Risk Of Thyroid Cancer Research Articles

Thyroid cancer burden and risk factors in China from 1990-2019: a systematic analysis using the global burden of disease study.

Thyroid cancer (TC) is the most common endocrine system malignancy with a rapidly increasing incidence in China. Epidemiological data on TC at the national level are lacking. This study aimed to quantify the TC disease burden in China between 1990 and 2019 and evaluate the current status and trends of the disease burden attributed to a high body mass index (HBMI). The 2019 Global Burden of Disease Study dataset was used to explore the TC disease burden. Age-standardized rates of incidence (ASIR), prevalence (ASPR), deaths (ASDR), and disability-adjusted life years (DALYs) were considered and the estimated annual percentage change (EAPC) was calculated as a measure of the average change in age-standardized rates. The trend in TC-related mortality and DALYs attributed to an HBMI, accounting for different age groups and sexes, was examined. Between 1990 and 2019, the ASDR and DALYs for TC decreased by 0.02/100000 and 1.17/100000, respectively. The ASPR and ASIR increased by 9.88/100000 and 1.04/100000, respectively. The EAPC for ASDR, age-standardized rates of DALYs, ASPR, and ASIR were 0.06 (95% CI: -0.09, 0.21), -0.20 (95% CI: -0.31, -0.10), 3.52 (95% CI: 3.35, 3.68), and 2.73 (95% CI: 2.58, 2.88), respectively. TC-related deaths, DALYs, and their prevalence and incidence in China increased by 118%, 350%, 81%, and 290%, respectively. The disease burden of TC was higher among male than female patients in different age groups, with varying distributions. The disease burden attributed to HBMI gradually increased over the past 30 years according to age-standardized DALYs, particularly in male patients. The TC burden has increased in China over the past 30 years, and population aging poses a challenge to TC prevention and control. HBMI has become an important factor in the TC disease burden and further research should focus on reducing the disease burden among Chinese male patients with TC.

Abstract 12095: Efficacy, Safety, and Cardio-Protective Effect of GLP-1 Receptor Agonists Among Patients With Diabetes Mellitus: A Meta-Analysis and Meta-Regression

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promising results in reducing the incidence of major adverse cardiovascular events (MACE) in patients with Diabetes Mellitus (DM). However, the reports of previous trials show inconsistent reports for other endpoints like myocardial infarction, stroke, and cancer. Objective: We sought to evaluate the efficacy and safety of GLP-1 receptor agonists among DM patients by including recently published trials evaluating cardiovascular outcomes. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10th March 2022. Primary clinical outcomes were the incidence of MACE. The secondary efficacy outcomes were cardiovascular mortality (CVM), all-cause mortality (ACM), myocardial infarction (MI), stroke, and heart failure hospitalization (HFH). Results: A total of 8 randomized controlled trials with xx (518,105 GLP-1 RA vs. 6,817,729 placebo) patients were included in the analysis. The mean age of the patients with GLP-1 RA and the placebo group was 70.0 and 69.2 years. The mean follow-up duration was xx years. Pooled analysis shows that GLP-1 receptor agonists were associated with significant 14% reduction in MACE [HR 0.86, 95% CI (0.80-0.93), p<0.01], 17% reduction in stroke [HR 0.83, 95% CI (0.76-0.92), p<0.01], 10% reduction in MI [HR 0.90, 95% CI (0.83-0.99), p=0.02], 13% reduction in CVM [HR 0.87, 95% CI (0.81-0.94), p<0.01), 12% reduction in ACM [HR 0.88, 95% CI (0.83-0.93), p<0.01] and 9% reduction in HFH [HR 0.91, 95% CI (0.84-0.99), p=0.04] compared to that of placebo. Among safety outcomes, the risk of thyroid cancer was significantly higher in GLP-1 RA [OR 2.33, 95% CI (1.08-5.03), p=0.03) compared to placebo. Conclusions: GLP-1 receptor agonists significantly reduced MACE, MI, ACM, CVM, HFH, and stroke. However, the risk of thyroid cancer significantly increased in GLP-1 RA patients.

