131I Therapy Research Articles

18F]-FDG-PET/CT and [18F]-FAZA-PET/CT Hypoxia Imaging of Metastatic Thyroid Cancer: Association with Short-Term Progression After Radioiodine Therapy.

To examine the relationships between 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) and hypoxia tracer [18F]fluoro-azomycinarabinofuranoside ([18F]-FAZA) and between 131I and [18F]-FAZA uptake in patients with metastatic thyroid cancer and to evaluate imaging features associated with short-term progression after 131I therapy. The study population was 20 patients (17 women and 3 men; mean age, 67years) with metastatic thyroid cancer who underwent both [18F]-FDG- and [18F]-FAZA-positron emission tomography (PET)/X-ray computed tomography (CT) examinations before 131I therapy. Short-term response to radioiodine was assessed (mean follow-up, 19months ± 9). PET parameters including [18F]-FDG-SUVmax, [18F]-FAZA-SUVmax, and [18F]-FAZA-tumor-to-muscle [T/M] were obtained. Mann-Whitney U, Wilcoxon signed-rank, or χ2 tests were used to assess differences between two quantitative variables or compare categorical data. Predictive factors for short-term progression were investigated with logistic regression analysis. Eleven lymph node metastatic lesions were identified in 9 patients and 46 distant metastatic lesions (lung, 19; bone, 17; and liver, 10) in 14 patients. A total of 24 131I-positive and 33 131I-negative lesions were detected. SUVmax was significantly lower with [18F]-FAZA-PET/CT (1.3 ± 0.6) than with [18F]-FDG-PET/CT (6.4 ± 5.9, p < 0.001). No significant correlation was observed between [18F]-FAZA-PET/CT and 131I imaging concerning visibility (p = 0.36). After 131I therapy, 31 of 57 metastatic lesions displayed short-term progression. Multivariate logistic regression revealed that [18F]-FDG-SUVmax (p = 0.022) and [18F]-FAZA-T/M (p = 0.002) showed significant associations with short-term progression. Although [18F]-FAZA uptake was low in metastatic thyroid cancers, not only glucose metabolism but also hypoxic conditions may be associated with progression after 131I therapy in patients with metastatic thyroid cancer.

Prognostic factors and the effect of radioiodine on patients with locally advanced differentiated thyroid cancer.

BackgroundLocally advanced differentiated thyroid cancer (DTC) is rare. The optimal treatment remains controversial. This study was to investigate the natural history and prognostic factors of patients with locally advanced DTC and assess the effects of radioiodine therapy for locally advanced DTC.MethodsA retrospective study was performed in 259 patients with locally advanced DTC. The clinicopathological features, prognostic factors and the effects of radioiodine therapy were evaluated using univariate and multivariate statistical analysis.ResultsAmong the clinicopathological characteristics of locally advanced DTC, the patient’s age (unfavourable >55 years), extent of primary tumour (more widely extrathyroidal extension showed a worse prognosis than others), tumor size, histopathological classifications and distant metastases were the significant prognostic factors. With regard to the effects of RAI on local invasive DTC, neither T3b nor T4 patients without distant metastases could benefit from performance of 131I therapy for over survival and locoregional relapse-free survival.ConclusionsIn patients with locally advanced DTC, the independent prognostic factors were age, extent of extrathyroidal invasion, tumor size, histopathological classifications and distant metastases. Adjuvant postoperative RAI did not affect overall survival and locoregional control in patients with locally advanced DTC who had no distant metastasis disease. Given the results, we suggested radioiodine would not be applied for metastasis-free patients with locally advanced DTC postoperatively.

The effects of radioiodine therapy on parathyroid function among patients with papillary thyroid cancer: a retrospective cohort study.

To explore the effects of initial radioiodine therapy on parathyroid function among postoperative papillary thyroid cancer (PTC) patients. Postoperative PTC patients who were admitted in our department from April 2018 to April 2019 were recruited. Patients were divided into two groups: Group A, who underwent surgery and initial radioiodine therapy in our hospital, and Group B, who did not receive radioiodine therapy after surgery. The levels of serum calcium, magnesium, phosphorus, parathyroid hormone (PTH), and 25 hydroxyvitamin D3 were collected. Data were analyzed by SPSS 25.0. A total of 252 patients were included. Between the two groups, no significant difference of PTH in 6th, 9th, and 12th month was found during postoperative follow-up (p = 0.493, p = 0.202, p = 0.814). No significant difference of PTH was found after stratifying Group A according to 131I dosage (p = 0.751 for 6th month after operation, p = 0.130 for 9th month after operation, p = 0.683 for 12th month after operation), interval time between surgery and radioiodine therapy (p = 0.522 for 3rd day after 131I therapy, p = 0.184 for 9th month after operation, p = 0.311 for 12th month after operation), and ratio of parathyroid autotransplantation (p = 0.545 for 3rd day after 131I therapy, p = 0.485 for 6th month after operation, p = 0.201 for 9th month after operation, p = 0.146 for 12th month after operation). Initial radioiodine therapy following PTC surgery had no significant adverse effect on parathyroid function in the short term. However, physicians should inform patients of possible risks of abnormal parathyroid function prior to RAI therapy, and parathyroid function was periodically reviewed after RAI therapy.

