Radioiodine Uptake Research Articles

A Retrospective Study of Lymph Node Yield in Lateral Neck Dissection for Papillary Thyroid Carcinoma.

Lateral neck dissection (LND) is important in managing papillary thyroid carcinomas (PTCs). This study aimed to evaluate the relationship between lymph node yield (LNY) for LND and patient outcomes, specifically postoperative serum thyroglobulin levels (sTG) and radioiodine uptake on thyroid scan, and to estimate a threshold LNY to signify adequate LND. Patients diagnosed with PTC who underwent LND from 2006 to 2015 at a single institution were included. Linear regression with restricted cubic splines was used to characterize the association of LNY with outcomes. Outcomes were log-transformed to achieve a more symmetric distribution prior to regression. For nonlinear associations, a Monte Carlo Markov Chain procedure was used to estimate a threshold LNY associated with postoperative outcome. This threshold was then used to define high LNY versus low LNY in the subsequent analyses. In total, 107 adult patients were included. There was a significant relationship between LNY and postoperative sTG level (P = .004), but not radioiodine uptake (P = .64). An LNY of 42.96 was identified, which was associated with the maximum change in sTG level. No association was found between LNY groups (LNY ≥ 43 vs < 43) and radioiodine uptake, risk of complication, or longer operative times (all P > .05). High LNY was associated with a decrease in log(sTG) (estimate = -1.855, P = .03), indicating that adequacy of LND is associated with an 84.4% decrease in sTG. These results suggest an association between LNY and postoperative sTG level, with an estimated threshold of 43 nodes. This has implications for adequate therapeutic LND; additional work is needed to validate thresholds for clinical practice.

The Role of Nuclear Medicine in the Clinical Management of Benign Thyroid Disorders, Part 1: Hyperthyroidism.

Benign thyroid disorders, especially hyper- and hypothyroidism, are the most prevalent endocrine disorders. The most common etiologies of hyperthyroidism are autoimmune hyperthyroidism (Graves disease, GD), toxic multinodular goiter (TMNG), and toxic thyroid adenoma (TA). Less common etiologies include destructive thyroiditis (e.g., amiodarone-induced thyroid dysfunction) and factitious hyperthyroidism. GD is caused by autoantibodies against the thyroid-stimulating hormone (TSH) receptor. TMNG and TA are caused by a somatic activating gain-of-function mutation. Typical laboratory findings in patients with hyperthyroidism are low TSH, elevated free-thyroxine and free-triiodothyronine levels, and TSH-receptor autoantibodies in patients with GD. Ultrasound imaging is used to determine the size and vascularity of the thyroid gland and the location, size, number, and characteristics of thyroid nodules. Combined with lab tests, these features constitute the first-line diagnostic approach to distinguishing different forms of hyperthyroidism. Thyroid scintigraphy with either radioiodine or 99mTc-pertechnetate is useful to characterize different forms of hyperthyroidism and provides information for planning radioiodine therapy. There are specific scintigraphic patterns for GD, TMNG, TA, and destructive thyroiditis. Scintigraphy with 99mTc-sestamibi allows differentiation of type 1 from type 2 amiodarone-induced hyperthyroidism. The radioiodine uptake test provides information for planning radioiodine therapy of hyperthyroidism. Hyperthyroidism can be treated with oral antithyroid drugs, surgical thyroidectomy, or 131I-iodide. Radioiodine therapy is generally considered after failure of treatment with antithyroid drugs, or when surgery is contraindicated or refused by the patient. In patients with TA or TMNG, the goal of radioiodine therapy is to achieve euthyroid status. In GD, the goal of radioiodine therapy is to induce hypothyroidism, a status that is readily treatable with oral thyroid hormone replacement therapy. Dosimetric estimates based on the thyroid volume to be treated and on radioiodine uptake should guide selection of the 131I-activity to be administered. Early side effects of radioiodine therapy (typically mild pain in the thyroid) can be handled by nonsteroidal antiinflammatory drugs. Delayed side effects after radioiodine therapy for hyperthyroidism are hypothyroidism and a minimal risk of radiation-induced malignancies.

In Memoriam: Marvin A. Van Dilla: 1919-2019.

© 2020 International Society for Advancement of Cytometry.

