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Background: Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome. Methods: A systematic review and meta-analysis of all reports published before February 13, 2020, were performed using PubMed, Web of Science, OVID MEDLINE, and Embase. Proportion of patients achieving nonhyperthyroid status was the primary outcome. Secondary outcomes were proportion of patients who were specifically euthyroid or hypothyroid. A random-effects meta-analysis of proportions was performed for primary and secondary outcomes, and the impact of the radiation absorbed dose on treatment outcome was assessed through meta-regression. The study is registered with PROSPERO (CRD42020175010). Results: A total of 1122 studies were identified of which 15, comprising 2303 Graves' disease patients, were eligible for the meta-analysis. A strong association was found between radiation absorbed dose and nonhyperthyroid and hypothyroid outcomes (odds ratio [OR] = 1.11 [95% confidence interval {CI} 1.08–1.14] and OR = 1.09 [CI 1.06–1.12] per 10 Gy increase). Higher rates of euthyroid outcome were found for radiation absorbed doses within the range 120–180 Gy when compared with outside this range (n = 1172, OR = 2.50 [CI 1.17–5.35], p = 0.018). A maximum euthyroid response of 38% was identified at a radiation absorbed dose of 128 Gy. Conclusions: The presented radiation absorbed dose–response relationships can facilitate personalized treatment planning for radioiodine treatment of patients with Graves' disease. Further studies are required to determine how patient-specific covariates can inform personalized treatments.

Background: Refining the risk of malignancy in patients presenting with thyroid nodules with indeterminate cytology (IC) is a critical challenge. We investigated the performances of 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) to predict malignancy. Methods: Between May 2016 and March 2019, 107 patients presenting with a thyroid nodule ≥15 mm with IC and eligible for surgery were included in this prospective study. Head-and-neck PET/CT acquisitions were performed 20 and 60 minutes after injection of 1.5 MBq/kg of FCH. PET/CT acquisition was scored positive when maximal standardized uptake value in the IC nodule was higher than in the thyroid background. Pathology was the gold standard for diagnosis. Results: At pathology, 19 (18%) nodules were malignant, 87 were benign, and one was a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Sensitivity, specificity, accuracy, positive-predictive value (PPV), and negative-predictive value (NPV) of FCH PET/CT in detecting cancer or NIFTP were 90%, 50%, 55%, 29%, and 96% at 20 minutes and 85%, 49%, 67%, 28%, and 94% at 60 minutes, respectively. Higher specificity (58% vs. 33%, p = 0.01) was observed in nononcocytic (n = 72) than in oncocytic IC nodules (n = 35). The pre-PET/CT probability of cancer or NIFTP in Bethesda III–IV nodules was 11% and the post-PET/CT probability was 19% in PET-positives and 0% in PET-negatives. In retrospective analysis, 42% of surgeries would have been unnecessary after PET/CT and 81% before (p

Background: Whether radioactive iodine ((131)I) treatments for differentiated thyroid cancer should be performed as an outpatient or inpatient remains controversial. The objective of this study was to survey selected aspects of radiation safety of patients treated with (131)I for differentiated thyroid cancer as an outpatient. Methods: An e-mail invitation was sent to over 15,000 members of ThyCa: Thyroid Cancer Survivors' Association, Inc. to complete a web-based survey on selected aspects of radiation safety regarding their last outpatient (131)I treatment. Results: A total of 1549 patients completed the survey. Forty-five percent (699/1541) of the respondents reported no discussion on the choice of an inpatient or outpatient treatment. Moreover, 5% (79/1541) of the respondents reported that their insurance company made the decision. Survey respondents recalled receiving oral and written radiation safety instructions 97% (1459/1504) and 93% (1351/1447) of the time, respectively. Nuclear medicine physicians delivered oral and written instructions to 54% (807/1504) and 41% (602/1462) of the respondents, respectively. Eighty-eight percent (1208/1370) of the respondents were discharged within 1 hour after receiving their (131)I treatment, and 97% (1334/1373) traveled in their own car after being released from the treating facility. Immediately post-therapy, 94% (1398/1488) of the respondents stayed at their own home or a relative's home, while 5% (76/1488) resided in a public lodging. The specific recommendations received by patients about radiation precautions varied widely among the respondents. Ninety-nine percent (1451/1467) of the respondents believed they were compliant with the instructions. Conclusion: This is the largest, patient-based survey published regarding selected radiation safety aspects of outpatient (131)I treatment. This survey suggests several concerns about radiation safety, such as the decision process regarding inpatient versus outpatient treatment, instructions about radiation safety, transportation, and lodging after radioiodine therapy. These concerns warrant further discussion, guidelines, and/or policies.

