Predictors of Prolonged Euthyroidism After Radioactive Iodine Treatment for Graves' Disease: A Pilot Study.

OBJECTIVE: Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI. METHODS: Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models. RESULTS: Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932. CONCLUSION: Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.

Immune reconstitution inflammatory syndrome-associated Graves disease in HIV-infected patients: clinical characteristics and response to radioactive iodine therapy.

OBJECTIVES: We aimed to describe the clinical characteristics and the response to radioactive iodine (RAI) treatment of immune reconstitution inflammatory syndrome-associated Graves disease (IRIS-GD) in comparison to Graves disease (GD) seen in HIV-uninfected patients. METHODS: We retrospectively reviewed the medical records of patients treated with RAI for GD. We obtained clinical, biochemical and HIV-related information of patients from their medical records. We compared patient characteristics and response to RAI treatment between patients with IRIS-GD and GD seen in HIV-uninfected patients. RESULTS: A total of 253 GD patients, including 51 patients with IRIS-GD, were included. Among IRIS-GD patients, CD4 cell nadir was 66 cells/µL (range: 37-103) with a peak HIV viral load of 60 900 copies/mL (range: 36 542-64 500). At the time of diagnosis of IRIS-GD, all patients had a completely suppressed HIV viraemia with a CD4 cell count of 729 cells/µL (range: 350-1279). The median interval between the commencement of HIV treatment and the onset of GD was 63 months. At 3 months follow-up, the proportion of patients with IRIS-GD achieving a successful RAI treatment outcome (euthyroid/hypothyroid state) was lower than that of HIV-uninfected patients (35.3% vs. 63.4%, respectively; p < 0.001). The response rate remained lower (60.8%) among patients with IRIS GD than among HIV-uninfected GD patients (80.2%, p = 0.004) at 6 months follow-up. After correcting for differences in age, gender and pre-treatment thyroid-stimulating hormone level, there was no significant difference in RAI treatment response between the two groups. CONCLUSIONS: After correcting for possible confounders, the response to RAI treatment was not different between patients with IRIS-GD and GD in HIV-uninfected patients.

Impact of thyroid cancer treatment on assisted reproductive technology outcomes in women with infertility.

PURPOSE: We investigated the effect of different surgical procedures and radioactive iodine treatment (RAIT) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and evaluated whether possible risk factors, including age, thyroid-stimulating hormone (TSH) levels, and thyroid antibody positivity, were associated with adverse IVF/ICSI outcomes. METHODS: This retrospective study included 76 women with infertility who had received thyroid cancer (TC) treatment among 137,698 infertile women who underwent IVF/ICSI cycles at the Peking University Third Hospital between 2010 and 2019. Clinical pregnancy and live birth rates were assessed. RESULTS: We found that the clinical pregnancy and live birth rates in women who underwent partial thyroidectomy were 7- and 6-fold higher, respectively, than those in women who underwent total thyroidectomy. We observed no significant differences in the clinical pregnancy and live birth rates between the RAIT and non-RAIT groups, even after adjusting for age, TSH levels, surgical treatment, and thyroid antibody positivity. Multivariate logistic regression analysis showed that age and TSH levels were not associated with decreased clinical pregnancy and live birth rates. Women with thyroid antibody positivity had significantly lower clinical pregnancy and live birth rates than women without thyroid antibody positivity. CONCLUSION: Our study showed lower clinical pregnancy and live birth rates in women who underwent total thyroidectomy than in women who underwent partial thyroidectomy. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment.

Predictors of thyroglobulin in the lymph nodes recurrence of papillary thyroid carcinoma undergoing total thyroidectomy.