Multiple endocrine neoplasia type 2: towards a risk-based approach integrating molecular and biomarker results

Purpose of review Significant advances have transformed our understanding of the molecular biology and natural history of multiple endocrine neoplasia type 2 (MEN2). This progress enacted a paradigm shift with regard to routine neck dissection for medullary thyroid cancer and total adrenalectomy for pheochromoytoma. The purpose of this review is to summarize key molecular and clinical data underpinning the current risk-based approach to MEN2 that integrates molecular and biomarker results. Recent findings Early identification and biochemical monitoring of rearranged during transfection (RET) carriers yield important lead time. Within these ‘windows of opportunity’, total thyroidectomy alone, avoiding incremental morbidity from node dissection; ‘tissue-sparing’ subtotal adrenalectomy, balancing risks of steroid dependency with pheochromocytoma recurrence in adrenal remnants; and parathyroidectomy of enlarged glands only, weighing risks of postoperative hypoparathyroidism against hyperactive parathyroid glands left behind, are adequate therapies. Summary All that is needed to determine a RET carriers’ risk of medullary thyroid cancer, pheochromocytoma and/or primary hyperparathyroidism in the molecular era is patient age, underlying RET mutation, and biomarker levels. As broader testing begins to penetrate healthcare, the needle on population genomic screening and education needs to be moved forward to complete the transition from symptom-based to preventive healthcare.

Associations of a mixture of eleven endocrine disruptors in human urine with the risk of papillary thyroid cancer

To examine the associations of human exposure to a mixture of 11 endocrine disruptors(EDCs) with the risk of papillary thyroid cancer(PTC), and to identify the priority of these EDCs. EDCs were determined in fasting urine specimens to represent human exposure. Logistics regressions were performed to examine the associations between individual EDC and PTC risk. Bayes kernel machine regression was applied to examine the associations between the mixture of EDCs and PTC risk. Weighted quantile sum(WQS) regression and LASSO regression were performed to identify the main contributor. In the multivariate logistic regression model, after adjusting for a series of variables, 11 endocrine disruptors were statistically significantly correlated with the risk of PTC(P<0.05). In BKMR models, the mixture of EDCs was positively correlated with the risk of PTC(P<0.05). The weight and coefficient of mono(2-ethyl-5-hydroxyhexyl) phthalate(MEHHP) was 0.62 and 1.58 in WQS and LASSO models, respectively, which were much higher than those of the other EDCs. Combined exposure to o a variety of EDCs might promote the risk of PTC, and MEHHP was identified as the main contributor.

Nonalcoholic Fatty Liver Disease and the Risk of Thyroid Cancer Among Young Adults in South Korea.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Obesity and metabolic syndrome are known risk factors for thyroid cancer. We investigated the association between NAFLD and thyroid cancer risk in young adults. This nationwide cohort study included 1 135 967 participants aged 20 to 39 years who underwent 4 consecutive health screenings in South Korea. NAFLD was categorized using the fatty liver index (FLI), as follows: ≥60, 30 to 60, and <30. The cumulative FLI points were defined as the number of times participants had a FLI of ≥30 (0-4). During a median follow-up of 5.2 years, 4126 participants (0.36%) were newly diagnosed with thyroid cancer. Compared with the participants with an FLI of <30, those with an FLI of 30 to 60 (men: hazard ratio [HR] 1.36 [95% CI, 1.22-1.51] and women: HR 1.44 [1.21-1.70]) and those with an FLI of ≥60 (men: HR 1.71 [1.53-1.92] and women: HR 1.81 [1.46-2.25]) had a significantly higher risk of thyroid cancer. Participants with higher cumulative FLI points had a higher risk of thyroid cancer compared to those with a cumulative FLI point of 0 (P < .001). During the follow-up period, the participants with an increased FLI exhibited an increased risk of thyroid cancer. NAFLD was associated with an increased risk of thyroid cancer in young adults. Repeatedly elevated FLI and progression of NAFLD were associated with an increased risk of thyroid cancer in this study.

Prediagnostic serum concentrations of per- and polyfluoroalkyl substances and risk of papillary thyroid cancer in the Finnish Maternity Cohort.

Human exposure to per- and polyfluoroalkyl substances (PFAS) occurs globally through contaminated food, dust, and drinking water. Studies of PFAS and thyroid cancer have been limited. We conducted a nested case-control study of prediagnostic serum levels of 19 PFAS and papillary thyroid cancer (400 cases, 400 controls) in the Finnish Maternity Cohort (pregnancies 1986-2010; follow-up through 2016), individually matched on sample year and age. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for log2 transformed and categorical exposures, overall and stratified by calendar period, birth cohort, and median age at diagnosis. We adjusted for other PFAS with Spearman correlation rho = 0.3-0.6. Seven PFAS, including perfluoroctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), N-ethyl-perfluorooctane sulfonamidoacetic acid (EtFOSAA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorohexane sulfonic acid (PFHxS) were detected in >50% of women. These PFAS were not associated with risk of thyroid cancer, except for PFHxS, which was inversely associated (OR log2 = 0.82, 95% CI: 0.70-0.97). We observed suggestive but imprecise increased risks associated with PFOA, PFOS, and EtFOSAA for those diagnosed at ages <40 years, whereas associations were null or inverse among those diagnosed at 40+ years (P-interaction: .02, .08, .13, respectively). There was little evidence of other interactions. These results show no clear association between PFAS and papillary thyroid cancer risk. Future work would benefit from evaluation of these relationships among those with higher exposure levels and during periods of early development when the thyroid gland may be more susceptible to environmental harms.

