Version May 2024
INTRODUCTION — Radioiodine therapy has been used in the management of patients with well-differentiated (papillary or follicular) thyroid cancer since the 1940s. Thyroid tissue has a unique ability to take up iodine from blood. Like iodine, radioiodine is taken up and concentrated in thyroid follicular cells because they have a membrane sodium-iodide transporter [1]. Compared with normal thyroid follicular cells, thyroid cancer cells have reduced expression of the transporter, which may account for the low iodine-131 (131-I) uptake in thyroid cancer tissue.
131-I causes acute thyroid cell death by emission of short path-length (1 to 2 mm) beta particles. The uptake of 131-I by thyroid tissue can be visualized by scanning to detect the gamma radiation that is also emitted by the isotope. 131-I must be taken up by thyroid tissue to be effective. As a result, it is of no value in patients whose thyroid cancers do not concentrate iodide (ie, patients with medullary cancer, lymphoma, or anaplastic cancer).
Radioiodine therapy for differentiated thyroid cancer will be reviewed here. Surgery, the primary therapy for differentiated thyroid cancer, and an overview of the management of thyroid cancer are discussed separately. (See "Differentiated thyroid cancer: Surgical treatment" and "Differentiated thyroid cancer: Overview of management".)
GOALS — In an effort to standardize terminology, an intersocietal working group with representatives from the American Thyroid Association (ATA), the European Thyroid Association, the European Association of Nuclear Medicine, and the Society of Nuclear Medicine and Molecular Imaging reached the following consensus regarding the goals of iodine-131 (131-I) therapy in differentiated thyroid cancer [2]:
●Remnant ablation – The primary goal of remnant ablation is destruction of presumably benign thyroid tissue after total thyroidectomy, to facilitate initial staging and follow-up studies. This will, in turn:
•Improve the specificity of measurements of serum thyroglobulin (Tg) as a tumor marker
•Increase the specificity of 131-I scanning for detection of recurrent or metastatic disease by eliminating uptake by residual normal tissue
●Adjuvant treatment – The primary goal of adjuvant treatment is destruction of subclinical tumor deposits that may or may not be present after surgical resection of all known primary tumor tissue and metastatic foci. Since adjuvant treatment is given based on the risk of having persistent/recurrent disease without definitive evidence of biochemical or structural evidence of disease, it is accepted that some patients selected for adjuvant treatment might already have been treated sufficiently by their primary surgery. Thus, the decision to recommend adjuvant treatment requires balancing oncological risk (risk of persistent/recurrent disease and disease-specific mortality) and the risks associated with adjuvant treatment (short- and long-term risks of 131-I) with the potential benefit of adjuvant treatment (potential to decrease recurrence, improve progression-free survival, and/or improve disease-specific mortality). Thus, in properly selected patients, the potential benefits of 131-I adjuvant treatment could include:
•Destruction of subclinical, microscopic foci of disease remaining after surgery
•Decreased risk of recurrence
•Improved disease-specific survival
•Improved progression-free survival
●Treatment of known disease – The primary goal in the treatment of known disease is destruction of clinically apparent macroscopic disease (evidenced by either abnormal thyroglobulin values or structural findings) that is not amenable to surgical therapy. Radioiodine treatment of residual disease and metastatic disease may reduce the risk of recurrence and mortality, especially in small-volume disease that is radioiodine avid. (See 'High risk' below.)
PATIENT SELECTION — The decision to administer radioiodine after thyroidectomy in patients with differentiated thyroid cancer is based upon the clinicopathologic features of each case (table 1). The efficacy of radioiodine depends upon tumor-specific characteristics, sites of disease, patient preparation, and dose. Because of the careful risk stratification used in some studies, it is possible to identify specific patient and tumor characteristics which suggest that radioiodine may be beneficial. Our approach outlined below is in agreement with the American Thyroid Association (ATA) guidelines on the role of postoperative radioiodine ablation (table 2) [3,4].
Low risk — We do not routinely administer radioiodine after lobectomy or total thyroidectomy to low-risk patients with differentiated thyroid cancer (table 1). This includes patients with:
●Unifocal cancer <1 cm without other high-risk features (eg, without distant metastases, vascular invasion, gross extrathyroidal extension, worrisome histologic subtypes), even in the presence of small-volume regional lymph node metastases (less than five lymph nodes measuring less than 2 mm)
●Multifocal cancer when all foci are <1 cm and there are no other high-risk features
●Intrathyroidal cancer in the 1 to 4 cm range without other high-risk features
Individual tumor- and patient-specific features may warrant radioiodine ablation in selected low-risk patients (table 2). As an example, we often administer low-dose radioiodine ablation (30 mCi) in low-risk patients with intrathyroidal tumors greater than 4 cm or follicular thyroid carcinomas with only one to three foci of vascular invasion. In addition, we do not disagree with the NCCN guidelines that note that an administered activity of 30 to 50 mCi may be considered for patients with 1 to 4 cm (T1a/T2) papillary thyroid cancer with small-volume N1a disease (fewer than five lymph node metastases <2 mm in diameter) and for patients with primary tumors <4 cm without distant metastases that demonstrate only minor extrathyroidal extension [5]. Depending on the clinical circumstances, radioiodine treatment in these situations may be reasonable to facilitate more complete initial staging and to simply follow-up.
This risk-adapted approach is supported by data from a randomized trial evaluating post-thyroidectomy radioiodine (1.1 GBq [30 mCi] after recombinant human TSH [rhTSH]) or no radioiodine therapy in 730 patients with low-risk differentiated thyroid cancer (multifocal pT1a with the sum of the longest diameters <2 cm, or PT1b, both with N0 or Nx, and without aggressive pathological subtypes or extrathyroidal extension (table 3)) that demonstrated no significant differences in any of the following outcomes at three years of follow-up [6]:
●Primary disease-related events (identification of residual or recurrent disease or an elevated level of thyroglobulin or thyroglobulin antibodies, 4.1 versus 4.4 percent in the no radioiodine group).
●ATA excellent response (table 4) rates (73 versus 74.1 percent).
●Quality-of-life scores related to anxiety, distress, and fear of recurrence.
Evaluation of retrospective observational data consistently shows no benefit of radioiodine in low-risk patients with regard to either overall recurrence rate or disease-specific mortality [7-11].
