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Background/Objectives: The management of differentiated thyroid cancer (DTC) patients has undergone a major paradigm shift in past years, especially regarding the role of a careful postoperative disease assessment both in deciding for or against the use of iodine-131 therapy (i.e., patients' selection) and in selecting the correct goal of the treatment: ablative, adjuvant or therapeutic. Furthermore, diagnostic and risk-oriented uses of iodine isotopes (i.e., 123/124/131I) should always be considered during both postoperative assessment and follow-up of DTC patients to improve early staging and response assessment to initial treatments, respectively. The present review summarizes current (and real-life-related) evidence and the emerging perspectives on the therapeutic, diagnostic, and theragnostic use of radioiodine isotopes. Methods: A review of the pertinent literature was performed in PubMed, Web of Science, and Scopus without language restrictions or time limits and using one or more fitting search criteria and terms. Results: According to the literature evidence and real-life clinical practice, a risk-oriented postoperative iodine-131 therapy remains pivotal for most DTC patients and improves early disease staging through post-therapy functional imaging (i.e., theragnostic aim). Accordingly, the goal of iodine-131 therapy, the optimal strategy (empiric vs. dosimetric approach), the appropriate stimulation method [i.e., levothyroxine (L-T4) withdrawal vs. recombinant human thyrotropin (rhTSH) administration] and, finally, the suggested radioiodine activity to deliver for iodine-131 therapy (RIT) should be personalized, especially in metastatic DTC patients. Conclusions: The evidence related to the diagnostic and theragnostic use of iodine isotopes leads to a significant improvement in the postoperative risk stratification and staging of DTC patients in addition to a more accurate assessment of the response to initial treatments. In conclusion, radioiodine is really an oldie but goldie radiotracer. It has both a current fundamental role and a future perspective for the more careful management of DTC patients. [ABSTRACT FROM AUTHOR]

Radioiodine (RAI) therapy after surgery, is an important component for the treatment of patients with papillary thyroid cancer (PTC), the most common thyroid cancer. In this study we sought to evaluate the cancer-specific survival (CSS) impact of RAI in specific thyroid cancer subgroups. The Surveillance, Epidemiology, and End Results (SEER) database were used to identify patients with PTC who underwent surgery between 2000 and 2019. Patients not treated with RAI were compared to those treated with RAI using propensity score matching (PSM) on the basis of identical inclusion criteria. A total of 106 333 patients were identified from the SEER database. RAI therapy was associated with improved CSS in the matched cohort (HR: 0.83; 95% CI: 0.72–0.96, p=0.01) but not in the unmatched data set (HR: 1.46; 95% CI: 1.30–1.64, p<0.001) among all PTC patients regardless of disease stage. Detailed analyses, however, showed that only patients with high-risk disease (pT3N1, pT4N1) experienced the greatest benefit in CSS. In the lower disease stages, no significant differences were recognized in the group of PTC patients with or without RAI therapy. One exception: in the group of PTC patients in stage pT1bN0, a significant difference was seen towards RAI. This is, however, most likely due to the large number of patients investigated. In summary, RAI therapy should not be used in low-risk PTC patients and might be used to some extent in intermediate-risk PTC patients. The histological suptype of the tumor needs to be considered in this context. [ABSTRACT FROM AUTHOR]

Purpose: Radioiodine-131 (RAI or iodine-131) is one of the most frequently used radionuclides for diagnosis and therapy of thyroid diseases (90% of all therapies in nuclear medicine). In order to optimize the patient protection, it is important to evaluate the long-term biological effects of RAI therapy on non-target organs. Materials and methods: An experimental animal model has been adopted, it consists on miming RAI therapy. An activity of RAI has been administrated in two models of Wistar rats: the first model with an intact thyroid gland (Thy + model), and the second one was thyroidectomized (Thy- model). For each model, 6 rats were orally contaminated with a solution 18.5 ± 1MBq of [131I]NaI and 6 others rats were used as controls. The 24 rats have been placed in individual cages for a period of 08 months then they were euthanized. The blood was collected by cardiac puncture and all organs were immediately removed. A fraction of thyroid, liver, kidneys and testicles was put in vials containing formaldehyde (10%) for histological investigation. Results: Histological observations show some liver disorders more accentuated in the case of the Thy- model, the appearance of kidney tissue effects (hemosiderin deposits, fibrosis and glomerular necrosis) for both models and an absence of any anomaly for the testicles slides. The disturbance of blood parameters specific to each organ has been revealed. Conclusions: Long-term biological effect of 131I-administration shows the appearance of various histological disorders confirmed by disturbances in hepatic and renal functions. [ABSTRACT FROM AUTHOR]

Background: The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. Methods: This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). Results: Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan–Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44–0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19–12.84]). Conclusions: RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans. [ABSTRACT FROM AUTHOR]

Context Over the past several decades, there have been indications of potential shifts in the diagnostic strategies, treatment, and monitoring of patients with Graves disease (GD). Objective To evaluate current practices in managing GD and compare them to previous surveys Methods We used a global online survey of endocrinologists to assess shifts in the diagnosis, monitoring, and treatment in a typical patient with GD, as well as treatment variation in 5 different clinical scenarios. Results A total of 1252 respondents from 85 countries completed the survey. Methods used to diagnose an uncomplicated GD case have changed over the past decade, reflecting increased use of thyrotropin receptor antibody (TRAb) and reciprocal decreases in nuclear medicine studies. The preferred mode of therapy for uncomplicated GD was antithyroid drugs (ATDs) by 91.5% of respondents, radioactive iodine (RAI) therapy by 7%, and thyroidectomy by 1.5%. Compared with previous surveys, the use of RAI as a first-line choice decreased in all geographic regions. The United States had the sharpest decline in the selection of initial therapy with RAI, decreasing from 69% in 1990 to 11.1% in 2023. In patients with persistent TRAb positivity after 18 months, 68.7% of respondents would continue the use of ATDs. After a relapse of GD, resumption of ATDs was selected by 59.9% of respondents. In patients with active thyroid eye disease or planning pregnancy, ATDs were the first choice (67.5% and 72.8%, respectively), and thyroidectomy emerged as the second choice (22.9% and 15.6%, respectively). Conclusion Paradigm shifts have occurred in the management of uncomplicated GD and its variants, as well as the response to persistent and recurrent hyperthyroidism. [ABSTRACT FROM AUTHOR]

Telomerase reverse transcriptase promoter (TERTp) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERTp's role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERTp mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAFV600E (9/143, 6.3%) than those with both BRAFV600E and TERTp mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAFV600E and TERTp mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAFV600E alone (33.3%, 3/9). Only one patient with both BRAFV600E and TERTp mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERTp mutations than in those without. Patients with BRAFV600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAFV600E alone (p < 0.01). Our findings suggest that molecular testing for TERTp and other mutations like BRAFV600E may inform early diagnosis, prognosis, and treatment strategies before progression to RAIR-DTC. [ABSTRACT FROM AUTHOR]

Purpose: Evaluating the impact of radioiodine therapy (RIT) on olfactory function in thyroid cancer patients through quantitative and qualitative olfactory tests. Method: In this cohort study, patients with thyroid cancer were included. Demographic, clinical, and laboratory data were collected. To subjectively evaluate the olfactory changes aftter RIT, the Visual Analog Scale (VAS), Self-Reported Mini-Olfactory Questionnaire (self-MOQ), and the University of Washington Quality of Life Questionnaire (UW-QOL) were assessed. Out of UW-QOL questions those related to saliva, taste, and overall health condition were analysed. For objective assessment, patients underwent both the Butanol Threshold Test (BTT) and the a version of Smell Identification Test (SIT). Patients were assessed before, one month, and six months after RIT. Results: Ninety eight patients were included (Male = 17). A statistically significant decrement was observed in olfaction based on the VAS, between the baseline and one (pvalue = 0.015) and six months (pvalue = 0.031) of follow-up. Additionally, saliva (pvalue = 0.001), taste (pvalue = 0.000), and overall health condition (pvalue = 0.010) significantly decreased one-month after RIT. The measures were not different between the baseline and 6-month follow up and the improvement of index of taste was significant from 1-month to 6-months follow ups (pvalue = 0.000). However, none of the objective tests (the BTT and the SIT) indicated a significant decline in olfaction during the follow up. Conclusion: A subjective RIT related decrease in smell function, taste, and saliva production was documented without any objective olfactory dysfunction. [ABSTRACT FROM AUTHOR]