Assessment of five typical environmental endocrine disruptors and thyroid cancer risk: a meta-analysis.

There are conflicting reports on the association between environmental endocrine disruptors (EEDs) and thyroid cancer. This meta-analysis aimed to elucidate the relationship between EEDs and thyroid cancer. We searched for epidemiological studies on EEDs and thyroid cancer published in PubMed and Web of Science up to December 2022. We then screened the articles that could extract data on EEDs concentration levels in both thyroid cancer patients and healthy controls. We excluded articles that could not calculate effect sizes, focused on other thyroid diseases, or lacked controls. Standardized mean difference (SMD) was calculated to analyze the association between EEDs and thyroid cancer. We measured the heterogeneity among the included studies using I2, assessed publication bias by Egger's and Begg's test, and evaluated article quality using the Newcastle-Ottawa Quality Score (NOS). In the end, fifteen eligible case-control studies were included. Our comprehensive analysis revealed that polychlorinated biphenyls (PCBs) were negatively associated with thyroid cancer{ SMD = -0.03, 95% confidence interval (CI) = (-0.05, -0.00), P = 0.03}, while polybrominated diphenyl ethers (PBDEs), phthalates (PAEs), and heavy metals were positively associated with thyroid cancer{PBDEs: SMD = 0.14, 95%CI = (0.04, 0.23), P = 0.007; PAEs: SMD = 0.30, 95%CI = (0.02, 0.58), P = 0.04; heavy metals: SMD = 0.21, 95%CI = (0.11, 0.32), P < 0.001}. We did not find a statistically significant relationship between bisphenol A (BPA) and thyroid cancer. Most of the included studies did not show publication bias, except for those on PCBs. Our results indicate that exposure to certain EEDs, such as PBDEs, PAEs, and heavy metals, increases the risk of thyroid cancer. However, further large-scale epidemiological studies and mechanism studies are needed to verify these potential relationships and understand the underlying biological mechanisms.

Height, Autoimmune Thyroid Disease, and Thyroid Cancer: A Mendelian Randomization Study.

Background: Increased height has been associated with increased risk of hypothyroidism or thyroid cancer in epidemiological studies. However, the potential causal association between height and hypothyroidism or thyroid cancer has not been thoroughly explored. Autoimmune thyroid disease (AITD) mainly presents as hypothyroidism, thus we aim to evaluate the causal relationship between height as exposure and its association with AITD or thyroid cancer. Methods: Mendelian randomization (MR) analyses were performed by using genetic instruments associated with height, which were selected from the largest genome-wide association meta-analysis for height in up to 5.4 million individuals. Summary-level data for AITD and thyroid cancer (including 30,234 and 3001 cases, respectively) were collected from the large number of available genome-wide association studies. Bidirectional MR was performed to test for reverse causal association between AITD and adult height. Results: MR analyses showed that increased genetically predicted height was associated with a 4% increased risk of AITD ([CI 1.02 to 1.07], p-value = 1.99E-03) per 1-standard deviation (SD) increase in genetically predicted height. The bidirectional MR did not show any causal association between AITD and adult height. Additionally, increased genetically predicted height was associated with 15% increased risk of thyroid cancer ([CI 1.07 to 1.23], p-value = 2.32E-04) per 1-SD increase in height. Sensitivity analysis confirmed the main results. Conclusions: This MR study showed that 1-SD increase in genetically predicted height was associated with increased risk of AITD and thyroid cancer. In contrast, there was no evidence of a causal association of genetically predicted AITD with height. These results could further aid in investigation of height-related pathways as a means of gaining new mechanistic insights into AITD and thyroid cancer.

Preoperative Thyroid-Stimulating Hormone Levels and Risk of Thyroid Cancer in Post-thyroidectomy Patients for Thyroid Nodules: A Study From a Tertiary Hospital in Western Saudi Arabia.

