Associations between paraben exposure, thyroid capacity, homeostasis and pituitary thyrotropic function in the general Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013.

Several studies have suggested that some endocrine disruptors such as synthetic phenols, parabens and phthalates may disrupt thyroid hormone signaling and associated negative feed-backs with the central hypothalamic-pituitary-thyroid (HPT) axis. Therefore, we investigated urinary paraben and blood thyroid hormone levels in the Taiwanese population. Our sample comprised 264 adults (aged 18-97 years) and 75 minors (aged 7-17 years) from Taiwan Environmental Survey for Toxicants 2013. Urinary levels of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were assessed. Hormones of particular interest include: thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). We sought integrated parameters to describe the transfer of thyroid hormones in homeostatic models. The geometric mean urinary paraben levels of the adults were higher than those of the minors (adults vs. minors; MeP: 383 vs. 62.4 ng/mL; PrP: 109 vs. 8.00 ng/mL; EtP: 39.5 vs. 2.38 ng/mL, and BuP: 6.36 vs. 2.13 ng/mL). In the male adults, we discovered that 0.253% (p = 0.032), 0.256% (p = 0.041) and 0.257% (p = 0.037) decreases in the TSH, TSH/T4 and TSH/FreeT4 ratio was associated with 1% EtP increases, respectively. In the female minors, 0.093% (p = 0.044), 0.072% (p = 0.047) and 0.156 (p = 0.004) increases in the TSH ratios were associated with a 1% MeP, EtP and BuP increase, respectively. Moreover, 0.151% (p = 0.008) and 0.177% (p = 0.001) increases in TSH/T4 and TSH/free T4 ratios were associated with a BuP 1% increase, respectively. Finally, EtP was positively associated with SPINA-GT (ß: 15.66, p = 0.036) in the male adults. By contrast, EtP were positively associated with Jostel's TSH index and sTSHI (ß: 0.072, p = 0.049; ß: 0.107, p = 0.049) in the female minors. The Taiwanese population is commonly exposed to parabens, which can potentially lead to alteration of thyroid hormone homeostasis.

How did we eliminate the hazards of water-borne excessive iodine in northern China?

Drinking water is the main cause of iodine excess among Chinese residents and we have found that water iodine concentration (WIC) reduction was the effective intervening measure. In this study, to eliminate the hazards of water-borne excessive iodine, we firstly investigated the WIC of villages in Tianjin in 2017 to determine the distribution range. Secondly, the risk characterization of excessive iodine on residents in 6∼< 9 years old, 9∼< 12 years old, 12∼< 15 years old, 15∼< 18 years old and adults were evaluated, and the safe upper limit of WIC was determined. Finally, WIC was investigated again after the completion of WIC reduction in water-borne excessive-iodine villages in 2020, and the differences in urinary iodine concentration (UIC) and thyroid volume (Tvol) of children aged 8-10 years before and after WIC reduction were analyzed. The WIC of 2459 villages surveyed was 22.30 (8.60-58.80) µg/L and the maximum was 514 µg/L. There were 422 villages with WIC > 100 µg/L. Under the conditions of non-iodized salt intake, recommended amount of iodized salt intake and actual amount intake, the maximum of excessive iodine exposure hazard quotient (HQ) were the highest in the age group of 6∼< 9 years, which were 2.300, 2.663 and 2.771, the safe upper WIC limits were 223 µg/L, 142 µg/L and 118 µg/L and villages with HQ> 1 accounted for 4.14%, 6.09% and 6.88% of all villages, respectively. After the WIC reduction, the WIC of the former water-borne iodine-excess villages decreased to < 100 µg/L, and the UIC and Tvol of children decreased (both P < 0.001) and was within normal range. Determining the distribution range of water-borne iodine-excess areas, exploring appropriate intervening measure, carrying out risk assessment, determining the WIC safe upper limit, intervening and evaluating the intervention effect can be the process to eliminate the hazards of water-borne excessive iodine.

6:2 Chlorinated Polyfluoroalkyl Ether Sulfonates Exert Stronger Thyroid Homeostasis Disruptive Effects in Newborns than Perfluorooctanesulfonate: Evidence Based on Bayesian Benchmark Dose Values from a Population Study.