Intermediate risk — We administer radioiodine after total thyroidectomy in selected intermediate-risk patients depending upon specific tumor characteristics, including microscopic invasion into the perithyroidal soft tissue, clinically significant lymph node metastases outside of the thyroid bed, or other higher-risk features (eg, vascular invasion, more aggressive histologic subtypes such as tall cell, columnar cell, insular, or poorly differentiated histologies) when the combination of age, tumor size or multifocality, lymph node status, and individual histology predicts an intermediate to high risk of recurrence (table 1) or death (table 3) from thyroid cancer. In the absence of evidence supporting survival benefit for all of the factors listed, clinical judgment and an individualized approach to care are important [4].
Although microscopic minor extrathyroidal extension is considered an intermediate risk feature, we agree with the updated 2022 NCCN guidelines that minimal extrathyroidal extension alone is not an indication for radioiodine ablation or adjuvant therapy [5].
Postoperative serum thyroglobulin is a critical factor that should be routinely integrated into clinical decision-making. For example, in a retrospective cohort study, there was no difference in the five-year recurrence-free survival among intermediate-risk patients who did or did not receive radioiodine therapy when postoperative unstimulated serum thyroglobulin levels were <1 ng/mL [12].
There are limited data showing a benefit of radioiodine in intermediate-risk patients [3,13]. In a study using the National Cancer Database registry, which included 21,870 patients with intermediate-risk papillary thyroid cancer who had total thyroidectomy with or without radioiodine, patients who received radioiodine had improved overall survival (hazard ratio [HR] 0.71, 95% CI 0.62-0.82) [13].
In the National Thyroid Cancer Treatment Cooperative Study Group, a multicenter thyroid cancer registry that has analyzed the outcomes of nearly 5000 patients with differentiated thyroid cancer, multivariate analysis showed that radioiodine ablation was associated with improvement in overall survival in stage II patients (table 5), but this did not reach statistical significance (relative risk [RR] 0.67, 95% CI 0.36-1.28) [14].
High risk — We routinely treat high-risk patients with radioiodine after total thyroidectomy (table 2), including patients with distant metastases, macroscopic tumor invasion, and/or incomplete tumor resection with gross residual disease (table 1).
In the National Thyroid Cancer Treatment Cooperative Study Group, radioiodine was associated with improved overall survival in stage III patients (RR 0.66, 95% CI 0.46-0.98), with similar but nonsignificant improvement in stage IV (RR 0.70, 95% CI 0.46-1.10) (table 5) [14].
In addition, data prospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database showed benefit from radioiodine in patients older than 45 years with primary tumors >2 cm, with disease in the lymph nodes at initial diagnosis, and with distant metastatic disease [15].
The benefits and dose limits of iodine-131 (131-I) therapy for metastatic disease were evaluated in a retrospective analysis of 444 patients treated between 1953 and 1994 (analysis of whole-body iodine scans and conventional radiographs) [16]. Forty-three percent of the 295 patients with radioiodine uptake achieved resolution of radioiodine-avid metastases on iodine scan and negative conventional radiographs. Additional features of patients in this group included the following:
●They were more likely to be younger, with differentiated tumors
●96 percent of these patients were given cumulative doses of 100 to 600 mCi (3700 to 22,000 MBq)
●7 percent had a recurrence
●10-year survival was 92 percent in this group, compared with only 19 percent in patients who did not achieve resolution of the radioiodine-avid metastatic lesions
CONTRAINDICATIONS — Pregnancy and breastfeeding are absolute contraindications to radioiodine therapy [17]. Fetal thyroid tissue is functional by 10 to 12 weeks and could be destroyed by the radioiodine, resulting in cretinism. Radioiodine should only be administered if a woman has a negative pregnancy test 72 hours before treatment is given or if the possibility of pregnancy is excluded by a history of surgical sterilization in the patient.
There is increased sodium iodide symporter activity in estrogenized breast tissue, resulting in breast uptake of radioiodine. Breastfeeding should be stopped at least six to eight weeks prior to radioiodine therapy so as to reduce uptake of radioiodine by breast tissue. There are reports of utilization of dopamine agonist drugs such as cabergoline to decrease serum prolactin and hence shorten the time that is required before iodine-131 (131-I) can be administered safely to lactating women [18].
PATIENT PREPARATION — Radioiodine causes cytotoxicity by the emission of short path-length (1 to 2 mm) beta radiation. Radioiodine uptake is dependent upon adequate stimulation by thyroid-stimulating hormone (TSH) and is reduced by the presence of excess stable iodide. Therefore, whenever radioiodine imaging and treatment are planned, the patient should be instructed to avoid all iodine-containing medications and to limit dietary intake of iodine for at least one week (table 6). (See 'Low-iodine diet' below.)
In addition, the intravenous contrast used for computed tomography (CT) scans contains a large iodine load and may interfere with radioiodine scanning and therapy for several months. (See 'Recent iodine exposure' below.)
Choice of method for increasing TSH — Radioiodine uptake by thyroid tissue is stimulated by TSH. There are two methods for increasing TSH, thyroid hormone withdrawal or administration of recombinant human TSH (rhTSH [thyrotropin alfa]). We prefer:
●rhTSH for routine radioiodine remnant ablation (destruction of residual normal thyroid tissue) and follow-up scanning.
●rhTSH when radioiodine is given as adjuvant treatment (destruction of microscopic residual disease) in low- and intermediate-risk patients.
●Thyroid hormone withdrawal when radioiodine is given as therapy for known gross residual disease or as adjuvant treatment in high-risk patients.
However, we use rhTSH for such patients in whom severe hypothyroidism might be relatively contraindicated (eg, older adults, patients with depression, congestive heart failure, or severe sleep apnea), allowing them to remain on thyroid hormone therapy.
This approach is consistent with the American Thyroid Association (ATA) guidelines [3].
In randomized trials and a meta-analysis, short-term rates of successful remnant ablation were similar after withdrawal of thyroid hormone or after administration of rhTSH (91 to 100 percent) [19-26].
There are few long-term randomized trial data on recurrence and disease-specific survival to guide choice of preparation. Five-year follow-up data from a multicenter prospective randomized trial demonstrated that 98 percent of the patients had no evidence of persistent/recurrent disease, while structural disease was identified in 0.6 percent and biochemical evidence of persistent disease in 0.7 percent. Neither the method of preparation (rhTSH versus thyroid hormone withdrawal), nor the administered activity (30 versus 100 mCi [1.1 versus 3.7 GBq]), was associated with short-term biochemical or structural disease [27].
In a prospective study reporting 10-year follow-up data, outcomes were similar in patients treated with radioiodine (30 mCi [1.1 GBq]) after stimulation by rhTSH versus thyroid hormone withdrawal [28]. Similarly, a retrospective study with median follow-up of nine years demonstrated similar effectiveness of rhTSH and thyroid hormone withdrawal in low-, intermediate-, and high-risk patients [29].