Background Although serum thyroid-stimulating hormone (TSH) is one of the basic investigations to assess thyroid nodules, its role in thyroid oncogenesis remains unclear. Previous literature has conflicting findings regarding TSH levels and the prediction of malignancy. This study aims to investigate the association between TSH levels and the risk of malignancy and advanced staging in patients who underwent thyroidectomy for nodular thyroid disease. Additionally, it aims to assess if higher TSH correlates with malignancy in Bethesda staging III, IV, and V. Methodology This retrospective cohort study was conducted among participants who underwent near-total/total thyroidectomy or hemithyroidectomy at King Abdulaziz Medical City between 2016 and 2021. Results A total of 378 cases were included, and 50.3% of the cases had malignant nodules in the surgical histopathology findings. The median TSH levels were higher in malignant nodules compared to benign ones (1.64 mIU/L versus 1.49 mIU/L; p < 0.001). Additionally, higher TSH levels were not associated with advanced staging or malignancy in patients with Bethesda stage III-V. Conclusions Higher TSH levels are associated with an increased risk of malignancy in patients with nodular thyroid disease. Using TSH levels as an adjunctive tool for identifying high-risk patients with thyroid nodules would aid in management planning.

Per- and polyfluoroalkyl substances (PFAS) exposure and thyroid cancer risk

Although per- and polyfluoroalkyl substances (PFAS) exposure is a potential contributor to the increasing thyroid cancer trend, limited studies have investigated the association between PFAS exposure and thyroid cancer in human populations. We therefore investigated associations between plasma PFAS levels and thyroid cancer diagnosis using a nested case-control study of patients with thyroid cancer with plasma samples collected at/before cancer diagnosis. 88 patients with thyroid cancer using diagnosis codes and 88 healthy (non-cancer) controls pair-matched on sex, age (±5 years), race/ethnicity, body mass index, smoking status, and year of sample collection were identified in the BioMe population (a medical record-linked biobank at the Icahn School of Medicine at Mount Sinai in New York); 74 patients had papillary thyroid cancer. Eight plasma PFAS were measured using untargeted analysis with liquid chromatography-high resolution mass spectrometry and suspect screening. Associations between individual PFAS levels and thyroid cancer were evaluated using unconditional logistic regression models to estimate adjusted odds ratios (ORadj) and 95% confidence intervals (CI). There was a 56% increased rate of thyroid cancer diagnosis per doubling of linear perfluorooctanesulfonic acid (n-PFOS) intensity (ORadj, 1.56, 95% CI: 1.17-2.15, P=0.004); results were similar when including patients with papillary thyroid cancer only (ORadj, 1.56, 95% CI: 1.13-2.21, P=0.009). This positive association remained in subset analysis investigating exposure timing including 31 thyroid cancer cases diagnosed ≥1 year after plasma sample collection (ORadj, 2.67, 95% CI: 1.59-4.88, P<0.001). This study reports associations between exposure to PFAS and increased rate of (papillary) thyroid cancer. Thyroid cancer risk from PFAS exposure is a global concern given the prevalence of PFAS exposure. Individual PFAS studied here are a small proportion of the total number of PFAS supporting additional large-scale prospective studies investigating thyroid cancer risk associated with exposure to PFAS chemicals. National Institutes of Health grants and The Andrea and Charles Bronfman Philanthropies.

Tumor Microbial Communities and Thyroid Cancer Development-The Protective Role of Antioxidant Nutrients: Application Strategies and Future Directions.

Thyroid cancer (TC), the most frequent malignancy of the endocrine system, has recorded an increasing incidence in the last decades. The etiology of TC remains at least partly unknown and, among modifiable risk factors, the gut microbiota and dietary nutrients (vitamins, essential microelements, polyphenols, probiotics) have been recognized to not only influence thyroid function, but exert critical effects on TC development and progression. Recent discoveries on the existence of tumor microbiota also in the TC microenvironment provide further evidence for the essential role of tumor microorganisms in TC etiology and severity, as well as acting as prognostic markers and as a potential target of adjuvant care in the treatment of TC patients. Therefore, in this review, we summarize current knowledge on the relationship of the tumor microbiome with the clinical tumor characteristics and TC progression, also illustrating the molecular mechanisms underlying this association, and how antioxidant nutrients may be used as a novel strategy to both control gut health and reduce the risk for TC. Furthermore, we discuss how new technologies might be exploited for the development of new foods with high nutritional values, antioxidant capability, and even attractiveness to the individual in terms of sensory and emotional features.

Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants.

