Risk Of Papillary Thyroid Cancer Research Articles

Reproductive Factors and Thyroid Cancer Risk: The Multiethnic Cohort Study.

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice.

Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Naive and regulatory B-cell transcription patterns guide the increased risk of papillary thyroid carcinoma in obesity.

A growing number of studies suggest a positive association between obesity and the high incidence of papillary thyroid cancer (PTC), suggesting that the abnormal levels of adipokines associated with obesity may be a risk factor for these aggressive thyroid cancers, but the underlying regulatory mechanisms are not yet clear. We downloaded bulk RNA sequence data for subcutaneous adipose tissue (SAT) in obesity and healthy population and tumor tissues of PTC from GEO database. Through analysis of Differential Expression Genes (DEGs), Gene Set Variation Analysis (GSVA) and Weighted Correlation Network Analysis (WGCNA), we identified co-expressed genes between obesity and PTC, and their pathways were mainly enriched in the regulation of B-cells. Furthermore, through TCGA-THCA (thyroid carcinoma) cohorts analysis, we identified B-cell regulatory-related genes LEF1, TNFRSF13C, SHLD2 and SHLD3 as independent prognostic markers of PTC. Next, we explored the transcriptional regulation mechanism of the increased risk of PTC in obesity through analysis of DNA methylation CpGs data and single-cell RNA sequences (scRNA-seq) from GEO database. PTC-induced hypomethylation of the promoter region may be involved in the transcriptional regulation of these genes, while these genes were further identified in naive and regulatory B-cells of both diseases. Notably, both of the gene expressions in naive and regulatory B-cells showed high similarity in both diseases. Our data reveals the high frequency of PTC in obese populations may be explained by the comparable transcriptional patterns of naive and regulatory B-cells, and offers novel insights for the analysis of critical genes and underlying biological mechanisms for obesity and PTC.

Influence of MiR-126-3p and MiR-146a-5p Dysregulation on The Risk and Clinicopathological Features of Papillary Thyroid Cancer in Patients with Thyroid Nodules

Influence of MiR-126-3p and MiR-146a-5p Dysregulation on The Risk and Clinicopathological Features of Papillary Thyroid Cancer in Patients with Thyroid Nodules

Decision Regret Following the Choice of Surgery or Active Surveillance for Small, Low-Risk Papillary Thyroid Cancer: A Prospective Cohort Study.

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3-18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery.

“Examining the link between tooth agenesis and papillary thyroid cancer: is there a risk factor?” Observational study

BackgroundMutations in one or multiple genes can lead to hypodontia and its characteristic features. Numerous studies have shown a strong genetic influence on the occurrence of hypodontia, and identified several genes, including AXIN2, EDA, FGF3, FGFR2, FGFR10, WNT10A, MSX1, and PAX9, that are directly associated with dental agenesis and carcinogenesis. The objective of this study was to investigate the occurrence and pattern of tooth agenesis, microdontia, and palatally displaced canine (PDC) in women diagnosed with papillary thyroid cancer (PTC), compared to a control group of women without any malignancy or thyroid disease.Materials and methodsThis case–control study was carried at the Department of Orthodontics, School of Dental Medicine University of Zagreb, and Department of Oncology and Nuclear Medicine Sestre Milosrdnice University Hospital Centre. The study involved a clinical examination and evaluation of dental status, panoramic X-ray analysis, and assessment of medical and family history of 116 female patients aged 20–40 with PTC, as well as 424 females in the control group who were of similar age.ResultsThe prevalence of hypodontia, microdontia, and PDC was statistically higher in women with PTC than in the control group. The prevalence rate of hypodontia was 11.3% in the experimental group and 3.5% in the control group. The experimental group showed a higher occurrence of missing upper lateral incisors, lower left central incisors, and all the third molars (except the upper left) compared to the control group. Women with PTC showed the prevalence of PDC significantly higher than the control group (3.5%, 0.7%, p = 0.002). The probability of hypodontia as a clinical finding increases 2.6 times, and microdontia occurs 7.7 times more frequently in women with PTC.ConclusionOur study suggests a possible link between odontogenesis and PTC. The absence of permanent teeth may increase the likelihood of PTC in women. Leveraging the age-7 orthopantomogram to identify women at high risk for PTC within a critical early detection window could significantly improve oral health outcomes and PTC prognosis through proactive interventions.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study