Estimation of Radiation Exposure to Some Iraqi Patients with Hyperthyroidism treated with Radioactive Iodine-131 as an Outpatient Basis

A broadly established therapy is radioactive iodine-131 for patients with hyperthyroidism (1). The radioactive iodine-131 dose is given to the patient as a single dose, which leads to a high radiation exposure surrounding the patient’s location for several days, depending on the amount of the received radiation dose, patient’s isolation in a special room is necessary for a period of time until the amount of radiation exposure decreases to an acceptable limits according to the National regulations. This study aimed to obtain a measurable estimation to the amount of radiation exposure resulting from patients treated with iodine-131 and assessment of compliance of patients and their family members to radiation safety instructions (RSI). In this study, (35) Iraqi patients with hyperthyroidism (15 male and 20 female) divided in to three groups according to 131I doses received that ranging from 3.7 to 7.4 GBq (100-200 mCi), the radiation dose rate was measured at different levels of the patient’s body as well as at different periods after receiving the I-131 treatment dose. Results shows that the external dose rates decrease rapidly and as a result, the greater amount of radioactive iodine is disposed of in the urine in the first two days after therapy. Also there is no observed differences appears in the average radiation dose rate (µSv/hr) resulting from patients after giving the dose of iodine-131 between males and females within the same group, while a significant difference was observed in the average dose rate between the divided groups, especially after an hour of giving the dose. Conclusion this study provide an estimation to the amount of radiation exposure resulting from patients for three days post 131I therapy on outpatient basis, also these results enables us to obtain a database that can be used in determining the amount of radiation reflected from patient to family members and contacts. Oral and written radiation safety instructions (RSI) are given in an appropriate way to patients and family members before patient’s discharge.

Salivary side effects after radioiodine treatment for differentiated papillary thyroid carcinoma: Long-term study.

Although many studies focus on short-term side effects of radioiodine therapy, almost none studied long-term side effects. We assessed radioiodine long-term salivary side effects after radioiodine treatment for differentiated papillary thyroid carcinoma and compared it to short-term morbidity within the same population. A standardized self-administrated questionnaire was submitted in 2019 by patients treated with radioiodine between January 2011 and December 2012. These patients had already answered the same questionnaire 6 years before. Our study showed a significant reduction for salivary side effects: discomfort in submandibular or parotid area, swelling, pain, a bad or salty taste in the mouth, allowing to get back to a "normal" diet. Our study suggests that a significant rate of patients will recover from I131 therapy salivary side effects. As almost 30% of these remissions happened during our late stage follow-up, we highlight the necessity of a long-term follow-up in these patients.

Discussion on radioactive iodine treatment of hyperthyroidism and the risk of induced cancer

Iodine-131 (131I, radioiodine) has been used for over eight decades for the treatment of Graves’ disease, either as initial therapy or following failure of thionamides, as well as for the treatment of autonomous thyroid nodules. 131I treatment is simple to administer, effective, and relatively inexpensive. Recently, there has been some turmoil after a study published in JAMA Internal Medicine reported an increased risk of cancer from 131I treatment. The impact was of short duration however, as the paper received severe criticisms from many nuclear medicine physicians as well as from endocrinologists. Here we explain why that paper's conclusions are doubtful. We also review the major data on the topic of 131I therapy of hyperthyroidism and the risk of cancer.

The role of stimulated thyroglobulin in the prognosis of persistent papillary thyroid carcinoma