There is a research gap between genetic predisposition, socioeconomic factors, and their interactions on thyroid tumorigenesis. Individual and genetic data were obtained from UK Biobank. Logistic regression models were used to evaluate the association between genetic risk, socioeconomic factors, and thyroid cancer (TCa). A stratified analysis was conducted to estimate their joint effects. A two-sample Mendelian randomization (MR) analysis was further used to examine the potential causality. A total of 502,394 participants were included in this study. Three index loci (rs4449583, rs7726159, and rs7725218) of telomerase reverse transcriptase (TERT) were found to be significantly related to incident TCa. Association analyses showed that high genetic risk, low household income, and high education level were independent risk factors, while unemployment and frequent social connection were suggestive risk factors for TCa. Interaction analyses showed that in participants with low genetic risk, low household income was significantly associated with TCa (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.00-2.46). In participants with high genetic risk, those with a high education level (OR = 1.32, 95%CI: 1.06-1.65) and frequent social connection (OR = 1.36, 95%CI: 1.02-1.81) had a significantly increased risk of TCa. However, no causal relationship was observed in the MR analysis. Interactions exist between genetic risk, household income, education level, and social connection and thyroid cancer.

Mortality among papillary thyroid cancer patients by detection route: a hospital-based retrospective cohort study.

Incidence rates of papillary thyroid cancer (PTC) have increased rapidly, with incidentally detected cancers contributing a large proportion. We aimed to explore the impact of incidental detection on thyroid cancer-specific and competing mortality among PTC patients. We conducted a retrospective cohort study of PTC patients at a cancer center in Guangzhou. Baseline information on detection route and other covariates were collected between 2010 and 2018, and death outcome was followed up for each patient. Cumulative incidence functions were used to estimate the mortality risk of thyroid cancer and competing risk. Cause-specific hazard models were then utilized to explore the association between detection routes and PTC-specific and competing mortality. Of the 2874 patients included, 2011 (70.0%) were detected incidentally, and the proportion increased from 36.9% in 2011 to 82.3% in 2018. During a median follow-up of 5.6 years, 42 deaths occurred, with 60% of them due to competing causes. The probability of competing mortality at 5 years in the non-incidental group and incidental group was 1.4% and 0.4%, respectively, and PTC-specific mortality in the non-incidental group and incidental group was 1.0% and 0.1%, respectively. After adjusting for covariates, the HRs of incidental detection were 0.13 (95% CI: 0.04-0.46; P = 0.01) and 0.47 (95% CI: 0.20-1.10; P = 0.10) on PTC-specific mortality and competing mortality, respectively. Incidental detection is associated with a lower risk of PTC-specific and competing mortality. Under the context of increasing magnitude of overdiagnosis, incorporation of detection route in clinical decision-making might be helpful to identify patients who might benefit from more extensive or conservative therapeutic strategies.

Thyroid cancer risk after radiation exposure in adults-systematic review and meta-analysis.

Notably, the growing use of radionuclear technology, especially in diagnostic and therapeutic procedures involving radiation exposure, raises concerns about the health effects of radiation. Although epidemiological studies have provided strong evidence for elevated thyroid cancer risk after radiation exposure in childhood, the risk of thyroid cancer associated with adult exposure remains to be investigated. We conducted a systematic review and meta-analysis of relevant studies on the risk of developing thyroid cancer after radiation exposure in adulthood. The PubMed and Web of Science databases were used to select eligible articles. After screening, a total of 15 studies were identified in which estimates of the standardized incidence ratio (SIR) and the relative risk (RR) of thyroid cancer were available in 8 and 11 studies, respectively. The overall SIR estimated by the random effects model was 2.19 [95% confidence interval (CI), 1.54, 3.10]. Cochran's Q test showed significant heterogeneity in the SIRs (Q= 178, P< 0.0001). The overall RR at 10mGy was 1.0038 (95% CI, 0.9991, 1.0085), with no significant heterogeneity (Q= 9.30, P= 0.5041). The total SIR, as well as that from each study, indicated a statistically significant excess, which could be related to screening bias. Radiation-related thyroid cancer risk was elevated in a few studies; however, the overall estimate of the RR at 10mGy was not significant. This study demonstrates no strong epidemiological evidence for the risk of thyroid cancer in radiation exposure during adulthood; however, further research is needed.

Hashimoto's Thyroiditis and the Risk of Papillary Thyroid Cancer in Children.

The association between Hashimoto's thyroiditis (HT) and pediatric thyroid cancer is controversial. Most studies examining this connection have been based on adults, and larger studies in children are lacking. We performed a retrospective study of all sequential pediatric patients who underwent a thyroidectomy for a neoplasm at our institution over a twenty-year period in order to explore the link between HT and pediatric thyroid cancer. A total of 153 patients, median age 16.5 (interquartile range [IQR] 14.2-18.3) years, underwent thyroid surgery for a neoplasm. Patients were mainly female (80%) and White (84%). Median follow-up was 58.6 (IQR 20.7-105.4) months. Thirty-five (23%) patients had HT. Patients who underwent thyroid surgery and had HT were more likely to harbor a malignant neoplasm (p = 0.05); specifically, papillary thyroid carcinoma (PTC, p = 0.02). There was a difference in the distribution of HT among the subtypes of PTC (p = 0.03). Despite this, there was no difference in terms of survival between patients with/without HT. In conclusion, children with a thyroid malignancy, specifically, PTC, are more likely to have HT. The association between HT and pediatric PTC appears to be subtype-specific but does not seem to affect patient survival.

SAT565 Is Firefighting An Occupational Risk For Papillary Thyroid Cancer? A Case Report

Abstract Disclosure: S.A. Diamond-Rossi: None. P. Lee: None. C. Thomas: None. R. Stanislawski: None. J. Kim: None. Background: Papillary thyroid cancer (PTC) is the most prevalent histologic type of thyroid cancer. The toxic exposures associated with firefighting from both protective gear and combustion products have brought to question whether this population is at an increased risk of developing certain malignancies, including thyroid cancer. The objective of this case report is to raise awareness of the possible association between firefighting and thyroid cancer. Case Presentation: A 46-year-old asymptomatic male career firefighter presented to our clinic following a mobile screening thyroid ultrasound which revealed bilateral suspicious nodules. FNAs of a 1.0 cm right nodule and 1.2 cm left nodule were consistent with papillary thyroid cancer. Lymph node mapping revealed bilateral suspicious lymph nodes in levels 3 and 4 with FNAs confirming metastatic PTC. He underwent total thyroidectomy with bilateral central and lateral lymph node dissections confirming multifocal disease, which included numerous submillimeter foci of PTC. 21 of 68 lymph nodes had metastatic disease. He is now scheduled for adjuvant radioactive iodine therapy. Discussion: Compared to the general population, firefighters have a higher incidence of thyroid cancer. In 2022, the International Agency for Research on Cancer (IARC) announced that occupational exposure as a firefighter would be considered a Group 1 carcinogen, designating this exposure as having sufficient evidence for carcinogenicity in humans. In recognition of this risk, our local fire department, the Fairfax County Fire &amp; Rescue, has implemented a cancer screening protocol offered to firefighters which includes a mobile thyroid ultrasound. Our patient had extensive disease with bilateral lymph node involvement requiring radioactive iodine after surgical resection. Without a screening ultrasound, it can be presumed that our patient would have presented later and perhaps with even more advanced disease. Firefighters are exposed to carcinogens and possible endocrine disrupting chemicals as part of their work, either via their protective equipment or products of the fire itself. More research is needed to determine if the higher incidence of thyroid cancer can be attributed to this occupational exposure versus surveillance bias due to increased screening of this population in recent years. Presentation: Saturday, June 17, 2023

SAT548 Incidental Papillary Thyroid Carcinoma Diagnosed After Total Thyroidectomy For Recurrent Grave's Disease

Abstract Disclosure: S.U. Perez-Martinez: None. S. Bao: None. Introduction: Whether Graves’ disease (GD) increases the risk of thyroid cancer (TC) has been a long-time topic of debate. Some studies reported increased risk of TC in GD, particularly when patients with GD have thyroid nodules. Other studies suggested the prevalence of incidental differentiated TC in GD is comparable to euthyroid goiter. Here we present a case of a 39-year-old female with a thyroid nodule and recurrent GD who underwent total thyroidectomy (TT) and was found to have a 0.4cm incidental papillary TC. Clinical case: 39 year-old female patient was diagnosed with hyperthyroidism due to GD and a 1.26x2.04x2.88cm complex right thyroid nodule at age 28, based on laboratory and thyroid ultrasound (US) studies, respectively. Fine needle aspiration showed a follicular lesion favoring colloid nodule. Patient preferred conservative measures at that time. She was treated with methimazole for 3 years and went into remission. Her thyroid nodule was monitored with serial thyroid US (every 1-2 years) for 7 years and remained stable. However, 7 years after discontinuation of methimazole, she developed recurrent hyperthyroidism, with laboratory findings of suppressed TSH of &amp;lt;0.04 (normal 0.35-5.5 mcu/mL), elevated free T4 of 2.4 (normal 0.8-1.8 ng/dL) and Thyroid Stimulating Immunoglobulin of 8.01 (normal &amp;lt; 0.054 IU/L). Patient was restarted on Methimazole 10mg daily. Her TSH remained to be low at &amp;lt; 0.015 (normal 0.35-3.6 mcu/mL) 4 months later, at which point more definitive treatment options including radioactive iodine ablation or TT were again discussed, and the patient opted to undergo TT, which was performed successfully 2 months later. Surgical pathology was consistent with GD, an encapsulated, fibrotic, and calcified nodule consistent with infarcted follicular lesion but also a 0.4cm incidental Papillary TC in right thyroid lobe. Surgical margin was clean, no extrathyroidal extension, one perithyroidal lymph node was negative for malignancy. Patient has been doing well afterwards. Discussion: The prevalence and clinical significance of incidental differentiated TC in patients with GD have been controversial topics. Incidence of TC in GD was mostly reported to be 7-17%, but may be as high as 42%, based on thyroidectomy studies. However, a recent retrospective multicenter study suggested the concomitant TC in GD was considerably lower. No difference in TC aggressiveness, US findings, or prognosis were observed between nodular GD and non-nodular GD groups. The clinical outcomes of TC were also excellent. A Cleveland Clinic study suggested nodule size &amp;gt; 1cm predicted incidental TC whereas Thyroid Stimulating Immunoglobulin titers and disease duration did not. These data argue for screening patients with GD more aggressively for TC or treating GD patients with coexisting thyroid nodule more aggressively; as in our case, even if incidental TC was found, prognosis is favorable. Presentation Date: Saturday, June 17, 2023

OR32-02 Thyroid Cancer Polygenic Risk Score Improves Risk Stratification Of Thyroid Nodules When Added To Ultrasound Imaging

Abstract Disclosure: N. Pozdeyev: None. M. Dighe: None. M. Barrio: None. C. Raeburn: None. H.A. Smith: None. M. Fisher: None. S. Chavan: None. N. Rafaels: None. J. Shortt: None. M. Leu: None. T. Clark: None. C. Marshall: None. B.R. Haugen: None. D. Subramanian: None. K. Crooks: None. C. Gignoux: None. T.A. Cohen: None. Purpose. Evaluating thyroid nodules to rule out malignancy is a common clinical task. Image-based risk stratification schemas rely on the presence of high-risk thyroid nodule sonographic features and, therefore, are less suitable for the diagnosis of malignant thyroid nodules that have a benign appearance on the ultrasound. To mitigate the deficiency of thyroid nodule evaluation relying solely on the sonographic characteristics, we used thyroid cancer polygenic risk score (PRS) to complement deep learning analysis of ultrasound images. Methods. A supervised deep learning classifier of thyroid nodules was trained on 32,545 thyroid US images from 621 nodules and tested on an independent set of 232 nodules from patients genotyped on the Illumina's MEGAEX platform. The deep-learning thyroid nodule classifier was developed by fine-tuning a BiT-M ResNet-50x1 convolutional neural network (CNN) pre-trained on the ImageNet-21k dataset. A polygenic risk score (PRS) was calculated using thyroid cancer genome-wide association meta-analysis summary statistics from the Global Biobank Meta-analysis Initiative. The thyroid cancer PRS was defined as a weighted sum of five alleles with the strongest association with thyroid cancer. CNN predictions and PRS were combined into a meta-classifier using logistic regression with or without genetic ancestry and demographic covariates. Results. The CNN classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.83 on the out-of-sample test set of 232 thyroid nodules. The CNN classifier incorrectly classified thyroid nodules without suspicious sonographic characteristics belonging to difficult-to-diagnose subtypes such as follicular thyroid cancer and follicular variant of papillary thyroid cancer. Combining predictions from the CNN classifier with PRS into a cross-validated classifier improved AUC to 0.868 (DeLong test, p = 0.05). Incorporating genetic ancestry in the form of five genetic principal components further improved AUC of the benign vs. malignant CNN + PRS thyroid nodule classifier to 0.885 (p = 0.007). Finally, when age, sex, and nodule dimensions were considered, the AUC of the meta-classifier increased to 0.915 (p = 2.3e-4). The meta-classifier including predictions from CNN, PRS, and genetic principal components showed a sensitivity of 0.95, specificity of 0.61, NPV of 0.97, and PPV of 0.5. This performance was superior to that of the clinical Thyroid Imaging Reporting and Data System (TI-RADS) as reported by radiologists in ultrasound reports. Conclusions. For the first time, we showed PRS provides an orthogonal thyroid cancer risk assessment complementary to the ultrasound image-based thyroid nodule risk evaluation. This proof-of-concept study opens an opportunity for developing next-generation schemas for thyroid nodule evaluation incorporating clinical, imaging, and genetic data. Presentation: Sunday, June 18, 2023