In addition, two small prospective studies suggest that rhTSH-stimulated radioiodine therapy is effective in destroying microscopic metastatic disease, typically in cervical nodes or pulmonary micrometastases [30], and is associated with a similar five-year survival as thyroid hormone withdrawal in the setting of macroscopic radioiodine-avid distant metastases [31].
Thyroid hormone withdrawal — In the setting of 131-I treatment of residual tumor or metastatic disease, thyroid hormone withdrawal remains the standard approach to raising TSH levels for adequate radioiodine uptake. Thyroid hormone should be withdrawn three to four weeks prior to radioiodine therapy [3]. After thyroidectomy or cessation of T4 (levothyroxine) therapy, the patient's serum thyroxine (T4) concentration must decline sufficiently to allow the serum TSH concentration to rise to above 25 to 30 mU/L [32].
To minimize hypothyroid symptoms for patients withdrawing from thyroid hormone, our approach is to reduce the dose of oral T4 by 50 percent for four weeks and then discontinue the T4 for one week prior to administration of radioiodine. Serum TSH should be measured immediately before any 131-I is given to confirm that the concentration is high. One study found that with this approach, the majority of patients taking half-dose T4 achieved a serum TSH concentration of 25 to 30 mU/L by five weeks [33]. In addition, their hypothyroid symptoms were milder than a group of patients undergoing T3 (liothyronine) withdrawal.
Another strategy is to give the shorter-acting hormone T3 in doses of 25 mcg two to three times per day for the first two weeks after stopping T4 [34]. Lower doses (eg, 10 to 12.5 mcg two or three times per day) should be used in older patients and those with ischemic heart disease. After cessation of T3, the serum TSH concentration should rise to 25 to 30 mU/L within one to two weeks. Thus, the interval during which the patient receives no thyroid hormone is shortened.
One randomized trial comparing administration of placebo or T3 for three weeks following T4 withdrawal found no symptomatic benefit of T3 during thyroid hormone withdrawal and confirmed that a two- to three-week period of withdrawal was adequate time duration to see a sufficient rise in TSH to allow radioiodine ablation [35].
Recombinant human TSH — For patients treated with radioiodine for thyroid remnant ablation, hypothyroidism can be avoided altogether by administering rhTSH before administration of 131-I.
With this method, the patient continues their usual dose of T4; rhTSH (0.9 mg) is administered by intramuscular injection on two consecutive days, followed by administration of radioiodine on the day following the second injection (ie, the third day). Serum thyroglobulin (Tg) levels are obtained 72 hours after the second rhTSH injection (the fifth day) and a posttreatment whole-body scan is performed two to seven days after the radioiodine administration.
In patients in whom pretreatment (diagnostic) scanning is performed, the scanning dose is administered on the afternoon of the second rhTSH dose, and the diagnostic scan and therapy, if needed, are performed the next day. (See 'Pretreatment scanning' below.)
Rarely, the high serum TSH concentrations that occur after withdrawal of thyroid hormone stimulate rapid growth of persistent or metastatic thyroid cancer. Such rapid growth has also been described in patients given rhTSH [36]. (See 'Tumor swelling' below.)
rhTSH has no adverse cardiovascular effects [37]. If it is used, a two-dose regimen is preferable to a three-dose regimen for ease of administration and lower cost.
Low-iodine diet — To maximize uptake of radioiodine into thyroid cells, we suggest that patients follow a low-iodine diet for 7 to 10 days before and for one to two days after 131-I is administered (table 6) [38-40]. This suggestion is consistent with ATA guidelines [3].
In a systematic review of eight observational studies, dietary iodine restriction (<50 mcg daily) lasting anywhere from four days to four weeks prior to radioiodine administration compared with a normal diet reduced urinary iodine concentrations and increased 131-I uptake or lesional uptake [41]. In one retrospective study that assessed clinical outcomes, patients prescribed a low-iodine diet (24-hour urine iodine excretion 27±12 mcg) compared with controls (24-hour urine excretion 159±9 mcg) were more likely to have negative radioiodine uptake and Tg values <2 mcg/L when assessed six months after radioiodine treatment [42]. On the other hand, a subsequent retrospective study (not included in the meta-analysis) showed no relationship between urinary iodine excretion (range 25 to 1890 mcg/L, mean 132 mcg/L) and ablation success rates in a group of patients who were not routinely given a low-iodine diet [43]. Remnant ablation was unsuccessful in another retrospective study only when urinary iodine concentration was greater than 250 mcg iodine/g creatinine [44].
Recent iodine exposure — Radioiodine uptake by the thyroid remnant is reduced by the presence of excess circulating stable iodide. Thus, patients who have been exposed to high iodine loads (eg, iodinated contrast materials or medications high in iodine content, such as amiodarone) cannot have diagnostic radioiodine scans or receive radioiodine treatment until the iodine load is excreted.
Iodinated contrast is cleared from the blood after one month [45], but radioiodine treatment is usually delayed for two to three months to be certain that there is no interference with iodine-avid cancer. Twenty-four-hour urinary iodine measurements (or estimated 24-hour measurements based on spot urine iodine measurements corrected for urine creatinine) can be used to document depletion of excess iodine loads in such patients. Once the 24-hour urine iodine content falls to approximately 100 mcg/24 hours, patients can proceed with diagnostic radioiodine scans and radioiodine therapies.
The iodine load associated with amiodarone administration can persist for months to years after discontinuation of the drug. Plasma exchange has been used to decrease whole-body iodine content in select patients who have persistent iodine contamination for months to years after discontinuation of amiodarone [46]. Patients with distant metastases in whom the amiodarone cannot be discontinued should be treated as if they have radioiodine refractory metastatic disease. (See "Differentiated thyroid cancer: Overview of management", section on 'Management of persistent or recurrent disease'.)
Other strategies to increase uptake — Each of the strategies listed below have the potential to increase radioiodine uptake into thyroid cancer cells in properly selected patients but can be associated with risks that need to be carefully managed. Thus, these approaches are not recommended for routine clinical practice and are probably best considered and implemented for highly selected individual patients within the context of an experienced multidisciplinary thyroid cancer management team.
●Regimens to deplete body stores of iodine, such as the use of loop diuretics, or mannitol with strict low-iodine diets may increase uptake by tumor; however, there may also be a concomitant increase in total body irradiation [47].