Objective —to study the incidence of regional metastases after radioiodine therapy in the absence of routine prophylactic neck dissection in patients with papillary thyroid carcinoma (PTC), depending on the levels of stimulated thyroglobulin (TG) and its use for predicting disease persistence. Material and methods. Treatment outcomes were investigated for 738 patients (78.2 % female, 21.8 % male; mean age 49.1 ± 11.9 years) with PTC who underwent thyroidectomy with neck dissection of varying volume in medical institutions of Ukraine with further radioiodine therapy. Risk groups are formed according to ATA 2015 recommendations. The stimulated TG testing was conducted in different laboratories in Ukraine and by different methods, but with comparable reference ranges. Statistical calculationswere done woth MSExcel, AtteStat and StatPlus 7 (AnalystSoftInc.), ROCanalysis, Z-test and Fisher-Freeman-Halton exact test.Particle confidence intervals were determined using Wilson method and VassarStats online calculator. Results and discussion. 738 patients were examined, of whom 22.6 %, 47.3 % and 30.1 % were in the low, medium, and high-risk groups. After the 131I therapy and SPECT (single-photon emission computed tomography) incidence of metastases was 19.1 % overall (2.6 % iodine negative), and 10.8 %, 16.3 %, and 29.7 %, respectively, depending on the TG level. Choosing a cut-off threshold for TG = 0.5 ng/ml (without taking into account the risk group) provides a minimum probability of missing metastases (4.96 %, 95 % CI: 2.42—9.89). In total, 148 (20.1 %) patients were identified in the total of 738 subjects with TG stimulated levels < 0.5 ng/ml, of which 7 (0.9 %) had metastasized after 131I. In 590 (79.9 %) patients with TG ≥ 0.5 ng/ml, 134 (18.2 %) had metastases, while in the low-risk group, 18 (10.8 %) had metastases, including 4 (2.3 %/22.2 %) were found to be iodine-negative. In 12 patients in the TG subgroup < 0.5 ng/ml, 4 (0.54 %/2.4 %) cases with metastases were identified, whereas in the TG subgroup ≥ 0.5 ng/ml, 14 (1,90 %/8.38 %). In the intermediate-risk group, 57 (16.33 %) patients had metastases and all of them were in the subgroup with TG ≥ 0.5 ng/ml. Patients with iodine-positive metastases had higher TG values than patients with iodine-negative ones, but the difference was not statistically significant. The highest incidence of metastases was recorded in the high-risk group, in which 66 (8.94 %/29.73 %) were detected. In all risk groups at TG values < 0.5 ng/ml, the detectability of metastases was low and practically independent of risk level (p > 0.05).At TG values ≥ 0.5 ng / ml, the difference in the detection of metastases between subgroups withmetastaticpositive and metastaticnegative were statistically significant: p < 0.05 in the low-risk group and p < 0.001 in the medium- and high-risk groups. Соnclusions. After thyroidectomy without routine neck dissection, the incidence of metastases in whole body 131I scintigraphy and SPECT was relatively high in all stratification risk groups (low — 10.8 %, medium — 16.3 %, high — 29.7 %). An elevated level of stimulated TG can be considered as a predictor of metastasis, which can be used to individualize further tactics for the treatment of patients with PTC. When the cut-off threshold TG = 0.5 ng/ml is selected, the highest sensitivity(0.95) and the predictive value of the negative result (-PV = 0.953) are provided, specificity and overall diagnostic efficiency are 0.236 and 37.26 %, respectively. Almost the same sensitivity and specificity (0.794 and 0.784, respectively) are reached at the cut-off threshold TG = 7.5 ng/ml (DE = 78.59 %). Regardless of the stratification risk groups in patients with stimulated TG up to 0.5 ng/ml, the probability of a false-negative result is 4.96 %, the detection of metastasis is quite low (0.54 %/0 %/0.41 %) and the need for radioiodine therapy is questionable. In patients with low and intermediate risk, postoperative values from 1.0 to 10.0 ng/ml are optimistic, but they do not completely exclude the detection of metastases (the probability of false-negative result is 6.4—24.2 %). With postoperative values of stimulated TG ≥ 10 ng/ml, the likelihood of persistence increases (probability of false-negative result > 26.2 %), which requires additional therapy.

Risk of structural persistent disease in pediatric patients with low or intermediate risk differentiated thyroid cancer.

In pediatric patients with differentiated thyroid cancer (DTC), the risk of recurrence is high and the indication for postoperative 131I administration is still debated. The aim of this study was to assess the outcome in low and intermediate risk pediatric DTC patients. We retrospectively evaluated 45 pediatric patients with low or intermediate risk DTC, treated with surgery and 131I between 1992 and 2002 and with no detectable antithyroglobulin (Tg) antibodies. Follow-up was performed every 6-12 months with Tg blood level determination and imaging procedures. During follow-up (64 ± 53 months), 15 events occurred (33% cumulative event rate, with an annual event rate of 5% person years). Five of these patients were submitted to additional surgery and all these 15 patients underwent a second 131I treatment course. All patients were alive at the end of the follow-up. Structural persistent disease occurred more frequently in patients at intermediate risk (p < 0.01) and in those with Tg values after thyroid hormone withdrawal >10 ng/ml before 131I therapy (p < 0.01). At multivariate analysis, only a postoperative thyroid stimulating hormone-stimulated Tg level >10 ng/ml was an independent predictor of persistent disease. In pediatric patients with DTC, postoperative high stimulated Tg values (>10 ng/ml) should be taken into account for deciding the extent of both initial treatment and follow-up.

A Population-Based Cohort Study on the Association of Hyperthyroidism With the Risk of Hyperlipidemia and the Effects of Anti-thyroid Drugs on Hepatic Gene Expression.