Abstract Telomerase reverse transcriptase promoter (TERTp) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERTp’s role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERTp mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAF V600E (9/143, 6.3%) than those with both BRAF V600E and TERTp mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAF V600E and TERTp mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAF V600E alone (33.3%, 3/9). Only one patient with both BRAF V600E and TERTp mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERTp mutations than in those without. Patients with BRAF V600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAF V600E alone (p

The radioiodine therapy is a one of the basic elements at combined treatment of differentiated thyroid cancer and is an alternative method for patients with distant metastases and a potentially high risk of tumor recurrence. It has been used in clinical practice for more than 80 years. The first report on the phenomenon of accumulation of 130I/131I in a metastatic focus of differentiated thyroid cancer was published by A. Keston et al. in 1942, and in 1946, the production of 131I was established, and the drug became available. In our country, radioiodine therapy has been widely used for the treatment of differentiated thyroid cancer since 1982.This article presents methodological recommendations for radioiodine therapy of patients with differentiated thyroid cancer, provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches treatment of this disease.

Purpose: To investigate the effect of combining radioiodine therapy with euthyrox in treating thyroid cancer with BRAF gene mutation following total thyroidectomy (TT). Methods: This retrospective study analyzed records of 98 differentiated thyroid cancer (TC) patients with BRAF gene mutation who underwent TT between February 2018 and January 2020 at Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. The patients were randomized into control (46 patients) and study groups (53 patients). Control group received euthyrox, while the study group received euthyrox in addition to radioiodine following total thyroidectomy. Efficacy, thyroid function before and after treatment, incidence of adverse reactions, and 3-year recurrence rates were evaluated. Results: The study group showed significantly higher overall response rate (ORR) compared to control group (p < 0.05). There were no significant differences in thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels between the groups before treatment (p > 0.05). After treatment, both groups exhibited significant changes in thyroid function, with decreased TSH, and increased FT4 and FT3 levels (p < 0.05). Post-treatment TSH levels were significantly lower while FT4 and FT3 levels were significantly higher in the study group compared to control group (p < 0.05). Conclusion: Combining radioiodine therapy and Euthyrox following total thyroidectomy enhances therapeutic outcomes in patients with BRAF-mutated TC, improves thyroid function and reduces recurrent risk without increasing adverse reactions. Further studies will aim to expand the sample size and stratify patients by severity to comprehensively validate these findings. [ABSTRACT FROM AUTHOR]

Purpose: This two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total thyroidectomy and radioiodine therapy (RAIT). Materials and Methods: All caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients' disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients' ultimate disease outcomes. Results: A total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p<0.001). The ROC curve showed that ps-Tg =20 ng/mL was the most accurate for predicting IR at the last follow-up. According to multivariate analysis, only ps-Tg, T stage and the therapeutic response to initial RAIT were significantly associated with IR. Conclusion: In caDTC patients, the ps-Tg level, T stage, and response to initial RAIT are critical final outcome indicators. [ABSTRACT FROM AUTHOR]

Objective: Radioiodine (I-131) therapy for hyperthyroidism is a well-established and safe treatment option. This study aimed to investigate the relationship between the computed tomography (CT) value and the function and volume of the thyroid gland by identifying the factors that induce changes in the CT value of patients with hyperthyroidism. Methods: This retrospective study evaluated 38 patients with Graves' disease and 10 patients with Plummer disease. To obtain the mean CT value and volume of the thyroid gland, the entire thyroid gland was set as the region of interest. A test dose of 3.7 MBq I-131 was administered before initiating I-131 therapy, and the radioiodine uptake (RIU) rate was assessed after 3, 24, 96, and 168 h. An approximate curve was plotted based on the RIU values obtained, and the effective half-life (EHL) was calculated. The correlation between the mean CT value and the volume of the thyroid gland, 24-h RIU, EHL, and the free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and TSH receptor antibody (TRAb) levels was evaluated. Results: The CT value exhibited a significant positive correlation with EHL in patients with Graves' disease (r = 0.62, p < 0.0001) as well as patients with Plummer disease (r = 0.74, p < 0.05). However, it did not display any correlation with the remaining parameters. Conclusion: The CT value is significantly correlated with EHL, suggesting that it reflects thyroid function and is mainly related to the factors associated with iodine discharge. [ABSTRACT FROM AUTHOR]

Aim: This research aimed to construct a clinical model for forecasting the likelihood of lung metastases in differentiated thyroid carcinoma (DTC) with intermediate- to high-risk. Methods: In this study, 375 DTC patients at intermediate to high risk were included. They were randomly divided into a training set (70%) and a validation set (30%). A nomogram was created using the training group and then validated in the validation set using calibration, decision curve analysis (DCA) and receiver operating characteristic (ROC) curve. Results: The calibration curves demonstrated excellent consistency between the predicted and the actual probability. ROC analysis showed that the area under the curve in the training cohort was 0.865 and 0.845 in the validation cohort. Also, the DCA curve indicated that this nomogram had good clinical utility. Conclusion: A user-friendly nomogram was constructed to predict the lung metastases probability with a high net benefit. Article highlights The study aimed to develop a predictive model for lung metastases in patients with differentiated thyroid cancer (DTC) who are at intermediate- to high-risk. Through univariate and multivariate analyses, histological type, multifocality, tumor size, BRAFV600E mutation and ps-Tg levels were identified as independent factors influencing the development of lung metastases. A nomogram was constructed based on these risk factors, with a high C-index of 0.86, indicating strong predictive accuracy for lung metastases. Calibration curves showed excellent consistency between predicted and actual probabilities of lung metastases, further validating the nomogram's reliability. Receiver operating characteristic analysis demonstrated high discrimination ability of the nomogram, with an area under the curve of 0.865 in the training cohort and 0.845 in the validation cohort. Decision curve analysis indicated that the nomogram had better clinical utility in predicting lung metastases rates compared with other models. The nomogram provides clinicians with a tool to assess the risk of lung metastases in DTC patients, incorporating factors such as histological type, tumor size, genetic mutations and ps-Tg levels to guide treatment decisions and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10–20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT. [ABSTRACT FROM AUTHOR]

Hyperthyroidism, characterized by elevated thyroid hormone levels and thyroid gland hyperplasia or adenoma, is a prevalent endocrinopathy in older cats. Treatment options include antithyroid drugs, surgical thyroidectomy, and radioiodine therapy (RAIT), which is non-invasive treatment option that can achieve complete remission. However, efficacy and safety of RAIT in hyperthyroid cats have not been investigated in South Korea. This study includes 10 hyperthyroid cats with RAIT. Initial assessments comprised history, physical examination, blood analysis, and serum total T4 (tT4) concentration. Thyroid scintigraphy revealed hyperactivity and enlargement of thyroid gland at 24 hours before the RAIT. Radioiodine (RAI) was injected subcutaneously with 2 to 6 mCi, determined by the fixed dose or the scoring system based on severity of clinical signs, tT4 concentration, and thyroid size individually. After RAIT, the concentration of serum tT4 and liver enzymes were significantly decreased at discharge. However, no significant differences were noted in blood urea nitrogen, creatinine, symmetric dimethylarginine, hematocrits, and white blood cell counts pre- and post-treatment. Although 4 cats received RAI twice, clinical signs disappeared and tT4 levels decreased following the RAIT. All 10 cats achieved complete remission after 6 months without critical adverse effect. The safety and the effectiveness of RAIT was confirmed based on protocols reported other countries. Therefore, RAIT could be considered the treatment option and prevent adverse effects from medication or surgery. This preliminary study presents the first evaluation of RAIT for hyperthyroid cats using locally produced RAI in South Korea and provide valuable insight for clinicians and further studies. [ABSTRACT FROM AUTHOR]

Radiopharmaceuticals for therapeutic have been increasingly used for the treatment of various pathologies. Beta-emitting radionuclides stand out in this modality due to the physical characteristics of the emitted particle. Iodine-131 (131I) is an example of a beta-emitting radionuclide, applied in the production of radiopharmaceuticals such as sodium iodine (131I), which represents an excellent therapeutic modality in the treatment of differentiated thyroid carcinomas. As well as other therapeutic modalities, radionuclide therapy using radiopharmaceuticals can also cause adverse reactions. This study aimed to evaluate the incidence of possible adverse events related to therapy with sodium iodine (131I), and evaluate the correlation with the administered activities, obtaining unprecedented pharmacovigilance data related to the use of therapeutic radiopharmaceuticals in Brazil. A retrospective analysis of medical records was carried out with electronic patients’ data diagnosed with differentiated thyroid carcinoma and undergoing therapy with radioiodine. A total of 116 patients were recovered from January/2019 to April/2021 and 89 were included according to the inclusion criteria. Of the patients, 54.6% reported an adverse event after radioiodine therapy. The most frequent events were those related to the gastrointestinal tract and local irradiation, and it was possible to identify that there was an increased incidence of events in those patients who were treated with greater activities. Based on the results obtained, the present study demonstrated the presence of acute events related to therapy in the studied population and that the incidence of events was correlated with the activity prescribed.

