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Background and aim: Atherosclerosis evolves or accelerates when arteries are exposed to ionizing radiation, both early and late after exposure. Radioiodine therapy of benign thyroid disease exposes the carotid arteries to 4–50 Gy, and may thereby increase the risk of atherosclerosis. Increased risk of cerebrovascular events has been reported after radioiodine therapy. This study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease. Method: Patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined with ultrasound for the main outcome, carotid intima media thickness (CIMT), and for plaque presence (plaque presence only in late damage). Signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. Late changes were studied in a cross-sectional case-control design, with radioiodine-treated patients as cases (n = 193) and patients treated with surgery as controls (n = 95). Data were analyzed with repeated measurement for longitudinal data, and with multivariate regression for cross-sectional data. Results were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index. Results: No changes in CIMT were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p = 0.58). In the study on late effects, there was no difference in CIMT (p = 0.25) or presence of plaques (p = 0.70) between those treated with radioactive iodine and those treated with surgery (9.8 and 5.6 years since treatment, respectively). Furthermore, the level of thyrotropin (TSH) did not influence these atherosclerosis markers. Conclusion: No early changes in CIMT were detected in patients treated with radioactive iodine for benign thyroid disease. No signs of late effects of radioactive iodine on CIMT or plaque presence were found after 10 years of follow-up. The radiation to the carotid arteries by radioactive iodine therapy for benign thyroid disease may therefore have no or low effect on atherosclerotic burden of the carotid arteries in general.

Rebound thymic hyperplasia (RTHP) is not an uncommon finding after radiation or chemotherapy in patients with various malignancies. However, there are limited case reports of this phenomenon after radioactive iodine ablation therapy (RIAT) in differentiated thyroid cancer (DTC). The goal of this study was to evaluate the incidence, patterns, and factors affecting RTHP after RIAT using (18)F-FDG PET/CT.The study design was a retrospective review of 2550 patients (568 men, 1982 women; age 13-79 years) who underwent FDG PET/CT imaging after total thyroidectomy and RIAT from June 2009 through June 2012. Patients were divided into four age-related subgroups. Overall incidence, age-related incidences, and sex distribution were evaluated in patients with thymic FDG uptake on PET/CT (RTHP+). The correlation between incidence of RTHP and age was assessed using the Cochran-Armitage trend test. The Wilcoxon rank-sum test and multiple regression were applied to investigate the effect of applied dose of radioactive iodine (RAI) and age on the incidence of RTHP. Correlations of standardized uptake value (SUV) and thymic volume with age and morphologic type were also evaluated.Overall incidence of RTHP after RIAT was 1.49%, and all of the RTHP+ patients except one were female. The Cochran-Armitage trend test revealed significantly decreased incidence from the second to fifth decade (8.84%, 1.74%, 0.98%, and 0.39% respectively; p0.001). In each age-related subgroup, the RAI dose was significantly higher in the RTHP+ than RTHP- group (p0.001), while there was no difference in RAI dose in RTHP+ patients among age-related subgroups (p=0.838). SUVmean and SUVmax of RTHP revealed no meaningful correlation with RAI dose or age. There were no differences among morphologic patterns of RTHP in age distribution and ablation dose.RTHP after RIAT showed a strong female predominance, despite the higher administration dose of RAI in male patients. Although the decreased incidence of RTHP after RIAT with age is similar to the pattern of RTHP induced by other causes, the fact that older patients, even sixth decade patients, can present with RTHP after RIAT is noteworthy in the management of DTC.

Ablation of the thyroid tissue using radioactive iodine (RAI) after the surgical removal of well-differentiated thyroid cancer can induce radiation-related salivary gland (SG) dysfunction. However, in vivo changes of SGs after RAI administration in appropriate animal models are not well described in the literature. This study was undertaken to document morphometric and functional changes during the 12 months after RAI administration in a murine model of RAI-induced SG dysfunction.Four-week-old female C57BL/6 mice (n = 60) were divided into an RAI-treated group (n = 30) that received RAI orally (0.01 mCi/g body weight) and an unexposed control group (n = 30). Mice in both groups were divided into five subgroups (n = 6 per subgroup) and euthanized at 1, 2, 3, 6, and 12 months post-RAI administration. Salivary flow rates and salivary lag times were measured at 1, 2, 3, 6, and 12 months after RAI administration. Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed. In addition, changes in salivary (99m)Tc pertechnetate uptake and excretion were observed by single-photon emission computed tomography.In RAI-treated mice, the SGs were significantly lighter than those of unexposed controls at all study time points. Lag times to salivation in the RAI-treated group were greater than in the unexposed controls, but mean salivary flow rates were lower. Histologic examinations of SGs in the RAI group showed pale cytoplasm, atypical ductal configuration, septal widening, cytoplasmic vacuolization with pleomorphism, lymphocyte infiltration, and increased fibrosis. Furthermore, more apoptotic cells were observed in acini and ducts in the RAI group. In addition, patterns of (99m)Tc pertechnetate uptake and excretion in the RAI group were quite different from those observed in controls at 1 and 12 months post-RAI.Various histological alterations were observed in mice exposed to RAI, that is, an increase in apoptotic acini and ductal cells and functional SG deterioration. The murine model of RAI-induced SG dysfunction used in the present study appears to be applicable to preclinical research on RAI-induced sialadenitis in patients with well-differentiated thyroid cancer.