Growing toxicologic evidence suggests that emerging perfluoroalkyl substances (PFASs), like chlorinated polyfluoroalkyl ether sulfonate (Cl-PFESA), may be as toxic or more toxic than perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA). However, further investigations are needed in terms of the human health risk assessment. This study examined the effects of emerging and legacy PFAS exposure on newborn thyroid homeostasis and compared the thyroid disruption caused by 6:2 Cl-PFESA and PFOS using a benchmark dose approach. The health effects of mixture and individual exposure were estimated using the partial least-squares (PLS) model and linear regression, respectively. A Bayesian benchmark dose (BMD) analysis determined the BMD value for adverse effect comparison between 6:2 Cl-PFESA and PFOS. The median (interquartile range) concentrations of 6:2 Cl-PFESA (0.573 [0.351-0.872] ng/mL), PFOS (0.674 [0.462-1.007] ng/mL), and PFOA (1.457 [1.034, 2.405] ng/mL) were found to be similar. The PLS model ranked the PFAS variables' importance in projection (VIP) scores as follows: 6:2 Cl-PFESA > PFOS > PFOA. Linear regression showed that 6:2 Cl-PFESA had a positive association with free triiodothyronine (FT3, P = 0.006) and triiodothyronine (T3, P = 0.014), while PFOS had a marginally significant positive association with FT3 alone (P = 0.042). The BMD analysis indicated that the estimated BMD10 for 6:2 Cl-PFESA (1.01 ng/mL) was lower than that for PFOS (1.66 ng/mL) in relation to a 10% increase in FT3. These findings suggest that 6:2 Cl-PFESA, an alternative to PFOS, has a more pronounced impact on newborns' thyroid homeostasis compared to PFOS and other legacy PFASs.

Tris(2-chloroethyl) Phosphate Exerts Hepatotoxic Impacts on Zebrafish by Disrupting Hypothalamic-Pituitary-Thyroid and Gut-Liver Axes.

The ubiquitous environmental presence of tris(2-chloroethyl) phosphate (TCEP) poses a potential threat to animals; however, little is known about its hepatotoxicity. In this study, the effects of TCEP exposure (0.5 and 5.0 µg/L for 28 days) on liver health and the potential underlying toxification mechanisms were investigated in zebrafish. Our results demonstrated that TCEP exposure led to hepatic tissue lesions and resulted in significant alterations in liver-injury-specific markers. Moreover, TCEP-exposed fish had significantly lower levels of thyrotropin-releasing hormone and thyroid-stimulating hormone in the brain, evidently less triiodothyronine whereas more thyroxine in plasma, and markedly altered expressions of genes from the hypothalamic-pituitary-thyroid (HPT) axis in the brain or liver. In addition, a significantly higher proportion of Bacteroidetes in the gut microbiota, an elevated bacterial source endotoxin lipopolysaccharide (LPS) in the plasma, upregulated expression of LPS-binding protein and Toll-like receptor 4 in the liver, and higher levels of proinflammatory cytokines in the liver were detected in TCEP-exposed zebrafish. Furthermore, TCEP-exposed fish also suffered severe oxidative damage, possibly due to disruption of the antioxidant system. These findings suggest that TCEP may exert hepatotoxic effects on zebrafish by disrupting the HPT and gut-liver axes and thereafter inducing hepatic inflammation and oxidative stress.

Sex-specific effect of urinary metabolites of polycyclic aromatic hydrocarbons on thyroid profiles: results from NHANES 2011-2012.

The current study aims to evaluate the associations between 10 urinary polycyclic aromatic hydrocarbon (PAH) metabolites and thyroid profiles. The levels of 10 PAH metabolites and thyroid profiles were obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2012. Spearman analysis was utilized to evaluate the correlation coefficients among these 10 PAH metabolites. Multivariate linear and logistic regression models assessed the relationship between urinary PAH metabolite levels, thyroid hormones, and thyroid autoantibodies after adjusting potential confounders. Stratified analysis by gender was performed to evaluate sex-specific effect of urinary metabolites of PAH on thyroid profiles. One thousand six hundred forty-five eligible adult participants with complete research data were enrolled. Of note, the concentrations of the majority of urinary PAH metabolites were remarkedly higher in females compared with males. 2-hydroxyfluorene (2-FLU) was associated with higher total triiodothyronine (T3) levels in whole population (ß = 2.113, 95% CI 0.339-3.888). In males, positive associations were observed in 1-hydroxynaphthalene (1-NAP) and free thyroxine (T4) (ß = 0.0002, 95% CI 0.0000-0.0004). 2-FLU was also found positively associated with total T3 (ß = 2.528, 95% CI 0.115-4.940) in male subjects. While in female participants, 2-hydroxynaphthalene (2-NAP) was associated with free T3 (ß = 0.002, 95% CI 0.000-0.005). 2-FLU was associated with total T3 (ß = 2.683, 95% CI 0.038-5.328), free T3 (ß = 0.050, 95% CI 0.012-0.087), and total T4 (ß = 0.195, 95% CI 0.008-0.382). 2-Hydroxyphenanthrene (2-OHP), 1-hydroxypyrene (1-HP), and 9-hydroxyfluorene (9-FLU) were all positively related to total T3 levels, and the corresponding coefficients were 16.504, 6.587, and 3.010. 9-FLU was also associated with free T3 (ß = 0.049, 95% CI 0.008-0.090). No statistical significances were found between PAH metabolite levels and increased prevalence of increased thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) when PAH metabolites were treated as continuous variables. Meanwhile, in the quartile analyses, increased prevalence of elevated TgAb was observed in participants with quartile 2 2-NAP compared with lowest quartile (OR = 1.753, 95% CI 1.021-3.008). Male subgroup analyses indicated that increased prevalence of elevated TgAb was observed in higher quartile of 1-NAP, 2-NAP, and 3-hydroxyfluorene (3-FLU). Increased prevalence of elevated TPOAb was associated with higher 2-NAP quartile. However, in subgroup analysis of females, no statistical significances were found between PAH quartiles and increased TgAb/TPOAb. Significant correlations were found among these 10 PAH metabolites. In conclusion, the cross-sectional study indicated that exposure to PAH might disturb the concentrations of thyroid hormones and thyroid autoantibodies. It is noteworthy that significant differences existed in males and females. Further prospective research is warranted to explore the causal relationship and underlying mechanism of PAH exposure on thyroid dysfunction.