There have been no reports on the association of hyperthyroidism with hyperlipidemia in patients undergoing treatment especially in Asia. To determine the association between hyperthyroidism and the risk of hyperlipidemia in patients, we conducted a retrospective cohort study using Longitudinal Health Insurance Database (LHID) from Taiwan, R.O.C. We also evaluate the influence of 6-n-propyl-2-thiouracil (PTU) and methimazole (MMI) on hepatic genes to explain changes in blood lipid levels in a hepatic cell line model. The cohort study involved 13,667 patients with hyperthyroidism, and the corresponding comparison cohort had four times as many patients. Using Kaplan-Meier analysis method, the results showed that, compared to patients without hyperthyroidism, the overall incidence of hyperlipidemia was significantly higher in the hyperthyroidism patients (18.7 vs. 11.8 cases/1,000 persons-years; adjusted HR 1.5; 95% CI, 1.41–1.59). With only PTU or MMI/carbimazole (CBM) treatment, patients with hyperthyroidism showed a 1.78-fold (95% CI, 1.50–2.11) and 1.43-fold (95% CI, 1.27–1.60) higher risk of hyperlipidemia than those without hyperthyroidism, respectively. Additionally, hyperthyroidism patients that received surgery only or surgery with I131 therapy tended to have a higher risk of hyperlipidemia. Although PTU and MMI treatment decreased the expression levels of genes responsible for circulating remnant lipoproteins, they increased the levels of lipogenic gene expression in hepatic cells. Thus, treatment of hyperthyroid patients with anti-thyroid drugs (ATDs), I131, or surgery is likely to induce hyperlipidemia. ATDs downregulate the expression of genes involved in lipoproteins clearance; increases lipogenic genes expression, which may partly contribute to abnormal blood lipid profiles.

MON-LB83 The Initial Dose of 131I as a Potential Independent Predictor for Residual/Relapsed Disease in Pediatric Differentiated Thyroid Cancer

Introduction: In the guidelines for management of pediatric Differentiated Thyroid Cancer (DTC) 131I therapy is recommended for treatment of iodine-avid persistent locoregional disease that cannot be resected as well as iodine-avid distant metastases. To date, no consensus has been reached regarding the 131I dose for treatment of DTC in children. We report our institutional experience and highlight the initial dose of 131I as a potential independent predictor of residual/relapsed disease. Methods: We performed a retrospective analysis of all pediatric patients diagnosed with DTC between 2010 and 2018. The cohort included all patients up to 21 years of age, with minimal length of follow-up of 24 months. The risk stratification was done following the American Thyroid Association guidelines for pediatric DTC. We defined residual/relapsed disease as detectable thyroglobulin and positive anatomical lesions in imaging studies during the follow-up period. The log-rank test was used to evaluate disease-free survival. The P value was set at < 0.05. Results: Among 59 eligible patients, females were 69.5% (n=41) and males were 30.5% (n=18). The mean age at diagnosis was 16 years (9-21 years). All patients were alive at follow-up (median, 42 months; range 24 to 144 months). Fifty-eight patients had classic papillary thyroid cancer (PTC) and only 1 patient had follicular thyroid cancer. Among the patient with PTC, 39.6% (23/58) had follicular-variant PTC, 8.6% (5/52) had diffuse-sclerosing PTC and 17.2% (10/58) had other variants. Nineteen (32%), 30 (51%), and 10 (17%) had low-risk, intermediate-risk, and high-risk disease, respectively.Within the Low-risk group, 68% (13/19) received 131I. The mean initial dose was 60.9 mCi [26-150 mCi]. Eighty four percent (11/13) received ≤100 mCi and 27% (3/11) had residual/relapsed disease. Fifteen percent (2/13) received >100 mCi and none had residual/relapsed disease. Sixteen percent (1/6) of patients without 131I therapy had residual/relapsed disease. (P=0.48)Within the Intermediate-risk group, all 30 patients received 131I. The mean initial dose was 97.5 mCi [27.3-215 mCi]. Sixty percent (18/30) received ≤100 mCi and 38.8% (7/18) had residual/relapsed disease. Forty percent (12/30) received >100 mCi and 16.6 % (2/12) had residual/relapsed disease. (P=0.15)Within the High-risk group all 10 patients received 131I. The mean initial dose was 159.9 mCi [129.3-384 mCi]. Fifty percent (5/10) received ≤150 mCi and 60% (3/5) had residual/relapsed disease. Fifty percent (5/5) received >150 mCi and 20% (1/5) had residual/relapsed disease. (P=0.2) Conclusion: There are no statistical differences of disease-free rate between the initial dose of 131I among all risk categories. However, the use of more than 100 mCi in the intermediate-risk category and more than 150 mCi in the high-risk category may be recommended.