●Lithium can prolong 131-I retention by thyroid tissue. In a small study of patients who had diagnostic 131-I scans before and then again after receiving lithium for one to two days, 131-I retention was higher and more prolonged during lithium administration in metastatic lesions and the thyroid remnants in most patients, so that the estimated 131-I dose to the metastases was higher [48]. Whether these findings will result in improved eradication of metastases remains to be determined.
●Inhibition of the mitogen-activated protein kinase (MEK) pathway with MEK inhibitors (selumetinib, trametinib, cobimetinib) or BRAF inhibitors (dabrafenib, or vemurafenib) have been reported to restore radioiodine sensitivity in 40 to 60 percent properly selected patients with radioactive iodine refractory thyroid cancer [49]. Ongoing studies are trying to define precisely which patients would be most likely to achieve a significant clinical benefit from these redifferentiation therapies based on clinical characteristics, histologic findings, and molecular characterization of the tumors. (See "Differentiated thyroid cancer refractory to standard treatment: Systemic therapy", section on 'Assessment for restoration of radioiodine uptake (redifferentiation)'.)
Pretreatment scanning
When to obtain — Diagnostic (pre-radioiodine treatment) whole-body scans for localization of uptake before remnant ablation, adjuvant treatment, or treatment of metastatic thyroid cancer are usually performed when the extent of residual disease cannot be determined from surgery and neck ultrasonography and when the presence of residual disease may alter the decision to treat with radioiodine or the administered activity [3]. However, even if the patient has no known persistent or metastatic disease, almost all patients have thyroid remnants (image 1), and therefore, an alternative approach is to omit the pretreatment diagnostic scan, administer empiric therapeutic doses of 131-I therapy, and obtain only a posttreatment scan [50]. (See 'Posttreatment scanning' below.)
No studies have demonstrated superior outcomes following one or another approach. The disadvantage of omitting the pretreatment scan is that those patients with metastases may be undertreated by a strategy that gives all patients the same initial dose of radioiodine. Furthermore, there are occasional patients whose thyroidectomy is so complete that there is no uptake seen on the pretreatment scan and who, therefore, would not benefit from radioiodine therapy. In one study of 355 scans, 53 percent of patients had findings on the pretreatment scan that might have altered management [51]. Omitting the pretreatment scan may be reasonable for patients with a very low risk of metastases in whom the goal is to ablate remnants.
Scanning dose — When pretreatment whole-body scanning is performed, low-dose, orally-administered activities of 2 to 5 mCi (74 to 185 MBq) 131-I should be used with whole-body imaging 48 to 72 hours later to identify thyroid tissue and metastases [52]. Alternatively, a 1.3 to 5 mCi (48 to 185 MBq) iodine-123 (123-I) scan can be performed with whole-body imaging 6 to 24 hours later. If present, the degree of uptake should be quantitated. Greater sensitivity for the detection of residual or metastatic tumor can be attained with the use of higher activities [53,54], but higher amounts (>5 to 10 mCi 131-I) could lead to "stunning," in which there is reduced uptake of the subsequent therapeutic radioiodine due to sublethal radiation delivered by the diagnostic dose [55,56]. Stunning may be the result of radiation-induced decrease in DNA synthesis as well as transcription of the sodium iodide symporter gene, as suggested by in vitro studies of porcine thyrocytes [57,58].
The importance of stunning may be overstated; one study found no difference in the success of subsequent treatment in patients who received 3 to 5 mCi (111 to 185 MBq) 131-I for scanning as compared with those not scanned before treatment [59]. A second study found no difference in the success rate of remnant ablation (negative iodine scan six to eight months later and undetectable Tg) when patients were scanned with 2 mCi (74 MBq) of 131-I versus 0.5 mCi (14.8 MBq) of 123-I before treatment [60]. The use of 123-I may be associated with a lower risk of stunning [61].
Scanning technique — Between one and seven days after administration of the diagnostic dose, whole-body scans are performed with a large field-of-view gamma-scintillation camera fitted with a high-energy parallel hole collimator. Spot images of the neck and other areas of uptake can be obtained using either the same equipment or a rectilinear scanner. In some institutions, quantitative dosimetry is performed to determine lesion uptake and to predict effective tumor radiation dose; however, this requires specialized equipment and software [62].
Because of the higher cost and shorter half-life of 123-I, most centers use 131-I (approximately 4 to 5 mCi) as the primary isotope for follow-up whole-body scan 6 to 12 months later. At our center, the initial diagnostic scan done prior to rhTSH ablation is done using 2 to 4 mCi of 123-I, while all other routine follow-up scans are done using 5 mCi of 131-I.
When rhTSH is used to ablate remnants, the standard protocol is either (1) to obtain only a posttreatment scan, or (2) to obtain a 24-hour 123-I scan on day 3 prior to administration of radioiodine ablation [63]. (See 'Recombinant human TSH' above.)
131-I SPECT/CT — Single-photon emission computed tomography/computed tomography (SPECT/CT) scanning provides significant advantages over radioactive iodine imaging using traditional, planar whole-body scan imaging [64,65]. SPECT/CT allows more precise localization and characterization of radioiodine-avid foci [64] and can significantly alter the initial assessment of risk with a resultant impact on initial clinical management [66].
123-I — Iodine-123 (123-I) may provide superior image quality when compared with 131-I for diagnostic scans [67,68]. Since 123-I is primarily a gamma emitter, it does not impair cellular function and should not cause stunning, but it is considerably more expensive than 131-I.
Findings — Between 75 and 100 percent of patients with thyroid cancer have 131-I uptake in the thyroid bed after thyroidectomy (image 2) [69]. Most often, this represents remnants of normal thyroid tissue rather than residual thyroid cancer [70]. In contrast, only approximately 50 percent of metastatic lesions in the lungs or bones concentrate 131-I (image 3) [71].
Combining results from multiple studies, there is probably no significant difference between papillary and follicular carcinomas in the frequency of detectable uptake by recurrent or metastatic disease [52]. However, certain histologic subtypes, such as oxyphilic follicular cancer (commonly called Hürthle cell cancer), the tall cell variant of papillary cancer, and poorly differentiated carcinomas, concentrate 131-I less often in metastatic sites. Older patients may also be less likely to have adequate uptake in metastases [62,71].
Scans performed during follow-up that show apparent distant metastases must be interpreted with caution. A few are false-positive scans due to physiologic uptake of the 131-I in the breast, salivary glands, or thymus [72]; false-positive scans can also occur with pathologic exudates, dilated hepatic ducts [73], or nonthyroid benign tumors [74].
