A Review of the Association between Exposure to Flame Retardants and Thyroid Function.

Flame retardants have been shown to cause widespread physiological effects, in particular on endocrine organs such as the thyroid. This review aims to provide an overview of the literature on the association between flame retardants and thyroid function within humans. A search in the National Library of Medicine and National Institutes of Health PubMed database through January 2024 yielded 61 studies that met the inclusion criteria. The most frequently analyzed flame retardants across all thyroid hormones were polybrominated diphenyl ethers (PBDEs), in particular BDE-47 and BDE-99. Ten studies demonstrated exclusively positive associations between flame retardants and thyroid stimulating hormone (TSH). Six studies demonstrated exclusively negative associations between flame retardants and TSH. Twelve studies demonstrated exclusively positive associations for total triiodothyronine (tT3) and total thyroxine (tT4). Five and eight studies demonstrated exclusively negative associations between flame retardants and these same thyroid hormones, respectively. The effect of flame retardants on thyroid hormones is heterogeneous; however, the long-term impact warrants further investigation. Vulnerable populations, including indigenous people, individuals working at e-waste sites, firefighters, and individuals within certain age groups, such as children and elderly, are especially critical to be informed of risk of exposure.

Thyroid abnormalities identified on CT screening for lung cancer.

PURPOSE: Because incidental thyroid nodules (ITNs) are common extrapulmonary findings in low-dose computed tomography (LDCT) scans for lung cancer screening, we aimed to investigate the frequency of ITNs on LDCT scans separately on baseline and annual repeat scans, the frequency of malignancy among the ITNs, and any association with demographic, clinical, CT characteristics. METHODS: Retrospective case series of all 2309 participants having baseline and annual repeat screening in an Early Lung and Cardiac Action Program (MS-ELCAP) LDCT lung screening program from January 2010 to December 2016 was performed. Frequency of ITNs in baseline and annual repeat rounds were determined. Multivariable regression analysis was performed to identify significant predictors. RESULTS: Dominant ITNs were seen in 2.5 % of 2309 participants on baseline and in 0.15 % of participants among 4792 annual repeat LDCTs. The low incidence of new ITNs suggests slow growth as it would take approximately an average of 16.8 years for a new ITN to be detected on annual rounds of screening. Newly detected ITNs on annual repeat LDCT were all smaller than 15 mm. Regression analysis showed that the increasing of age, coronary artery calcifications score and breast density grade were significant predictors for females having an ITN. No significant predictors were found for ITNs in males. CONCLUSION: ITNs are detected at LDCT however, no malignancy was found. Certain predictors for ITNs in females have been identified including breast density, which may point towards a common causal pathway.

Investigating potential disparities by exploring time to surgical thyroid cancer treatment.

(1) Delays in initial treatment have been a frequently used metric for assessing disparities in medicine; however, there has been sparse literature on treatment delays in thyroid cancer. We therefore aimed to assess disparities by investigating the association between race/ethnicity, insurance type, and socioeconomic status and time to surgical treatment of thyroid cancer. (2) A retrospective chart review was conducted to collect demographic and clinical data from 443 surgical thyroid cancer patients at Mount Sinai Hospital in 2018-2019. We investigated the time between thyroid cancer diagnosis and surgery by race/ethnicity, insurance, and income groups. (3) Univariate analysis showed that race/ethnicity, insurance type, and SES alone were not statistically significant predictors of earlier time to treatment (p = 0.766, 0.339, 0.435, respectively). On multivariable linear regression, time between diagnosis and surgical treatment was not significantly different for racial minorities compared to non-Hispanic White patients, patients with Medicare/Medicaid compared to private insurance, and patients with lowest income quartile (<$54,585) compared to those with the highest (≥$116,560). (4) Present study showed no significant delays in treatment for different racial/ethnic, insurance, and income groups.

Anxiety and Depression as Potential Predictors for Shorter Time to Undergo Initial Surgical Treatment for Papillary Thyroid Cancer.