Background: (131)I treatment (tx) of differentiated thyroid cancer (DTC) is associated with hematopoietic toxicity. It was hypothesized that metformin could have radioprotective effects on bone-marrow function. The objective was to determine whether metformin prevents (131)I-induced changes in complete blood counts (CBC) in patients with DTC. Methods: A retrospective analysis was performed of CBC values in DTC patients who were (40 patients: metformin group) or were not taking metformin (39 patients: control group) at the time of administration of (131)I. Repeated measures analysis of variance was used for the analysis of the differences in the averages of CBC that were documented at baseline and at 1, 6, and 12 months post (131)I tx. Results: The groups were comparable in terms of age, sex, stage of DTC, (131)I dose administered, and baseline CBC values. In the control group, the decrease in white blood cells (WBC) was 35.8% (p

Initial management recommendations of papillary thyroid carcinoma (PTC) are very dependent on preoperative studies designed to evaluate the presence of PTC with aggressive features. The purpose of this study was to evaluate whether diffusion-weighted magnetic resonance imaging (DW-MRI) before surgery can be used as a tool to stratify tumor aggressiveness in patients with PTC.In this prospective study, 28 patients with PTC underwent DW-MRI studies on a three Tesla MR scanner prior to thyroidectomy. Due to image quality, 21 patients were finally suitable for further analysis. Apparent diffusion coefficients (ADCs) of normal thyroid tissues and PTCs for 21 patients were calculated. Tumor aggressiveness was defined by surgical histopathology. The Mann-Whitney U test was used to compare the difference in ADCs among groups of normal thyroid tissues and PTCs with and without features of tumor aggressiveness. Receiver operating characteristic (ROC) analysis was performed to assess the discriminative specificity, sensitivity, and accuracy of and determine the cutoff value for the ADC in stratifying PTCs with tumor aggressiveness.There was no significant difference in ADC values between normal thyroid tissues and PTCs. However, ADC values of PTCs with extrathyroidal extension (ETE; 1.53±0.25×10(-3) mm2/s) were significantly lower than corresponding values from PTCs without ETE (2.37±0.67×10(-3) mm2/s; p0.005). ADC values identified 3 papillary carcinoma patients with extrathyroidal extension that would have otherwise been candidates for observation based on ultrasound evaluations. The cutoff value of ADC to discriminate PTCs with and without ETE was determined at 1.85×10(-3) mm2/s with a sensitivity of 85%, specificity of 85%, and ROC curve area of 0.85.ADC value derived from DW-MRI before surgery has the potential to stratify ETE in patients with PTCs.