BACKGROUND: To investigate the association between postoperative lymph nodes (LNs) recurrence and distinct serum thyroglobulin (Tg) levels in patients with papillary thyroid carcinoma (PTC). METHODS: This study included PTC patients who underwent total thyroidectomy (TT) with at least central neck dissection and then re-operated due to recurrence of LNs between January 2013 and June 2018. These patients were grouped by negative or positive serum Tg levels according to the American Thyroid Association guidelines. RESULTS: Of the 60 included patients, 49 underwent radioactive iodine (RAI) treatment. Maximum unstimulated Tg (uTg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs (P = 0.027), and higher rate of metastatic LNs (P < 0.001). Serum-stimulated Tg (off-Tg) ≥ 1 ng/mL (P = 0.047) and unstimulated Tg (on-Tg) ≥ 0.2 ng/Ml (P = 0.013) were associated with larger diameter of recurrent LNs. Number of metastatic LNs ≥ 8 was an independent predictor for postoperative maximum uTg ≥ 0.2 ng/mL (OR = 8.767; 95% CI = 1.392-55.216; P = 0.021). Ratio of metastatic LNs ≥ 25% was an independent predictor for off-Tg ≥ 1 ng/mL (OR = 20.997; 95% CI = 1.649-267.384; P = 0.019). CONCLUSION: Postoperative Tg-positive status was associated with larger size of recurrent LNs. Number of metastatic LNs ≥ 8 and ratio of metastatic LNs ≥ 25% were independent predicators for uTg-positive and off-Tg-positive status, respectively.

Poorly differentiated thyroid carcinoma (PDTC) characteristics and the efficacy of radioactive iodine (RAI) therapy as an adjuvant treatment in a tertiary cancer care center.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is biologically more aggressive. Surgery remains the mainstay of treatment. The utility of radioactive iodine (RAI) after surgery is unclear. METHODS: In this retrospective study, patients treated between Jan 2012 and Dec 2017 were included. The demographic, clinical and treatment-related details, including RAI ablation, were recorded and their survival analyzed. RESULTS: Thirty-five patients fulfilled the eligibility criteria. Majority was treatment naïve at presentation. All patients underwent surgery followed by RAI ablation, with a cumulative median dose of 220 mCi (range 40-1140). Sixteen patients received more than one radioiodine treatment for distant metastases. Incomplete resection, age > 45 years and the presence of distant metastasis influenced survival the most. The 3-year PFS of patients with PDTC was 69%. CONCLUSION: All patients in our series showed uptake and responded to treatment. Further use of molecular markers and functional molecular imaging would better our understanding of this entity.

Investigation on low-iodine diet implementation by medical staff before radioactive iodine treatment for differentiated thyroid carcinoma.

OBJECTIVE: To explore the implementation of low-iodine diets by medical staff caring for patients with differentiated thyroid carcinoma prior to 131I therapy across 58 hospitals, and offer valuable insights for the development of guidelines on low-iodine diets. METHODS: Convenience sampling was utilized to conduct a survey among 163 medical staff members working in nuclear medicine departments across 58 tertiary hospitals using a self-designed questionnaire. RESULTS: Concerning the duration of the low-iodine diet prior to treatment, the medical staff's recommendations were as follows: 58.28% suggested 2-4 weeks, 31.29% recommended more than 4 weeks, 9.2% opted for 7-13 days, and 1.23% favored less than 1 week. Regarding the timing of resuming a normal diet, the respondents' recommendations ranged from immediately after treatment (1.84%) to 3 months post-treatment (8.58%), with intermediate recommendations of 2 h (8.58%), 24-48 h (14.11%), post-discharge (12.26%), and 1 month (42.94%). Furthermore, the surveyed medical staff unanimously recommended abstaining from seafood, with 90.8% also advising against the consumption of iodized salt, 91.41% recommending avoidance of iodine-containing medications, and 71.17% advising caution with moderately high-iodine foods. Notably, 75.46% of the medical staff evaluated patient compliance with the low-iodine diet. When patients failed to adhere to the diet preparation, 33.74% of healthcare workers chose to proceed with treatment. In terms of guidance sources, 96.93% of respondents relied on relevant guidelines, 66.26% referred to the literature, and 49.69% drew upon their clinical experience. During hospitalization, 58.28% of the medical staff continued to guide patients on the low-iodine diet, while only 8.59% provided such guidance after discharge. Notably, only 20.25% of the staff considered consulting the nutrition department. CONCLUSION: This study underscored substantial variations in the duration and selection criteria for low-iodine diets, which were linked to a scarcity of standardized evaluations. Consequently, there is an urgent need for further research to establish detailed, practical, accessible, comprehensive, and dependable implementation programs for low-iodine diets.

