[J] If 131I therapy is chosen, how should it be accomplished?

[J] If 131I therapy is chosen, how should it be accomplished?

[J1] Preparation of patients with TMNG or TA for 131I therapy

    Patients with TMNG or TA who are at increased risk for complications due to worsening of hyperthyroidism, including the elderly and those with cardiovascular disease or severe hyperthyroidism, should be treated with beta-blockade prior to radioactive iodine therapy and until euthyroidism has been achieved. 1/+00

Medical management before 131I therapy should be tailored to the vulnerability of the patient based on the severity of the hyperthyroidism, patient age, and comorbid conditions. Worsened chemical hyperthyroidism with increased heart rate and rare cases of supraventricular tachycardia, including atrial fibrillation and atrial flutter, have been observed in patients treated with 131I for either TMNG or nontoxic multindoular goiter (MNG) (162–164). In susceptible patients with pre-existing cardiac disease or in the elderly, this may produce significant clinical worsening (163). Therefore, the use of beta-blockers to prevent post-treatment tachyarrhythmias should be considered in all patients with TMNG or TA who are older than 60 years of age and those with cardiovascular disease or severe hyperthyroidism (26). The decision regarding the use of MMI pretreatment is more complex and is discussed below.

    Pretreatment with methimazole prior to radioactive iodine therapy for TMNG or TA should be considered in patients who are at increased risk for complications due to worsening of hyperthyroidism, including the elderly and those with cardiovascular disease or severe hyperthyroidism. 2/+00
    Task force opinion was not unanimous; one member held the opinion that pretreatment with methimazole in patients already treated with beta adrenergic blockade is not indicated in this setting.

The minority position regarding the above recommendation held that pretreating TMNG patients with MMI before radioactive iodine therapy is not necessary and delays the time to definitive treatment and cure. Beta-blockade alone was thought to be sufficient to prevent the majority of adverse events related to worsening of chemical hyperthyroidism that can occur following 131I treatment for TMNG. Young and middle-aged patients with TMNG or TA generally do not require pretreatment with ATDs (MMI) before receiving radioactive iodine, but may benefit from beta-blockade if symptoms warrant and contraindications do not exist.

Technical remarks: If methimazole is used in preparation for radioactive iodine therapy in patients with TMNG or TA, caution should be taken to avoid radioiodine therapy when the TSH is normal or elevated to prevent direct 131I treatment of perinodular and contralateral normal thyroid tissue, which increases the risk of developing hypothyroidism.

[J2] Evaluation of thyroid nodules before radioactive iodine therapy

    Nonfunctioning nodules on radionuclide scintigraphy or nodules with suspicious ultrasound characteristics should be managed according to recently published guidelines regarding thyroid nodules in euthyroid individuals. 1/++0

Thorough assessment of suspicious nodules within a TMNG, according to the recently published guidelines (143,144), should be completed before selection of radioactive iodine as the treatment of choice. The prevalence of thyroid cancer in TMNG historically has been estimated to be about 3% (148). More recently, it has been estimated to be as high as 9%, which is similar to the 10.6% prevalence noted in nontoxic MNG (165).

Technical remarks: Both the ATA and AACE, the latter in conjunction with the European Thyroid Association and Associazione Medici Endocrinologi, have recently published updated management guidelines for patients with thyroid nodules (143,144).

[J3] Administration of radioactive iodine in the treatment of TMNG or TA

    For radioactive iodine treatment of TMNG, sufficient radiation should be administered in a single dose to alleviate hyperthyroidism. 1/++0

The goal of radioactive iodine therapy, especially in older patients, is elimination of the hyperthyroid state. Higher activities of 131I, even when appropriately calculated for the specific volume or mass of hyperthyroid tissue, result in more rapid resolution of hyperthyroidism and less need for retreatment, but a higher risk for early hypothyroidism. One study showed a 64% prevalence of hypothyroidism 24 years after radioactive iodine therapy for TMNG, with a higher prevalence among patients who required more than one treatment (150). The prevalence of hypothyroidism following 131I therapy is increased by normalization or elevation of TSH at the time of treatment resulting from ATD pretreatment and by the presence of antithyroid antibodies (166).