Micro-single-photon emission computed tomography (SPECT) provides a noninvasive way to evaluate the effects of genetic and/or pharmacological modulation on sodium-iodide symporter (NIS)-mediated radionuclide accumulation in mouse thyroid and salivary glands. However, parameters affecting image acquisition and analysis of mouse thyroids and salivary glands have not been thoroughly investigated. In this study, we investigated the effects of region-of-interest (ROI) selection, collimation, scan time, and imaging orbit on image acquisition and quantification of thyroidal and salivary radionuclide accumulation in mice.The effects of data window minima and maxima on thyroidal and salivary ROI selection using a visual boundary method were examined in SPECT images acquired from mice injected with (123)I NaI. The effects of collimation, scan time, and imaging orbit on counting linearity and signal intensity were investigated using phantoms filled with various activities of (123)I NaI or Tc-99m pertechnetate. Spatial resolution of target organs in whole-animal images was compared between circular orbit with parallel-hole collimation and spiral orbit with five-pinhole collimation. Lastly, the inter-experimental variability of the same mouse scanned multiple times was compared with the intra-experimental variability among different mice scanned at the same time.Thyroid ROI was separated from salivary glands by empirically increasing the data window maxima. Counting linearity within the range of 0.5-14.2 μCi was validated by phantom imaging using single- or multiple-pinhole collimators with circular or spiral imaging orbit. Scanning time could be shortened to 15 minutes per mouse without compromising counting linearity despite proportionally decreased signal intensity. Whole-animal imaging using a spiral orbit with five-pinhole collimators achieved a high spatial resolution and counting linearity. Finally, the extent of inter-experimental variability of NIS-mediated radionuclide accumulation in the thyroid and salivary glands by SPECT imaging in the same mouse was less than the magnitude of variability among the littermates.The impacts of multiple variables and experimental designs on micro-SPECT imaging and quantification of radionuclide accumulation in mouse thyroid and salivary glands can be minimized. This platform will serve as an invaluable tool to screen for pharmacologic reagents that differentially modulate thyroidal and salivary radioiodine accumulation in preclinical mouse models.

Background: Dietary iodine is often restricted before radioactive iodine (RAI) scanning or treatment of welldifferentiated thyroid cancer. Our objective was to examine the impact of a low-iodine diet (LID) before RAI treatment or scanning on the following outcomes: (i) the efficacy of thyroid remnant ablation (or residual disease elimination), (ii) urinary iodine measurements, (iii) RAI kinetics, and (iv) long-term thyroid cancer outcomes. Methods: We performed a systematic review of the English literature. We searched four electronic databases and conducted a hand search. Two reviewers independently screened citations and reviewed full-text articles and reached consensus on included articles. Two reviewers independently abstracted data. Results: We reviewed 76 abstracts or citations and 26 full-text articles. Eight studies were included in the review. The most commonly studied diets allowed � 50mg/day of iodine for 1‐2 weeks. In one study, 6-month successful remnant ablation rates were higher in patients following an LID than in controls. However, in another study, there was no significant benefit of an LID. LIDs reduce urinary iodine measurements and appear to increase I-131 uptake or lesional radiation compared to regular diets. No studies have examined long-term recurrence or mortality rates. Conclusions: Given that LIDs reduce urinary iodine measurements, increase I-131 uptake, and possibly improve efficacy of I-131 treatment, we currently favor the use of a 1‐2-week LID before I-131 therapy or scanning. However, more research is needed to clarify the role of this dietary intervention.

Background: Thyroid nodules are a common finding in the general population, and their detection is increasing with the widespread use of ultrasound (US). Thyroid cancer is found in 5–15% of cases depending on sex, age, and exposure to other risk factors. Some US parameters have been associated with increased risk of malignancy. However, no characteristic seems sufficiently reliable in isolation to diagnose malignancy. The objective of this meta-analysis was to evaluate the diagnostic performance of US features for thyroid malignancy in patients with unselected thyroid nodules and nodules with indeterminate fine-needle aspiration (FNA) cytology. Methods: Electronic databases were reviewed for studies published prior to July 2012 that evaluated US features of thyroid nodules and reported postoperative histopathologic diagnosis. A manual search of references of review and key articles, and previous meta-analyses was also performed. A separate meta-analysis was performed including only nodules with indeterminate cytology. Analyzed features were solid structure, hypoechogenicity, irregular margins, absence of halo, microcalcifications, central vascularization, solitary nodule, heterogeneity, taller than wide shape, and absence of elasticity. Results: Fifty-two observational studies (12,786 nodules) were included. Nine studies included nodules with indeterminate cytology as a separate category, comprising 1851 nodules. In unselected nodules, all US features were significantly associated with malignancy with an odds ratio varying from 1.78 to 35.7, and microcalcifications, irregular margins, and a taller than wide shape had high specificities (Sp; 87.8%, 83.1%, 96.6%) and positive likelihood ratios (LHR; 3.26, 2.99, 8.07). Absence of elasticity was the single feature with the best diagnostic performance (sensitivity 87.9%, Sp 86.2%, and positive LHR 6.39). The presence of central vascularization was the most specific US feature in nodules with indeterminate cytology (Sp 96% and positive LHR 2.13). Conclusions: US features in isolation do not provide reliable information to select nodules that should have a FNA performed. A combination of US characteristics with higher likelihood ratios and consequently with higher post-test probabilities of malignancy—microcalcifications, or a taller than wide shape, or irregular margins, or absence of elasticity—will probably identify nodules with an increased risk for malignancy. Further studies are required to standardize elastography techniques and evaluate outcomes, especially in nodules with an indeterminate cytology.