BackgroundThe effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk.MethodsThis study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined.ResultsThere was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 1.61, 95% CI, 1.09, 2.38; p for trend = 0.05) and significantly decreased risk of follicular variant PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 0.38, 95% CI, 0.16, 0.91; p for trend = 0.04). Further stratified by sex, risk of classical PTC was higher for females (third tertile above LOD vs. <LOD, OR = 2.23, 95% CI: 1.23, 4.06; p-trend = 0.02) than for males (OR = 1.22, 95%CI: 0.72–2.08; p-trend = 0.56), though the test for interaction by sex was not statistically significant (p-interaction = 0.30). Similarly, β-hexachlorocyclohexane (β-HCCH) was associated with a higher risk for classical PTC for women with concentrations ≥LOD versus <LOD (OR = 1.76, 95% CI: 1.07, 2.89), while the effects were null for men. There were no consistent trends when stratified by race or birth year. ConclusionsThe U.S. Environmental Protection Agency has classified HCB and other OCPs we studied here as probable human carcinogens. Our findings of increased risks for classical PTC associated with increased concentrations of HCB and β-HCCH, which were stronger among females, should be replicated in future studies of other populations.

Occupational daily walking steps have inverse relationship with papillary thyroid cancer risk and progression: a retrospective analysis.

Investigate the impact of daily occupational walking steps on the progression of papillary thyroid cancer (PTC), a topic hitherto underresearched. The authors analyzed the data from 800 individuals with PTC across stages 0-IV. Participants were evenly divided into 2 distinct occupational groups: office workers and construction workers (N = 400 each). Data included comprehensive records of daily walking steps, demographic information, and clinical indicators. Pearson's correlation coefficients or analysis of variance (ANOVA) were employed to assess the linkage between daily walking steps and PTC risk and stage, as well as associated biochemical markers. The analysis revealed a significant inverse relationship between daily walking steps and PTC risk. A higher frequency of daily steps was associated with reduced chances of PTC onset and a lower diagnostic stage of the disease. This protective effect of physical activity was particularly pronounced in the construc- tion worker cohort. Subsequent evaluations showed that construction workers who consistently logged higher daily steps had markedly lower levels of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, thyroid peroxidase antibody, thyroglobulin antibody, and thy- roglobulin (Tg). Notably, daily walking steps exhibited a strong inverse correlation with body mass index (BMI), age, PTC volumes, and levels of TSH and Tg across both occupational groups (ρ < -0.37). The increase in daily steps was associated with the reduction in PTC stages (p < 0.001). The research underscores the potential benefits of increased daily walking steps, suggesting that they may play a protective role in reducing PTC risk and moderating its progression. Int J Occup Med Environ Health. 2024;37(1):58-71.

TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer.

The telomerase reverse transcriptase (TERT) is overexpressed and associated with poor prognosis in papillary thyroid cancer (PTC), the most common subtype of thyroid cancer. The overexpression of TERT in PTC was partially attributed to transcriptional activation by two hotspot mutations in the core promoter region of this gene. As one of the major epigenetic mechanisms of gene expression regulation, DNA methylation has been proved to regulate several tumor-related genes in PTC. However, the association of TERT promoter DNA methylation with TERT expression and PTC progression is still unclear. By treating PTC cell lines with demethylating agent decitabine, we found that the TERT promoter methylation and the genes' expression were remarkably decreased. Consistently, PTC patients with TERT hypermethylation had significantly higher TERT expression than patients with TERT hypomethylation. Moreover, TERT hypermethylated patients showed significant higher rates of poor clinical outcomes than patients with TERT hypomethylation. Results from the cox regression analysis showed that the hazard ratios (HRs) of TERT hypermethylation for overall survival, disease-specific survival, disease-free interval (DFI) and progression-free interval (PFI) were 4.81 (95% CI, 1.61-14.41), 8.28 (95% CI, 2.14-32.13), 3.56 (95% CI, 1.24-10.17) and 3.32 (95% CI, 1.64-6.71), respectively. The HRs for DFI and PFI remained significant after adjustment for clinical risk factors. These data suggest that promoter DNA methylation upregulates TERT expression and associates with poor clinical outcomes of PTC, thus holds the potential to be a valuable prognostic marker for PTC risk stratification.

Risk stratification of papillary thyroid cancers using multidimensional machine learning.

Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a challenge in the worldwide. Here, the authors first report a Preoperative Risk Assessment Classifier for PTC (PRAC-PTC) by multidimensional features including clinical indicators, immune indices, genetic feature, and proteomics. The 558 patients collected from June 2013 to November 2020 were allocated to three groups: the discovery set [274 patients, 274 formalin-fixed paraffin-embedded (FFPE)], the retrospective test set (166 patients, 166 FFPE), and the prospective test set (118 patients, 118 fine-needle aspiration). Proteomic profiling was conducted by FFPE and fine-needle aspiration tissues from the patients. Preoperative clinical information and blood immunological indices were collected. The BRAFV600E mutation were detected by the amplification refractory mutation system. The authors developed a machine learning model of 17 variables based on the multidimensional features of 274 PTC patients from a retrospective cohort. The PRAC-PTC achieved areas under the curve (AUC) of 0.925 in the discovery set and was validated externally by blinded analyses in a retrospective cohort of 166 PTC patients (0.787 AUC) and a prospective cohort of 118 PTC patients (0.799 AUC) from two independent clinical centres. Meanwhile, the preoperative predictive risk effectiveness of clinicians was improved with the assistance of PRAC-PTC, and the accuracies reached at 84.4% (95% CI: 82.9-84.4) and 83.5% (95% CI: 82.2-84.2) in the retrospective and prospective test sets, respectively. This study demonstrated that the PRAC-PTC that integrating clinical data, gene mutation information, immune indices, high-throughput proteomics and machine learning technology in multicentre retrospective and prospective clinical cohorts can effectively stratify the preoperative risk of PTC and may decrease unnecessary surgery or overtreatment.

Abstract B125: Reproductive factors and thyroid cancer risk: The multiethnic cohort study

Abstract Background : Thyroid cancer is the most common endocrine cancer worldwide, with the incidence in women being three times that of men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and hormone replacement therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods : A prospective cohort study of women of diverse racial and ethnic groups in the Multiethnic Cohort Study (n=118,344) was used. Included were 373 papillary thyroid cancer cases, linked to SEER cancer incidence and statewide death certificate files in Hawaii and California. Exposures investigated include age at menarche, parity, menopausal status and type, birth control use, and outcomes of first pregnancy. Cox proportional hazards models of papillary thyroid cancer were used to obtain relative risk (RR) and 95% confidence intervals (CI) to examine the associations with reproductive/hormonal factors. Results : We observed a statistically significant increased risk of papillary thyroid cancer for hysterectomy, oophorectomy, surgical menopause, and not having a child by age 20. The adjusted estimates for oophorectomy RR 1.66 (95% CI: 1.31, 2.11) and hysterectomy RR 1.82 (95% CI: 1.42, 2.34). Menopause due to surgery was associated with a 55% increase in risk (RR 1.55, 95% CI: 1.22, 1.97) and nulliparity vs ≤ 20 years of age at first livebirth was related to a 51% increased risk (adjusted RR 1.51, 95% CI: 1.07, 2.15). Adjustment factors included age and race/ethnicity and menopausal status, menopausal type, and oral contraception where appropriate. Former use of estrogen menopausal hormone therapy was associated with a 35% increased risk (adjusted RR: 1.35, 95% CI: 1.02, 1.79). No significant heterogeneity was seen in these associations by race/ethnicity (p het &amp;gt;0.48). Conclusion : The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in our multiethnic population. Our analysis finds having a hysterectomy or oophorectomy and the use of MHT are associated with an increased risk of papillary thyroid cancer, and having a child at a younger age is associated with a reduction in thyroid cancer risk. Citation Format: Janine V. Abe, Song-Yi Park, Christopher A. Haiman, Loïc Le Marchand, Brenda Y. Hernandez, Lynne R. Wilkens. Reproductive factors and thyroid cancer risk: The multiethnic cohort study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B125.

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&lt;0.05). In BKMR models, the mixture of EDCs was positively correlated with the risk of PTC(P&lt;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.

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.

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

FRI525 Gender Differences In Fears Related To Low Risk Papillary Thyroid Cancer And Its Treatment