SUN-120 Regional Hyperthermia Enhances Selective Mesenchymal Stem Cell Migration Towards the Tumor Stroma

The tumor homing characteristics of mesenchymal stem cells (MSCs) make them attractive vehicles for the tumor-specific delivery of therapeutic agents, such as the sodium iodide symporter (NIS). NIS is a theranostic protein that allows non-invasive monitoring of the in vivo biodistribution of functional NIS expression by radioiodine imaging as well as the therapeutic application of 131I. To enhance the actively recruitment of MSCs to growing tumor stroma and thereby trigger targeted delivery of the NIS gene to the tumor, we examined the combination with regional hyperthermia, as heat induces the secretion of immunomodulatory chemokines, cytokines and growth factors, well-known attractants of MSCs.Human hepatocellular carcinoma cells (HuH7) were heat-treated in a water bath at 41 °C for 1h, followed by incubation at 37 °C for 0-48h. mRNA and protein levels of chemokines involved in MSC migration was analyzed by RT-PCR and ELISA. Chemotaxis of MSCs in relation to a gradient of supernatants was tested in a 3D live cell tracking migration assay. In a subcutaneous HuH7 mouse xenograft tumor model, a single systemic injection of CMV-NIS-MSCs was applied 6h, 24h, 48h after or 24h, 48h before hyperthermia treatment and tumoral 123I accumulation was assessed by 123I-scintigraphy. Ex vivo NIS analysis of tumor sections was performed by RT-PCR and immunohistochemistry. The optimal imaging regime was then used for a 131I therapy study.Chemokine mRNA and protein analysis indicated a substantial increase in expression levels of chemokines and growth factors, involved in MSC tumor homing, after heat exposure. In addition, MSCs showed directed migration towards the supernatant of thermo-stimulated cancer cells. In vivo, with the optimal regime, we observed a significantly increased uptake of 123I in tumors of heat-treated animals (41 °C) when thermostimulated 24h after CMV-NIS-MSC injection compared to control animals (37 °C). Immunohistochemical staining of tumor sections showed strong tumoral NIS-specific immunoreactivity and RT-PCR an increased NIS mRNA expression in heat-treated tumors, thereby confirming tumor-selective, temperature-dependent MSC migration. CMV-NIS-MSC-mediated 131I therapy combined with regional hyperthermia resulted in a reduced tumor growth that was associated with prolonged survival of regional heat-treated animals compared to normothermic mice and to the saline control group.In summary, we have demonstrated a significantly increased, selective MSC migration towards the tumor stroma after regional hyperthermia in the 123I imaging study. The combination of MSC-mediated NIS gene therapy with mild regional hyperthermia resulting in stimulated therapeutic efficacy of NIS-mediated 131I therapy.

SAT-510 Association of Myotonic Dystrophy with Autoimmune Endocrinopathies and Thyroid Carcinoma

Myotonic dystrophy (MD) is a multisystemic, autosomal dominant disorder associated with progressive muscle weakness, premature cataracts, frontal baldness, and cardiac disturbances. MD has been associated with several endocrinopathies including primary testicular failure, autoimmune endocrinopathies (hypothyroidism, hyperthyroidism, multinodular goiter, and Addison’s disease), thyroid carcinoma (primarily papillary), insulin resistance, and type 2 DM. Development of diabetes is thought to be related to formation of an insulin-resistant receptor because of aberrant regulation of mRNA. We describe the first reported case of a patient with MD associated with type I diabetes mellitus, Hashimoto’s thyroiditis with hypothyroidism, and follicular variant of papillary thyroid cancer. A 49-year-old female presented with acute congestive heart failure. The patient had history of type I DM diagnosed at the age of 26, complicated by mild background retinopathy, peripheral neuropathy, and nephropathy with microalbuminuria. The patient first noticed proximal muscle weakness 1 year ago that gradually progressed resulting in multiple falls. She had history of bilateral cataracts status post cataract extraction at age 26. She also had progressive dysphagia requiring PEG placement, and cognitive dysfunction with mood disorder and depression. Family history was significant for myotonic dystrophy in both maternal aunt and uncle as well as 2 cousins. EMG confirmed myotonia however genetic testing was not obtained due to cost. Due to her cognitive dysfunction and depression, she had difficult to control diabetes with HbA1c of 9.9%, and multiple previous admissions for DKA. She was status post total thyroidectomy in 2008 for follicular variant of papillary carcinoma and Hashimoto’s thyroiditis followed by I-131 therapy in 2009 and maintained on levothyroxine suppression therapy. Most recent Tg and Tg Ab were undetectable. On physical exam, the patient had a narrow, sallow face with temporal muscle atrophy, percussion myoclonus involving the thenar eminence of the hands, but no frontal balding. Work up showed LVEF of 20-24% with regional hypokinesis that led to catherization and PCI to LAD. The patient had recurrent NSTEMI which eventually resulted in CABG 1 year after presentation. The association of autoimmune endocrinopathies, thyroid carcinoma and MD suggests a possible cause and effect relationship between these disorders. In patients with diabetes and MD, previously described insulin resistance as well as cognitive dysfunction can hinder good glycemic control increasing risk for complications. Although patients with MD are typically treated by neurologists, evaluation and therapy of endocrine dysfunctions are also necessary.