RADIOIODINE DOSE (ACTIVITY)
●When the primary goal is to ablate residual normal thyroid tissue (remnant ablation), administered activities of 30 mCi (1.1 GBq) are typically used. Higher doses may be necessary for patients who have had less than a total thyroidectomy where a larger remnant is suspected [3].
●When the primary goal is to provide adjuvant treatment of subclinical micrometastatic disease, administered activities of 75 to 150 mCi are used, based on assessment of the individual's risk of having clinically significant microscopic residual disease.
●When the primary goal is to provide treatment of clinically apparent residual or metastatic thyroid cancer, administered activities of 100 to 200 mCi are typically used.
Remnant ablation — Radioiodine is administered using a fixed-activity (fixed-dose) regimen, typically 30 mCi (1.1 GBq) for remnant ablation [75-78]. Consistent with the 2015 American Thyroid Association (ATA) guidelines and the updated NCCN guidelines (2022 Version 2.2022), we choose the iodine-131 (131-I) dose based upon the goals of radioiodine administration and risk of recurrence/disease-specific mortality (table 2) [3,5]. NCCN guidelines recommend an administered activity of 30 to 50 mCi (following either recombinant human TSH (rhTSH) stimulation of thyroid hormone withdrawal) if RAI ablation is used for 1 to 4 cm (T1b/T2) tumors that are clinical N0 and have no other adverse pathologic, laboratory, or imaging features [5]. (See 'Patient selection' above.)
Many studies have attempted to determine an optimal dose of radioiodine for remnant ablation. In a 2013 meta-analysis of nine randomized trials, there was no difference between low activity (30 mCi [1.1 GBq]) and high activity (100 mCi [3.7 GBq]) for successful thyroid remnant ablation [79]. There were fewer adverse effects in the low-dose group. Other meta-analyses have reported similar findings [80-82]. These analyses are confounded by differences in the definition of successful ablation used in the various studies, the method of TSH stimulation, the adherence to a low-iodine diet, and the length of time between ablation and the follow-up diagnostic scan.
There are no randomized trials that evaluate long-term outcomes of patients treated with low or high radioiodine dose (activity). In retrospective studies, there was no difference in thyroid cancer recurrence after 5 and 14.7 years of follow-up in patients treated with low versus high radioiodine activity [83,84].
The controversy about the role of 131-I remnant ablation in general, particularly in patients with low-risk disease (ie, no soft tissue invasion and no distant metastases), is reviewed above. (See 'Low risk' above.)
Adjuvant treatment — Patients with intermediate-risk differentiated thyroid cancer are treated with 131-I to destroy both remnant normal thyroid tissue remaining after total thyroidectomy (remnant ablation), and subclinical microscopic foci of disease remaining after surgery (adjuvant treatment). (See 'Patient selection' above.)
For patients with intermediate-risk differentiated thyroid cancer who are treated with radioiodine to provide adjuvant treatment of subclinical microscopic residual disease, we administer between 75 and 150 mCi, usually between 75 and 100 mCi (2.8 to 3.7 GBq). The updated 2022 NCCN guidelines recommend using an administered activity of 50 to 150 mCi for adjuvant therapy, and 30 to 50 mCi could be considered for patients with primary tumors <4 cm without distant metastases that demonstrate only minor extrathyroidal extension or for patients with 1 to 4 cm (T1a/T2) papillary thyroid cancer with small-volume N1a disease (fewer than five lymph node metastases <2 mm in diameter) [5].
In retrospective analyses of patients with intermediate-risk differentiated thyroid cancer (microscopic extrathyroidal extension, lateral neck lymph node metastases, or other higher-risk features [eg, vascular invasion, more aggressive histologic subtypes such as tall cell, columnar cell, insular, or poorly differentiated histologies]), there was no significant difference in the rate of successful radioiodine ablation in patients receiving high (100 to 150 mCi [3.7 to 5.6 GBq]) versus low (30 mCi [1.1 GBq]) activities [85,86]. Another retrospective analysis compared 100, 150, and 200 mCi radioiodine adjuvant treatment and found that the administration of more than 100 mCi radioiodine was unlikely to improve response to therapy [87]. In another study, higher doses of radioiodine (>54 mCi) were associated with improved cause-specific survival in a cohort of patients older than age 45 years [88].
Macroscopic residual or metastatic disease — Patients with macroscopic residual postoperative disease in the thyroid bed or in local regional lymph nodes are usually treated with higher administered activities of 131-I.
Since rhTSH is not US Food and Drug Administration (FDA) approved as an adjunct to radioiodine therapy in the setting of gross residual disease, these patients are usually prepared with thyroid hormone withdrawal unless there are medical contraindications to iatrogenic hypothyroidism. (See 'Choice of method for increasing TSH' above.)
We suggest the following activities for patients with macroscopic residual or metastatic disease in patients less than 70 years old with normal renal function:
●150 mCi (5.6 GBq) 131-I to treat uptake in lymph nodes in the neck and mediastinum.
●150 to 200 mCi dose (5.6 to 7.5 GBq) for patients with pulmonary metastases. Repeated dose of 131-I over several years has been shown to be highly effective in the treatment of younger patients with small-volume pulmonary metastases [16].
●200 mCi (7.5 GBq) for patients with skeletal or other distant metastatic disease.
●Higher activities may be given to patients who have recurrent disease after previous therapy but should be based on dosimetry to ascertain their safety.
Empiric dosing regimens may exceed the maximum tolerable doses as predicted by dosimetry, especially in older adults [89,90]. As an example, in one study, a dose of 200 mCi (7.5 GBq) exceeded the maximum tolerable dose in only 8 percent of younger patients and over 22 percent of patients over age 70 years [89]. Therefore, doses should seldom exceed 150 mCi in patients 70 years or older unless guided by dosimetry studies. For patients with diffuse pulmonary metastases in whom pulmonary fibrosis could be a complication of radioiodine therapy, dosimetry can be used to limit the whole-body radioiodine retention to 80 mCi at 48 hours, which will minimize pulmonary damage [91].
In patients with renal failure or on hemodialysis, there are two dosing approaches to radioiodine therapy: a substantially lower dose of radioiodine followed by the patient's usual dialysis schedule, or a standard radioiodine dose followed by more frequent dialysis [92,93].
MONITORING AFTER RADIOIODINE
Posttreatment scanning — Tumor uptake of the treatment dose of radioiodine should be confirmed by performing a whole-body scan two to eight days after radioiodine treatment. In approximately 6 to 13 percent of these posttreatment scans, foci of uptake that were not seen on the corresponding low-dose iodine-131 (131-I) pretherapy scan are seen [56,94,95]. However, in only 10 percent of cases does the posttreatment scan reveal new sites of uptake that significantly alter the patient's prognosis and were not known to exist by other means, such as radiography or surgery [56].