BACKGROUND: Thyroid nodules are a prevalent issue, with an estimated incidence of 19% to 35% based on ultrasound examination and 8% to 65% based on autopsy findings [1]. In some cases, Plummer’s disease is observed, and nodular masses may be observed in 10% to 35% of Graves’ disease cases, with iodine accumulation of a different nature [2, 3]. One of the principal treatments for Graves’ and Plummer’s diseases is radioiodine therapy, which serves to exclude the possibility of malignancy in nodules. Furthermore, the pharmacokinetics of iodine is investigated, which represents the most time-consuming and labor-intensive stage of preparation for radioiodine therapy. In clinical practice, ultrasound is performed in accordance with the TI-RADS system, followed (if necessary) by fine-needle aspiration puncture biopsy, stratified according to the Bethesda system. However, the interpretation of ultrasound examinations is inherently subjective, whereas the use of decision support systems can reduce the number of fine-needle aspiration puncture biopsies by 27% and the number of missed malignant neoplasms by 1.9%. Furthermore, the quantitative characterization of nodal ultrasound may enhance the investigation of the pharmacokinetics of I-131 [4, 5]. AIM: The study aimed to develop a method for quantitatively characterizing ultrasound images of thyroid nodular masses for predicting malignancy and I-131 accumulation by nodular masses. MATERIALS AND METHODS: The study included 125 nodules with pathomorphologic findings (65 benign, 60 malignant) and 25 benign nodules (established by cytologic examination) of patients who underwent radioiodotherapy as part of the Russian Science Foundation grant project No. 22-15-00135. Longitudinal and transverse projections of thyroid nodules were obtained using GE Voluson E8 (36% of all benign nodules and 27% of malignant nodules) and GE Logiq E (64% of benign and 73% of malignant nodules). A pharmacokinetics study was conducted on 25 nodes obtained on a GE Logiq V2 device. The accumulation index of I-131 was determined after 24 hours. A spatial adjacency matrix, gray level line length matrix, gray level zone size matrix, and histogram were employed to investigate features based on ultrasound images. RESULTS: The malignancy prediction model, developed on the basis of the most significant features and after KNN correlation analysis, exhibited a diagnostic accuracy value of 72±3%, a sensitivity of 73±5%, and a specificity of 73±5%. An investigation of I-131 pharmacokinetics revealed that the maximum histogram intensity gradient (r=–0.48, p=0.08) and intensity entropy (r=–0.51, p=0.06) exhibited the highest Spearman correlation coefficient modulus with I-131 accumulation after 24 hours. CONCLUSIONS: The present study demonstrates the feasibility of using quantitative characterization of ultrasound images of nodal masses as a tool to monitor nodules before radioiodotherapy. This is with a view to subsequent adjunctive fine-needle aspiration puncture biopsy and prediction of I-131 accumulation after 24 hours.

Purpose: Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients. Methods: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre. Results: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively). Conclusions: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies. [ABSTRACT FROM AUTHOR]

Objective: The BRAFV600E mutation is the universal genetic mutation in papillary thyroid microcarcinoma (PTMC). The present study is to estimate the role of the BRAFV600E mutation in the clinical outcome of PTMC with intermediate to high recurrence risk after radioactive iodine (RAI) therapy, which is considered to be an indolent tumor. Methods: We conducted a single-center retrospective study. Between May 2016 and March 2019, PTMC patients with known BRAFV600E status who received RAI therapy were reviewed at the Second Hospital of Shandong University. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The association between the BRAFV600E mutation and clinicopathological characteristics, response to RAI therapy, and recurrence after a period of follow-up were analyzed. Propensity score matching (PSM) and logistic regression were used to control confounding variables. Results: Of the 322 patients with intermediate to high recurrence risk in PTMC, the mean age of the patients were 43.7 ± 12.2 years, and 72.1% were women. BRAFV600E mutation was found in 64.9% (209/322). After PSM, 112 pairs of patients were matched, and except for multifocality (P = 0.001), extrathyroidal invasion (P = 0.003) and tumor size (P = 0.03), there was no significant difference in all baseline characteristics between the two groups. An excellent response (ER) to RAI therapy was observed in 273 patients (84.7%). At the end of the study, 17(5.2%) and 6(1.8%) patients showed structural incomplete response (SIR) and biochemical incomplete response (BIR) status. The proportion of patients who achieved ER status in the BRAFV600E mutation positive and negative groups was 86.6% and 81.4%, respectively. Kaplan–Meier analyses showed that the BRAFV600E mutation was not related to lower ER reached time. The median follow-up was 51 months. Conclusions: We found the BRAFV600E mutation was associated with multifocality, extrathyroidal invasion, and tumor size in papillary thyroid microcarcinoma. However, the BRAFV600E mutation had no significant association with clinical outcomes in patients with intermediate to high recurrence risk after RAI therapy. Furthermore, the extra-thyroid uptake results and distant metastasis had been proven to be independent factor predicting the clinical response. Registration number: ChiCTR2200062911 [ABSTRACT FROM AUTHOR]

Radioiodine (131I) is widely used in the treatment of hyperthyroidism and as an effective ablative therapy for differentiated thyroid cancer. Radioiodine (131I) constitutes 90% of the currently used therapies in the field of nuclear medicine. Here, we report the cytogenetic findings of a long-term follow-up study of 27 years on a male patient who received two rounds of radioiodine treatment within a span of 26 months between 1992 and 1994 for his papillary thyroid cancer. A comprehensive cytogenetic follow-up study utilizing cytokinesis blocked micronucleus assay, dicentric chromosome assay, genome wide translocations and inversions was initiated on this patient since the first administration of radioiodine in 1992. Frequencies of micronuclei (0.006/cell) and dicentric chromosomes (0.008/cell) detected in the current study were grossly similar to that reported earlier in 2019. The mFISH analysis detected chromosome aberrations in 8.6% of the cells in the form of both unbalanced and balanced translocations. Additionally, a clonal translocation involving chromosomes 14p; 15q was observed in 2 of the 500 cells analyzed. Out of the 500 cells examined, one cell showed a complex translocation (involving chromosomes 9, 10, and 16) besides 5 other chromosome rearrangements. Collectively, our study indicates that the past radioiodine exposure results in long-lasting chromosome damage and that the persistence of translocations can be useful for both retrospective biodosimetry and for monitoring chromosome instability in the lymphocytes of radioiodine exposed individuals. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether adherence to a low-iodine diet (LID) enhances the therapeutic efficacy of radioiodine therapy (RAI) in Graves' hyperthyroidism (GH) in iodine-rich areas. Methods: We retrospectively evaluated 185 patients with GH from Aichi (n = 114) and Hokkaido (n = 71) Prefectures. Patients aged ≥ 18 years with GH who underwent RAI between December 2012 and March 2022 were divided into subgroups based on pretreatment with anti-thyroid drug (ATD) or potassium iodide (KI). Patients were followed up with LID from 18 days (group A) or 7 days (group H) before RAI to 3 days after RAI. The dose of radioactive iodine 131 (131I) was adjusted to deliver > 100 Gy to the thyroid. The associations between urinary iodine concentration on UIC2 vs. 24hRU and UIC2 vs. the 1-year RAI success rate (SR) were investigated. Results: Compared with UIC1, UIC2 was significantly decreased in all subgroups (P < 0.01). An inverse correlation between UIC2 and 24hRU was observed in the four groups; however, the difference was insignificant. The SR in groups A and H was 85% and 89%, respectively. Univariate analysis revealed no association between UIC2 and SR in each group. Additionally, stratification of the 185 patients into quartiles using UIC2 yielded no significant differences in SR (p = 0.79). Conclusions: LID sufficiently reduced UIC in patients undergoing RAI. Although a lower UIC2 may increase 24hRU, it did not increase the success of RAI. The benefit of LID in enhancing the efficacy of RAI in GH treatment remains uncertain. [ABSTRACT FROM AUTHOR]