Is second 131I treatment necessary for differentiated thyroid cancer patients and who could not benefit from it? A real-world retrospective study in China.

BACKGROUND: The efficacy of a second radioactive iodine-131 (131I) treatment in patients with differentiated thyroid cancer (DTC) who did not achieve an excellent response (ER) following initial 131I therapy remains controversy and the population that would derive limited benefit from it is currently unclear. OBJECTIVES: The aim of this retrospective study was to assess the efficacy of the second 131I treatment in DTC patients with non-ER after the initial 131I therapy, and to identify potential risk factors associated with non-benefit of the second 131I treatment. METHODS: 127 DTC patients who underwent two 131I treatments following thyroidectomy were included in this study, and the therapeutic response was evaluated after each 131I treatment. Beneficial treatment was defined as an improvement in therapy response grade (e.g. from indeterminate response to ER) after the second 131I treatment, while unbeneficial treatment was defined as no change or a downgrade in therapy response grade. The potential risk factors associated with the non-benefit of the second 131I treatment were identified using univariate and multivariate logistic regression models. RESULTS: Following the second 131I treatment, therapy responses of 55.12% (70/127) of patients were reclassified to a better grade indicating treatment benefit, while 44.88% (57/127) showed no change or were reclassified to a worse grade suggesting no benefit from treatment. The non-benefit of the second 131I treatment was significantly associated with potential risk factors including stimulated thyroglobulin (sTg) level ≥ 11.46 ng/mL before the second 131I treatment, primary tumor size > 2 cm, status T2 or higher, N1b status and ATA high risk. CONCLUSIONS: The study results demonstrated that more than half of DTC patients could potentially benefit from a second 131I therapy. However, over 40% of patients exhibited no benefit in response to the second 131I treatment, suggesting potential overtreatment for this subgroup. Therefore, clinicians should exercise meticulous and precise decision-making based on identified risk factors when considering the necessity of a second 131I treatment.

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects.

INTRODUCTION: Patients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies. Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. MATERIAL AND METHODS: Patients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy. Patients were reclassified in the following 6-18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels. The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. RESULTS: Sixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses. A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). CONCLUSIONS: In selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK.

Radioactive iodine is a highly effective treatment for thyroid cancer and has now been used in clinical practice for more than 80 years. In general, the treatment is well tolerated. However, it can be logistically quite complex for patients due to the need to reduce iodine intake and achieve high levels of thyroid-stimulating hormone prior to treatment. Radiation protection precautions must also be taken to protect others from unnecessary radiation exposure following treatment. It has been well documented by thyroid cancer patient support groups that there is significant variation in practice across the UK. It is clear that some patients are being asked to observe unnecessarily burdensome restrictions that make it more difficult for them to tolerate the treatment. At the instigation of these support groups, a multidisciplinary group was assembled to examine the evidence and generate guidance on best practice for the preparation of patients for this treatment and the management of subsequent radiation protection precautions, with a focus on personalising the advice given to individual patients. The guidance includes advice about managing particularly challenging situations, for example treating patients who require haemodialysis. We have also worked together to produce a patient information leaflet covering these issues. We hope that the guidance document and patient information leaflet will assist centres in improving our patients' experience of receiving radioactive iodine. The patient information sheet is available as Supplementary Material to this article.

Risk of Adverse Pregnancy Outcomes in Young Women with Thyroid Cancer: A Systematic Review and Meta-Analysis.