Similarly, in a comparison of diagnostic iodine-123 (123-I) scans with posttreatment scans, additional areas of uptake were found in 6 percent of patients scanned for the first time, 18 percent of patients scanned for the second time, and 44 percent of patients with high serum thyroglobulin (Tg) concentrations and negative diagnostic scans; however, treatment was altered in few patients [96].
Repeat scanning and treatment — In the absence of evidence for possible or proven persistent disease (abnormal serum thyroglobulin, rising antithyroglobulin antibodies, indeterminate/suspicious structural findings), we seldom recommend routine follow-up whole-body radioactive iodine scans for routine surveillance. Rather, follow-up radioactive scans (usually 131-I) are used to localize and characterize radioiodine avidity in patients with biochemical or structural findings that could indicate persistent/recurrent disease (see "Differentiated thyroid cancer: Overview of management", section on 'Monitoring response to therapy'). If significant uptake is seen within the thyroid bed (>1 percent), one more treatment with 100 to 150 mCi (3.7 to 5.6 GBq) of 131-I may be given to complete the ablation; generally, we are reluctant to repeat treatment of minor thyroid bed uptake (<1 percent) in the absence of clear evidence of residual cancer by other imaging techniques, such as ultrasound.
If there is uptake outside of the thyroid bed, we give doses of 131-I appropriate to the site of uptake. Prior to incorporating stimulated Tg testing into diagnostic algorithms, a common approach was to continue scanning to obtain two successive negative 131-I scans, which predicted a 97 percent 10-year relapse-free survival compared with 91 percent after only one negative scan [97].
For each scan, the patient's serum TSH concentration must be high enough to maximize the uptake of 131-I by any residual thyroid tissue. This may be achieved with thyroid hormone withdrawal or by administration of rhTSH [98]. (See 'Choice of method for increasing TSH' above.)
We suggest using rhTSH support in all patients who require radioiodine scanning, unless they are thought to be likely in need of subsequent radioiodine therapy that is preferably done using thyroid hormone withdrawal. Imaging is usually done at 48 hours using the rhTSH approach or at 48 to 72 hours following thyroid hormone withdrawal.
COMPLICATIONS — Acute and chronic complications of radioiodine can limit the usefulness of this treatment. In the short term, radiation thyroiditis, painless neck edema, sialadenitis, and tumor hemorrhage or edema occur in 10 to 30 percent of patients, particularly when higher doses are given [52,99]. Nausea after iodine-131 (131-I) administration can be treated with oral prochlorperazine (10 mg). To promote more rapid clearance of radioiodine from the urinary bladder, patients are encouraged to drink large volumes [100].
Laxatives that do not contain iodine should be given if the patient has not had a bowel movement within 12 to 24 hours after administration of the radioiodine (to purge radioiodine from the colon). Some clinicians routinely give laxatives to everyone to reduce colonic exposure.
Sialadenitis — Most patients treated with 131-I experience dose-related reductions in salivary flow [101], and some experience transient decreased or altered sense of taste. Although previously thought to reduce the risk of sialadenitis, the use of lemon candies in the first 24 hours was associated with higher rates of sialadenitis, hypogeusia, and xerostomia due to increased hematogenous delivery of radioiodine to salivary gland tissue [102,103]. Therefore, the use of lemon candies or other sialogogues as a means to reduce radiation sialadenitis remains controversial [102-104]. Since radioiodine is washed out rapidly after the administration of lemon juice [104], additional studies are needed to determine optimal timing of administration to reduce delivery of radioiodine to the salivary glands and provide optimal washout.
Nonsteroidal antiinflammatory drugs (NSAIDs) are usually adequate for relieving symptoms of acute sialadenitis; glucocorticoids are rarely required but are effective in more severe cases. Small series have demonstrated a potential therapeutic role for sialoendoscopy in patients with chronic parotid sialadenitis caused by ductal stenosis, mucous plugs, and fibrosis in Stensen duct following radioactive iodine therapy [105,106].
Amifostine, which functions as a radioprotectant by scavenging radiation-induced free radicals in nonmalignant tissue, has been advocated to reduce the frequency and severity of sialadenitis after radioiodine therapy [107,108]. However, it is possible that amifostine would protect normal thyroid tissue from radiation-induced damage [109], and therefore, its use should probably be limited to the occasional patient who requires multiple radioiodine administrations for metastatic disease rather than for adjuvant remnant ablation. Fewer side effects have been reported with subcutaneous administration (500 mg) before radioiodine ingestion [108].
In a related observation, dental caries and teeth extraction were markedly higher in patients who developed postradioiodine xerostomia [110], and patients should be advised about proper oral hygiene and regular dental care. (See "Management of late complications of head and neck cancer and its treatment", section on 'Salivary gland damage and xerostomia'.)
Secondary malignancy — An excess risk of secondary malignancies has been reported after radioiodine therapy for thyroid cancer [99,111,112], although the data are heterogeneous and the quality of the evidence is generally low [113,114]. Given the presence of sodium iodide symporters in salivary glands and estrogenized breast tissue and the gastrointestinal and urinary routes of excretion of radioiodine, salivary gland, breast, bladder, and gastrointestinal cancers can be plausibly hypothesized to occur more frequently in thyroid cancer patients treated with radioiodine [115-119]. The risk of leukemia is also increased, with a reported cumulative incidence per 100,000 person-years of approximately 20 to 30 [113,120]. The risk of leukemia is considerably lower when the total blood dose per treatment is less than 100 mCi [120]. The risk of secondary malignancy requires a careful analysis of the risk versus benefit of radioiodine treatment in patients with low-risk thyroid cancer and of additional radioiodine therapies in patients with persistent or recurrent thyroid cancer [121].
In a report of 6840 patients treated for thyroid cancer in Sweden, Italy, and France, 62 percent received radioiodine therapy (mean cumulative activity 162 mCi [6.0 GBq]) [122]. Secondary malignancies that occurred with significantly increased risk included bone and soft tissue (relative risk [RR] 4), female genital organs (RR 2.2), central nervous system (RR 2.2), and leukemia (RR 2.5). A dose-response relationship was seen between the administered activity and the risk for solid malignancies as well as leukemia. Although breast cancer was more commonly diagnosed in women treated for thyroid cancer, no relationship was identified between radioiodine and breast disease. Another retrospective cohort study also did not show a significant increase in the incidence of breast cancer among women treated with radioiodine therapy [123].