Abstract Background The Otsu method and the Chan–Vese model are two methods proven to perform well in determining volumes of different organs and specific tissue fractions. This study aimed to compare the performance of the two methods regarding segmentation of active thyroid gland volumes, reflecting different clinical settings by varying the parameters: gland size, gland activity concentration, background activity concentration and gland activity concentration heterogeneity. Methods A computed tomography was performed on three playdough thyroid phantoms with volumes 20, 35 and 50 ml. The image data were separated into playdough and water based on Hounsfield values. Sixty single photon emission computed tomography (SPECT) projections were simulated by Monte Carlo method with isotope Technetium-99 m ( $$^{\text {99m}}$$ 99m Tc). Linear combinations of SPECT images were made, generating 12 different combinations of volume and background: each with both homogeneous thyroid activity concentration and three hotspots of different relative activity concentrations (48 SPECT images in total). The relative background levels chosen were 5 %, 10 %, 15 % and 20 % of the phantom activity concentration and the hotspot activities were 100 % (homogeneous case) 150 %, 200 % and 250 %. Poisson noise, (coefficient of variation of 0.8 at a 20 % background level, scattering excluded), was added before reconstruction was done with the Monte Carlo-based SPECT reconstruction algorithm Sahlgrenska Academy reconstruction code (SARec). Two different segmentation algorithms were applied: Otsu’s threshold selection method and an adaptation of the Chan–Vese model for active contours without edges; the results were evaluated concerning relative volume, mean absolute error and standard deviation per thyroid volume, as well as dice similarity coefficient. Results Both methods segment the images well and deviate similarly from the true volumes. They seem to slightly overestimate small volumes and underestimate large ones. Different background levels affect the two methods similarly as well. However, the Chan–Vese model deviates less and paired t-testing showed significant difference between distributions of dice similarity coefficients (p-value $$

Background: The Otsu method and the Chan–Vese model are two methods proven to perform well in determining volumes of different organs and specific tissue fractions. This study aimed to compare the performance of the two methods regarding segmentation of active thyroid gland volumes, reflecting different clinical settings by varying the parameters: gland size, gland activity concentration, background activity concentration and gland activity concentration heterogeneity. Methods: A computed tomography was performed on three playdough thyroid phantoms with volumes 20, 35 and 50 ml. The image data were separated into playdough and water based on Hounsfield values. Sixty single photon emission computed tomography (SPECT) projections were simulated by Monte Carlo method with isotope Technetium-99 m ( 99m Tc). Linear combinations of SPECT images were made, generating 12 different combinations of volume and background: each with both homogeneous thyroid activity concentration and three hotspots of different relative activity concentrations (48 SPECT images in total). The relative background levels chosen were 5 %, 10 %, 15 % and 20 % of the phantom activity concentration and the hotspot activities were 100 % (homogeneous case) 150 %, 200 % and 250 %. Poisson noise, (coefficient of variation of 0.8 at a 20 % background level, scattering excluded), was added before reconstruction was done with the Monte Carlo-based SPECT reconstruction algorithm Sahlgrenska Academy reconstruction code (SARec). Two different segmentation algorithms were applied: Otsu's threshold selection method and an adaptation of the Chan–Vese model for active contours without edges; the results were evaluated concerning relative volume, mean absolute error and standard deviation per thyroid volume, as well as dice similarity coefficient. Results: Both methods segment the images well and deviate similarly from the true volumes. They seem to slightly overestimate small volumes and underestimate large ones. Different background levels affect the two methods similarly as well. However, the Chan–Vese model deviates less and paired t-testing showed significant difference between distributions of dice similarity coefficients (p-value < 0.01 ). Conclusions: The investigations indicate that the Chan–Vese model performs better and is slightly more robust, while being more challenging to implement and use clinically. There is a trade-off between performance and user-friendliness. [ABSTRACT FROM AUTHOR]

Background: Radioiodine (131I) therapy (RAIT) is associated with oxidative stress (OS)-induced DNA damage in patients with differentiated thyroid cancer (DTC). The goal of this study was to evaluate the possible ameliorating effects of Panax Ginseng (PG) on RAIT-induced genotoxicity in patients with DTC. Materials and Methods: Forty DTC patients who had received 131I (100 to 175 mCi) were enrolled in this study. The patients were randomly classified (n = 10) into control, placebo, PG1 groups (receiving 500 mg/day of PG for 2 days before RAIT), and PG2 group (receiving 500 mg/day of PG for 2 days before to 1 day after RAIT). Blood samples were collected before and 2 days after RAIT. Lymphocyte micronuclei (MN) frequency was measured using the MN assay. Serum total antioxidant capacity (TAC) and ischemia-modified albumin (IMA) were measured using colorimetric assays. Serum albumin, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using commercial kits. Results: The mean of baseline MN frequency was the same in the four groups. RAIT increased the MN frequencies to at least three times the baseline values in the control (39 ± 5) and placebo groups (38 ± 6) (P < 0.001). PG caused a significant decrease in the MN frequencies in the treated groups compared to the control and placebo groups (P < 0.001). RAIT and PG administration had no significant effects on the serum IMA, TAC, and markers of liver and kidney toxicity. Conclusion: PG could be considered a useful remedy for the protection against RAIT-induced chromosomal damage in DCT patients. KEY WORDS: Differentiated thyroid cancer, genotoxicity, Panax ginseng, radioiodine therapyBackground: Radioiodine (131I) therapy (RAIT) is associated with oxidative stress (OS)-induced DNA damage in patients with differentiated thyroid cancer (DTC). The goal of this study was to evaluate the possible ameliorating effects of Panax Ginseng (PG) on RAIT-induced genotoxicity in patients with DTC. Materials and Methods: Forty DTC patients who had received 131I (100 to 175 mCi) were enrolled in this study. The patients were randomly classified (n = 10) into control, placebo, PG1 groups (receiving 500 mg/day of PG for 2 days before RAIT), and PG2 group (receiving 500 mg/day of PG for 2 days before to 1 day after RAIT). Blood samples were collected before and 2 days after RAIT. Lymphocyte micronuclei (MN) frequency was measured using the MN assay. Serum total antioxidant capacity (TAC) and ischemia-modified albumin (IMA) were measured using colorimetric assays. Serum albumin, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using commercial kits. Results: The mean of baseline MN frequency was the same in the four groups. RAIT increased the MN frequencies to at least three times the baseline values in the control (39 ± 5) and placebo groups (38 ± 6) (P < 0.001). PG caused a significant decrease in the MN frequencies in the treated groups compared to the control and placebo groups (P < 0.001). RAIT and PG administration had no significant effects on the serum IMA, TAC, and markers of liver and kidney toxicity. Conclusion: PG could be considered a useful remedy for the protection against RAIT-induced chromosomal damage in DCT patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the risk of second primary malignancy after radioiodine (RAI) therapy in patients with thyroid cancer, using the National Health Insurance Service (NHIS) database. Methods: We extracted data from the NHIS database of South Korea, which covers the entire population of the nation. Risk of second primary malignancy in the thyroid cancer patients who received RAI therapy were compared with the thyroid cancer patients who received surgery only. Results: Between January 1, 2004, and December 31, 2018, we identified 363,155 patients who underwent thyroid surgery due to thyroid cancer for analysis. The surgery only cohort was 215,481, and the RAI cohort was 147,674 patients. A total of 19,385 patients developed second primary malignancy (solid cancer, 18,285; hematologic cancer, 1,100). There was no significant increase in the risk of second primary malignancy in patients who received a total cumulative dose of 100 mCi or less (hazard ratio [HR], 1.013; 95% confidence interval [CI], 0.979–1.049). However, a statistically significant increase in the risk of second primary malignancy was observed in patients who received 101–200 mCi (HR, 1.214; 95% CI, 1.167–1.264), 201–300 mCi (HR, 1.422; 95% CI, 1.258–1.607), and > 300 mCi (HR, 1.693; 95% CI, 1.545–1.854). Conclusion: Total cumulative doses of 100 mCi or less of RAI can be safely administered without concerns about second primary malignancy. However, the risk of second primary malignancy increases in a dose-dependent manner, and the risk–benefit needs to be considered for doses over 100 mCi of RAI therapy. [ABSTRACT FROM AUTHOR]

