# Radioiodine Therapy for Hyperthyroidism ## Overview I-131 is the most commonly used definitive treatment for Graves disease and toxic nodular goiter in North America. Beta particles emitted during I-131 decay cause thyroid follicular cell destruction through direct DNA damage and radiation-induced apoptosis. The therapeutic goal is to render the patient euthyroid or, more commonly, hypothyroid, since hypothyroidism is easier to manage with lifelong levothyroxine replacement. ## Mechanism of Action I-131 is trapped by the sodium-iodide symporter and organified within thyroid follicular cells, just as stable iodine would be. The beta particle emission has a maximum energy of 606 keV and a mean range of 0.4 mm in tissue, delivering highly localized radiation to the thyroid. The gamma emission at 364 keV allows post-therapy imaging but also necessitates radiation safety precautions. The physical half-life is 8.02 days, while the effective half-life in the thyroid is approximately 5 to 7 days. The radiation effect develops gradually over weeks to months, with full therapeutic effect typically reached by 3 to 6 months. ## Dosing Strategies ### Fixed-Dose Approach For Graves disease, a typical fixed dose is 10 to 15 mCi (370 to 555 MBq). Toxic multinodular goiter generally requires higher doses of 15 to 30 mCi because of heterogeneous uptake, and toxic adenoma is similarly treated with 15 to 29 mCi. The fixed-dose approach is simple and does not require uptake measurement or gland size estimation. Its main disadvantage is that larger fixed doses produce higher hypothyroidism rates, while smaller doses may under-treat the condition. ### Calculated-Dose Approach The calculated-dose method bases the administered activity on estimated gland size, 24-hour RAIU, and a desired delivered dose, typically 150 to 200 microCi per gram for Graves disease and 200 to 300 microCi per gram for toxic nodular goiter. The formula is: administered dose equals the desired dose per gram multiplied by gland weight, divided by fractional RAIU. This approach is theoretically more precise and may produce lower hypothyroidism rates, but gland size estimation is inherently imprecise and the calculations assume uniform radioiodine distribution. | Condition | Fixed Dose (mCi) | Calculated Dose (μCi/g) | Notes | |---|---|---|---| | Graves disease | 10–15 | 150–200 | Hypothyroidism in 50–80% at 1 year | | Toxic multinodular goiter | 15–30 | 200–300 | Higher dose needed; heterogeneous uptake | | Toxic adenoma | 15–29 | 200–300 | Directed to autonomous nodule | ### Controversy: Fixed vs. Calculated Dose No clear evidence demonstrates that calculated dosing produces better outcomes than fixed dosing. Many centers have adopted fixed dosing for its simplicity. Regardless of approach, hypothyroidism develops in 50 to 80% of Graves disease patients within the first year. I-131 therapy planning showing thyroid uptake and scan with gland size estimation for calculated dose approach in Graves disease ## Pre-Treatment Evaluation Before therapy, the diagnosis is confirmed with TSH, free T4, T3, and thyroid antibodies (TRAb or TSI). Thyroid scintigraphy and RAIU are performed to confirm the etiology and assess uptake. A pregnancy test is mandatory for all women of childbearing age, as pregnancy is an absolute contraindication. The presence and severity of Graves ophthalmopathy should be assessed, as it influences the choice between RAI and other treatment modalities. A baseline CBC may be obtained if subsequent monitoring is planned. ## Pre-Treatment Considerations ### Antithyroid Drug Management Methimazole or PTU should be discontinued 3 to 7 days before RAI therapy to optimize uptake. These medications may be resumed 3 to 7 days after RAI if symptom control is needed in severely thyrotoxic patients. Pre-treatment with antithyroid drugs may reduce RAI efficacy, though the significance of this stunning effect is debated. In elderly patients or those with cardiac disease, pre-treatment with antithyroid drugs to achieve a near-euthyroid state is prudent because it reduces the risk of thyroid storm triggered by post-therapy hormone release. ### Beta-Blocker Therapy Beta-blockers such as propranolol or atenolol should be continued or initiated for symptomatic control. They do not interfere with RAI uptake or efficacy and are essential in patients with significant tachycardia, tremor, or cardiac arrhythmias. ### Graves Ophthalmopathy For mild to moderate ophthalmopathy, RAI therapy may worsen eye disease, and prophylactic corticosteroids should be considered. A typical regimen is prednisone 0.3 to 0.5 mg/kg starting 1 to 3 days after RAI and tapered over 2 to 3 months. Severe or active ophthalmopathy is a relative contraindication to RAI, and surgery or antithyroid drugs should be considered instead. Risk factors for post-RAI exacerbation of ophthalmopathy include smoking, high TRAb levels, and uncontrolled hypothyroidism after therapy. Pre-treatment thyroid scintigraphy in Graves disease showing diffusely enlarged gland with markedly elevated uptake (65% at 24 hours), and post-treatment