OR32-03 mRNA Expression Based Tumor Behavior Prediction Models In Thyroid Nodules

Abstract Disclosure: A. Golding: None. G. Correa: None. E. Valenzuela Sheker: None. R. Jiang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Liu: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J. Huang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R.T. Kloos: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. G.C. Kennedy: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. D. Bimston: None. The 2015 ATA thyroid cancer risk stratification system is driven primarily by the extent of vascular and extrathyroidal extension, as well as lymph node metastases. The objectives of this study were to evaluate the prevalence of invasion and lymph node metastases in a cohort enriched with thyroid malignancies and provide a risk signature with a high negative predictive value ruling out these tumor features. Histopathology reports from Afirma Genomic Sequencing Classifier (GSC) algorithm training and from thyroid cancer patients managed at an integrative endocrine surgery community care practice (total 697 and ∼50% from each) were reviewed for invasion and metastases. An integer from 0-3 was assigned based on the extent of invasion (ranging from none to extensive extra-thyroidal) or extent of lymph node metastases (ranging from none to lateral node metastases). To develop predictive signatures for invasion/metastases, over 400 literature-derived expression-based signatures were evaluated; they cover a broad spectrum of molecular processes, including cancer hallmarks such as endothelial to mesenchymal transition, tumor microenvironment, immune-oncology, metabolism, and treatment sensitivity. Further, acknowledging that multiple complex molecular processes are associated with invasion/metastases, over 200 machine-learning (ML) models were trained within the repeated and nested cross-validation (CV) framework. They utilized these literature-derived signatures as well as differentially expressed genes between high and low risk of invasion/metastases as the basic building blocks. The application of top performing signatures among Bethesda (B) V/VI nodules as well as indeterminate thyroid nodules (ITN - BIII/IV) that are GSC-suspicious, showed that 40-50% of these lesions were marked as low risk for invasion/metastases. With a starting prevalence of 10.0% of high-level invasion (scored 2 or 3), 41.3% of the cohort is ruled out for clinically relevant invasion with a negative predictive value (NPV) of 97.6%. With a starting prevalence of 11.3% of high-level metastases (scored 2 or 3), 49.8% of the cohort is ruled out for clinically relevant metastases with an NPV of 98.6%. The rule-out capability represents more than 4-fold or 7-fold reduction in high-level invasion/metastases from the baseline prevalence, respectively. Expression-based signatures that confidently rule out tumor invasion and metastasis may help personalize the surgical approach for individuals. This may reduce excess surgery and overtreatment, optimizing the initial response to therapy and decreasing the rates of surgical complications and post-operative hypothyroidism. Presentation: Sunday, June 18, 2023

Surgical Decision-Making in Thyroiditis: A Review Article.

Thyroiditis is a common thyroid disorder worldwide. Its commonest variant is Hashimoto's thyroiditis (HT). The usual presenting symptom is hypothyroidism at the time of diagnosis. Most patients are asymptomatic. A few cases may experience more obvious symptoms. The standard treatment is medical, and surgery is rarely indicated. This review aims to shed light on the most relevant articles discussing surgery in thyroiditis and compare them.The author included 16 relevant articles focused on the surgical management of thyroiditis. Of the studies, 10 were designed as retrospective reviews, four as prospective studies, and two as systematic reviews. The included studies aimed to focus on certain objectives. Three of them discussed indications of surgical intervention in cases of thyroiditis. Five covered postoperative complications. Six looked at the thyroid cancer association with thyroiditis. Two explored the impact of thyroiditis on surgery. Five discussed the postoperative improvement of symptoms and the effect on the quality of life. All the studies listed in this review engaged cases of HT except two. This review concentrates on conceptualizing and organizing the parameters in the minds of surgeons who manage cases of thyroiditis to enable them to decide whether to operate or not. These factors are indications of surgery, improvement of local compressor symptoms post thyroidectomy like dysphasia and shortness of breath, risk of thyroid cancer, intraoperative difficulty, and postoperative complications. Different variants of thyroiditis cases are treated medically, and surgery is rarely indicated. The surgeons should consider the mentioned factors affecting their decision to operate on this special entity. Thus, each case should be individualized in deciding whether to operate or not by assessing the benefit-risk ratio.