The role for pre-thyroidectomy (pre-Tx) imaging with F-18 flurodeoxyglucose (FDG) positron emission tomography (PET), FDG PET-computed tomography (CT), in differentiated thyroid cancer is controversial as is the significance of positive and negative FDG uptake in this setting. We reviewed the records of patients with papillary thyroid carcinoma (PTC) who had pre-Tx FDG PET-CT to determine whether FDG uptake was associated with features noted on pre-Tx ultrasonography (US) and parameters determined after post-Tx.Patients were selected for a retrospective review of their records if they had a total Tx with central lymph node dissection for PTC and pre-Tx FDG PET-CT and US between 2006 and 2009. Sixty patients who met these criteria were studied. Patients who had a history of head and neck irradiation, surgery, or sclerotherapy with ethanol in the last 3 months were excluded. The clinicopathologic factors-age, sex, size, tumor-node-metastasis (TNM) staging, the presence of extrathyroidal extention, multifocality, cervical lymph node metastases (CLNM), Hashimoto thyroiditis, and US characteristics-were evaluated to determine whether they were associated with positive pre-Tx FDG uptake.Forty-three (71.6%) of patients in the study had positive FDG uptake. Larger tumors and the presence of CLNM were associated with a greater likelihood of positive FDG uptake. The sensitivity, specificity, positive predictive value, and negative predictive value for CLNM detection by FDG PET-CT showed low statistical values. When considering the excellence of US for evaluating a thyroid nodule size and the presence of CLNM, the clinical value of pre-Tx FDG PET-CT is comparatively limited.Pre-Tx FDG PET is not recommended for routine use in patients with PTC.

Salivary dysfunction is the most common side effect associated with (131)I therapy in patients with differentiated thyroid cancer. The purpose of this study was to evaluate the effect of parotid gland (PG) massage on radioisotope accumulation in the salivary gland.Sixty patients were included in this study. Using Tc-99m pertechnetate, two salivary scans were performed in all patients. In 30 patients, PG massage was performed between the two salivary gland scans, whereas in the other 30 patients no massage was performed between the two scans. Total counts of both PGs and accumulation ratios were calculated.In the patients who received massage, no difference was observed between the mean PG counts of first and second images (8556.9±3333.4 count vs. 8598.3±3341.3 count, p=0.39). In the patients who did not receive massage, the mean PG count on second images was significantly higher than that on first images (8581.2±3618.0 count vs. 9096.4±3654.0 count, p0.01). Mean accumulation ratio in the patients who received massage was significantly lower than in the patients who did not receive massage (0.5%±3.3% vs. 6.8%±3.8%, p0.01). Further, among the patients who received massage there was a higher percentage of patients with a negative accumulation ratio than among the patients who did not receive massage (43.3% vs. 0%, p0.01).PG massage can reduce Tc-99m pertechnetate accumulation in the PG, and thus, should be helpful to prevent salivary damage associated with (131)I therapy.