This meta-analysis investigated whether thyroidectomy or radioactive iodine treatment (RAIT) in patients with differentiated thyroid cancer (DTC) was associated with an increase in adverse pregnancy outcomes, such as miscarriage, preterm delivery, and congenital malformations. A total of 22 articles (5 case-control and 17 case series studies) from 1262 studies identified through a literature search in the PubMed and EMBASE databases from inception up to 13 September 2021 were included. In patients with DTC who underwent thyroidectomy, the event rates for miscarriage, preterm labor, and congenital anomalies were 0.07 (95% confidence interval [CI], 0.05-0.11; 17 studies), 0.07 (95% CI, 0.05-0.09; 14 studies), and 0.03 (95% CI, 0.02-0.06; 17 studies), respectively. These results are similar to those previously reported in the general population. The risk of miscarriage or abortion was increased in patients with DTC when compared with controls without DTC (odds ratio [OR], 1.80; 95% CI, 1.28-2.53; I2 = 33%; 3 studies), while the OR values for preterm labor and the presence of congenital anomalies were 1.22 (95% CI, 0.90-1.66; I2 = 62%; five studies) and 0.73 (95% CI, 0.39-1.38; I2 = 0%; two studies) respectively, which showed no statistical significance. A subgroup analysis of patients with DTC according to RAIT revealed that the risk of miscarriage, preterm labor, or congenital anomalies was not increased in the RAIT group when compared with patients without RAIT. The results of this meta-analysis suggest that thyroid cancer treatment, including RAIT, is not associated with an increased risk of adverse pregnancy outcomes, including miscarriage, preterm labor, and congenital anomalies.

Non-Iodine-Avid Disease Is Highly Prevalent in Distant Metastatic Differentiated Thyroid Cancer With Papillary Histology.

CONTEXT: Patients with radioactive iodine (RAI) refractory metastatic differentiated thyroid cancer (DTC) have poor prognosis. Early identification of RAI refractoriness may improve care. OBJECTIVE: This work aimed to characterize DTC patients with distant metastases (DM) at diagnosis who presented with non-iodine-avid disease. METHODS: Retrospective analyses of DTC patients with DM at diagnosis who presented between 2012 and 2020 were performed. Iodine uptake in DM was correlated with tumor histology and mutational profile. The difference in uptake between BRAFV600E-like (BVL) and RAS-like (RL) cancers based on insights from The Cancer Genome Atlas was evaluated. RESULTS: Among 78 patients, 48.7% had negative uptake in DM on the first posttherapy scan. Negative scans were highly prevalent in papillary thyroid carcinoma (PTC) with papillary architecture, PTC with BRAFV600E mutation, and PTC with both BRAFV600E and TERT promoter mutations (71.1%, 80.9%, and 100%, respectively). BVL and RL tumors exhibited distinct uptake patterns with negative scan prevalence of 76.9% and 14.3% (P = .005). Multivariate logistical regression confirmed high odds of negative uptake in BVL tumors with either BVL mutations or papillary architecture, 19.8 (95% CI, 2.72-144), and low odds of negative uptake in RL tumors with either RL mutations or follicular architecture, 0.048 (95% CI, 0.006-0.344), after adjusting for age, sex, race, RAI preparation method, bone metastases, and RAI dose. Patients with negative scans were significantly older (62.4 vs 47.0 years, P = .03). CONCLUSION: Among DTC patients with DM at diagnosis, non-iodine-avid disease is highly prevalent in patients with BVL cancers, particularly with BRAFV600E and TERT promoter mutations, and is associated with an older age. Better strategies are needed to improve RAI treatment response for these patients.

Association between Thyroid Cancer and Breast Cancer: Two Longitudinal Follow-Up Studies Using a National Health Screening Cohort.

Background: The purpose of this study was to evaluate the association between thyroid cancer and breast cancer. Methods: Data from the Korean National Health Insurance Service-Health Screening Cohort were collected from 2002 to 2013. In study I, 3949 thyroid cancer participants were 1:4 matched with 15,796 control I participants, and hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer were evaluated using a stratified Cox proportional hazard model. In study II, 3308 breast cancer participants were 1:4 matched with 13,232 control II participants, and HRs with 95% CIs for thyroid cancer were assessed in the same way as in study I. In the subgroup analyses, associations were analyzed according to radioactive iodine (RAI) treatment and age (<60 years old and ≥60 years old). Results: The adjusted HR for breast cancer in the thyroid cancer group was 1.64 (95% CI = 1.13-2.39, p = 0.010). The adjusted HR for thyroid cancer in the breast cancer group was 1.91 (95% CI = 1.47-2.49, p < 0.001). In the subgroup analyses, the groups that were older and not treated with RAI treatment showed consistent results in study I, and the younger and older groups showed consistent results in study II. Conclusions: Based on this cohort study, breast and thyroid cancer have a reciprocal positive association.