In an analysis of patients in the National Cancer Institute (NCI)'s Surveillance, Epidemiology, and End Results (SEER database) who had low-risk (T1N0) well-differentiated thyroid cancer, the excess absolute risk was 4.6 cases of secondary malignancies per 10,000 person-years [124]. Secondary malignancies with significantly elevated risk due to radioiodine were salivary gland malignancies and leukemia (standardized incidence ratios 11.13 and 5.68, respectively). During the 35-year study period, the rate of radioiodine use in patients with low-risk well-differentiated thyroid cancer increased from 3.3 to 38.1 percent.
Because of the known relationship between ionizing radiation and myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), the relationship between initial therapies and the risk of subsequently being diagnosed with MDS/MPN was examined in 148,215 well-differentiated thyroid cancer patients in the SEER database (54 percent thyroidectomy and 46 percent thyroidectomy and radioactive iodine therapy). Radioiodine therapy was associated with a statistically significant increase in MDS and MPN diagnosed two to three years after treatment [125,126]. While data on administered radioiodine activities were not available, patients with clinical features more likely to have received higher activities of radioiodine demonstrated an increased risk of MDS, suggesting that a dose-response effect could be present.
The magnitude of risk of secondary malignancies (absolute risk) appears to be small. As an example, in an analysis of the 36,311 pediatric and young adult patients with differentiated thyroid cancer, 1524 patients were diagnosed with a second solid malignancy (median follow-up 15.6 years) and 146 patients were diagnosed with a second hematologic malignancy (median follow-up 13 years) [127].
●The 20-year cumulative incidence of a second solid malignancy was 5.6 percent for radioiodine-treated patients compared with 5 percent for those not treated with radioiodine and at 30 years increased to 12.5 versus 10.2 percent.
●The 5-year cumulative incidence rate of second hematologic malignancies was 0.10 percent for radioiodine-treated patients and 0.05 percent for those not treated with radioiodine and, at 20 years, increased to 0.6 percent and 0.37 percent.
There is lower total body radiation exposure in patients prepared with recombinant human TSH (rhTSH) compared with thyroid hormone withdrawal, due to the more rapid clearance of radioiodine from euthyroid versus hypothyroid patients. In one study, the frequency of translocations in peripheral lymphocytes after radioiodine was higher in patients prepared by withdrawal compared with those prepared with rhTSH [128].
Gonadal function and fertility — Transient oligospermia and decreases in ovarian function may occur, but subsequent infertility is rare except after high doses [129-134]:
●In a study of men receiving less than 150 mCi (5.5 GBq) of radioiodine, there was a transient rise in follicle-stimulating hormone (FSH) but no oligospermia or change in serum testosterone levels [130]; one-third of men who received 350 to 750 mCi (13 to 27.7 GBq) developed transient oligospermia. A systematic review concluded that biochemical evidence of gonadal damage can be seen for up to 18 months after radioiodine treatment, but effects on fertility and offspring were not identified [135].
●Transient amenorrhea for one to four months occurs in roughly 10 to 25 percent of women treated with radioiodine [132]. In a study of women who had received 131-I therapy for thyroid cancer before age 45 years, menopause occurred on average 1.5 years earlier than in women with nodular goiter treated with equivalent doses of T4 (levothyroxine) [131].
In a subsequent study of 2360 women diagnosed with differentiated thyroid cancer at ages 15 to 39 years, there was no difference in the cumulative incidence of birth (maximum follow-up 14.5 years) in women who did or did not receive radioiodine (30 versus 29 percent, respectively) [134].
●Several studies now demonstrate that radioiodine therapy is associated with a statistically significant and sustained decline in anti-müllerian hormone (AMH), a measure of ovarian reserve [136-141]. Even though AMH levels were somewhat lower, pregnancy-related outcomes did not differ between patients treated with radioiodine and either normal controls or thyroid cancer patients managed without radioiodine, indicating that infertility is uncommon despite the reduction in AMH levels [137,138].
●Genetic and chromosomal abnormalities in children due to parental exposure to 131-I probably occur in only 1 percent of live births after cumulative administered doses of 500 mCi (18.500 GBq) and even less frequently after lower doses [132,133,142].
Nasolacrimal duct obstruction — Nasolacrimal duct obstruction, presenting as epiphora (excessive tearing), has been reported to occur after as low an administered activity as 100 mCi [143] and can be a cause of a false-positive radioiodine scan in the orbit [144].
Tumor swelling — As noted above, tumor swelling can occur due to significant serum TSH elevations after thyroid hormone withdrawal. After rhTSH administration, tumor swelling resulting in airway obstruction, bone pain, or neurologic symptoms may occur within hours. When patients with known or suspected lesions in confined spaces are exposed to TSH increases, whether after thyroid hormone withdrawal or rhTSH, meticulous clinical attention is necessary. Dexamethasone 8 mg twice a day or prednisone 60 mg daily for one to two days before and tapering over several weeks has been shown to prevent adverse reactions related to tumor swelling [145].
RADIATION SAFETY — In 2011, the American Thyroid Association (ATA) published recommendations on radiation safety for patients, families, caregivers, and the public after radioiodine therapy [17]. The recommendations are based upon clinical experience and available data. However, data on long-term outcomes are limited. The recommendations are in keeping with Nuclear Regulatory Commission (NRC) regulations and the principle of reducing radiation exposure to levels that are as low as reasonably achievable.
Patient release criteria — According to NRC regulations, a patient treated with iodine-131 (131-I) may be released from the care of the treating clinician as long as the radiation exposure to another individual caring for the patient will not exceed 5 millisieverts (mSv, 500 mrem) per year and the exposure to the public, a child, or a pregnant woman will not exceed 1 mSv (100 mrem) in one year [146,147]. Radiation exposure can be calculated in mrem or mSv using dose rate meters or a total effective dose equivalent (TEDE) table. The calculation of the TEDE takes into account patient-specific information such as the administered 131-I activity, the physical and biological half-life of the 131-I, and the projected duration of exposure time for family members or caregivers. Dose rates are established for a distance of 1 m (approximately three feet) from the radiation source (ie, the patient). Patients receiving a dose of 150 mCi (5550 MBq) for thyroid cancer can typically be released without exceeding dose limits [17,148]. When the TEDE exceeds NRC regulations and/or when patients are unable to comply with posttreatment precautions, inpatient 131-I dosing is necessary. A Radiation Safety Officer will generally oversee radiation safety calculations and precautions.
