Endocrine disrupting chemical mixture exposure and risk of papillary thyroid cancer in U.S. military personnel: A nested case-control study.

Single-pollutant methods to evaluate associations between endocrine disrupting chemicals (EDCs) and thyroid cancer risk may not reflect realistic human exposures. Therefore, we evaluated associations between exposure to a mixture of 18 EDCs, including polychlorinated biphenyls (PCBs), brominated flame retardants, and organochlorine pesticides, and risk of papillary thyroid cancer (PTC), the most common thyroid cancer histological subtype. We conducted a nested case-control study among U.S. military servicemembers of 652 histologically-confirmed PTC cases diagnosed between 2000 and 2013 and 652 controls, matched on birth year, sex, race/ethnicity, military component (active duty/reserve), and serum sample timing. We estimated mixture odds ratios (OR), 95% confidence intervals (95% CI), and standard errors (SE) for associations between pre-diagnostic serum EDC mixture concentrations, overall PTC risk, and risk of histological subtypes of PTC (classical, follicular), adjusted for body mass index and military branch, using quantile g-computation. Additionally, we identified relative contributions of individual mixture components to PTC risk, represented by positive and negative weights (w). A one-quartile increase in the serum mixture concentration was associated with a non-statistically significant increase in overall PTC risk (OR = 1.19; 95% CI = 0.91, 1.56; SE = 0.14). Stratified by histological subtype and race (White, Black), a one-quartile increase in the mixture was associated with increased classical PTC risk among those of White race (OR = 1.59; 95% CI = 1.06, 2.40; SE = 0.21), but not of Black race (OR = 0.95; 95% CI = 0.34, 2.68; SE = 0.53). PCBs 180, 199, and 118 had the greatest positive weights driving this association among those of White race (w = 0.312, 0.255, and 0.119, respectively). Findings suggest that exposure to an EDC mixture may be associated with increased classical PTC risk. These findings warrant further investigation in other study populations to better understand PTC risk by histological subtype and race.

Organochlorine pesticides and epigenetic alterations in thyroid tumors.

Purpose: Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients. Methods: OCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis. Results: Further TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, P=0.001) and P16 (OR=5.65, P<0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (P<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, P<0.001) and H4K16 (OR=6.03, P<0.001) acetylation. Conclusion: The current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.

The effect of selenium supplementation on sonographic findings of salivary glands in papillary thyroid cancer (PTC) patients treated with radioactive iodine: study protocol for a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Thyroid cancer is a very damaging disease. The most common treatment for this disease includes thyroidectomy and then using radioactive iodine (RAI). RAI has many side effects, including a decrease in salivary secretions, followed by dry mouth and oral and dental injuries, as well as increased inflammation and oxidative stress. Selenium can be effective in these patients by improving inflammation and oxidative stress and by modulating salivary secretions. So far, only one clinical trial has investigated the effect of selenium on thyroid cancer patients treated with radioiodine therapy (RIT) conducted on 16 patients; considering the importance of this issue, to show the potential efficacy of selenium in these patients, more high-quality trials with a larger sample size are warranted. METHODS: This is a parallel double-blind randomized controlled clinical trial that includes 60 patients aged 20 to 65 years with papillary thyroid cancer (PTC) treated with RAI and will be conducted in Seyyed al-Shohada Center, an academic center for referral of patients to receive iodine, Isfahan, Iran. Thirty patients will receive 200 µg of selenium for 10 days (3 days before to 6 days after RAI treatment) and another 30 patients will receive a placebo for the same period. Sonographic findings of major salivary glands, salivary secretions, and sense of taste will be evaluated before and 6 months after 10-day supplementation. DISCUSSION: Due to its anti-inflammatory and antioxidant effects, as well as improving salivary secretions, selenium may improve the symptoms of thyroid cancer treated with radioactive iodine. In past studies, selenium consumption has not reduced the therapeutic effects of radiation therapy, and at a dose of 300 to 500 µg/day, it has not had any significant side effects in many types of cancer under radiation therapy. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201129049534N6 . Registered on 16 September 2021.

Chronic Myeloid Leukemia following Exposure to Radioactive Iodine (I131): A Systematic Review.

BACKGROUND: Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia that arises de novo. Many agents and host factors contribute to this entity of leukemias. Therapy-related acute myeloid leukemia has an extensive literature review in contrast to therapy-related chronic myeloid leukemia (t-CML). Radioactive iodine (RAI), an established agent in the management of differentiated thyroid carcinomas, has raised concern due to its possible carcinogenic effects. SUMMARY: In this article, we reviewed all the reports from the 1960s to date related to t-CML following RAI on Google Scholar and PubMed. We have identified 14 reports and found that most reports were for men under the age of 60 years with primary papillary thyroid carcinoma and mixed follicular-papillary thyroid carcinoma who developed t-CML mainly between 4 and 7 years after exposure to varying doses of I131. However, the mean dose was 287.78 millicuries (mCi). It was reported that a statistically significant increase in leukemia following RAI therapy (relative risk of 2.5 for I131 vs. no I131). Also, there was a linear relationship between the cumulative dose of I131 and the risk of leukemia. Doses higher than 100 mCi were associated with a greater risk of developing secondary leukemia, and most of the leukemias developed within the initial 10 years of exposure. The precise mechanism through which RAI provokes leukemia is largely unclear. A few mechanisms have been proposed. KEY MESSAGES: Although the risk for t-CML appears to be low based on current reports and does not represent a contraindication to RAI therapy, it should not be disregarded. We suggest including it in the risk-benefit discussion before initiating this therapy. Long-term follow-up for patients is advisable for those who received doses over 100 mCi with a complete blood count, possibly yearly, for the first 10 years. The new onset of significant leukocytosis post RAI exposure should raise the suspicion for t-CML. Further studies are needed to establish or refute a causal relationship.

Socioeconomic disparity in the association between fine particulate matter exposure and papillary thyroid cancer.

BACKGROUND: Limited data exists suggesting that cumulative exposure to air pollution in the form of fine particulate matter (aerodynamic diameter ≤ 2.5 µm [PM2.5]) may be associated with papillary thyroid carcinoma (PTC), although this relationship has not been widely established. This study aims to evaluate the association between PM2.5 and PTC and determine the subgroups of patients who are at the highest risk of PTC diagnosis. METHODS: Under IRB approval, we conducted a case-control study of adult patients (age ≥ 18) newly diagnosed with PTC between 1/2013-12/2016 across a single health care system were identified using electronic medical records. These patients were compared to a control group of patients without any evidence of thyroid disease. Cumulative PM2.5 exposure was calculated for each patient using a deep learning neural networks model, which incorporated meteorological and satellite-based measurements at the patients' residential zip code. Adjusted multivariate logistic regression was used to quantify the association between cumulative PM2.5 exposure and PTC diagnosis. We tested whether this association differed by gender, race, BMI, smoking history, current alcohol use, and median household income. RESULTS: A cohort of 1990 patients with PTC and a control group of 6919 patients without thyroid disease were identified. Compared to the control group, patients with PTC were more likely to be older (51.2 vs. 48.8 years), female (75.5% vs 46.8%), White (75.2% vs. 61.6%), and never smokers (71.1% vs. 58.4%) (p < 0.001). After adjusting for age, sex, race, BMI, current alcohol use, median household income, current smoking status, hypertension, diabetes, COPD, and asthma, 3-year cumulative PM2.5 exposure was associated with a 1.41-fold increased odds of PTC diagnosis (95%CI: 1.23-1.62). This association varied by median household income (p-interaction =0.03). Compared to those with a median annual household income <$50,000, patients with a median annual household income between $50,000 and < $100,000 had a 43% increased risk of PTC diagnosis (aOR = 1.43, 95%CI: 1.19-1.72), and patients with median household income ≥$100,000 had a 77% increased risk of PTC diagnosis (aOR = 1.77, 95%CI: 1.37-2.29). CONCLUSIONS: Cumulative exposure to PM2.5 over 3 years was significantly associated with the diagnosis of PTC. This association was most pronounced in those with a high median household income, suggesting a difference in access to care among socioeconomic groups.

A case-control study of urinary concentrations of bisphenol A, bisphenol F, and bisphenol S and the risk of papillary thyroid cancer.

The incidence of thyroid cancer (TC), especially papillary thyroid cancer (PTC), has dramatically increased globally. Whereas some endocrine disruptors have been linked to neoplastic processes, the associations between human exposure to bisphenol analogs and the risk of TC remain unclear. This present case-control study examined the associations between the urinary concentrations of bisphenol A (BPA) and other bisphenols, namely bisphenol F (BPF) and bisphenol S (BPS), and the risk of PTC. After adjusting for confounders and creatinine standardization, significantly positive associations were observed for BPF (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.27-2.54), but negative associations observed for BPA (OR = 0.38, 95% CI = 0.19-0.77) and BPS (OR = 0.63, 95% CI = 0.43-0.93), in the total population. However, after stratification by age and smoking, statistical significance was retained only in non-smoking women, suggesting the adverse effects of BPF exposure on PTC risk, especially in women. These findings require replication and confirmation in further research.

Emerging drugs for the treatment of radioactive iodine refractory papillary thyroid cancer.

INTRODUCTION: The most frequent radioactive (RAI) refractory thyroid cancers are papillary thyroid carcinoma, followed by poorly differentiated thyroid carcinoma. They are rare and lethal. In recent years, significant therapeutic progress has been achieved. AREAS COVERED: This paper offers insights on refractoriness to RAI treatment and the optimization of treatment initiation and treatment choice. Clinical trials performed with anti-angiogenic kinase inhibitors and with targeted inhibitors in patients with BRAF, RAS mutation or RET, TRK or ALK fusion are discussed. EXPERT OPINION: These treatments provide high response rates. Anti-angiogenic kinase inhibitors improve median progression-free-survival; however, their benefit in terms of overall survival has been shown in only few subsets of patients. Treatment sequencing is challenging; in the absence of targetable abnormality, lenvatinib should be used as first-line treatment. Options for second-line treatment include lenvatinib (if not given at first line), cabozantinib or the addition of an anti-checkpoint antibody. In patients with a targetable abnormality, specific inhibitors, might be used as first-line treatment and lenvatinib as second line or vice-versa. Further studies are needed, based on documented genomic and immunologic characteristics of the tumor to assess the potential role of combination and redifferentiation therapy.

A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members.

BACKGROUND AND OBJECTIVES: Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype. METHODS: We carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC. RESULTS: Four PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis. DISCUSSION: This study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Potential role of iodine excess in papillary thyroid cancer and benign thyroid tumor: A case-control study.

BACKGROUND AND OBJECTIVES: The relationship between nutritional status of iodine and thyroid tumor is unclear. We investigated the association between urinary iodine concentration and thyroid function in patients with papillary thyroid cancer, benign thyroid tumor and healthy individuals. METHODS AND STUDY DESIGN: We compared the biomarkers of thyroid function and urinary iodine concentration within and between each group. A regression analysis was used to identify risk factors for papillary thyroid cancer. Correlation analysis was performed to determine whether any significant correlation exists between urinary iodine concentration and thyroid function biomarkers. RESULTS: The iodine nutrition statuses of these three groups were adequate (median urinary iodine concentration= 100-199 µg/L). However, the median urinary iodine concentration of papillary thyroid cancer (174.7 µg/L) and benign thyroid tumor (165.04 µg/L) groups was significantly higher than that of the healthy control group (135.8 µg/L) (p<0.05). The regression analysis showed that thyroglobulin antibody was an independent risk factor for papillary thyroid cancer. After adjusting for age and gender, the association between thyroglobulin antibody and urinary iodine concentration was significant (ß: 0.002; p<0.05). In subgroup analyses, significant correlations was noted only in the papillary thyroid cancer group (adjusted ß: 0.002; 95% confidence interval: 0.000- 0.003). CONCLUSIONS: Excessive iodine in patients with thyroid tumors may affect thyroglobulin antibody, which may be an independent risk factor for papillary thyroid cancer.

An Animal Model Further Uncovers the Role of Mutant BrafV600E during Papillary Thyroid Cancer Development.

Papillary thyroid carcinomas (PTCs) account for 90% of human thyroid cancer cases, which represent 1% of all cancer cases. They are likely to develop from papillary thyroid microcarcinomas (PTMCs), found in up to 36% of healthy individuals, due to rare progression events (0.01%). Although the prognosis of PTCs is excellent, 5% to 10% of tumors display an unfavorable outcome. About 45% of PTCs exhibit activating BRAFV600E mutations. Rats of the inbred BD strains postnatally exposed to the carcinogen N-ethyl-N-nitrosourea developed PTMCs, which closely resembled their human counterparts judging from their histology, size, and marginal tendency to progress. DNA sequencing revealed mutations in exon 15 of the Braf gene identical to the human BRAFV600E mutation in 82% of the cases. Predominantly a 50:50 ratio of wild-type to mutant Braf alleles was seen regardless of tumor size or animal age, indicating that the Braf mutation is an early, if not the initial, event in rat PTMC development. Surprisingly, most PTMCs carrying a confirmed BrafV600E mutation did not display BrafV600E protein expression. As the BrafV600Egene is supposed to be the driver in PTC development, down-regulation of expression should contribute to the low risk for progression of PTMC. This model system will enable further insights into the molecular mechanisms of PTMC initiation and progression to PTC, further translating into targeted tumor prevention strategies/therapies.

Associations of urinary phthalate metabolites with risk of papillary thyroid cancer.

Some studies have revealed thyrotoxicity of phthalates; however, associations of phthalate exposure with papillary thyroid cancer (PTC) remain unclear. We conducted a pair-matching case-control study of 111 PTC cases and 111 age- and sex-matched non-PTC controls to examine associations between urinary concentrations of phthalate metabolites and PTC. Phthalate metabolites were determined in fasting urine specimens by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS). After adjusting for potential confounders and other phthalate metabolites, the concentrations of the sum of di (2-ethylhexly) phthalate (DEHP) metabolites in urine were positively associated with PTC [odds ratio (OR) = 5.35; 95% confidence interval (CI): 1.61-17.83], suggesting the effect of phthalates exposure on PTC development. The findings require confirmation.

Polybrominated Diphenyl Ethers, Polybrominated Biphenyls, and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study.

A nested case-control study was carried out using data from the US Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 histologically confirmed PTC cases (in 341 women and 401 men) and 742 matched controls with prediagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of 8 congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by sex. BDE-28, a polybrominated diphenyl ether congener, was associated with significantly increased risk of classical PTC (for the third tertile vs. below the limit of detection, odds ratio = 2.09, 95% confidence interval: 1.05, 4.15; P for trend = 0.02), adjusting for other congeners, body mass index, and branch of military service. This association was observed mainly for larger classical PTC (tumor size > 10 mm), with a significantly stronger association among women than men (P for interaction = 0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by sex and tumor size.

Exposure to Polybrominated Diphenyl Ethers and a Polybrominated Biphenyl and Risk of Thyroid Cancer in Women: Single and Multi-Pollutant Approaches.

BACKGROUND: Thyroid cancer incidence is the most rapidly increasing malignancy; rates are three times higher in women than men. Thyroid hormone-disrupting flame-retardant chemicals, including polybrominated diphenyl ethers (PBDE) and polybrominated biphenyls (PBB), may contribute to this trend. METHODS: We investigated the relationship between PBDE/PBB exposure and papillary thyroid cancer (PTC) in 250 incident female papillary thyroid cancer cases and 250 female controls frequency-matched on age. Interviews and postdiagnostic serum samples were collected from 2010 to 2013. Serum samples were analyzed for 11 congeners. We calculated ORs and 95% confidence intervals (95% CI) using single-pollutant logistic regression models for continuous and categorical lipid-adjusted serum concentrations of PBDE/PBB, adjusted for age, alcohol consumption, and education. We applied three multi-pollutant approaches [standard multipollutant regression models, hierarchical Bayesian logistic regression modeling (HBLR), principal components analysis (PCA)] to investigate associations with PBDE/PBB mixtures. RESULTS: In single-pollutant models, a decreased risk was observed at the highest (>90th percentile) versus lowest (

Mouse Model of Thyroid Cancer Progression and Dedifferentiation Driven by STRN-ALK Expression and Loss of p53: Evidence for the Existence of Two Types of Poorly Differentiated Carcinoma.

Background: Thyroid tumor progression from well-differentiated cancer to poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) involves step-wise dedifferentiation associated with loss of iodine avidity and poor outcomes. ALK fusions, typically STRN-ALK, are found with higher incidence in human PDTC compared with well-differentiated cancer and, as previously shown, can drive the development of murine PDTC. The aim of this study was to evaluate thyroid cancer initiation and progression in mice with concomitant expression of STRN-ALK and inactivation of the tumor suppressor p53 (Trp53) in thyroid follicular cells. Methods: Transgenic mice with thyroid-specific expression of STRN-ALK and biallelic p53 loss were generated and aged on a regular diet or with methimazole and sodium perchlorate goitrogen treatment. Development and progression of thyroid tumors were monitored by using ultrasound imaging, followed by detailed histological and immunohistochemical evaluation. Gene expression analysis was performed on selected tumor samples by using RNA-Seq and quantitative RT-PCR. Results: In mice treated with goitrogen, the first thyroid cancers appeared at 6 months of age, reaching 86% penetrance by the age of 12 months, while a similar rate (71%) of tumor occurrence in mice on regular diet was observed by 18 months of age. Histological examination revealed well-differentiated papillary thyroid carcinomas (PTC) (n = 26), PDTC (n = 21), and ATC (n = 8) that frequently coexisted in the same thyroid gland. The tumors were frequently lethal and associated with the development of lung metastasis in 24% of cases. Histological and immunohistochemical characteristics of these cancers recapitulated tumors seen in humans. Detailed analysis of PDTC revealed two tumor types with distinct cell morphology and immunohistochemical characteristics, designated as PDTC type 1 (PDTC1) and type 2 (PDTC2). Gene expression analysis showed that PDTC1 tumors retained higher expression of thyroid differentiation genes including Tg and Slc5a5 (Nis) as compared with PDTC2 tumors. Conclusions: In this study, we generated a new mouse model of multistep thyroid cancer dedifferentiation with evidence of progression from PTC to PDTC and ATC. Further, PDTC in these mice showed two distinct histologic appearances correlated with levels of expression of thyroid differentiation and iodine metabolism genes, suggesting a possibility of existence of two PDTC types with different functional characteristics and potential implication for therapeutic approaches to these tumors.

Cadmium as main endocrine disruptor in papillary thyroid carcinoma and the significance of Cd/Se ratio for thyroid tissue pathophysiology.

BACKGROUND: The etiology of papillary thyroid carcinoma (PTC) is unknown and some literature data support the hypothesis that heavy metals, as endocrine disrupters, could play a major role in the pathogenesis of thyroid cancer. This study aimed to estimate the content of selected toxic and essential trace metals (Mn, Co, Ni, Cu, Zn, As, Se, Cd, Pb, Th, and U), as well as the selected ratio's (Cu/Zn and Cd/Se) in the malignant thyroid tissues according to sex, age, smoking habits, familial history of any thyroid disease, pathohistological (PH) types of PTC, tumor size, the existence of a thyroid capsular invasion, intrathyroid tumor dissemination, retrosternal thyroid growth, and TNM progress of PTC. METHODS: The study included 66 patients with PTC (women/men ratio = 46/20, mean age: 54 ± 14 years). A comparative analysis was made by collecting the healthy thyroid tissues (HTTs) of the same patients, making the total number of samples 132. All trace metals were quantified by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Metals that significantly separated papillary thyroid tissues (PTTs) from the HTTs were Cd, U and Se (p < 0.05). The obtained negative correlation between Cd and Se in the PTTs could explain extrusion of essential Se caused by increased content of Cd. Only Cd had an influence on the retrosternal thyroid growth, while the essential metals (Mn, Co, and Zn) had an influence on thyroid capsular invasion. CONCLUSION: It was found that Cd act as the main endocrine disrupter, which could highlight its role in the etiology of PTC. Considering that the Cd/Se ratio significantly separated two studied groups and had an influence on the retrosternal thyroid growth, its altered content could contribute to the better understanding of the molecular basis for pathophysiological changes in the PTC.

Association of exposure to multiple metals with papillary thyroid cancer risk in China.

Papillary thyroid cancer (PTC) has inflicted huge threats to the health of mankind. Metal pollution could be a potential risk factor of PTC occurrence, but existing relevant epidemiological researches are limited. The current case-control study was designed to evaluate the relationships between exposure to multiple metals and the risk of PTC. A total of 262 histologically confirmed PTC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Urine samples were used as biomarkers to reflect the levels of environmental exposure to 13 metals. Conditional logistic regression models were adopted to assess the potential association. Single-metal and multi-metal models were separately conducted to evaluate the impacts of single and co-exposure to 13 metals. The increased concentration of urinary Cd, Cu, Fe, and Pb quartiles was found significant correlated with PTC risk. We also found the decreased trends of urinary Se, Zn, and Mn quartiles with the ORs for PTC. These dose-response associations between Pb and PTC were observed in the single-metal model and remained significant in the multi-metal model (OR25-50th=1.39, OR50-75th=3.32, OR>75th=7.62, p for trend <0.001). Our study suggested that PTC was positively associated with urinary levels of Cd, Cu, Fe, Pb, and inversely associated with Se, Zn, and Mn. Targeted public health policies should be made to improve the environment and the recognition of potential risk factors. These findings need additional studies to confirm in other population.

[Papillary thyroid carcinoma in a patient with Turner syndrome treated with human growth hormone].

Thyroid cancer is a rare pathology in childhood and adolescence, being responsible for 1.5-3% of all carcinomas in this age group. Differentiated thyroid carcinoma is the most commonly found variant, especially papillary carcinoma of the thyroid (PCT). Currently available data support the hypothesis that growth hormone (GH) as well as insulin-like growth factor 1 (IGF-1) can facilitate carcinogenesis. There is a confirmed role of the GH/IGF-1 axis in cancer progression as an initiator of tumorigenesis and neoplastic transformation, metastasis, and resistance to chemotherapy and radiotherapy. Presently, application of recombinant GH is an acceptable method to treat female patients with growth failure during the course of Turner syndrome (TS). This article reports the case of a fourteen-year-old female patient with Turner syndrome, Hashimoto thyroiditis, and papillary thyroid carcinoma diagnosed during GH treatment. The immunochemical analysis of tumour tissue in our patient revealed intensive brown reaction that labelled expression of the IGF-1R vs. traced reaction or its lack in normal thyroid tissue. A significant role is played by IGF-1 in the pathogenesis of invasion of thyroid cancer; however, this effect is complex, and how it works is not well established.

[Diagnostic value of combination of US and MRI in preoperative prediction for the extrathyroidal extension of papillary thyroid carcinoma].

Objective: The purpose of the present study was to evaluate the diagnostic performance of preoperative ultrasonography(US), magnetic resonance imaging(MRI) and US combined with MRI in the prediction of extrathyroidal extension(ETE) in patients with papillary thyroid carcinoma(PTC). Methods: Between January 2013 and December 2016, a total of 83 consecutive patients underwent surgery for pathologically confirmed PTCs with ETE. We analyzed all patients with PTC with ETE who received preoperative combination of US and MRI scan to evaluate ETE. Results: For minimal ETE, the accuracy was 92.2%(47/51) of US, 74.5%(38/51) of MRI, and their combination was 98.0%(50/51). The differences of the three methods for minimal ETE were statistically significantly different(P=0.000). For extensive ETE, the accuracy was 62.5%(20/32) of US, 87.5%(28/32) of MRI, and their combination was 93.8%(30/32). The different of the three methods for extensive ETE was statistically significantly different(P=0.000). For the total accuracy of ETE, US was 80.7%(67/83), MRI was 79.5% (66/83), and their combination was 96.4%(80/83). The difference of the three methods for ETE was statistically significantly different(P=0.001). Conclusion: The combination of US and MRI can improve the preoperative diagnostic accuracy of ETE for PTC.