Platelet-Lymphocyte Ratio as a Novel Surrogate Marker to Differentiate Thyrotoxic Patients with Graves Disease from Subacute Thyroiditis: a Cross-Sectional Study from South India

Graves disease (GD) and the toxic phase of subacute thyroiditis (SAT) have similar clinical and biochemical presentations, and differentiating them requires sophisticated investigations. Since thyroid hormones have been noted to affect all hematologic cell lines, we have used the platelet lymphocyte ratio (PLR)-an index usually utilized in inflammatory or malignant disorders-to compare patients with and without thyrotoxicosis and to analyze its use in distinguishing between patients with GD and SAT prior to therapy. This was a cross-sectional study conducted in the Department of Endocrinology, Christian Medical College, Vellore, India. During the study period, 800 patients with features of thyrotoxicosis visited the outpatient clinic. Those who had thyroid radioiodine (131I) uptake (RAIU) study and complete blood count (CBC) at diagnosis were included (N = 500). Based on the RAIU values, these were divided as GD (n = 354) and SAT (n = 146). Baseline characteristics, thyroid function tests, and components of the CBC and PLR were obtained. The data were compared with a group of 250 matched euthyroid controls. Analyses were performed using SPSS version 21.0 software. PLR showed significant reductions in both GD and SAT patients when compared to euthyroid controls (P = .01), with greater reductions seen in GD than SAT (74.5 ± 19 vs. 84.4 ± 26; P = .01). Using receiver operating characteristic analysis of PLR, an optimal PLR cut-off of 70.4 was found to differentiate GD from SAT with a sensitivity of 86% and specificity of 74%. PLR can be used as a novel surrogate marker to differentiate between patients with GD and SAT prior to therapy, especially in resource-limited settings.

1921P Prognostic impact of [18F]FDG-PET/CT in differentiated thyroid cancer with bone metastasis: A French TUTHYREF study

Bone metastases (BM) are frequent in differentiated thyroid cancer (DTC), affecting the skeleton at various extents, impacting negatively quality of life, being the leading cause of DTC-related morbidity and death. We aimed to evaluate (a) the overall survival (OS) and (b) assess predictive factors of radioiodine treatment (RAI) response in patients with DTC and BM. 178 consecutive DTC patients harboring BM were enrolled in this retrospective study conducted in two tertiary referral centres of the French national TUTHYREF network between 1989 and 2015. OS analysis was performed for the whole cohort while the 145 non-RAI refractory patients at BM diagnosis were evaluated for total RAI response (T-RAI-R) defined as the complete resolution of RAI uptake in the absence of morphologic progression of BM. The median OS, calculated from BM diagnosis, was 57 months (24-93). The OS rate at 5 and 10 years from BM detection was 56.5% and 15.3% respectively for patients with BM RAI uptake but only 28.6 and 4.8% for patients without any significant radioiodine uptake. In multivariate analysis, OS was significantly reduced by T4 stage, BM FDG-PET/CT uptake and RAI refractory status (HR, 2.91; 95% CI, 1.27-6.65, p=0.113; HR, 3.79; 95% CI 1.23-11.71, p=0.0204; HR, 5.16; 95% CI 1.21- 21.93, p=0.0264, respectively). Among the 145 DTC non-RAI refractory patients at BM diagnosis, 46 patients (31.7%) achieved a T-RAI-R (32 patients with radioiodine alone and 14 with further local BM treatments). Patients without extra-skeletal metastasis and absence of BM FDG-PET/CT uptake were more likely to achieve T-RAI-R (OR, 0.11; 95% CI, 0.02-0.46, p=0.005; OR, 0.2; 95% CI, 0.04-0.80, p=0.0236, respectively). Among DTC patients with newly diagnosed BM. BM FDG-PET/CT uptake is a prognostic factor for a T-RAI-R and for OS. FDG-PET/CT should be performed as soon as the BM diagnosis.