Simultaneous measurements of single gamma ray of 131I and annihilation radiation of 18F with Compton PET hybrid camera.

In internal 131I therapy for thyroid cancer, a decision to continue treatment is made by comparing 131I scintigraphy and [18F]FDG-PET. However, with current SPECT and PET systems, simultaneous imaging of diagnostic PET nuclides and therapeutic 131I nuclides has not been achieved so far. Therefore, we demonstrated that the recently developed Compton PET hybrid camera with Ce:Gd3(Al,Ga)5O12 (GAGG)- Silicon Photomultiplier(SiPM) scintillation detectors can be used to simultaneously image 131I Compton image and 18F PET image.

Predictive Factors for RAI-Refractory Disease and Short Overall Survival in PDTC.

BACKGROUND: The clinical phenotype of poorly differentiated thyroid cancer (PDTC) can vary substantially. We aim to evaluate risk factors for radioiodine refractory (RAI-R) disease and reduced overall survival (OS). METHODS: We retrospectively screened our institutional database for PDTC patients. For the assessment of RAI-R disease, we included patients who underwent dual imaging with 18F-FDG-PET and 124I-PET/131I scintigraphy that met the internal standard of care. We tested primary size, extrathyroidal extension (ETE), and age >55 years as risk factors for RAI-R disease at initial diagnosis and during the disease course using uni- and multivariate analyses. We tested metabolic tumor volume (MTV), total lesion glycolysis (TLG) on 18F-FDG-PET, and the progression of stimulated thyroglobulin within 4-6 months of initial radioiodine therapy as prognostic markers for OS. RESULTS: Size of primary >40 mm and ETE were significant predictors of RAI-R disease in the course of disease in univariate (81% vs. 27%, p = 0.001; 89% vs. 33%, p < 0.001) and multivariate analyses. Primary tumor size was an excellent predictor of RAI-R disease (AUC = 0.90). TLG/MTV > upper quartile and early thyroglobulin progression were significantly associated with shorter median OS (29.0 months vs. 56.9 months, p < 0.05; 57.8 months vs. not reached p < 0.005, respectively). DISCUSSION: PDTC patients, especially those with additional risk factors, should be assessed for RAI-R disease at initial diagnosis and in the course of disease, allowing for early implementation of multimodal treatment. Primary tumor size >40 mm, ETE, and age >55 are significant risk factors for RAI-R disease. High MTV/TLG is a significant risk factor for premature death and can help identify patients requiring intervention.

An impact of microscopic positive margin on incomplete response after I-131 treatment in differentiated thyroid cancer.

OBJECTIVE: To find an impact of microscopic positive margin on incomplete response after initial I-131 therapy in differentiated thyroid cancer. METHODS: We retrospectively recruited patients with differentiated thyroid cancer who underwent total thyroidectomy and received the first dose of radioiodine during January 2014-February 2018. Patients with grossly incomplete tumor resection or distant metastasis at the time of radioiodine therapy were excluded. Thyroid specimens were re-evaluated by one pathologist who was blinded to clinical information to determine microscopic margin status. Treatment response was evaluated at 6-12 months after therapy and was categorized according to the 2015 American Thyroid Association guidelines. Univariable and multivariable analyses were used to find an association between microscopic positive margin and incomplete response. RESULTS: A total of 101 patients (78 females; mean age 50.3 years) were enrolled. Ninety-four patients (93.1%) had papillary thyroid carcinoma. Microscopic positive margin was found in 27 patients (26.7%). After the median follow-up time of 10.3 months, incomplete response was observed in 13 patients (48.5%) and 17 patients (23.0%) with positive and negative margins, respectively. Multivariable analysis showed a significant association between microscopic positive margin and incomplete response after adjusting for tumor size, ETE, and cervical lymph node metastasis with adjusted odds ratio of 3.04 (95% CI 1.05-8.75, p value = 0.04). Moreover, after adding pre-ablative Tg as a covariate in 69 patients with negative TgAb, positive margin had a trend toward being associated with incomplete response with adjusted odds ratio of 3.43 (95% CI 0.73-16.07, p value = 0.118). CONCLUSIONS: Microscopic positive margin was found to be significantly associated with incomplete response after I-131 therapy in patients with differentiated thyroid cancer after adjusting for tumor size, ETE, and cervical lymph node metastasis and also had a trend toward being associated with incomplete response after adjusting for pre-ablative Tg.