BackgroundLithium inhibits iodine and thyroid hormone release from thyroid cells, possibly increasing radioiodine retention and anti-hyperthyroid efficacy when given adjunctively to radioiodine therapy (RAI) of Graves’ disease (GD). However, the literature contains limited dosimetric data regarding the influence of concomitant lithium in this setting.MethodsWe retrospectively compared dosimetric variables in patients undergoing RAI with/without adjunctive lithium (n = 52 each). We assessed two low-dose, short-duration oral lithium carbonate regimens, 450 mg/d (n = 22) or 900 mg/d (n = 30), for a mean of 4.7 ± 1.4 d starting upon RAI administration. Patients underwent diagnostic testing to measure thyroidal radioiodine uptake (RAIU) 24 h ± 2 h after ingesting up to 5 MBq radioiodine, receiving individualized RAI activities 24 h later. Using ≥3 RAIU daily measurements starting 24 h post-RAI, researchers were able to determine the effective radioiodine half-life and absorbed dose to the thyroid; we also calculated the absorbed dose per administered activity concentration within that organ. Rates of GD cure, defined as reaching euthyroidism or hypothyroidism post-RAI, were evaluated in patients with ~6 months or longer post-RAI follow-up.ResultsThe lithium dosage subgroups had similar dosimetric values and thus are considered together. Lithium patients and controls had similar average “diagnostic” RAIU (51.1% ± 15.7% vs. 50.6% ± 13.8%, p = 0.820), but the former had significantly higher RAIU post-RAI (56.3% ± 13.5% vs. 49.1% ± 13.5%, p = 0.002), reflecting significantly greater change in the former (+16.2% ± 30.4% vs. -1.8% ± 16.1%, p = 0.001). Radioiodine effective half-life was non-significantly longer in lithium patients (5.43 ± 1.50 d vs. 5.08 ± 1.16 d, p = 0.192). The mean RAI administered activity was 27% less in lithium patients (677 ± 294 MBq vs. 930 ± 433 MBq, p = 0.001), but GD cure rates were similar (83% [39/47] vs. 82% [33/40], p = 0.954), possibly due to the significantly higher thyroid dose in the lithium patients, especially in thyroid gland with a volume ≤ 20 mL (1.04 ± 0.44 Gy/MBq vs. 0.76 ± 0.30 Gy/MBq, p = 0.020). Day 3 serum lithium concentrations were low (450 mg/d: 0.26 ± 0.12 mmol/L, 900 mg/d: 0.50 ± 0.18 mmol/L); no lithium toxicity was noted.ConclusionLithium augmentation may increase the RAIU and thyroid absorbed dose, permitting potentially decreased RAI activities without sacrificing efficacy. Our observations should be confirmed in a prospective, randomized trial.

Purpose: The aim was to investigate the effect of radioactive iodine (RA I) treatment for differentiated thyroid cancer (DTC) on male gonadal function. Methods: PubMed, Embase, Web of Science, OVID, Scopus, and Wanfang data bases were searched up to June 10, 2022, to identify published studies related to RAI and male gonadal function. ReviewManager version 5.4.1 software was used to calculate mean differences (MDs) with 95% CIs. Results: Initially, 1958 articles were retrieved from the databases, and 6 articles were included in the quantitative analysis. The meta-analysis results showed that follicle-stimulating hormone (FSH) increased when the follow-up duration was ≥12 months after RAI, but the difference was not statistically significant (MD = −2.64, 95% CI = (−5.61, 0.33), P = 0.08). But the results of the subgroup analysis showed that when the follow-up time was ≤6 months, FSH levels were significantly higher after RAI (MD = −7.65, 95% CI = (−13.95, −1.34), P = 0.02). The level of inhibin B was significantly lower at ≥12 months and ≤6 months after RAI (MD = 66.38, 95% CI = (8.39, 124.37), P = 0.02) and (MD = 116.27, 95% CI = (43.56, 188.98), P = 0.002). Additionally, luteinizing hormone (LH) and testosterone have similar results – that is, L H and testosterone levels were higher after RAI, but the difference was not statistically significant (MD = –0.87, 95% CI = (−2.04, 0.30), P = 0.15) and (MD = −1.69, 95% CI (−7.29, 3.90), P = 0.55). Conclusions: Male gonadal function may be temporarily impaired within 6 months after RAI but may return to normal levels afterward.

Purpose: To determine whether thyroid-stimulating hormone level ≥ 30 mU/L is necessary for radioiodine (131I) remnant ablation (RRA) in patients with differentiated thyroid cancer (DTC), as well as its influencing factors and pre dictors. Methods: A total of 487 DTC patients were retrospectively enrolled in t his study. They were divided into two groups (TSH < 30 and ≥ 30 mU/L) and further divided into eight subgroups (0–

Graves' disease (GD) is the leading cause of hyperthyroidism in pediatric patients. Radioactive iodine therapy (RAIT) is widely used to treat GD. However, it is still unclear exactly what determines the efficacy of RAIT in childhood and adolescence. The objective of our study was to reveal the most significant predictors of the efficacy of RAIT in pediatric GD patients. A single-center prospective observational exploratory study enrolled 144 pediatric patients (124 females and 20 males) between 8 and 18 years of age who underwent dosimetry-guided RAIT for GD for the first time. The estimated parameters included sex, age, thyroid volume, thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone receptor antibodies (TRABs) at baseline and 12 months after RAIT, 10- to 20-min 99mTc thyroid uptake (%), maximum thyroid 131I uptake (%), specific 131I uptake (MBq/g), and therapeutic activity of 131I (MBq), which was limited to 1100 MBq. The Fisher's exact test, Mann–Whitney U-test, Wilcoxon signed-rank test, ROC analysis, and the Youden index were used for statistical analysis. Twelve months after RAIT, 119 patients (83%) successfully achieved remission, 6 patients (4%) had euthyroidism, and hyperthyroidism persisted in 19 patients (13%). Thyroid volume decreased from 17.6 [14.6; 24.1] to 9.3 [7.6; 13.3] mL 12 months after the treatment (p < 0.001). The main predictor that showed a statistically significant difference between the groups of patients who achieved and did not achieve remission of GD hyperthyroidism after RAIT was the initial thyroid volume. Using the Youden index, the optimal cut-off point for the initial thyroid volume at 45.4 mL was determined. Conclusion: The dosimetry-guided RAIT in pediatric GD patients was 83% effective at 12 months after the treatment, and the initial thyroid volume of less than 45.4 mL was the most important predictor of RAIT success. Other predictors identified in our work included FT4 levels, TRABs levels, 99mTc-pertechnetate uptake, and specific 131I uptake. What is Known: •Radioiodine therapy is a common, effective, and safe treatment for pediatric patients with Graves' disease. What is New: •The initial thyroid volume in pediatric GD patients is an important predictor of achieving hypothyroidism following radioiodine therapy. If the thyroid volume is less than 45.4 ml, radioiodine therapy limited to 1100 MBq will be effective definitive treatment. [ABSTRACT FROM AUTHOR]

Purpose: Patients with persistent or recurrent papillary and poorly differentiated thyroid cancer can be effectively treated with radioiodine, if the tumour tissue is iodine-avid. However, iodine-avidity status is often unknown at the time of initial radioiodine treatment, limiting any adaptive approach. This study aimed to clarify the relationship between pre-therapeutic iodine avidity in primary tumour tissue, initial lymph node metastases and iodine uptake in subsequent metastases. Methods: Iodine avidity was prospectively assessed pre-therapeutically in 35 patients by injection of tracer amounts of iodine-131 two days prior to surgery. Iodine concentrations in resected tissue samples were measured, enabling accurate and histologically verifiable iodine avidity data for both primary tumour and initial lymph node metastases. Iodine uptake in persistent metastatic disease was assessed by review of radiology, and treatment response was examined through journal studies. Results: Out of data from 35 patients, 10 had persistent disease at presentation or during follow-up (range 19–46 months). Four patients had non-avid persistent metastatic disease, all with low iodine avidity in their primary tumours and initial lymph node metastases. Patients with low pre-therapeutic iodine avidity did not appear to have greater risk of persistent disease. Conclusion: The results indicate a close link between pre-therapeutically measured iodine concentrations in primary tumours with iodine avidity of any subsequent metastases. [ABSTRACT FROM AUTHOR]

Introduction: Differentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients. Methods: Eighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up. Results: Prepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, pvalue 0.06). None of our patients died disease-related over the observed period. Conclusion: Prepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/ postpubertal groups. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the predictive value of stimulated thyroglobulin (sTg) and pre-ablation antithyroglobulin (pa-TgAb) products for the effect of radioiodine therapy (RAIT) on TgAb-positive differentiated thyroid cancer (DTC) patients. Methods: In this study, we enrolled 265 patients with TgAb-positive DTC who underwent RAIT after total thyroidectomy (TT). Based on the last follow-up result, the patients were divided into two groups: the excellent response (ER) group and the non-excellent response (NER) group. We analyzed the factors related to the effect of RAIT. Results: The ER group consisted of 197 patients. The NER group consisted of 68 patients. For the univariate analysis, we found that the maximal tumor diameter, whether with extrathyroidal extension (ETE), bilateral or unilateral primary lesion, multifocality, preoperative TgAb (preop-TgAb), pa-TgAb, sTg x pa-TgAb, initial RAIT dose, N stage, and surgical extent (modified radical neck dissection or not), showed significant differences between the ER group and NER group (all p-values <0.05). The receiver operating characteristic (ROC) curves showed that the cutoff value was 724.25 IU/ml, 424.00 IU/ml, and 59.73 for preop-TgAb, pa-TgAb, and sTg x pa-TgAb, respectively. The multivariate logistic regression analysis results indicated that pa-TgAb, sTg x pa-TgAb, initial RAIT dose, and N stage were independent risk factors for NER (all p-values <0.05). For the Kaplan- Meier analysis of disease-free survival (DFS), the median DFS of the patients with sTg x pa-TgAb < 59.73 and initial RAIT dose < 100 mCi was significantly longer than that of the patients with sTg x pa-TgAb > 59.73 (50.27 months vs. 48.59 months, p = 0.041) and initial RAIT dose >100 mCi (50.50 months vs. 38.00 months, p = 0.030). Conclusion: We found the sTg and pa-TgAb conducts is a good predictor of the efficacy of RAIT in TgAb-positive DTC patients. It can play a very positive and important role in optimizing treatment, improving prognosis, and reducing the burden of patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the factors influencing the short-term response to the initial radioiodine therapy (RT) course in patients with intermediate- and high-risk papillary thyroid carcinoma (PTC). A total of 182 patients with intermediate- and high-risk PTC who underwent RT in our hospital from March 2018 to October 2020 were retrospectively enrolled. The patients were divided into incomplete response (IR) and nonincomplete response (Non-IR) groups according to the response observed in clinical follow-up within 6–12 months after RT. Univariate and multivariate logistic regression analyses were used to investigate the effects of 15 observed factors on the response to RT. Receiver operating characteristic (ROC) curve analysis was used to determine the value of factors found to be significant in multivariate analyses for predicting an IR. A total of 182 patients with intermediate- and high-risk PTC were analyzed; the percentage of patients with a Non-IR was 61.54% (112/182), and the percentage of patients with an IR was 38.46% (70/182). The CD4+ T-cell percentage (t = 4.757, P = 0.000), CD4/CD8 (z = − 2.632, P = 0.008), stimulated thyroglobulin (sTg) level (z = − 8.273, P = 0.000) and M stage (χ2 = 17.823, P = 0.000) of the two groups were significantly different. Multivariate analysis showed that only the sTg level (OR: 1.116, 95% CI 1.068–1.165, P < 0.001) and CD4+ T-cell percentage (OR: 0.909, 95% CI 0.854–0.968, P = 0.003) were independent factors associated with the therapeutic response to RT. The cutoff sTg level and CD4+ T-cell percentage for predicting an IR were 7.62 μg/L and 40.95%, respectively. The sTg level and CD4+ T-cell percentage were verified to be independent predictive factors of RT response. Higher sTg levels and lower CD4+ T-cell percentages were related to an IR in patients with intermediate- and high-risk PTC. [ABSTRACT FROM AUTHOR]

Objectives: In differentiated thyroid cancer (DTC), radioiodine (RAI) therapy is most frequently employed for remnant ablation or as adjuvant therapy for the remaining disease. The application of RAI to patients classified as intermediate risk (InR) is still a matter of debate. The aim of this study is to analyze the effect of early postoperative risk assessment on RAI use on papillary thyroid cancer patients who are classified as low risk (LoR) or InR. Methods: This is a single-center, prospective registry study. One-hundred-eighty-six patients operated between January 2012 and August 2021 and categorized as LoR or InR were included in this study. All patients had total thyroidectomy and central lymph node dissection by the same endocrine surgeon. An early dynamic risk assessment (EDRA) consisting of neck ultrasonography, serum thyroglobulin (Tg) and anti-Tg levels was performed 6 weeks after surgery. Most of the patients were either followed up without RAI or received ablative low activity (30-50 mCi) RAI based on predetermined criteria. Results: Median follow-up was 63 months. Sixty-six (61%) patients in the LoR group and 43 (56%) patients in the InR group did not receive RAI treatment. Thirty-eight (35%) and 22 (29%) patients in LoR and InR groups received ablative (30-50 mCi) RAI therapy, respectively. In LoR group 5 (4.6%) patients and in InR group 12 (16%) patients received 100 mCi or more RAI activity. Only one patient in the InR group recurred during follow-up. No statistically significant difference regarding local recurrence was found between patients who didn't receive RAI or were treated with RAI within both LoR (p=0.152) and InR (p=0.272) groups. Conclusion: There is consensus for LoR patients about omitting RAI therapy after surgery. Indications for RAI treatment in InR DTC are still under debate. RAI use based on EDRA seems to be a better option than decisions solely made on histopathological risk factors and decreases adjuvant high-activity RAI use without increasing recurrence risk. [ABSTRACT FROM AUTHOR]

131-I radioactive iodine (RAI) scan is an important modality in the management of differentiated thyroid cancer to detect recurrent or residual disease. Thus it is important to have knowledge about the possibility of false positive findings in these scans to avoid wrongful diagnosis and unnecessary treatment. We here by present a patient who underwent total thyroidectomy with lymph node dissection and followed by radioactive iodine therapy for papillary thyroid cancer. He had 131-I iodine avid nodular lesion in the left parotid gland which was later proven to be oncocytoma on histopathology. False positive findings on radioactive iodine scans are a possibility which should be known to surgeons as well as nuclear medicine physicians for accurate diagnosis and appropriate management. [ABSTRACT FROM AUTHOR]