scan at 6 months demonstrating reduced gland size with decreased activity ## Post-Treatment Management ### Expected Course Thyrotoxicosis may transiently worsen in the first 1 to 2 weeks as preformed hormone is released from damaged follicles. Symptomatic improvement typically begins at 4 to 8 weeks. Hypothyroidism develops in 50 to 80% of patients within the first year and in nearly 100% by 10 years in Graves disease. TSH and free T4 should be checked at 4 to 6 weeks, then every 4 to 8 weeks until stable. Levothyroxine is initiated when hypothyroidism develops, as indicated by an elevated TSH and low free T4. ### Treatment Failure If hyperthyroidism persists at 6 months, a second dose of RAI can be administered. Repeat treatment is needed in approximately 10 to 20% of patients, and a higher activity should be considered for retreatment. ### Radiation Thyroiditis Mild neck pain and tenderness may develop 1 to 2 weeks after therapy. This is self-limited and managed with NSAIDs. Radiation thyroiditis is uncommon and more frequent with large glands and higher doses. ## Radiation Safety Instructions for Patients ### General Precautions (First 2 to 5 Days Post-Therapy) Patients are instructed to maintain distance from others, especially pregnant women and young children. They should sleep in a separate bed, use separate utensils or wash them thoroughly, flush the toilet twice after use, and practice good hand hygiene. Prolonged close contact within 1 meter should be avoided. The specific duration of precautions depends on the administered activity and the patient's living situation. ### Pregnancy and Breastfeeding RAI is absolutely contraindicated during pregnancy because the fetal thyroid concentrates iodine after 10 to 12 weeks of gestation. Pregnancy should be avoided for 6 months after therapy, though some guidelines recommend 4 months for women and 3 months for men. Breastfeeding must be discontinued before RAI therapy and cannot be resumed after treatment. ### Workplace and Travel Most patients treated with less than 33 mCi can be released immediately per NRC regulation 10 CFR 35.75. Patients may trigger radiation detectors at airports or nuclear facilities for days to weeks after therapy. Written documentation in the form of a therapy card should be provided. Patient radiation safety instruction card showing recommended precautions, duration of isolation measures, and activity-specific guidance following I-131 therapy for hyperthyroidism ## Special Populations ### Pediatric Patients RAI therapy is used in children, generally those older than 5 to 10 years, though age thresholds vary by institution. A fixed dose of 15 mCi is commonly administered to achieve ablation and definitive hypothyroidism. Long-term cancer risk is a consideration, though large studies have not demonstrated increased malignancy risk at therapeutic doses used for hyperthyroidism. ### Toxic Multinodular Goiter Toxic multinodular goiter generally requires higher RAI activities of 20 to 30 mCi compared to Graves disease. The cure rate per dose is lower because of heterogeneous uptake and areas of autonomy. Pre-treatment with recombinant TSH to increase uptake in non-toxic nodular goiter has been investigated but is not standard practice. ### Amiodarone-Induced Thyrotoxicosis Type 1 amiodarone-induced thyrotoxicosis, caused by an iodine load in patients with underlying thyroid disease, may respond to RAI if uptake is sufficient, though it is often suppressed by the iodine load. Type 2, which is a destructive thyroiditis, is not amenable to RAI because there is no uptake. Mixed types exist, and RAI is rarely the first-line treatment for amiodarone-induced thyrotoxicosis. Comparison of thyroid scintigraphy patterns: Graves disease (diffuse increased uptake amenable to RAI), toxic multinodular goiter (heterogeneous uptake requiring higher RAI dose), and subacute thyroiditis (absent uptake, RAI not effective) ## Clinical Pearls Hypothyroidism after RAI is the expected outcome, not a complication. Patients should be counseled about this before treatment. RAI must never be administered without a negative pregnancy test in women of childbearing potential. Prophylactic corticosteroids should be considered in patients with Graves ophthalmopathy, especially those who smoke. Methimazole should be discontinued 3 to 5 days before and after RAI. PTU may have a more prolonged effect on RAI efficacy and should be stopped 2 weeks before therapy. Lithium can be used as an adjunct to increase RAI retention in the gland when uptake is borderline. A transient rise in TRAb levels after RAI therapy may exacerbate ophthalmopathy. ## References - Ross, D. S., et al. "2016 ATA Guidelines for Diagnosis and Management of Hyperthyroidism." *Thyroid*, 2016. - Stokkel, M. P. M., et al. "EANM Guidelines for Radioiodine Therapy of Differentiated Thyroid Cancer." *European Journal of Nuclear Medicine*, 2010. - ACR-SNM Practice Guideline for I-131 Therapy for Hyperthyroidism. - Bartalena, L., et al. "Management of Graves Ophthalmopathy: ETA/EUGOGO Consensus." *European Thyroid Journal*, 2016.