Targeting poor proteasomal function with radioiodine eliminates CT26 colon cancer stem cells resistant to bortezomib therapy

We tested the hypothesis that tumor response to conventional bortezomib (BTZ) treatment is enhanced by targeted radiotherapy of resistant cancer stem cells (CSCs) that have characteristically poor proteasome function. This was accomplished by augmenting 131I uptake through expression of a sodium-iodide symporter (NIS) fusion protein that accumulates in cells with low proteasome activity. The NIS gene fused with the C-terminal of ornithine decarboxylase degron (NIS-cODC) was cloned. Stably expressing CT26/NIS-cODC cells and tumorsphere-derived CSCs were evaluated for NIS expression and radioiodine uptake. CT26/NIS-cODC cells implanted into mice underwent PET imaging, and tumor-bearing mice were treated with BTZ alone or with BTZ plus 131I. CT26/NIS-cODC cells accumulated NIS protein, which led to high radioiodine uptake when proteasome activity was inhibited or after enrichment for stemness. The cell population that survived BTZ treatment was enriched with CSCs that were susceptible to 131I treatment, which suppressed stemness features. Positron emission tomography and uptake measurements confirmed high 124I and 131I uptake of CT26/NIS-cODC CSCs implanted in living mice. In CT26/NIS-cODC tumor-bearing mice, whereas BTZ treatment modestly retarded tumor growth and increased stemness markers, combining 131I therapy suppressed stemness features and achieved greater antitumor effects. The NIS-cODC system offer radioiodine-targeted elimination of CSCs that are tolerant to proteasome inhibition therapy.

Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients

ObjectiveAfter 131I treatment in patients with differentiated thyroid carcinoma (DTC), we sometimes find a star-shaped intense uptake of 131I on therapeutic whole body scans (Rx-WBS), called star artifacts. Therefore, we analyzed the relevant clinical factors and prognostic value of star artifacts in DTC patients. Methods809 DTC patients who received 131I treatment were retrospectively evaluated and divided into 2 groups of patients with and without star artifacts. We evaluated the therapeutic response which was divided into excellent response (ER), biochemical incomplete response (BIR), indeterminate response (IR), and structural incomplete response (SIR). Clinical factors for the presence of star artifacts were analyzed. We also compared the rate of ER, BIR, IR, SIR and recurrence rate between group 1 and group 2. ResultsThe major clinical factors included stimulated thyroglobulin (sTg)>1.8ng/ml, 24h radioiodine uptake (RAIU)>2.2%, and positive 99mTcO4− thyroid imaging for the presence of star artifacts. In patients with sTg levels>10ng/ml, patients in group 1 had a higher rate of ablation success and ER than patients in group 2 (80.2% vs 65.6%, P=0.038, 31.6% vs 13.1%, P=0.008, respectively) and had a similar rate of BIR, IR, SIR. Recurrence rate was similar between group 1 and group 2 (5.2% vs 3.1%, P=0.13). ConclusionMore remnant thyroid tissue is one of the factors associated with the presence of star artifacts on Rx-WBS. Patients with star artifacts exhibit a better therapeutic response (ER) when sTg levels are >10ng/ml. However, star artifacts have no effect on the recurrence rate.

Drug repurposing identifies inhibitors of the proteostasis network to augment radioiodine uptake in combinatorial approaches targeting thyroid cancer

Drug repurposing identifies inhibitors of the proteostasis network to augment radioiodine uptake in combinatorial approaches targeting thyroid cancer

Experiences of low iodine diets in the treatment of differentiated thyroid cancer with radioactive iodine ablation therapy.

International guidelines on the treatment of differentiated thyroid cancers (DTC) promote the use of low iodine diets (LID) prior to radioactive iodine remnant ablation (RIA), as high iodine status may interfere with radioiodine uptake. Most UK treatment centres adhere to these guidelines and advise people to consume a LID. There is limited research as to how people cope with the LID or its impact on daily life and wellbeing, and no studies have been conducted in the UK. This study explored peoples' views and experiences in relation to consuming a LID during treatment for DTC with RIA. Twenty-eight semi-structured interviews were conducted with people from across three treatment centres where differing advice had been delivered regarding a LID. Interviews were recorded, transcribed verbatim and key themes were developed through inductive thematic analyses. Individuals advised to consume a LID believed that adhering to the diet would help their treatment. Most restricted their diets beyond what was recommended and there was confusion surrounding what they could eat as part of the diet. Food selection and preparation were important which included substitution of foods and ingredient checking. Being on the diet was considered to have both a physical and psychological impact. The findings of this study provide a qualitative insight into the lived experiences of people with DTC in relation to consuming a LID. The results have relevance for professionals providing dietary guidance at oncology centres treating patients with RIA therapy in the UK.