A low-iodine diet (LID) is usually recommended for a week or two before radioactive iodine (RAI) ablation therapy in papillary thyroid cancer (PTC) patients after total thyroidectomy. However, it is still controversial whether an LID affects ablation outcomes. We therefore evaluated the association between urinary iodine excretion and the rate of successful ablation and investigated the determinants of successful RAI ablation outcomes.We retrospectively reviewed the records of 295 consecutive patients with PTC who received 1110 MBq RAI remnant ablation therapy with thyroid hormone withdrawal after total thyroidectomy. Successful ablation was defined as either no visible or faint uptake on a follow-up scan (definition 1), or no visible or faint uptake on a follow-up scan and a stimulated thyroglobulin level2 ng/mL (definition 2).The proportion of patients with appropriate LID status (defined as a urinary iodine concentration [UIC]66.2 μg iodine/g creatinine [μg/gCr]) was significantly higher in the successfully ablated group (81% vs. 67%, p=0.03). Based on definition 1, 80.3% (237/295) of patients were successfully ablated. The ablation rate was significantly lower in patients who had a UIC250 μg/gCr at the time of RAI ablation (p0.05). In multivariate analysis, a UIC250 μg/gCr was the only significant variable associated with ablation failure (p=0.002, odds ratio [OR] 4.74 [95% confidence interval (CI) 1.78-12.63]). Based on definition 2, 74.9% (221/295) of patients were successfully ablated. A UIC250 μg/gCr at RAI administration showed a significant association with ablation failure (p0.05). The OR of a UIC250 μg/gCr for ablation failure was 3.88 [CI 1.42-10.57] (p=0.008).Excessive iodine intake (UIC250 μg/gCr) was associated with poor RAI ablation outcomes. Because this amount of iodine is very high, we propose that the level of strictness of the LID protocol should be modified according to the region that the patient is from and the food that the patient is accustomed to eating. Even in those areas where iodine intake is high, overly strict compliance with an LID protocol is not necessary and simple recommendations to avoid iodine-rich foods would be appropriate.

There is variation in the use of radioactive iodine (RAI) as treatment for well-differentiated thyroid cancer. The factors involved in physician decision-making for RAI remain unknown.We surveyed physicians involved in postsurgical management of patients with thyroid cancer from 251 hospitals. Respondents were asked to rate the factors important in influencing whether a thyroid cancer patient receives RAI. Multivariable analyses controlling for physician age, gender, specialty, case volume, and whether they personally administer RAI, were performed to determine correlates of importance placed on patients' and physicians' worry about death from cancer and differences between low- versus higher-case-volume physicians.The survey response rate was 63% (534/853). Extent of disease, adequacy of surgical resection, patients' willingness to receive RAI, and patients' age were the factors physicians were most likely to report as quite or very important in influencing recommendations for RAI to patients with thyroid cancer. Interestingly, both physicians' and patients' worry about death from thyroid cancer were also important in determining RAI use. Physicians with less thyroid cancer cases per year were more likely than higher-volume physicians to report patients' (p0.001) and physicians' worry about death (p=0.016) as quite or very important in decision-making. Other factors more likely to be of greater importance in determining RAI use for physicians with lower thyroid cancer patient volume versus higher include the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI expressed by colleagues comanaging patients (p=0.003), and patient distance from the nearest facility administering RAI (p=0.012).In addition to the extent of disease and adequacy of surgical resection, physicians place importance on physician and patient worry about death from thyroid cancer when deciding whether to treat a patient with RAI. The factors important to physician decision-making differ based on physician thyroid-cancer case-volume, with worry about death being more influential for low-case-volume physicians. As the mortality from thyroid cancer is low, the importance placed on death in decision making may be unwarranted.