Objective Our objective was to study the radiation exposure rate as function of time in the administration of radioiodine iodine-131 (I-131) for the treatment of thyrotoxicosis or Graves' disease and remnant ablation on an outpatient basis at the Department of Nuclear Medicine, and also, to study the impact of revised discharge criteria for radioiodine therapy enforced by the Atomic Energy Regulatory Board (AERB) of India. Materials and Methods This study included patients who underwent low-dose radioiodine therapy using I-131. Patients were classified into two different groups, that is, group A and group B. Group A included patients receiving low dose I-131 for the treatment of thyrotoxicosis, whereas group B included patients receiving I-131 therapy for the ablation of residual thyroid tissue after total thyroidectomy. The radiation exposure rate was measured using a radiation detector in milli roentgen per hour (mR/h) at 5 cm distance of stomach and neck levels and with the patient standing at the distance of 1 m after oral administration of I-131 at 0, 1, and 2 hours. Results A total of 134 (17 males and 117 females) patients were included in the study. Group A comprised 102 (14 male and 88 females) patients and group B of 32 (3 males and 29 females) patients. At the neck level, the average exposure rate in group A versus group B after 0, 1, and 2 hours was observed to be 6.9 versus 22.27 mR/h, 33.67 versus 43.39 mR/h, and 41.75 versus 48.90 mR/h, respectively. At the stomach level, the exposure rate was 23.65 versus 71.32 mR/h, 13.27 versus 48.45 mR/h, and 9.91 versus 39.43 mR/h after 0, 1, and 2 hours, respectively. At a distance of 1 m, the exposure rate was 1.31 versus 2.99 mR/h, 1.05 versus 2.58 mR/h, and 0.92 versus 2.21 mR/h, respectively. Conclusion Exposure rate measured for patients treated with up to 1,110 MBq (30 mCi) of I-131 was under permissible limits as per revised discharged limits, that is, 50 µSv/h (5 mR/h) prescribed by AERB, India. The patients undergoing radioiodine therapy I-131 (up to 1,110 MBq/30 mCi) can be discharged safely 2 hours postadministration following good work practice along with providing proper radiation safety instructions to patients. [ABSTRACT FROM AUTHOR]

IntroductionDifferentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients.MethodsEighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up.ResultsPrepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, p-value 0.06). None of our patients died disease-related over the observed period.ConclusionPrepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/postpubertal groups.

Background: The clinical features and prognosis of children and adolescents with differentiated thyroid carcinoma (caDTC) are different from that of adults. Postoperative radioiodine therapy (RIT) was recommended for some intermediate and high risk caDTC patients. The objective of this study was to evaluate the long-term prognosis of pediatric caDTC patients with different responses to initial RIT and to explore the related influencing factors. Methods: All subjects were assigned to no clinical evidence of disease (NED) group, biochemical persistent disease (BPD) group, or structural/functional persistent disease (S/FPD) group based on the therapeutic response to initial RIT. Then, disease status was evaluated in all three groups at the last follow-up using ATA guidelines. Meanwhile, disease-free survival (DFS) for NED group and the progression-free survival (PFS) for the BPD and S/FPD groups were also assessed. Results: 117 subjects were divided into NED group (n=29), BPD group (n=48) and S/FPD group (n=34) after initial RIT. At the last follow-up, excellent response (ER), indeterminate response (IDR), biochemically incomplete response (BIR) and structurally incomplete response (SIR) rates were 93.10%, 6.90%, 0% and 0% in NED group; 29.17%, 25.00%, 43.75% and 2.08% in BPD group; and 11.77%, 2.94%, 0%, and 85.29% in S/FPD group. The 5-year DFS rate in NED group was 95.5%. The 5-year PFS rates in BPD and S/FPD groups were 79.2% and 48.6%, respectively. For children with structural or functional lesions, longer PFS were found in male children with 131I-avid lesions, and post-operative stimulated serum thyroglobulin (sti-Tg) < 149.80 ng/ml. Conclusion: The response to initial RIT could be helpful for defining subsequent treatment and follow-up strategies for caDTC patients. Post-operative sti-Tg and 131I-avidity of lesions are correlated with PFS. [ABSTRACT FROM AUTHOR]

Purpose: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. Methods: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. Results: We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD (P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (DLDL) was the only factor correlated negatively with the change of FMD (DFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Conclusion: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy. [ABSTRACT FROM AUTHOR]

Background: Faecalibacterium prausnitzii, one of the most important bacteria of the human gut microbiota, produces butyrate (a short-chain fatty acid). Short-chain fatty acids are known to influence thyroid physiology and thyroid cancer's response to treatment. We aimed to analyze the relative abundance of Faecalibacterium prausnitzii on the gut microbiota of differentiated thyroid cancer patients compared to controls and its variation after radioiodine therapy (RAIT). Methods: Fecal samples were collected from 37 patients diagnosed with differentiated thyroid cancer before and after radioiodine therapy and from 10 volunteers. The abundance of F. prausnitzii was determined using shotgun metagenomics. Results: Our study found that the relative abundance of F. prausnitzii is significantly reduced in thyroid cancer patients compared to volunteers. We also found that there was a mixed response to RAIT, with an increase in the relative and absolute abundances of this bacterium in most patients. Conclusions: Our study confirms that thyroid cancer patients present a dysbiotic gut microbiota, with a reduction in F. prausnitzii's relative abundance. In our study, radioiodine did not negatively affect F. prausnitzii, quite the opposite, suggesting that this bacterium might play a role in resolving radiation aggression issues. [ABSTRACT FROM AUTHOR]

Purpose: The role of adjuvant external-beam radiotherapy (EBRT) in the treatment of locally advanced papillary thyroid carcinoma (PTC) remains controversial due to the lack of prospective data and the conflicting retrospective data. This study aimed to determine the benefits of adjuvant EBRT in patients with PTC and other organ invasions using propensity score matching to reduce the heterogeneity of the patient population. Methods: Data from patients with PTC with other organ invasions but no distant metastases who underwent surgery and adjuvant radioactive iodine (RAI) alone (Non-EBRT group) or adjuvant EBRT plus RAI (EBRT group) were retrospectively reviewed. Propensity matching was used to reduce heterogeneity. Survival outcomes and toxicities associated with EBRT were evaluated. Results: Between January 2005 and December 2019, 102 patients in the Non-EBRT group and 26 patients in the EBRT group were evaluated. In the 48 propensity score-matched patients, no significant differences in baseline characteristics between the Non-EBRT and EBRT groups were detected. The locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were significantly higher in the EBRT group compared with the rates in the Non-EBRT group (5y-LRRFS: 100% vs. 74%, p = 0.003, 5y-RFS: 91% vs. 74%, p = 0.035). EBRT was well-tolerated, with no grade ≥ 3 toxicity, and all patients completed the therapy as planned. Conclusion: Adjuvant EBRT plus RAI exhibited acceptable toxicity and improved LRRFS and RFS in patients with PTC with other organ invasions compared with RAI alone. [ABSTRACT FROM AUTHOR]

Introduction: The occurrence of non-thyroidal second primary malignancy (NTSPM) in patients with papillary thyroid cancer (PTC) is well documented, but epidemiological data are conflicting. Objective: The aim of this study was to evaluate the incidence of NTSPM in a large series of patients with PTC and to assess its potential risk factors. Methods: Single-center cohort study with retrospective data collection conducted on consecutive PTC patients diagnosed from 1988 to 2018 with a minimum follow-up time of 2 years. NTSPM was defined as any primary malignancy with histological confirmation occurring in an anatomical site other than the thyroid. According to the timing of occurrence, NTSPM were subdivided into anachronous, synchronous or metachronous (diagnosed >6 months before, within 6 months and >6 months after PTC diagnosis, respectively). Results: We included 773 individuals (83.3% females), median age at PTC diagnosis was 47.0 (IQR: 37.0–58.0) years and median follow-up time was 9.9 (6.2–16.3) years. Incidence of NTSPM was 15.5% (n = 120) and its standard incidence ratio (SIR) was higher when compared to the general population (SIR: 2.70). Family history of malignancy and younger age at diagnosis were associated respectively with 206 and 4% increased risk of developing metachronous neoplasia (HR: 2.06 (95% CI: 1.10–3.86) and 1.04 (95% CI: 1.02–1.05), respectively). Conclusion: In our series, the occurrence of NTSPM was not uncommon and its incidence was higher compared to the general population. First-degree family history of malignancy was a strong risk factor for multiple primary malignancies.