A comparison of thyroidal protection by stable iodine or perchlorate in the case of acute or prolonged radioiodine exposure

In the case of a nuclear power plant accident, repetitive/prolonged radioiodine release may occur. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of non-radioactive iodine may protect the thyroid by inhibiting radioiodine uptake into the gland (iodine blockade). Protection is based on a competition at the active carrier site in the cellular membrane and the Wolff–Chaikoff effect, the latter being, however, only transient (24–48 h). Perchlorate may alternatively provide protection by a carrier competition mechanism only. Perchlorate has, however, a stronger affinity to the carrier than iodide. Based on an established biokinetic–dosimetric model developed to study iodine blockade, and after its extension to describe perchlorate pharmacokinetics and the inhibition of iodine transport through the carrier, we computed the protective efficacies that can be achieved by stable iodine or perchlorate in the case of an acute or prolonged radioiodine exposure. In the case of acute radioiodine exposure, perchlorate is less potent than stable iodine considering its ED50. A dose of 100 mg stable iodine has roughly the same protective efficacy as 1000 mg perchlorate. For prolonged exposures, single doses of protective agents, whether stable iodine or perchlorate, offer substantially lower protection than after acute radioiodine exposure, and thus repetitive administrations seem necessary. In case of prolonged exposure, the higher affinity of perchlorate for the carrier in combination with the fading Wolff–Chaikoff effect of iodine confers perchlorate a higher protective efficacy compared to stable iodine. Taking into account the frequency and seriousness of adverse effects, iodine and perchlorate at equieffective dosages seem to be alternatives in case of short-term acute radioiodine exposure, whereas preference should be given to perchlorate in view of its higher protective efficacy in the case of longer lasting radioiodine exposures.

Comparison of simultaneous 18F-2-[18F] FDG PET/MR and PET/CT in the follow-up of patients with differentiated thyroid cancer

18F-FDG PET/CT is the most accurate imaging modality in differentiated thyroid cancer (DTC) patients with either an aggressive histology, an absence of radioiodine uptake in neoplastic foci, or in the absence of imaging abnormalities in patients with an elevated serum thyroglobulin (Tg) level that progresses with time. We evaluated the diagnostic performance of FDG PET/MR in comparison with that of PET/CT. Following the injection of a single 18F-FDG activity, PET/MR and PET/CT were sequentially performed in 40 consecutive patients with DTC previously treated with total thyroidectomy and radioiodine ablation. All patients were then followed up for at least 6months. PET/MR was positive in 11 patients and PET/CT in 10. PET/MR detected 33 tumor foci and PET/CT 30. During the follow-up of the 12 patients with negative initial PET studies and with a detectable serum Tg, only one patient had a neck recurrence and the administration of an empiric high activity of 131I in the other 11 patients did not reveal any tumor focus. In the 17 patients with an initial serum Tg level < 2ng/mL, no recurrence occurred. This study confirms the high diagnostic accuracy of FDG PET studies in DTC patients with elevated serum Tg levels and shows that PET/MR brings similar information as compared to PET/CT imaging.

Success rate of radioactive iodine treatment for children and adolescent with hyperthyroidism.

To assess the success rate of first dose radioiodine for treatment of hyperthyroidism in children and adolescent. This is a retrospective data analysis of children and adolescent with hyperthyroidism who received radioiodine (RAI) therapy from January 2013 to December 2017. Age, gender, family history of hyperthyroidism, duration of anti-thyriod drugs (ATDs) treatment, rapid turnover status, 2h and 24h I-131 radioiodine uptake (RAIU), thyroid volume, and treatment dose were also analyzed. The goal of RAI therapy was to achieve hypothyroidism within 3-6months after treatment. Treatment result was evaluated at 6months after treatment and divided into 2 groups: treatment success (hypothyroid and euthyroid) and treatment failure (hyperthyroid). The same parameters were compared between both groups. 32 hyperthyroid patients, 26 female with mean age at treatment of 13.84 ± 1.83years. All patients had prior treatment with ATDs, with a median treatment duration of 32.5months (range 2-108). The median estimated thyroid gland size was 24.62g, range 9.29-72.8. RAI doses ranged from 4.1 to 29.9mCi (median dose = 7.54mCi). Significant difference in 24-h I-131 uptake and RI status was demonstrated. Successful treatment rate after single dose of therapeutic I-131 was 65.63%. With the I-131 dose of 220μCi/g of thyroid tissue, successful treatment rate after single dose of therapeutic I-131 was 65.63%. RAI therapy with I-131 dose of 250-400μCi/g of thyroid tissue might be suitable in patients with medical failure from ATDs. Possible role of RI as the predictor for RAI therapy failure are needed to investigate in both adult and children clinical settings.