Abstract Disclosure: A.M. Sawka: None. S. Ghai: None. L. Rotstein: None. J.C. Irish: None. J.D. Pasternak: None. P.J. Gullane: None. E. Monteiro: None. J. Su: None. W. Xu: None. J.M. Jones: None. A. Gafni: None. N.N. Baxter: None. D.P. Goldstein: None. Background: It is important to understand the fears of individuals newly diagnosed with papillary thyroid cancer (PTC) to optimize patient counselling and supportive care. Our aim was to explore for potential gender differences in fears experienced by individuals with PTC prior to treatment. Methods: In this prospective study conducted in Toronto, Canada, we enrolled patients with untreated small low risk PTC (&amp;lt; 2 cm in maximal diameter), and offered them the choice of thyroidectomy or active surveillance (Clinicaltrials.gov: NCT03271892). All participants had a surgical consultation prior to assessment. Participants completed Fear of Progression (Short Form) and Fear of Surgery (referring to thyroidectomy) questionnaires, prior to making a decision on PTC management. We also evaluated potential fears that were specific to thyroidectomy (e.g. voice change, thyroid hormone treatment, hypocalcemia, and scar appearance). Total fear scores were calculated for the respective questionnaires. We compared data collected in women and men and explored for factors associated with respective fears using multivariable linear regression analyses. Results: We included 153 women of mean age 50.7 years (standard deviation, SD 15.0) and 47 men of mean age 56.3 years (SD 13.8). There were no significant differences in primary tumor size, marital status, education, parental status, or employment status of women and men. On a scale of 5 to 60 (where 60 is the worst), the mean total fear of disease progression questionnaire score was 26.2 (SD 9.7) in women and 23.0 (SD 9.2) in men (p=0.031). On a scale of 0 to 80 (80 being the worst), the mean total surgical fear questionnaire score was 34.1 (SD 20.3) in women and 22.0 (17.9) in men (p&amp;lt;0.001). Women were also more fearful than men about potential postoperative change in voice (p=0.001), hypocalcemia (p=0.003), and scar appearance (p&amp;lt;0.001). In respective multivariable linear regression analyses, age group (p&amp;lt;0.001) was independently inversely associated with fear of disease progression, whereas being a woman was independently associated with surgical fear (p=0.002). Conclusions: Demographic factors appear to be associated with fears of low-risk PTC patients who are considering primary disease management. Younger patients may have a greater fear of disease progression while women may have a greater fear of the morbidity from thyroidectomy. These factors may be important to consider in patient counselling. Presentation: Friday, June 16, 2023

SAT515 Searching For Markers To Identify Angioinvasion In Papillary Thyroid Cancer

Abstract Disclosure: A. Buczyńska: None. M. Kościuszko: None. I. Sidorkiewicz: None. A. Wiatr: None. K. Siewko: None. A. Adamska: None. A. Krętowski: None. A. Popławska-Kita: None. The incidence of Papillary Thyroid Cancer (PTC) has increased significantly over last decades. Despite the great progress in PTC clinical management, the association of angioinvasion with tumor aggressiveness in PTC remains as significant clinical problem, suggesting worse patients prognosis. Therefore cancer metastasis occurs through cell detachment and angioinvasion, epithelial–mesenchymal transition (EMT) and cell migration, changes in cell morphology are initiated through Rho-GTPase-dependent actin cytoskeleton polymerization. 8-hydroxydeoxyguanosine (8-OHdG) is generated accordingly to increased oxidative stress, however has been characterized by paradoxical anti-oxidative, anti-inflammatory and anti-mutagenic effects following Rho-GTPase inhibition, which were noted in various cancer models. Since oxidative stress has been recognized as one of the main risk factors for thyroid cancer development and progression, the total oxidative and antioxidant capacities may also be potentially involved in the process of angioinvasion. Regardless, the identification of angioinvasion in PTC remains controversial mainly due to loose criteria in judging vascular invasion. Thus, searching for laboratory biomarkers of angioinvasion is of paramount importance.In this study, the potential screening utility of oxidative stress-related markers, such as total oxidative capacity (TOC), total antioxidant capacity (TAC) and 8-OHdG was assessed to identify angioinvasion in PTC patients.For the purpose od this study, 50 patients diagnosed with angioinvasive PTC (study group) and 50 patients with very low risk PTC (control group) were enrolled. The TOC, TAC and 8-OHdG concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA). Following the received results, the TAC and 8-OHdG concentrations were decresed among study group comparing to control group (p&amp;lt;0.001; p&amp;lt;0.02, respectively). However, there were no differences in TOC among studied groups (p&amp;gt;0.05). The AUC values for TAC=0.76 and AUC for 8-OHdG= 0.70 (all, p&amp;lt;0.05) suggest their screening utility. The results indicate that angioinvasion process is associated with decreased antioxidant defense in PTC patients which may insight new medical targets in the future. Presentation Date: Saturday, June 17, 2023

Development of a novel clinical support tool for active surveillance of low risk papillary thyroid cancer.

Active surveillance (AS) is an alternative to surgery in select patients with very low risk papillary thyroid cancer (PTC). Many clinicians feel ill-equipped in selecting appropriate patients. We aimed to 1) Develop an evidence-based web delivered decision support tool to assist clinicians in identifying patients appropriate for AS; and 2) Evaluate the prevalence of patients suitable for AS in a tertiary high volume thyroid cancer centre. A REDCap web based clinical support tool was developed utilising evidence-based characteristics for AS suitability available to clinicals during initial assessment. A retrospective database was interrogated for patients who underwent hemithyroidectomy between 2012 - 2021 with final histopathology demonstrating PTC. Patients with PTCs>2cm, missing data, benign disease on surgical histopathology or incidental PTC were excluded. Between 2012 - 2021, 763 patients underwent hemithyroidectomy with final histopathology confirming PTC. Of these, 316 patients were excluded (missing data, incidental PTC, concomitant hyperparathyroidism were most common reasons for exclusion) and 114/447 remaining patients had a pre-operative fine needle aspirate (FNA) of Bethesda V or VI (high likelihood of malignancy). Using the tool, 59/114 (52%) met criteria for AS. The majority of patients were female (85% vs 15% male); median age 36 years (range 19 - 78). Following initial surgery, 10/59 patients had a completion thyroidectomy, with 4/10 demonstrating malignancy in contralateral lobe and eight of those patients undergoing I131 ablation. During a median follow up of over 3 years, 49/59 (83%) did not require further surgery or intervention with no patients developing recurrence. A subgroup analysis with second radiology assessment excluded 4/59 patients as meeting criteria for AS based on presence of ETE on preoperative ultrasound. None of these 4 patients had completion thyroidectomy. Our clinical support tool identifies patients with PTC potentially suitable for AS which could be utilised during initial patient assessment. In a retrospective cohort of patients who had hemithyroidectomy for PTC with a pre-operative FNA diagnosis of Bethesda V or VI, 55/114 (48%) patients may have been suitable for AS. Prospective validation studies are required for implementation of the tool in clinical practice.

Impaired thyroid hormone sensitivity increases the risk of papillary thyroid cancer and cervical lymph node metastasis.

The association of thyroid hormone sensitivity with papillary thyroid carcinoma (PTC) is unclear. This study investigated the relationship between the thyroid hormone sensitivity indices and the risk of PTC and the influence of thyroid hormone sensitivity on the aggressive clinicopathologic features of PTC. This retrospective study recruited 1225 PTC patients and 369 patients with benign nodules undergoing surgery in Zhongshan Hospital in 2020. The thyroid hormone sensitivity indices were thyroid feedback quantile-based index (TFQI), TSH index (TSHI) and thyrotropin thyroxine resistance index (TT4RI). We employed logistic regression models to explore the correlation between the thyroid hormone sensitivity indices and the risk of PTC and its cervical lymph node metastasis (LNM). PTC patients had significantly higher levels of TSH, TFQI, TSHI and TT4RI compared to the patients with benign nodules, but thyroid hormone levels did not differ significantly between the two groups. Logistic regression analysis revealed that the higher levels of TFQI, TSHI, and TT4RI were associated with an increased risk of PTC after adjustment for multiple risk factors (TFQI: OR = 1.92, 95% CI: 1.39-2.65, P < 0.001; TSHI: OR = 2.33, 95% CI:1.67-3.26, P < 0.001; TT4RI: OR = 2.41, 95% CI:1.73-3.36, P < 0.001). In addition, patients with decreased thyroid hormone sensitivity had a higher risk of cervical LNM in multiple logistic regression analysis (TFQI: OR = 1.38, 95% CI:1.03-1.86, P = 0.03; TSHI: OR = 1.37, 95% CI:1.02-1.84, P = 0.04; TT4RI: OR = 1.41, 95% CI:1.05-1.89, P = 0.02). Impaired sensitivity to thyroid hormone was associated with an increased risk of PTC, and it is also associated with a higher risk of cervical LNM in PTC patients.

Glucagon-like peptide 1 receptor agonists and thyroid cancer: is it the time to be concerned?

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have changed considerably the management of type 2 diabetes (T2D). However, recently published data from retrospective cohort studies suggest that chronic exposure to GLP-1RAs in T2D may increase the risk of papillary and medullary thyroid cancer. In this perspective, the role of the incretin system in thyroid carcinogenesis has been reviewed and critically commented on, aiming to understand if the time has arrived to be concerned about the risk. Although evidence suggested, speculative hypotheses should be verified, and further studies are urgently needed to clarify the issue.