Radioactive iodine 131I is a theranostic isotope used both for diagnosis and therapy of benign thyroid diseases and thyroid cancer for 85 years. The formation of nuclear medicine is closely linked with the use of 131I. The history of radioiodine therapy began in 1941, when endocrinologist Saul Hertz for the first time used 131I to treat patients with Graves' disease. Since 1946 radioactive iodine 131I became widely available, and its effectiveness became public knowledge after reports on thyrotoxicosis treatment published in the Journal of the American Medical Association by multidisciplinary groups of scientists physicists and endocrinologists. In 1951, isotope 131I became the first Food and Drug Administration approved RP for the treatment of thyroid disorders. Around the same time on the basis of the First Moscow Medical Institute studies on the use of radioiodine isotopes in patients with thyrotoxicosis began. The head of the Soviet group on the studying of radioactive iodine was the physician-scientist Vera Georgievna Spesivtseva. The research works of medical physicists Edith Quimby and Leonidas Marinelli in optimizing therapeutic strategies using radioactive substances in the late 1940s and the wording of the ALARA (As Low As Reasonably Achievable) principle of minimizing exposure of ionizing radiation by the International Commission on Radiological Protection in 1954 contributed to the greater introduction of radionuclides into the medicine.

Abstract Background While the most suitable approach for treating persistent/recurrent papillary thyroid carcinoma (PTC) remains controversial, reoperation may be considered an effective method. The efficacy of reoperation in patients with locoregional persistent/recurrent PTC, especially those with unsatisfactory radioactive iodine (RAI) ablation results, is still uncertain. This study aimed to clarify the clinical management strategies for locoregional persistent/recurrent PTC and to explore factors that may affect long-term patient outcomes after reoperation. Methods In total, 124 patients who initially underwent thyroidectomy and variable extents of RAI therapy and finally received reoperation for locoregionally persistent/recurrent PTC were included. The parameters associated with recurrence-free survival (RFS) were analysed using a Cox proportional hazards model. Results Overall, 124 patients presented with structural disease after initial therapy and underwent secondary surgical resection, of whom 32 patients developed further structural disease during follow-up after reoperation. At the time of reoperation, metastatic lymph nodes with extranodal extension (P = 0.023) and high unstimulated thyroglobulin (unstim-Tg) levels after reoperation (post-reop) (P = 0.001) were independent prognostic factors for RFS. Neither RAI avidity nor the frequency and dose of RAI therapies before reoperation affected RFS. Conclusions Reoperation is an ideal clinical treatment strategy for structural locoregional persistent/recurrent PTC, and repeated empirical RAI therapies performed prior to reoperation may not contribute to the long-term outcomes of persistent/recurrent PTC patients. Metastatic lymph nodes with extranodal extension and post-reop unstim-Tg > 10.1 ng/mL may predict a poor prognosis.

The aim of the present study was to evaluate the subpopulation profile of T and B lymphocytes, and their relationships during therapy of the patients with Graves’ disease (GD) treated by means of radioactive iodine. We have examined 36 women with verified diagnosis of GD. The contents of thyroid hormones were determined by immunoradiometric analysis. The levels of thyroid-stimulating hormone receptor autoantibodies (rTSH) were evaluated by enzyme-linked immunosorbent assay. On the basis of comprehensive pre-therapeutic examination, all patients were exposed to the fixed-activity therapy with radioactive iodine-131 at a dose of 400 to 700 MBq administered orally in isotonic aqueous solution of sodium iodide. 56 practically healthy women were examined as a control group. The phenotype of T and B cells in whole blood was studied by flow cytometry using direct immunofluorescence. It was shown that the patients, prior to treatment with radioactive iodine, had high levels of cellular functional activity, as determined by expression of CD25 antigen on T cells and CD23-antigen on B lymphocytes. Higher functional activity of the cells responsive for adaptive immunity in the patients with GD manifests in the presence of increased levels of autoantibodies to rTSH. By means of correlation analysis, we found that the patients with GD examined before the therapy had the thyroid status may determine the functional stimulation of T and B cells, thus increasing the levels of autoimmune processes. One month after radioiodine therapy (RIT), the GD patients, along with transient hyperthyroidism with increased concentration of autoantibodies to rTSH, showed a reduction of activated T lymphocyte contents (including T helpers and cytotoxic T cells) to control values. However, the level of cytotoxic T lymphocytes in the blood remained low, and the content of Treg cells was significantly increased in the patients. Decreased contents of B cells activated memory B cell to the control levels were found in patients with GD over 1 month after RIT when studying the phenotype of blood B lymphocytes. In this case, increased levels of naive B lymphocytes and B2 cells were detected, as well as decreased numbers of activated B1 lymphocytes. The observed changes in the subpopulation composition of T and B cells, and in their phenotype developed against the background of complete absence of relationships between the studied parameters, thus suggesting loss of thyroid control of immune processes and cooperative cell interaction during the development of the immune response. Generally, the phenotypic changes of T and B lymphocyte subsets in the blood of patients with GD through 1 month after treatment with radioactive iodine may reflect a trend for decreased functional activity of adaptive cellular immunity which may also account for inhibition of autoimmune processes.

Simple Summary: The most appropriate treatment for local/regional recurrent differentiated thyroid cancers (DTC) is surgical excision if feasible, followed by adjuvant radioiodine administration. However, depending on the location or extent of the recurrence, surgical excision may not be possible, thus creating a need for alternative therapeutic interventions to maintain the otherwise excellent prognosis for this disease. In light of the increased incidence of this disease and the plethora of available systemic options, a detailed knowledge of the available treatment options is essential for successful management of recurrent DTC. Differentiated thyroid carcinomas (DTC) have an excellent prognosis, but this is sometimes overshadowed by tumor recurrences following initial treatment (approximately 15% of cases during follow-up), due to unrecognized disease extent at initial diagnosis or a more aggressive tumor biology, which are the usual risk factors. The possible sites of recurrence are local, regional, or distant. Local and regional recurrences can usually be successfully managed with surgery and radioiodine therapy, as are some isolated distant recurrences, such as bone metastases. If these treatments are not possible, other therapeutic options such as external beam radiation therapy or systemic treatments should be considered. Major advances in systemic treatments have led to improved progression-free survival in patients previously considered for palliative treatments; among these treatments, the most promising results have been achieved with tyrosine kinase inhibitors (TKI). This review attempts to give a comprehensive overview of the current treatment options suited for recurrences and the new treatments that are available in cases where salvage surgery is not possible or in cases resistant to radioiodine. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of the present study was to retrospectively evaluate the efficacy of low (1.1 GBq) versus moderate (2.2 GBq) 131I activities in a large series (n = 299) of low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative 131I ablation. At the follow-up, according to the ATA criteria, an excellent response was observed in 96.9% of patients treated with moderate 131I activities versus 85.6% of patients treated with low 131I activities (p = 0.029). Conversely, a biochemically indeterminate or incomplete response was observed in 22.2% of patients treated with low 131I activities versus 1.8% of patients treated with moderate 131I activities (p = 0.001), and an incomplete structural response was observed in three patients treated with low 131I activities versus two patients treated with moderate 131I activities (p = 0.654). In conclusion, we encourage the use of moderate instead of low activities when 131I ablation is indicated in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease. Objectives: To compare the efficacy of low and moderate 131I activities in low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative thyroid remnant ablation in a real-world clinical setting. Methods: We retrospectively reviewed the records of 299 low-risk DTC patients (pT1-T2, Nx(0) Mx) who had undergone (near)-total thyroidectomy followed by 131I therapy, using either low (1.1 GBq) or moderate (2.2 GBq) radioiodine activities. The response to initial treatments was evaluated after 8–12 months, and patient responses were classified according to the 2015 American Thyroid Association guidelines. Results: An excellent response was observed in 274/299 (91.6%) patients, specifically, in 119/139 (85.6%) and 155/160 (96.9%) patients treated with low and moderate 131I activities, respectively (p = 0.029). A biochemically indeterminate or incomplete response was observed in seventeen (22.2%) patients treated with low 131I activities and three (1.8%) patients treated with moderate 131I activities (p = 0.001). Finally, five patients showed an incomplete structural response, among which three and two received low and moderate 131I activities, respectively (p = 0.654). Conclusions: When 131I ablation is indicated, we encourage the use of moderate instead of low activities, in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease. [ABSTRACT FROM AUTHOR]