Breast Uptake of Radio-iodine in Differentiated Thyroid Cancer

Radioiodine is often seen to accumulate within breast tissue in patients with differentiated thyroid cancer. Although the risk of secondary breast malignancy in patients with differentiated thyroid cancer treated with radioiodine is controversial, the identification and reduction of this uptake is prudent to minimize the radiation absorbed dose to the breast tissue. This article reviews the literature describing the etiology, frequency and patterns of radioiodine uptake in breast tissue. Approaches and techniques to help minimize the radioiodine uptake in lactating and nonlactating breasts are presented.

Painless thyroiditis in a dupilumab-treated patient.

SummaryDupilumab an inhibitor of the interleukin (IL)-4R-alpha subunit is used for the treatment of allergic diseases. The patient was a 49-year-old man who received dupilumab for the treatment of severe atopic dermatitis. He presented hyperthyroidism with elevated thyroglobulin and anti-thyroid antibody negativity at 4 months after the initiation of therapy. On scintigraphy, the thyroid radioiodine uptake was low. Ultrasonography showed a diffuse hypoechoic area in the thyroid gland. A pathological study revealed lymphocytic infiltration. The administration of dupilumab was continued because of his atopic dermatitis that showed an excellent response. The patient`s hyperthyroidism changed to hypothyroidism 3 weeks later. Six months later his thyroid function normalized without any treatment. We herein describe the case of a patient with atopic dermatitis who developed painless thyroiditis under treatment with dupilumab. To the best of our knowledge, this is the first report of this event in the literature.Learning points:Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has been shown to be effective in the treatment atopic dermatitis and asthma with eosinophilia.Painless thyroiditis is characterized by transient hyperthyroidism and hypothyroidism and recovery without anti-thyroid treatment.This is the first report of painless thyroiditis as an adverse effect of dupilumab, although conjunctivitis and nasopharyngitis are the main adverse effects of dupilumab.

OR28-03 Drug Repurposing Identifies Inhibitors of the Proteostasis Network to Augment Radioiodine Uptake in Combinatorial Approaches Targeting Thyroid Cancer

New combinatorial drug strategies are urgently needed to improve radioiodine (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. Drug repurposing offers the promise of identifying already approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. However, a lack of thyroid cell-based assays amenable to high-throughput screening has limited progress. We utilised the mutated yellow fluorescent protein (YFP) as a surrogate biosensor of intracellular iodide and screened the Prestwick Chemical Library (1200 drugs; 95% approved) for quenching of YFP fluorescence. This allowed us to identify putative candidate drugs which increased iodide uptake >2 SD above mean. Categorisation of these revealed a high proportion of drugs that modulate the proteostasis network (19/48; ~40%), including key processes in protein homeostasis such as endoplasmic reticulum-associated protein degradation (ERAD) and autophagy. Secondary screening validated the activity of proteostasis modulators in enhancing iodide uptake after ranking 73 leading compounds based on their pharmacologic (AUC, EMAX and EC50) and specificity of response (NIS+ve vs NIS-ve YFP-thyroid cells) at ten different drug doses (0.1 to 50 μM). Of importance, several repurposed drugs (e.g. ebastine, Prestwick N, Prestwick C and clotrimazole) in combination with the HDAC inhibitor vorinostat induced a robust enhancement in RAI uptake in thyroid cancer cells (TPC-1 and 8505C NIS+ve cells, up to 11-fold vs DMSO, P<0.001), which was significantly greater than using vorinostat alone (up to 3-fold, P<0.01). For clotrimazole, we designed 7 new chemical derivatives, 3 of which showed enhanced aqueous solubility and retained the ability to significantly enhance RAI uptake. TaqMan RT-PCR revealed that, in contrast to vorinostat, our repurposed drugs failed to alter NIS mRNA expression, highlighting post-transcriptional mechanisms. Critically, 11 repurposed drugs induced significant gains in RAI uptake in human primary thyroid cells (up to 4.1-fold; P<0.05), the most physiological setting for NIS function. In conclusion, we performed high-throughput screening and identified proteostasis modulators, as well as other repurposed drugs, that markedly enhance radioiodine uptake. Further clinical investigation of these drugs might offer new combinatorial approaches, especially with existing therapies, to improve the treatment of thyroid cancer.