MON-443 SPECT/CT Localization of Incidental Diverticular Bleed After Radioiodine (i131) Therapy for Metastatic Thyroid Cancer

Background: Radioiodine therapy for patients with metastatic papillary and follicular thyroid cancer status post total thyroidectomy improves overall survival and is standard of care. Physiologic and pathologic biodistribution of I131 is dependent on tissue sodium iodine symporter expression with nonspecific radioiodine distribution seen secondary to physiologic routes of excretion. Clinical Case: Whole body scintigraphy (WBS) was performed seven days after I131 therapy in a 37-year-old male treated for metastatic papillary thyroid cancer with extension to a thyroglossal duct cyst at the time of surgery. His post-procedural course was uncomplicated with the exception of self-limited hematochezia six days after ablation. WBS images demonstrated a focus more superiorly in the neck concordant with metastatic thyroglossal duct cyst involvement. Activity was also present in the small and large bowel distribution reflecting normal routes of radioiodine excretion. WBS images depicted a discrete focus of radioiodine activity in the right lower quadrant, which SPECT/CT further localizes as activity in the sigmoid colon. Non-contrast CT images demonstrate an associated linear pattern of hyperdense hyperattenuation in the colonic lumen consistent with fresh blood. It is well established that the physiologic and pathologic biodistribution of I131 is dependent on tissue sodium-iodine symporter expression with additional distribution secondary to normal routes of excretion. Nonspecific radioiodine localization has been described at sites of inflammation secondary to vasodilation and increased vascular permeability resulting in leakage and accumulation in tissues. Sodium-iodine expression is found in many tissues, including salivary glands, lactating mammary glands, gastric mucosa, thymus, and small bowel; however, they are not expressed in the colon, nasopharyngeal mucosa, or orbital fibroblasts. I131 localization has been previously described within numerous body diverticula, such as Zenker’s and Meckel’s diverticula; however, radioiodine activity in association with an acute colonic diverticular bleed has not been reported. Conclusion: We propose that the isolated focus of radioiodine activity in the sigmoid colon associated with transient self-limited bleed could be either related to preexisting diverticulitis leading to I131 accumulation secondary to hyperemia, increased vascular capillary permeability, and subsequent aggravation of colonic mucosa resulting in a transient bleed or due to incidental nonspecific pooling of radioiodine in a colonic diverticulum resulting in secondary mucosal irritation with subsequent minor bleeding. To our knowledge this is the first reported case of SPECT/CT localization of radioiodine to an isolated colonic diverticular bleed in a patient status post I131 therapy for metastatic papillary thyroid cancer.

SUN-510 Prolonged RAIA Induced Thyroiditis After 131 I Therapy for Graves’ Hyperthyroidism

Radioactive iodine ablation (RAI) has been used for the treatment of Graves’ hyperthyroidism since 1946 and it is the primary recommended modality for Graves’ disease treatment in many countries. Acute painful radiation thyroiditis after radioiodine treatment for hyperthyroidism of Graves’ disease is considered uncommon. The prevalence is 1-5% in patients treated with 131I therapy for hyperthyroidism. Dose of RAI and thyroid volume can be precipitating factors for post radiation thyroiditis. The higher RAI dose increases the chance of RAI thyroiditis while the larger goiter size decreases the absorbed radiation dose in the thyroid gland. We present a 25-year-old Emirati male previously healthy, who was referred to our service for hyperthyroidism management. He presented with thyrotoxicosis in absence of goiter. All investigations revealed that graves’ disease is the primary cause of his hyperthyroidism. He was treated with RAI ablation 18.3 mCi. Day four after RAI, he presented with severe pain in the anterior neck associated with fatigue, tremor, palpitation and weight loss. Symptoms lasted for 6 weeks post RAI. There was laboratory evidence of thyrotoxicosis presented with further suppression of TSH and higher fT4 than the baseline. Acute radiation thyroiditis was diagnosed and has been commenced on propranolol 10mg BID. Symptoms completely resolved after 6 weeks of treatment and thyroid function returned to normal level. The patient has remained asymptomatic on continued follow up care till eventually became hypothyroid clinically and biochemically. Our case reflects that radioiodine thyroiditis can last for longer period and occur after larger doses of 131I treatment in absence of goiter. Our patient has RAIA induced thyroiditis lasted for 6 weeks post 18.3mCi of 131I, and has no goiter, which were both contributing factors for RAIA induced thyroiditis

SUN-484 Complex Thyroid Cancer with Several Recurrences and Metastases

56-year-old male with metastatic papillary thyroid cancer who underwent total thyroidectomy in 8/2014, and I-131 ablation in 9/2014, with post-operative pathology revealing multifocal, bilateral papillary thyroid cancer with extrathyroidal extension with surgical resection margins uninvolved. There were positive lymphovascular spread and multiple central compartments and bilateral neck nodes metastases with extranodal extension. Subsequent thyrogen stimulated whole-body scan in 2/2016 showed no areas of uptake.However, in 12/2016 he was found to have right supraclavicular lymph nodes positive for recurrence which was resected and given another 168 mCi I-131 and 33 treatments of XRT to R shoulder.A repeat PET in 7/2019 showed persistent hyper metabolic lesion in C7, multiple hyper metabolic nodules throughout the R lung, and a new 1.1 cm left Hilar lymph node suggesting disease progression. Biopsy of the C7 lesion confirmed dedifferentiated papillary thyroid cancer and demonstrated the presence of an NTRK mutation.This time he was given lenvatinib 24 mg daily for 4 weeks, followed by 200 mCi I-131. Post-treatment whole body scan showed good uptake in all lesions, except the C7 lesion which was treated with external radiation. DiscussionWhile cure is achieved in most cases of differentiated thyroid cancer, a minority of cases demonstrate disease progression. Loss of response to I-131, very low serum thyroglobulin levels despite known disease, and high PET avidity provide clinical evidence of dedifferentiation, confirmed with tissue sampling.If feasible targeted systemic therapy remains the best tolerated treatment option.While several studies demonstrate an increase in iodine avidity in approximately 50-60% of patients with dedifferentiated thyroid cancer that were treated with tyrosine kinase inhibitors (TKI), (cite alan Ho’s 2013 NEJM article, and the 2015 debrafenib study Rothenberg SM et al, clin cancer res 2015), selumetanib remains unavailable for clinical use and dabrafenib may only be beneficial in cases with known BRAF V600E mutations. Moreover, it is unknown whether a planned short course of TKI therapy would potentially induce resistance to future TKI therapy.Therefore, lenvatinib, which inhibits activity of at least 6[VM1] different tyrosine kinase enzymes important in thyroid cancer was chosen rather than entrectanib, which was reserved for use if the need arises. This patient demonstrated excellent response to I-131 therapy with lenvatinib pretreatment.A number of formal studies of various TKIs for thyroid cancer re-differentiation are currently underway. (cite Brown SR, Hall A, et al BMC cancer 2019; and also cite the CIII trial with cabozatanib)Conclusion This case represents the emerging paradigm for the ability of TKI therapy to redifferentiate advanced thyroid cancer and allow for re-treatment with I-131 targeted therapy.

Radioiodine Ablation of Remaining Thyroid Lobe in Patients with Differentiated Thyroid Cancer Treated by Lobectomy: A Systematic Review and Metaanalysis.

We aimed to conduct a systematic review and metaanalysis of studies reporting the performance of radioactive iodine (131I) therapy in differentiated thyroid cancer (DTC) patients requiring a completion treatment after lobectomy. We also evaluated the response to 131I therapy according to 2015 American Thyroid Association guidelines and the adverse events. Methods: A specific search strategy was designed to find articles evaluating the use of 131I in patients with evidence of DTC after lobectomy. PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science were searched. The search was updated until January 2020, without language restriction. Data were cross-checked and any discrepancy discussed. A proportion metaanalysis (with 95% confidence interval) was performed using the random-effects model. Metaregressions on 131I success were attempted. Results: The pooled success ablation rate was 69%, with better results in patients receiving a single administration of about 3.7 GBq; high heterogeneity was found (I2 test, 85%), and publication bias was absent (Egger test, P = 0.57). Incomplete structural responses were recorded in only 14 of 695 (2%) patients enrolled in our analysis. Incomplete biochemical responses were observed in 8%-24% of patients, with higher rates (24%) in patients receiving low radioiodine activities (∼1.1 GBq) and lower rates (8%-18%) in patients receiving higher activities of radioiodine (∼3.7 GBq). Neck pain due to thyroiditis was reported in up to 18% of patients, but in most cases, symptoms resolved after oral paracetamol or a short course of prednisone. Conclusion: Lobar ablation with 131I is effective, especially when high 131I activities are used. However, the rate of incomplete biochemical response to initial treatment appears to be slightly higher than in the classic scheme of initial treatment of DTC. Radioisotopic lobectomy should be considered for patients with low- to intermediate-risk DTC requiring completion treatment after lobectomy due to specific individual risk factors or patient preferences.

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

To find an impact of microscopic positive margin on incomplete response after initial I-131 therapy in differentiated thyroid cancer. 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 6-12months 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. A total of 101 patients (78 females; mean age 50.3years) 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 10.3months, 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). 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.