Effects of radioactive iodine treatment on cardiovascular disease in thyroid cancer patients: a nationwide cohort study.

BACKGROUND: Radioactive iodine (RAI) treatment is a standard treatment in differentiated thyroid cancer (TC). However, its adverse effects on cardiovascular diseases (CVDs) have not been clearly elucidated. METHODS: In this retrospective cohort study based on the Korean National Health Insurance Service-National Health Screening Cohort (2002-2015), we analyzed 4,845 patients with TC with a median follow-up of 66 months. We evaluated and compared the risk of CVD between patients treated with and without RAI therapy. The primary CVD outcome was defined as a composite of ischemic stroke (IS), ischemic heart disease (IHD), hemorrhagic stroke (HS), or heart failure (HF). RESULTS: Overall, 2,533 patients (52.3%) received RAI treatment with a median cumulative dosage of 103 mCi [interquartile range (IQR), 40-162 mCi]. The incidence of the primary CVD outcome in patients who did not receive RAI therapy and those who did was 17.32 [95% confidence interval (CI), 15.07-19.90] and 13.96 (95% CI, 12.17-16.01) per 1,000 person-years, respectively, indicating an adjusted hazard ratio (HR) of 0.87 (95% CI, 0.71-1.07) after multivariate adjustments for variable confounding factors. The risks of IS (HR, 0.83; 95% CI, 0.51-1.34), IHD (HR, 0.90; 95% CI, 0.71-1.13), HS (HR 1.01; 95% CI, 0.49-2.09), and HF (HR 0.89; 95% CI, 0.49-1.63) were comparable between the patients who received RAI therapy and those who did not. There was no cumulative dose-dependent risk for CVD in TC patients who received RAI treatment. CONCLUSIONS: RAI treatment is a prevalent and crucial treatment for TC, and has been used in more than half of TC patients in Korea from 2004 to 2015. This study found no significant between-group difference for the CVD risk in patients with TC who received RAI treatment and those who did not, giving further evidence to allay concerns related to the adverse effects of RAI.

Graves' disease in children.