(1) Background: A pre-existing psychiatric condition may impact decision making by patients and/or physicians following a thyroid cancer diagnosis, such as potentially electing surgery over active surveillance, thus shortening the time to cancer removal. This is the first study to investigate the association between pre-existing anxiety and/or depression and time to receive surgical treatment for thyroid cancer. (2) Methods: Retrospective data were collected from 652 surgical thyroid cancer patients at our institution from 2018 to 2020. We investigated the time between thyroid cancer diagnosis and surgery, comparing patients with pre-existing anxiety and/or depression to those without. (3) Results: Patients with anxiety, depression, and both anxiety and depression had a significantly shorter time between diagnosis and surgery (51.6, 57, and 57.4 days, respectively) compared to patients without (111.9 days) (p = 0.002, p = 0.004, p = 0.003, respectively). (4) Conclusions: Although little is known about the impact of pre-existing psychiatric conditions in the decision-making process for thyroid cancer surgery, this present study showed that anxiety and/or depression may lead to more immediate surgical interventions. Thus, psychiatric history may be an important factor for physicians to consider when counseling patients with thyroid cancer.

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

BACKGROUND: 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. METHODS: 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). FINDINGS: 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). INTERPRETATION: 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. FUNDING: National Institutes of Health grants and The Andrea and Charles Bronfman Philanthropies.

Per- and Polyfluoroalkyl Substances (PFAS) in Community Water Systems (CWS) and the Risk of Thyroid Cancer: An Ecological Study.

Thyroid cancer incidence has been steadily increasing over the past decade in the United States (US). A discussion exists regarding the potential contribution of exposure to endocrine-disrupting chemicals, encompassing certain per- and poly-fluoroalkyl substances (PFASs). This ecological study evaluated the potential correlation between PFAS levels in drinking water and thyroid cancer incidence in the US. Data on age-adjusted thyroid cancer incidence rate (per 100,000 persons) by county were obtained from the Centers for Disease Control and Prevention (CDC) for US counties with available data in 2015-2019. Data on PFAS concentrations in the drinking water of selected community water systems (CWSs) were obtained from the CDC National Environmental Public Health Tracking Network in 2013-2015. The correlation between PFASs in CWSs and thyroid cancer incidence was calculated using Spearman correlation. A statistically significant correlation was found between perfluorooctanoic acid (PFOA) (r = 0.031; p = 0.043), perfluorononanoic acid (PFNA) (r = 0.058; p ≤ 0.001), and thyroid cancer incidence. The results suggest a potential link between certain PFAS exposures and thyroid cancer risk. However, due to the nature of an ecological study, no conclusions can be drawn at the individual level or causality. More research is needed, particularly on an individual level to allow for more detailed exposure assessment.

Omega-3 Fatty Acid Supplementation for the Treatment of Persistent COVID-Related Olfactory Dysfunction.

OBJECTIVE: To evaluate the efficacy of omega-3 fatty acid (O3FA) supplementation in the treatment of COVID-related olfactory dysfunction (OD). METHODS: Patients with laboratory-confirmed or clinically-suspected COVID-19 infection and new-onset OD from August 2020 to November 2021 were prospectively recruited. Patients with quantitative OD, defined as a brief smell identification test (BSIT) score of 9 or less, were eligible for study inclusion. The experimental group received 2 g of O3FA supplementation, while the control group received an identical placebo to be taken daily for 6 weeks. The primary outcome was a change in BSIT score between the initial and 6-week follow-up tests. RESULTS: One hundred and seventeen patients were included in the analysis, including 57 patients in the O3FA group and 60 in the placebo group. O3FA group patients demonstrated a mean BSIT improvement of 1.12 ± 1.99 compared to 0.68 ± 1.86 in the placebo group (p = 0.221). Seventy-seven patients, 42 within the O3FA group and 35 in the placebo group, completed a follow-up BSIT survey at an average of 717.8 days from study onset. At long-term follow-up, there was an average BSIT score improvement of 1.72 within the O3FA group compared to 1.76 within the placebo group (p = 0.948). CONCLUSION: Among patients with persistent COVID-related OD, our study showed no clear evidence of relative short-term or long-term olfactory recovery among patients receiving high doses of O3FA supplementation.

TERT and BRAF V600E mutations in thyroid cancer of World Trade Center Responders.

The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust exposure, containing carcinogenic and endocrine disruptive elements, on the thyroid. This study investigated the presence of TERT promoter and BRAF V600E mutations in 20 WTC-exposed versus 23 matched non-exposed thyroid cancers as potential mechanism explaining the excess risk. Although no significant difference in BRAF V600E mutation was found, TERT promoter mutations were significantly more prevalent in WTC thyroid cancer versus non-exposed thyroid cancers (P = 0.021). The odds of a TERT promoter mutation was significantly higher in the WTC versus the non-WTC thyroid cancers after adjustment [ORadj: 7.11 (95% CI: 1.21-41.83)]. These results may indicate that exposure to the mixture of pollutants present in the WTC dust resulted in an excess thyroid cancer risk and potentially more aggressive thyroid cancer, warranting investigating WTC responders on thyroid-associated symptoms during their health checkups. Future studies should include long-term follow-up to provide important insights in whether thyroid-specific survival is negatively affected by WTC dust exposure and whether this is because of the presence of one or more driver mutations.

Human 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure and thyroid cancer risk.

Thyroid cancer incidence has been steadily rising since the 1970s and exposure to environmental pollutants, including persistent organic pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins, has emerged as a potential explanation for this increase. This study aimed to summarize available human studies on the association between TCDD exposure and thyroid cancer. A systematic review of the literature was performed searching the National Library of Medicine and National Institutes of Health PubMed, Embase, and Scopus databases, through January 2022, using the following keywords: "thyroid", "2,3,7,8-tetrachlorodibenzo-p-dioxin", "TCDD", "dioxin", and "Agent Orange". Six studies were included in this review. Three studies evaluated the acute exposure to the chemical factory accident in Seveso, Italy, and found a non-significant increase in the risk of thyroid cancer. Two studies investigating Agent Orange exposure among United States Vietnam War veterans found a significant risk of thyroid cancer following exposure. No association was found in one study evaluating TCDD exposure through herbicides. The current study highlights the limited information on the potential association between TCDD exposure and thyroid cancer and thus the need for future human studies, especially considering the persistent human exposure to dioxins in the environment.

Endosulfan use and the risk of thyroid cancer: an ecological study.

Endosulfan, an organochlorine pesticide, has been understudied in the literature on thyroid cancer. The aim of this ecological study was to assess the correlation between endosulfan exposure and thyroid cancer incidence rates (IRs) in the United States (US). Age-adjusted thyroid cancer IRs per 100,000 people per state for the years 1999 to 2019 were obtained from the Center for Disease Control and Prevention (CDC). To assess the state-level use of endosulfan, data were obtained from the US Geological Survey (USGS). Endosulfan usage estimates (kilograms/acres cropland; quintiles) and thyroid cancer IRs were mapped together. The correlation between age-adjusted thyroid cancer IRs and statewide endosulfan use was calculated using the Spearman correlation. Overall endosulfan usage in the US trended downwards between 1992 and 2007 (T = -0.77; P < 0.001), while thyroid cancer IR trended upwards between 1999 and 2019 (T = 0.69; P < 0.001). There was a statistically significant correlation between 1992 endosulfan use and 2012 (r = 0.32; P = 0.03) and 2014 (r = 0.32; P = 0.03) thyroid cancer IRs. Although restrictions on endosulfan use seem effective, the potential impact of endosulfan exposure remains due to the persistent, semi-volatile, bioaccumulative, and biomagnifying properties of endosulfan metabolites in particular, indicating the need for future thyroid research of highly exposed populations.

Association between polychlorinated biphenyl exposure and thyroid hormones: a systematic review and meta-analysis.

Purpose: To conduct a comprehensive meta-analysis investigating the association between polychlorinated biphenyl (PCB) exposure and serum thyroid hormone levels among adults. Methods: Eleven studies met inclusion criteria for analysis following systematic search of PubMed, Embase, and Scopus databases. Of these, 7 studies measured exposure by the total sum of PCB congeners (∑PCB), 1 study measured individual PCB congener levels, and 3 studies measured both ∑PCB levels and PCB congener levels. Correlation coefficients (r) were extracted from each study. Summary estimates were calculated for ∑PCB levels and PCB congeners reported by 2 or more studies: PCB 28, 52, 101, 105, 118, 138, 153, and 180, using random effects model. Results: Significant negative correlation was found between ∑PCBs and T3 (r: -0.09; 95% CI: -0.17, -0.02) and FT3 (r: -0.24; 95% CI: -0.36, -0.12). Congener-specific analysis found T3 to be negatively correlated with PCB-153 (r: -0.19; 95% CI: -0.34, -0.03) and PCB-180 (r: -0.14; 95% CI: -0.26, -0.01), whereas TSH was positively correlated with PCB-105 (r: 0.15; 95% CI: 0.02, 0.28). Conclusions: The present study is the first meta-analysis to investigate the association between PCB exposure and thyroid hormone dysfunction among adults. Results suggest a significant association between PCB exposure and thyroid hormone dysregulation.

Correlation between Lindane Use and the Incidence of Thyroid Cancer in the United States: An Ecological Study.

The increasing rate of thyroid cancer may be attributable to endocrine disruptive chemicals. Lindane is a persistent organochlorine pesticide with endocrine disruptive properties that has been classified as carcinogenic to humans. The aim of this ecological study was to evaluate potential correlation between lindane exposure and thyroid cancer incidence in the United States (US). Data on statewide age-adjusted thyroid cancer incidence rate (per 100,000 people) was obtained from the Centers for Disease Control and Prevention for all US states for 2019. Lindane use estimates per cropland (kg/acres cropland) were then overlaid on the map of age-adjusted thyroid cancer incidence rate using ArcGIS. The trend of lindane use in the US between 1992 and 2007 was calculated using the Mann Kendall correlation test. The correlation between statewide lindane use and age-adjusted thyroid cancer incidence rates was calculated using Spearman correlation. Lindane use in the US decreased significantly between 1992 and 2007 (T = -0.617; p < 0.001). There was no statistically significant correlation between lindane use in 1992 and thyroid cancer incidence rate for any of the years between 1999 and 2019. Our results suggest that restrictions clearly seem to be effective in reducing lindane use, however, more research is needed for individual pesticides and thyroid cancer.

Interferon gamma expression and mortality in unselected cohorts of urothelial bladder cancer patients.

BACKGROUND: The role of interferon gamma (IFN-γ) expression in long-term survival has not been studied in patients with urinary bladder cancer (UBC). IFN-γ expression was characterized among various UBC patient cohorts to assess if IFN-γ status is associated with overall survival (OS). METHODS: A tumor-based IFN-γ gene signature was evaluated among adult UBC patients newly diagnosed between 2004 and 2017 from two hospital systems in New York. Patient cohorts included metastatic (stage IV or progressing to stage IV [MBC]), muscle-invasive (stages T2a to T4a [MIBC]), and non-muscle-invasive (carcinoma in situ or stages 0a, 0is, and I [NMIBC]) disease. Descriptive analyses were conducted comparing IFN-γ signature in the highest tertile to those in the lowest two tertiles. RESULTS: 234 patients with bladder cancer were evaluated (56 MBC, 38 MIBC, and 140 NMIBC). Median OS was only reached in the MIBC cohort for those with an IFN-γ signature in the lowest two tertiles (15.03 months [95% CI, 8.50-50.60]). Those with an IFN-γ signature in the highest tertile had a decreased risk of mortality in all cohorts indicating better survival, but this was statistically significant in only the MIBC cohort (adjusted HR = 0.09 [95% CI, 0.01-0.73]). CONCLUSION: IFN-γ signature status was associated with a decreased mortality risk in all cohorts, particularly MIBC, indicating that it may be a prognostic marker of survival in patients with UBC.

Global DNA methylation of WTC prostate cancer tissues show signature differences compared to non-exposed cases.

There is increased incidence of prostate cancer (PC) among World Trade Center (WTC)-exposed responders and community members, with preliminary evidence suggestive of more aggressive disease. While previous research is supportive of differences in DNA methylation and gene expression as a consequence of WTC exposure, as measured in blood of healthy individuals, the epigenetics of WTC PC tissues has yet to be explored. Patients were recruited from the World Trade Center Health Program. Non-WTC PC samples were frequency matched on age, race/ethnicity and Gleason score. Bisulfite-treated DNA was extracted from tumor tissue blocks and used to assess global DNA methylation with the MethylationEPIC BeadChip. Differential and pathway enrichment analyses were conducted. RNA from the same tumor blocks was used for gene expression analysis to further support DNA methylation findings. Methylation data were generated for 28 samples (13 WTC and 15 non-WTC). Statistically significant differences in methylation were observed for 3,586 genes; on average WTC samples were statistically significantly more hypermethylated (P = 0.04131). Pathway enrichment analysis revealed hypermethylation in epithelial mesenchymal transition (EMT), hypoxia, mitotic spindle, TNFA signaling via NFKB, WNT signaling, and TGF beta signaling pathways in WTC compared to non-WTC samples. The androgen response, G2M and MYC target pathways were hypomethylated. These results correlated well with RNA gene expression. In conclusion, long-term epigenic changes associated with WTC dust exposure were observed in PC tissues. These occurred in genes of critical pathways, likely increasing prostate tumorigenesis potential. This warrants analysis of larger WTC groups and other cancer types.

Trends for In- and Outpatient Thyroid Cancer Surgery in Older Adults in New York State, 2007-2017.