REPORT OF A CASE AND REVIEW OF THE LITERATURE: AXILLARY LYMPH NODES METASTASIS IN PAPILLARY THYROID CANCER PATIENT

Introduction: thyroid cancer (ТС) is the most common endocrine malignancy. Typical and frequent type of TC is papillary carcinoma (PC). Metastases of papillary TC have more often cervical location in II-VI neck lymph nodes groups. Axillary metastasis is not a common finding in the classic type of PC. Adequate Surgery and radioiodine therapy, if necessary, provide the excellent prognosis for most papillary TC patients. Case presentation. 87-year-old woman was presented in our Center with metastatic axillary lymphadenopathy. She had a history of thyroidectomy with central neck dissection 31 years ago for papillary TC. Earlier she underwent right and left lateral neck dissection and 131-I therapy (3 times: after 6 months - 86 mCi, after 12 months- 92 mCi, after 24 months - 98 mCi). On the time of patient presentation in the Center we have found right axillary lymphadenopathy, occipital lymphadenopathy and multiple pulmonary metastases. In our clinic we have performed removal of occipital lymph node metastases and right axillary metastases dissection. Postoperative pathology report has shown infiltration of the cervical and axillary lymph nodes by metastatic papillary TC. After Surgery patient received 131-I therapy one more again (after 3 months - 110 mCi, after 9 months - 150 mCi). Unfortunately, she died after 18 months later. The reason of death was progression of distant metastases at lungs. Follow up period from the initial operation made 32.5 years. Conclusion and discussion. Papillary thyroid cancer patient’s progression free survival is more 10 years. As a rule a papillary TC patients has survived for many years after the initial surgery. Exclusively rarely TC metastases can emerge in different atypical places and in the axillary lymph nodes also (more than 31 years after initial Surgery) that maybe associated with a poor prognosis. Case report is unique, because there are 16 equal clinical cases in world literature.

Monitoring and Evaluation of Thyroid Function Tests, Serum Electrolytes and Creatinine Levels Before and After 131I Therapy.

Serum electrolytes, Creatinine, and thyroid profile play an important role in 131I treated patients of thyroid disorders. To determine the effect of radioactive iodine (131I) on renal parameters, serum electrolytes and the correlation among TFT'S, creatinine, and chloride levels before and after I131 treatment in thyroid disorders. The study was performed on 55 patients of thyrotoxicosis with age ranging from 16-65 years (mean age= 41±14years and BMI=24.8±4.46). The significance of the differences between the results of 1st, 2nd, and 3rd-time serum analysis was assessed by paired Student's t-test. Association between parameters was assessed by Spearman correlation analysis. 40 patients were taking Carbimazole, and 15 were directly recommended for I131 therapy. Strongly significant variations were observed for TFT'S (T3=0.012, T4 =0.017, and TSH=0. 001) during the follow-up treatment. Before taking I131 (Serum analyzed at 1st time), there observed negative correlation of T3(r=-.46, p=0. 002) and TSH (r=-0.31, p=0.02) with creatinine, and positive correlation of TSH(r=0.29,p=0.02) with chloride. BMI was negatively correlated with potassium(r=-0.30, p=0.02). At the 2nd time (after stopping the Carbimazole), no correlation results were observed. Two months after oral administration of 131I, creatinine, and chloride level was significantly increased (p=0.000), (P=0. 03) respectively, but had no correlation with TFT'S. Our findings suggest that patients with goiter (diffused or toxic) have association of TFT'S and BMI with serum electrolytes and creatinine, 131I therapy is also associated with the increase in creatinine and chloride levels of patients leading to kidney problems.

Treatment and prognosis for patients with differentiated thyroid carcinoma bone metastases.

BackgroundTo investigate reasonable treatment modalities and prognostic factors for patients with differentiated thyroid carcinoma (DTC) bone metastases (BM).MethodsThe clinicopathological characteristics and follow-up data for all patients with DTC BM who received treatment in the Third Affiliated Hospital of Kunming Medical University between November 1, 1993 and December 31, 2016 were analyzed retrospectively with respect to mortality and survival rates. Multivariate analysis was performed using the Cox proportional hazard model.ResultsThe 5- and 10-year overall survival (OS) rates were 51.5% and 17.2%, respectively, for all 60 patients. Univariate analysis showed that patients diagnosed with BM at <45 years of age, with controlled thyroid-stimulating hormone (TSH) levels and those undergoing surgery or 131I therapy had better prognoses. Patients with cervical vertebra metastases, multiple organ metastases other than bone, and those receiving chemotherapy had worse prognoses. Gender, pathological type, number of BM lesions, skeletal-related events (SREs) and whether or not the patient received radiotherapy were not related to prognosis. Cox regression analysis showed that age at diagnosis of BM, undergoing surgery for bone lesions, and not receiving chemotherapy were independent factors of favorable prognosis for patients with DTC BM.ConclusionsPatients with DTC BM have poor prognoses. Age at diagnosis with BM <45 years old, undergoing surgery for bone lesions, and not receiving chemotherapy were independent factors of favorable prognosis for patients with DTC BM. 131I combined with surgery for bone metastatic lesions may be the best treatment model for most patients with DTC BM disease.