The activity of radioiodine used to treat TMNG, calculated on the basis of goiter size to deliver 150–200 µCi per gram of tissue corrected for 24-hour RAIU, is usually higher than that needed to treat GD. In addition, the RAIU values for TMNG may be lower, necessitating an increase in the total dose of radioactive iodine. Radiation safety precautions may be onerous if high activities of 131I are needed for large goiters. Pretreatment with MMI to a slightly elevated TSH increased RAIU enough to allow more efficacy from a fixed activity (30 mCi) of 131I in a recent study of patients with TMNG (167). Use of recombinant human TSH is not indicated in TMNG due to risk of exacerbating the patient’s hyperthyroidism (168).

Technical remarks: Swelling of the thyroid is very rare after 131I treatment. However, patients should be advised to immediately report any tightening of the neck, difficulty breathing, or stridor following the administration of radioactive iodine. Any compressive symptoms, such as discomfort, swelling, dysphagia, or hoarseness, which develop following radiotherapy, should be carefully assessed and monitored, and if clinically necessary, corticosteroids can be administered. Respiratory compromise in this setting is extremely rare and requires management as any other cause of acute tracheal compression.

    For radioactive iodine treatment of TA, sufficient radiation to alleviate hyperthyroidism should be administered in a single dose. 1/++0

Radioactive iodine administered to treat TA can be given either as a fixed activity (approximately 10–20 mCi) or an activity calculated on the basis of nodule size using 150–200 µCi 131I per gram corrected for 24-hour RAIU (169). A long-term follow-up study of patients with TA, where patients with small (<4 cm) nodules were administered an average of 13 mCi and those with larger nodules an average of 17 mCi, showed a progressive increase in hypothyroidism over time in both groups, suggesting that hypothyroidism develops over time regardless of activity adjustment for nodule size (154). A randomized trial of 97 patients with TA compared the effects of high (22.5 mCi) or low (13 mCi) fixed activity radioactive iodine, with a calculated activity that was either high (180–200 µCi/g) or low (90–100 µCi/g) and corrected for 24-hour RAIU (169). This study confirmed previous reports showing an earlier disappearance of hyperthyroidism and earlier appearance of hypothyroidism with higher activity treatments. Use of a calculated activity allowed for a lower 131I activity to be administered for a similar efficacy in the cure of hyperthyroidism.

[J4] Patient follow-up after 131I therapy for TMNG or TA

    Follow-up within the first 1–2 months after radioactive iodine therapy for TMNG or TA should include an assessment of free T4, total T3 and TSH. This should be repeated at 1–2 month intervals until stable results are obtained, then at least annually thereafter according to clinical indication. 1/+00

Radioactive iodine therapy for TMNG results in resolution of hyperthyroidism in approximately 55% of patients at 3 months and 80% of patients at 6 months, with an average failure rate of 15% (147–149). Goiter volume is decreased by 3 months, with further reduction observed over 24 months, for a total size reduction of 40% (149). For TA, 75% of patients were no longer hyperthyroid at 3 months, with nodule volume decreased by 35% at 3 months and by 45% at 2 years (152). Risk of persistent or recurrent hyperthyroidism ranged from 0% to 30%, depending on the series (147–149,152). Long-term follow-up studies show a progressive risk of clinical or subclinical hypothyroidism of about 8% by 1 year and 60% by 20 years for TA (154), and an average of 3% by 1 year and 64% by 24 years for TMNG (150).

Technical remarks: If thyroid hormone therapy is necessary, the dose required may be less than full replacement due to underlying persistent autonomous thyroid function.

[J5] Treatment of persistent or recurrent hyperthyroidism following 131I therapy for TMNG or TA

    If hyperthyroidism persists beyond 6 months following 131I therapy for TMNG or TA, retreatment with radioactive iodine is suggested. 2/+00

Technical remarks: In severe or refractory cases of persistent hyperthyroidism due to TMNG or TA, surgery may be considered. As some patients with mild hyperthyroidism following radioactive iodine administration will continue to improve over time, use of MMI with close monitoring may be considered to allow control of the hyperthyroidism until the radioactive iodine is effective.