BACKGROUND: In view of the 2013 American Thyroid Association consensus statement on outpatient thyroidectomy, the present study assessed the trends and factors associated with thyroid cancer surgery setting in older adults, using the New York Statewide Planning and Research Cooperative System database. MATERIALS AND METHODS: There were 14,495 patients with surgically treated thyroid cancer in New York State between 2007 and 2017. Trends were plotted over time and stratified by surgery type. Significance of the trend was assessed using the Mann-Kendall test. Multivariable logistic regression was used to assess independent associations with surgical setting. RESULTS: The overall outpatient surgery rate significantly increased over time (correlation coefficient 0.82; P < 0.001), for both total thyroidectomy (P < 0.001) and lobectomy (P < 0.001). Factors associated with increased odds of inpatient surgery were medium- and high-volume hospitalization (adjusted odds ratio [ORadj] 2.12, 95% confidence interval [CI] 1.93-2.32; ORadj 1.69, 95% CI 1.55-1.85, respectively) versus low volume, undergoing total thyroidectomy (ORadj 1.75, 95% CI 1.61-1.90), as well as having Medicare insurance (ORadj 1.13, 95% CI 1.02-1.24) versus private insurance. CONCLUSIONS: The present study shows that outpatient thyroidectomy is increasingly favored over inpatient thyroidectomy over time in an older patient population. A clear changepoint following 2011 preceded the publication of the American Thyroid Association statement on outpatient thyroidectomy in 2013 and was likely associated with multiple publications reporting safety of outpatient thyroid surgery and clear economic benefits.

Patient-reported outcomes following total thyroidectomy and lobectomy in thyroid cancer survivors: an analysis of the PROFILES Registry data.

PURPOSE: Patient-reported outcomes are important in the surgical decision-making process for low-risk, differentiated thyroid cancer. Current study aimed to assess patient-reported outcomes in thyroid cancer survivors comparing total thyroidectomy (TT) and lobectomy (LT) using the Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship (PROFILES) registry. METHODS: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scales, illness perception questions, Beliefs about Medicines Questionnaire (BMQ) scales and questions about thyroid surgery-related medication use were compared between thyroid cancer patients who underwent TT versus LT using descriptive analyses. RESULTS: In total, 58 thyroid cancer patients who underwent TT or LT were included in this study. None of the EORTC QLQ-C30 scales or questions regarding illness perception were significantly different between the surgical groups. Patients in the TT group had significantly higher belief in the necessity of their medication (21.0 vs 15.4; p = 0.003) and greater concerns about taking their medicines (14.7 vs 11.1; p = 0.008) versus patients in the LT group. CONCLUSION: Concerns about post-surgical medication use specifically in the TT group may indicate that clinicians should consider LT in patients with low-risk, differentiated thyroid cancer when LT and TT are viable surgical options. Clinicians should be aware of the impact of post-surgical medication use in particular following TT and use this knowledge to align goals of treatment with the extent of surgery, allowing for a better-informed decision-making process.

The role of heavy metals in thyroid cancer: A meta-analysis.

INTRODUCTION: Metal ions are known to accumulate in the thyroid and some play an important role in the function and homeostatic mechanisms of the thyroid gland. Certain metal ions are known endocrine disruptors while others are classified to be carcinogenic. Although higher thyroid cancer incidence rates have been reported in regions with high metal levels in soil and drinking water, including volcanic regions, the effect of heavy metals on the thyroid is still poorly understood. To investigate the association between heavy metals and thyroid cancer, a comprehensive meta-analysis was performed to draw a more evidence-based conclusion for individual metal ions. MATERIAL AND METHODS: Nineteen studies were included in this meta-analysis, of which 9 studies reported blood metal ion levels, 8 studies reported tissue metal ion levels and 2 studies reported blood and tissue metal ion levels. The standardized mean difference (SMD) was calculated between thyroid cancer patients group and a control group (benign thyroid patients group or healthy controls group) per study. RESULTS: A significant positive SMD in manganese tissue levels between thyroid cancer patients and benign thyroid patients (SMD: 0.56 (95 % CI: 0.16, 0.95)) and a significant negative SMD in cobalt blood levels between thyroid cancer patients and healthy controls (SMD: -2.03 (95 % CI: -3.95, -0.10)) was found. No difference in levels of other metals in blood or thyroid tissue between thyroid cancer patients and non-thyroid cancer patients was noted. DISCUSSION AND CONCLUSION: The present meta-analysis therefore demonstrates the urgent need for future studies, especially given the increasing exposure of the general population to various environmental pollutants, including metal ions, and the thyroid cancer burden worldwide.