • Because it is known that low-dose thyroid radiation exposure in children increases the risk of thyroid cancer later in life, larger doses of131 I are recommended for children. [49] If patients are aged 6-10 years, ablative doses of131 I (100-150 mCi/g of thyroid tissue) may be used to prevent the survival of thyroid cells that may be transformed later into malignant cells. In a national database analysis, Graves disease patients had increased risk of developing malignancies (especially in the first 3 y of diagnosis) compared with controls, especially for breast and thyroid cancer. [50] Detection bias because of Graves disease diagnosis could be a factor for this epidemiological association.

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