R1 The diagnosis of Graves' disease in children is based on detecting a suppression of serum TSH concentrations and the presence of anti-TSH receptor antibodies. 1/+++. R2 Thyroid ultrasound is unnecessary for diagnosis, but can be useful for assessing the size and homogeneity of the goiter. 2/+. R3. Thyroid scintigraphy is not required for the diagnosis of Graves' disease. 1/+++. R4. The measurement of T4L and T3L levels is not necessary for the diagnosis of Graves' disease in children but can be useful for the management and assessment of prognosis. 1/++. R5. In the absence of TSH receptor autoantibodies, the possibility of genetically inherited hyperthyroidism must be considered. 1/++. R6. Drug therapy is the primary line of treatment for children and consists of imidazole, carbimazole or thiamazole, with an initial dosage of 0.4 to 0.8mg/kg/day (0.3 to 0.6mg/kg/day for thiamazole) depending on the initial severity, up to maximum of 30mg. 1/++. R7. Propylthiouracil is contraindicated for children with Grave's disease. 1/+++. R8. Before starting treatment, it may be useful to perform a CBC in order to assess the degree of neutropenia caused by hyperthyroidism. It is not necessary to perform systematic CBCs during follow-up. 2/+. R9. An emergency CBC should be performed if symptoms include fever or angina. If neutrophil counts are <1000/mm3, synthetic antithyroid therapy should be discontinued or decreased and may be permanently contraindicated in severe (<500) and persistent neutropenia. Otherwise treatment may be resumed. 1/++. R10. Transaminases levels should be measured before initiating treatment. Systematic monitoring of liver function is not consensually validated. 2/+. R11. In cases of jaundice, digestive disorders or pruritus, measuring liver enzymes (AST, ALT), total and conjugated bilirubin and alkaline phosphatases is indicated. 1/++. R12. Patients and parents should be informed of the possible side effects of antithyroid agents. 1/+. R13. Therapeutic education of parents and children is important in ensuring the best possible treatment compliance. 2/++. R14. Given the specificities involved in the treatment of Graves' disease in children, medical care should be provided by a specialist accustomed to treating endocrinopathies in pediatric patients. 2/+. R15. Depending on patient age, the severity of the disease at diagnosis and the persistence of anti-TSH receptor antibodies, the initial course of treatment must take place over an extended period of 3 to 6 years. R16.The anticipated success rates of medical treatment (50% of patients in remission following several years of treatment) should be explained to the family and the child. The possibility that radical treatment may be required in case of failure or intolerance of medical treatment should also be discussed. 1/++. R17.In females with Graves' disease, it is important to explain that they must undergo an assessment by an endocrinologist before planning future pregnancies, from the start of pregnancy and during the course of pregnancy. This is true in all female patients, even those in remission after medical treatment, or those who have undergone radical treatment. R18.Indications for a radical treatment can arise in cases of: 1/+: contraindication to antithyroid agents; poorly controlled hyperthyroidism due to lack of compliance; relapse despite prolonged medical treatment; a request made by the family and child for personal reasons. R19.Surgery is the radical method of treatment used in children under 5 years of age, or in cases of very large, nodular, or compressive goiters. 2/++. R20. The surgeon's experience in dealing with thyroidectomies in children is likely to be the most significant determining factor in limiting the morbidity of the procedure (alongside any collaboration between a pediatric surgeon and an adult surgeon). 1/++. R21 When radical treatment is indicated, I-131 treatment may be discussed after 5 years (but more often after puberty), if the goiter is not too large. Experience from monitoring Graves' disease in North American children is reassuring. 1/++.

Histologic Findings and Cytological Alterations in Thyroid Nodules After Radioactive Iodine Treatment for Graves' Disease: A Diagnostic Dilemma.

Unlike the well-documented relation between radiation to the neck and development of papillary thyroid carcinoma, a causal association between radioactive iodine treatment for Graves' disease and development of thyroid malignancy is less defined. However, patients with a background of thyroid dysfunction presenting with clinically palpable thyroid nodules are followed more closely than the average population, and fine needle aspiration is recommended in such circumstances. Cytological examination of aspirates, and histologic examination of tissue provided from patients with a known history of Graves' disease, managed by radioactive iodine therapy can create a diagnostic dilemma, as the distinction between radiation effect and a malignant primary thyroid neoplasm can be very challenging. Thus, pathologists should be aware of the existence of these changes in the setting of radiation therapy for Graves' disease. Providing pathologists with appropriate clinical history of Graves' disease treated with radioactive iodine is of paramount importance in order to prevent an overdiagnosis of malignancy.

Mucoepidermoid carcinoma post-radioactive iodine treatment of papillary thyroid carcinoma: unique presentation and putative etiologic association.

We report the development of mucoepidermoid carcinomas of the parotid gland in 2 adult patients after a relatively short duration of radioactive iodine (RAI) treatment of papillary thyroid carcinoma. Both instances, together with those previously reported, underscore the selective nature of the mucoepidermoid carcinoma phenotype development in patients with papillary thyroid carcinoma as a consequence of RAI treatment. Efforts to alleviate salivary pathophysiologic damage by RAI in these patients are warranted.

Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer?

Objective Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors.