Procedure Guideline for Therapy of Thyroid Disease with ¹³¹Iodine

Benign Conditions

• Hyperthyroidism. ¹³¹I may be indicated for the treatment of Graves’ disease, toxic multinodular goiter, or toxic autonomously functioning thyroid nodules.

• Nontoxic multinodular/diffuse goiter. ¹³¹I therapy has been used successfully to diminish the size of nontoxic multinodular/diffuse goiter.

Thyroid Cancer

• ¹³¹I therapy has been used for postoperative ablation of thyroid remnants after thyroidectomy.

• ¹³¹I therapy has been used to treat residual thyroid cancer and metastatic disease after partial or complete thyroidectomy.

Patient Preparation

1. For All Patients

   1. All patients must discontinue use of iodide-containing preparations, iodine supplements, thyroid hormones, and other medications that could potentially affect the ability of thyroid tissue to accumulate iodide for a sufficient time before contemplated therapy (Table 1).

   2. The treating physician must explain the procedure, treatment, complications, side effects, therapeutic alternatives, and expected outcome to the patient. Written information should be provided to the patient.

   3. The treating physician must obtain written informed consent before therapy.

2. For Therapy of Hyperthyroidism and Nontoxic Multinodular Goiter

   1. The results from recent measurements of thyroid hormone levels (free T4, free T3) and thyroid stimulating hormone (TSH) should be available and reviewed. The avidity of the thyroid gland for iodide must be established. This can be accomplished quantitatively using a recent radioiodine uptake (RAIU), or qualitatively using a thyroid scan. These procedures will differentiate silent thyroiditis and thyrotoxicosis factitia from other forms of hyperthyroidism.

   2. Pretreatment of selected patients with antithyroid drugs (ATD) to deplete thyroid hormone stores may be helpful. ¹³¹I therapy can cause radiation thyroiditis with release of stored thyroid hormone into the circulation, resulting in occasional worsening of hyperthyroidism and, rarely, precipitation of thyroid storm. This is more likely to occur in patients with large, iodine-avid multinodular glands who are given larger amounts of ¹³¹I. Accordingly, elderly patients and patients with significant preexisting heart disease, severe systemic illness, or debility may benefit from pretreatment with ATD. The ATD needs to be discontinued for at least 3 d before the radioiodine therapy is given. The ATD can be resumed 2–3 d after treatment with ¹³¹I. Some experts recommend administering a larger amount of ¹³¹I in patients who have been pretreated with ATD. Treatment with β-blockers can be helpful for symptomatic control. β-Blockers need not be discontinued before treatment with ¹³¹I.

   3. The consent form should include the following items specific for the therapy of hyperthyroidism:

      • More than one ¹³¹I treatment may be necessary.

      • The risk of eventual hypothyroidism is high, especially after treatment of Graves’ disease, and lifelong daily ingestion of a thyroid hormone tablet would then be necessary.

      • Long-term follow-up will be necessary.

      • Ophthalmopathy may worsen or develop after ¹³¹I therapy.

      • Rarely, there can be transient neck soreness or exacerbation of hyperthyroid symptoms secondary to radiation thyroiditis.

3. For Therapy of Thyroid Cancer

   1. Thyroid hormone medications must be withheld for a time sufficient to permit an adequate rise in TSH (>30 μIU/ml). This is at least 2 wk for triiodothyronine (T3) and 4 to 6 wk for thyroxine (T4). TSH may not rise to this level if a large volume of functioning tissue remains. Recombinant human TSH is not currently approved in the United States for use in ¹³¹I therapy, although there is FDA approval for use in diagnostic testing.

   2. For patients receiving an ablative dose or treatment dose of radioiodine following a partial or complete thyroidectomy for thyroid cancer, the results from a recent measurement of TSH and the operative and histology reports should be available and reviewed. A baseline serum thyroglobulin should be obtained in the hypothyroid state. A complete blood count before treatment may be useful. Other laboratory tests such as a serum calcium (to exclude hypoparathyroidism postthyroidectomy) may be helpful.

   3. Many experts recommend a low iodide diet for 7–10 d before administration of therapy to improve iodine uptake. Since iodized salt is a major dietary source of iodide, compliance with a low iodide diet may be difficult, especially if restaurant food is eaten. Table 2 lists major food groups and other common sources of iodine. Red dye is found in many processed red- or pink-colored foods and medications.

   4. The presence of iodine accumulating thyroid tissue is routinely documented by uptake measurement and imaging (see “Procedure Guideline for Extended Scintigraphy of Differentiated Thyroid Cancer,” Society of Nuclear Medicine Procedure Guidelines Manual, 1999, p. 15). In selected patients, an uptake measurement and/or imaging may not be necessary. In the absence of antithyroglobulin antibodies, an elevated or rising serum thyroglobulin may also be a useful indicator of residual or recurrent thyroid cancer and may be an indication for radioiodine therapy even in the absence of discernible activity following a diagnostic dose of ¹³¹I. An elevated serum thyroglobulin does not guarantee iodine avidity of the tumor.

   5. A written informed consent form must be obtained and could include the following items specific for the therapy of thyroid cancer:

      • The purpose of the treatment is to destroy normal and cancerous thyroid tissue. Other normal tissues may also be affected.

      • More than one ¹³¹I treatment may be necessary.

      • Early side effects may include nausea, occasional vomiting, pain and tenderness in the salivary glands, loss of saliva or taste, neck pain and swelling if a sizeable thyroid remnant remains after surgery, and decreased white blood cells that may result in increased susceptibility for infection. Generally these side effects are temporary.

      • Late side effects may include temporary infertility (in men this can be permanent as dosages progressively exceed 11.1 GBq [300 mCi]); rarely, permanent damage to the salivary glands resulting in loss of saliva or stones; excessive dental caries; reduced taste; and the very rare development of other cancers, including those of the stomach, bladder, colon, and salivary glands, and leukemia (only with very high cumulative doses).

      • These late side effects are rarely seen and should not deter a patient from taking ¹³¹I for treatment of thyroid cancer.

4. Information Pertinent to Performing the Procedure

   1. For All Patients

      1. The treating physician must obtain the patient’s thyroid-related medical history and perform a directed physical examination. The cumulative administered activity of ¹³¹I should be reviewed and recorded in the patient’s record.

      2. The treating physician must confirm that appropriate laboratory testing has been performed and must review the results of these tests.

      3. Female patients who have the potential to be pregnant should routinely be tested for pregnancy within a few days before administration of the ¹³¹I treatment. Occasionally, when historical information clearly indicates pregnancy is impossible, a pregnancy test may be omitted at the discretion of the treating physician.

      4. All potentially breastfeeding/lactating women should be asked if they are lactating. If so, they should be asked to stop breastfeeding and therapy delayed until lactation ceases in order to minimize the radiation dose to the breast. The patient may not resume breastfeeding for that child. Nursing may resume with the birth of another child.

      5. The treating physician should confirm that the patient is continent of urine or that arrangements are made to prevent contamination caused by incontinence.

      6. The patient’s identity must be confirmed in accordance with institutional policy before administration of ¹³¹I.

   2. For Hyperthyroid Patients

      • Dose selection. A variety of methods have been used to select the amount of administered activity. A common method is to use the estimated thyroid gland size and the results of a 24-h RAIU test to calculate the amount of ¹³¹I to administer in order to achieve a desired concentration of ¹³¹I in the thyroid gland. Delivered activity of 2.96–7.4 MBq (80–200 μCi) per gram of thyroid tissue is generally appropriate. The thyroid radiation dose depends on the RAIU as well as the biological and effective half-life of the radioiodine in the thyroid gland. This biological half-life can vary widely. Thyroid concentrations toward the upper end of the range (i.e., 7.4 MBq/gm [200 μCi/gm]) are especially suitable for patients with nodular goiters, very large toxic diffuse goiters, and repeat therapies. In much of Europe, empiric rather than calculated dosage strategies are often used.

   3. For Thyroid Cancer Patients

      1. Dose selection. A variety of approaches have been used to select the amount of administered activity. General guidelines are listed below:

         • For postoperative ablation of thyroid bed remnants, activity in the range of 2.75–5.5 GBq (75–150 mCi) is typically administered, depending on the RAIU and amount of residual functioning tissue present.

         • For treatment of presumed thyroid cancer in the neck or mediastinal lymph nodes, activity in the range of 5.55–7.4 GBq (150–200 mCi) is typically administered.

         • For treatment of distant metastases, activity of >7.4 GBq (200 mCi) is often given. The radiation dose to the bone marrow is typically the limiting factor. Most experts recommend that the estimated radiation dose to the bone marrow be less than 200 rad. Detailed dosimetry may be indicated in patients who are treated with large amounts of radioactive iodine to determine how much ¹³¹I can be safely administered. Retention of radioiodine in the body at 48 h should be <4.44 GBq (120 mCi), or <2.96 GBq (80 mCi) if diffuse lung metastases are present, to reduce toxicity.

      2. Oral administration of lithium carbonate prolongs the biological half-life of administered ¹³¹I and occasionally may be useful in patients who have a rapid turnover of radioactive iodine. A short effective ¹³¹I half-life can be a source of failure of ¹³¹I therapy in metastatic lesions.

      3. Side effects may occur and are generally dose related. These are listed above in the consent form outline found in Section IV.A.3.e. Hydration of the patient, with instructions urging frequent urination for several days and efforts to increase salivary flow may reduce radiation exposure to the bladder and salivary glands. Antiemetics may be helpful. The patient should have at least 1 bowel movement a day to reduce colon exposure. Laxatives may be necessary.

      4. Patients should have extended scintigraphy approximately 1 wk after treatment for staging purposes.

5. Precautions

   1. The treating physician must instruct the patient on how to reduce unnecessary radiation exposure to family members and members of the public. Written instructions should be provided and may be required in some jurisdictions.

   2. Following treatment, patients should not become pregnant until their medical condition has been optimized. Opinions vary widely as to how long to defer pregnancy, but some centers recommend 6 mo after ¹³¹I therapy for patients with hyperthyroidism and 12 mo for patients with thyroid cancer. The 12-mo interval allows for follow-up imaging to evaluate the effectiveness of the cancer treatment dose. Radiation exposure before conception is a very small risk compared with the usual risks of pregnancy.

   3. If the patient is to be treated as an inpatient, nursing personnel must be instructed on radiation safety. Selected nursing personnel may be provided appropriate radiation monitors (film badge, direct-reading dosimeters, etc.). Any significant medical conditions should be noted and contingency plans made in case radiation precautions must be breached for a medical emergency. Concern about radiation exposure should not interfere with the prompt, appropriate medical treatment of the patient should an acute medical problem develop.

   4. Radiation surveys of the thyroid gland should be performed periodically on personnel administering ¹³¹I.

6. Radiopharmaceutical

   1. See Sections IV.B.2 and IV.B.3 for guidance on selection of the amount of administered activity for the treatment of hyperthyroidism and thyroid cancer, respectively. Therapeutic ¹³¹I can be administered in liquid or capsule form, but the prescribed amount must be verified in a dose calibrator before administration. If a liquid form is used, strategies for minimizing volatilization during dosage preparation and administration should be used such as venting the dose into a filtering system such as a fume hood and administering the dose to the patient shortly thereafter.

   2. Radiation Dosimetry in Adults. See Tables 3 and 4.

7. Reporting

   • The report to the referring physician should include the justification for therapy, pertinent historical data, physical findings, and laboratory tests, and should indicate that informed consent was obtained and the patient was informed of possible side effects.