SAT-415 Clinical Performance of Thyroid-Stimulating Immunoglobulin for Graves′ Disease Diagnosis

INTRODUCTION The diagnosis of Graves′disease (GD) is likely when patient presents hyperthyroidism, symmetrical goiter and orbitopathy and further evaluation is unnecessary. Nevertheless patient with nodular thyroid or in the absence of clinical orbitopathy, measurement of TSH receptor antibodies (TRAb) is recommended to distinguish GD from toxic multinodular goiter, toxic adenoma and other etiologies. Radioiodine uptake (RAIU) also helps to diagnosis when TRAb is unavailable. Third generation TRAb assays measure all types of TSH receptor antibodies: stimulating, blocking and neutral with an excellent sensitivity and specificity for GD diagnosis. Recently, an automated bioassay for the thyroid stimulating immunoglobulin (TSI) was introduced to improve GD diagnosis. OBJECTIVE To analyze clinical performance of TSI and compare with TRAb assay for GD diagnosis. MATERIAL AND METHODS Serum samples of 117 patients with thyrotoxicosis due to GD, toxic multinodular goiter and toxic adenoma were runned simultaneously in two analytical system commercially available. TRAb was analyzed by Elecsys Anti-TSHR assay (Roche Diagnostics, Germany) in a Cobase411 analyzer (Roche Diagnostics, Germany) and results, according to the manufacturer interval reference, were negative if < 1.75 IU/L (analytical range: 0.3 to 40 IU/L). TSI was measured by Immulite TSI assay (Siemens Healthcare, UK) in Immulite XPi 2000 and results, according to the manufacturer interval reference, were negative if < 0.55 IU/L (analytical range: 0.1 to 40 IU/L). Clinical diagnoses of thyrotoxicosis were determined according to ATA guideline (2016). Statistical analyses were performed using SPSS and MedCalc softwares. Comparison were evaluated by regression equations and were considered significant when p values were < .05. RESULTS From 2017 to 2019 a total of 312 serum samples from 117 patients (96 females) were evaluated with mean age 49.5 ±15.8 years-old (18 to 90 yrs). We excluded 26 results above the analytical measurement range of both assays. A high degree correlation was observed with a slope of 0.647 and an intercept -.094 IU/L. Spearman correlation coefficient was 0.858 (p < 0.0001, 95% CI 0.825 to 0.886). TSI assay had higher sensibility and negative predictive value compared to TRAb (95.6% vs 88.5% and 83.6% vs 54.8%, respectively) but lower specificity and positive predictive value (90.3% vs 100% and 97.5% vs 100%, respectively). The results of TSI assay showed good agreement with those of the TRAb assay (k=0.74). A total of 31 samples were discordant, favoring to TSI assay in all but one case of GD according to clinical diagnosis (TRAb positive and TSI negative). CONCLUSION TSI assay showed an excellent performance for GD diagnosis with a better sensibility than TRAb assay.