Posttreatment precautions — Patients who receive radioiodine have the potential to expose their home and household contacts to very low levels of radiation via saliva, urine, or radiation emitting from their body. To ensure the safety of family members, caregivers, and other individuals, several precautions are recommended. We agree with ATA guidelines as described below [17].
Safety for the general public and household members — Treated patients should be given patient-specific advice on the necessary precautions to reduce radiation exposure (table 7). The treated patient should remain ≥1.8 m (6 feet) away from family members, caregivers, and the general public as much as possible for approximately 24 hours after treatment. Adult caregivers may be closer than 1 m (3 feet) for brief intervals. In general, the treated patient should be instructed to avoid public transportation and extended time in public places and should not stay overnight in a hotel or motel within 24 hours of 131-I treatment.
To protect household members from radiation exposure, the treated patient should avoid the following during the restricted period:
●Sleeping in the same bed with another adult, pregnant woman, infant, or child
●Sexual contact
●Kissing
●Sharing cups, utensils, towels, razors, toothbrushes
The duration of the restricted period depends upon the dose received, amount of thyroid tissue, and rate of clearance. As an example, treated patients should avoid sleeping in the same bed with an adult for four days and for up to three weeks with a pregnant partner, infant, or child after treatment with 200 mCi (7400 MBq). The restricted period is calculated individually for each treated patient (table 8).
There are few long-term data to assess the protective benefits of these precautions. In a study of 30 patients with thyroid cancer who received 75 to 150 mCi (2.775 to 5.550 GBq) of 131-I as outpatients, exposure of family members was minimal when precautions were followed [149]. Patients were instructed to sleep alone, drink fluids liberally, and avoid prolonged close personal contact with family members for two days after treatment. Surveillance of family members and pets demonstrated that doses to household members were well below the limit (5 mSv) mandated by NRC regulations.
Personal hygiene — 131-I is renally excreted, and excretion is maximal during the first 48 hours after treatment. Patients should stay well hydrated (3 to 4 L of fluid daily) and void frequently. To avoid personal or caregiver contamination, patients should be meticulous in their personal hygiene, wiping any surfaces that may become contaminated with urine, stool, vomitus, blood, or perspiration for 48 hours after treatment (table 7). For 48 hours after therapy, men should sit when urinating. Exercise equipment should be wiped with flushable or disposable wipes. Exercise and bed clothes can be laundered in a washing machine. Dishes and utensils can be washed by hand or in a dishwasher. Flushable waste can be flushed down the toilet. Non-flushable waste (ie, incontinence pads) should be disposed of in a plastic trash bag devoted to radiation waste. Caregivers should wear disposable plastic gloves during clean-up. Radiation waste bags can be returned to the nuclear medicine facility one to two weeks after treatment or stored in the household (6 feet away from people or animals) for 80 days. After 80 days, radiation-related trash can be disposed of with regular household trash.
International travel — Low levels of 131-I activity (0.0003 mCi [0.01 MBq]) can be picked up by radiation detection systems at airports or international borders. Treated patients may trigger alarms for as long as 95 days posttherapy. Thus, patients who are traveling within three to four months of receiving 131-I require documentation specifying the date of treatment, type and dose of radionuclide, the treating facility, and contact information for the treating clinician.
Future pregnancy — In female thyroid cancer patients, pregnancy should generally be delayed for at least six months after radioiodine therapy to ensure that additional diagnostic imaging or additional radiation treatment is not required. In men, it seems reasonable to delay attempts to produce pregnancy for a period of three to four months to allow recovery of the transient oligospermia that may follow radioiodine therapy. However, in some men, full fertility may not be restored until one year or more after treatment, especially in men receiving high cumulative doses of radioiodine (>350 mCi) [135].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Thyroid nodules and cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Low-iodine diet (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Goals – Radioiodine is administered after thyroidectomy in patients with differentiated thyroid cancer to provide one of the following (see 'Goals' above):
•Remnant ablation – The primary goal is destruction of residual presumably benign thyroid tissue to facilitate initial staging and follow-up studies.
•Adjuvant treatment – The primary goal is destruction of subclinical tumor deposits that may or may not be present after surgical resection of all known primary tumor tissue and metastatic foci.
•Treatment of known disease – The primary goal is destruction of known disease evidenced by either abnormal thyroglobulin values or structural findings.
●Patient selection
•Low risk – For low-risk patients with unifocal tumors <1 cm without other high-risk features, we recommend against routine radioiodine ablation or adjuvant treatment (Grade 1B), owing to the absence of a proven benefit on either disease-free survival or recurrence. (See 'Low risk' above.)
•Intermediate risk – For selected intermediate-risk patients (microscopic invasion into the perithyroidal soft tissue; documented lymph node metastases outside of the thyroid bed; vascular invasion; more aggressive histologic subtypes, such as tall cell, columnar cell, insular, or poorly differentiated histologies) (table 1), we suggest postoperative radioiodine as remnant ablation or adjuvant treatment (Grade 2C). (See 'Intermediate risk' above.)
•High risk – For high-risk patients (table 1 and table 2), including those with distant metastases, macroscopic tumor invasion, and/or incomplete tumor resection with gross residual disease, we recommend postoperative radioiodine therapy (Grade 1B). (See 'High risk' above.)
●Patient preparation
•rhTSH – To prepare for radioiodine remnant ablation or diagnostic (pretreatment imaging), we suggest recombinant human thyroid-stimulating hormone (rhTSH [thyrotropin alfa]) for most patients without known distant metastases to raise serum TSH levels for effective scanning and therapeutic purposes (Grade 2B). Thyroid hormone withdrawal is an alternative option. (See 'Recombinant human TSH' above.)
•Low-iodine diet – We suggest that patients follow a low-iodine diet for 7 to 10 days before radioiodine is given for scanning or treatment purposes (Grade 2C). (See 'Low-iodine diet' above.)
●Radioiodine dose – The radioiodine dose (activity) depends on the purpose of administration (remnant ablation, adjuvant treatment, treatment of clinically apparent macroscopic disease). (See 'Radioiodine dose (activity)' above.)
●Radiation safety – To protect household members from radiation exposure, the treated patient should avoid sleeping in the same bed with another adult, pregnant person, infant, or child; sexual contact; kissing; and sharing cups, utensils, towels, razors, and toothbrushes during the restricted period (table 8). The duration of the restricted period depends upon the dose received, amount of thyroid tissue, and rate of clearance. (See 'Radiation safety' above.)
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