SAT-LB89 Choriocarcinoma Induced Hyperthyroidism: Molecular Mimicry Between HCG and TSH

Introduction: Human chorionic gonadotropin(HCG) induced hyperthyroidism is a rare cause of hyperthyroidism. It is usually seen in conditions with extremely high beta HCG levels like hyperemesis gravidarum, hydatiform moles and germ cell tumors. We present a young male patient who had primary mediastinal choriocarcinoma with widespread lung metastasis and hyperthyroidism. Case: 18-year-old male presented to the emergency department for a fever of 105 F, cough, shortness of breath and night sweats for 9 days. He also reported unintentional weight loss for the past few weeks. Upon presentation, he was tachycardic at 104 beats/min, tachypneic and febrile. Physical examination revealed bibasilar crackles. Thyroid and scrotal examination were unremarkable. Laboratory work was significant for leukocytosis of 18.7 k/cmm, AST: 69 Unit/L, ALT: 60 Unit/L, ALP: 123 unit/L and LDH: 438Unit/L. Chest radiology showed bilateral multiple cannonball lesions with mediastinal and periaortic lymphadenopathy. CT chest, abdomen, and pelvis revealed innumerable diffuse bilateral lung masses, large anterior mediastinal mass, enlarged periaortic and paratracheal lymph nodes. Infectious workup was unremarkable. MRI brain revealed leptomeningeal involvement and vasogenic edema. Ultrasound of testicles revealed bilateral severe microlithiasis. CT guided biopsy of lung mass showed poorly differentiated choriocarcinoma. Treatment was initiated with systemic steroids, bleomycin, and cisplatin. Additional blood work revealed, B-HCG:736,598 mIU/mL, TSH:0.009UIU/ml, free T4:2.95ng/dL and total T3: 292.3ng/Dl. Thyroid radioiodine uptake scan was normal and planar imaging was also normal. Treatment with methimazole was deferred due to the up-trending transaminases and the resolution of tachycardia. Repeat labs after chemotherapy were TSH: 0.005UIU/mL, free T4: 2.04ng/dL, free T3:1.70pg/mL and BHCG: 202,471UIU/mL. Unfortunately, the patient had chemotherapy-resistant choriocarcinoma and succumbed to death after 4 cycles. Discussion: Beta HCG has an intrinsic thyroid-stimulating activity. The HCG -alpha subunit is common to all glycoprotein hormones like follicle-stimulating hormone, luteinizing hormone or thyroid-stimulating hormone. Frankly elevated levels should be treated symptomatically with beta-blockers and/or anti-thyroid drugs. Subclinical hyperthyroidism should be monitored closely. Some patients do not develop hyperthyroidism or a toxic goiter, as it is dependent on the timing of onset of cancer or due to the secondary modifications of HCG that can affect the bioactivity of HCG on the TSH receptor. This case draws our attention to the importance of focusing on the molecular mimicry of the HCG and TSH and management of HCG mediated hyperthyroidism.

SAT-417 Personalized Treatment Planning for Radioiodine Therapy of Graves’ Disease;The Collar Therapy Indicator(CoTI)

Introduction Since its introduction 80 years ago, the therapeutic I-131 dosage has usually been tailored to individual patient requirements based on the uptake of a tracer radio-iodine(RAI) dose. Estimated exposure has typically been extrapolated from the results of activity measurements at one or two time points, e.g., at 4 and 24 hours. We now know that treatment of hyperthyroid Graves disease with these methods lead to a 13–25% rate of failure to cure hyperthyroidism and a 46–80% rate of long-term hypothyroidism in cured patients. There is a need for a much more personalized approach to RAI dosing based on individual RAI tissue uptake, kinetics. This can be achieved only after including multiple data points during the evaluation of tissue uptake. The Collar Therapy Indicator (CoTI), a device placed in cloth collar around the neck resembling a turtle neck sweater collar with a connecting wire and recording box, has been shown in small feasibility studies to provide data regarding radioiodine exposure that correlates with conventional methods of measuring I-123 and I-131 uptakes after diagnostic dose administration and/or therapy for thyroid disorders Methods; We hypothesized that the device’s continuous measurement capability will permit more accurate estimates of radiation exposure to thyroid tissue than conventionally employed methods assessing fractional uptake at one or a few time points. It may also provide information about the extent of variability in the absorbed radiation dose among patients with hyperthyroidism. We performed a feasibility study in a patient with graves’ disease to see the difference between tradition methods of I-123 uptake and the CoTI; (1) We compared the conventional quantitative uptake-derived thyroid time activity curve (TAC) as well as the Area Under the Curve (AUC)(based on percent uptake at 6 hour and 24 hour time points) to that obtained using the CoTI.(2) We evaluated the uptake and clearance kinetics of diagnostic I-123 administered.(3) We also evaluated patient experience in using the CoTI device with a survey instrument. Results; The CoTI plotted TAC and AUC offered a different approach from the conventional methods of calculation (6 hr and 24 hr % uptake) of I-123 TAC and AUC. The patient reported no difficulty in using the device and the device itself was not inconvenient. Conclusions; The calculation of % uptake as well as rate of uptake within the thyroid by CoTI might help us, in achieving a more personalized approach to I-131 RAI dose calculation for treatment of Graves’ disease. The preliminary research findings that we have generated will help us investigate different aspects of RAI uptake within the thyroid and will hopefully lead to solutions, for some of the common issues and problems arising out of random dosing of RAI.

Unexpected radioactive iodine accumulation on whole-body scan after I-131 ablation therapy for differentiated thyroid cancer.

ABSTRACTWe retrospectively evaluated the frequency of unexpected accumulation of radioactive iodine on the post-therapy whole-body scan (Rx-WBS) after radioactive iodine (RAI) ablation therapy in patients with differentiated thyroid cancer (DTC). We searched our institutional database for Rx-WBSs of DTC patients who underwent RAI ablation or adjuvant therapy between 2012 and 2019. Patients with distant metastasis diagnosed by CT or PET/CT before therapy, and those had previously received RAI therapy were excluded. In total, 293 patients (201 female and 92 male, median age 54 years) were selected. Two nuclear medicine physicians interpreted the Rx-WBS images by determining the visual intensity of radioiodine uptake by the thyroid bed, cervical and mediastinal lymph nodes, lungs, and bone. Clinical features of the patients with and without the metastatic accumulation were compared by chi-square test and median test. Logistic regression analyses were performed to compare the association between the presence of metastatic accumulation and these clinical factors. Eighty-four of 293 patients (28.7%) showed metastatic accumulation. Patients with metastatic RAI accumulation showed a significantly higher frequency of pathological N1 (pN1) and serum thyroglobulin (Tg) > 1.5 ng/ml under TSH stimulation (p = 0.035 and p = 0.031, respectively). Logistic regression analysis indicated that a serum Tg > 1.5 ng/ml was significantly correlated with the presence of metastatic accumulation (odds ratio = 1.985; p = 0.033). In conclusion, Patients with Tg > 1.5 ng/ml were more likely to show metastatic accumulation. In addition, the presence of lymph node metastasis at the initial thyroid surgery was also associated with this unexpected metastatic accumulation.

Thyroid-disrupting effects and mechanism of thiazole-Zn-induced thyroid cell hypertrophy and hyperplasia in male Sprague-Dawley rats.

Thiazole-Zn is a systemic fungicide synthesized and developed in China that has been used for the prevention and treatment of bacterial and fungal diseases on fruits and vegetables. Thiazole-Zn is a new thyroid disruptor chemical. The purpose of this study was to clarify the thyroid-disrupting property of thiazole-Zn and the mechanism responsible for thyroid hormone (TH) biosynthesis inhibition in male rats induced by thiazole-Zn. First, the effects of different thiazole-Zn doses and exposure times on the thyroid weights, thyroid morphology and serum hormone levels of rats were investigated. The results showed that thiazole-Zn increased thyroid weights and serum thyroid-stimulating hormone (TSH) levels and induced thyroid cell hypertrophy and hyperplasia in a dose-related and time-related manner. Furthermore, measurement of thyroid radioiodine uptake in vivo in rats confirmed that thiazole-Zn inhibited active iodide uptake into the thyroid, which reduced circulating levels of serum T3 and T4. Decreases in circulating THs resulted in a compensatory increase in serum TSH levels through a negative feedback system. Subsequently, sustained excessive stimulation of the thyroid gland by TSH led to thyroid follicular cell hypertrophy and hyperplasia. In addition, thiazole-Zn increased sodium/iodide symporter (NIS) expression in the rat thyroid, and the increased NIS expression promoted and restored iodide uptake into the thyroids of rats. The risk of iodine intake inhibition by thiazole-Zn to humans, especially susceptible individuals, such as children and pregnant women, warrants additional attention.