Sodium/Iodide Symporter Metastable Intermediates Provide Insights into Conformational Transition between Principal Thermodynamic States.

The Sodium/Iodide Symporter (NIS), a 13-helix transmembrane protein found in the thyroid and other tissues, transports iodide, a required constituent of thyroid hormones T3 and T4. Despite extensive experimental information and clinical data, structural details of the intermediate microstates comprising the conformational transition of NIS between its inwardly and outwardly open states remain unresolved. We present data from a combination of enhanced sampling and transition path molecular dynamics (MD) simulations that elucidate the principal intermediate states comprising the inwardly to outwardly open transition of fully bound and apo NIS under an enforced ionic gradient. Our findings suggest that in both the absence and presence of bound physiological ions, NIS principally occupies a proximally inward to inwardly open state. When fully bound, NIS is also found to occupy a rare "inwardly occluded" state. The results of this work provide novel insight into the populations of NIS intermediates and the free energy landscape comprising the conformational transition, adding to a mechanistic understanding of NIS ion transport. Moreover, the knowledge gained from this approach can serve as a basis for studies of NIS mutants to target therapeutic interventions.

Thyroid dose assessments due to inhalation of 131I for nuclear medicine workers.

Background: In general, medical staff who work in nuclear medicine should be entirely safe in their professional environment. Nevertheless, we already know that the working environment of the nuclear medicine staff is not completely safe due to the handling of high amounts of radionuclides for diagnostic and therapy applications, which is especially relevant for 131I (as a non-sealed source). Purpose: The goal of this study was to assess the inhaled 131I thyroid dose in nuclear medicine workers and to introduce a simple method for internal exposure monitoring. Methods: Using 2-IN*2-in NaI (Tl) scintillation spectrometer and its supporting software (InSpector Maintenance Utility and Genie 2000), from 2019 to 2021, internal thyroid irradiation monitoring, an internal thyroid irradiation monitoring investi A NaI (Tl) scintillation spectrometer and its sugation was carried out for 3 consecutive years, between 2019 and 2021, in staff members of nuclear medicine departments engaged with iodine therapy. Results: 131I activity was found highest in the thyroid of nuclear medicine workers involved with the manual packaging and delivery of the radioisotope, while it was not detected in staff members involved with the automatic packaging and drug delivery. The activity range was found to be 30.00 ± 6.60-6070.00 ± 1335.40 Bq for the exposed personnel, and the estimated dose was 0.05-6.77 mSv. In 2021, three workers had an annual equivalent dose above 5 mSv. Conclusion: By monitoring the thyroid 131I in staff members of the nuclear medicine department, it was found that there are 131I internal occupational exposure risks. The best solution is automatic packaging and drug delivery.

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.

Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study (Di@bet.es study).

BACKGROUND: Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. METHODS: The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5µm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche). RESULTS: In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 µg/m3). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women. CONCLUSIONS: Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.

Exploring the influence mechanism of dissolved organic matter on the bioavailability and thyroid hormone disrupting effect of zinc: A case study of effluents from galvanizing plants.

The effect of dissolved organic matter (DOM) on metal bioavailability and toxicity is a complex process. Effluents from galvanizing plants containing large amounts of DOM and Zn were selected to investigate the potential influence and mechanism of DOM on Zn bioavailability and its role in inducing thyroid hormone disrupting effects. Thyroid hormone disrupting effects were evaluated using a recombinant thyroid hormone receptor ß gene yeast assay. The results suggest that Zn could be the main metal contributor to the toxic effects. Then, Zn-binding characteristics with different fluorescent components of DOM were analyzed using three-dimensional excitation emission matrix fluorescence spectroscopy (3DEEM) and revealed that Zn was more susceptible to interactions with fulvic-like materials. Furthermore, DOM altered the cellular biouptake and compartmentalization processes of Zn by downregulating Zn transmembrane transport-related genes (ZRT1, ZRT2 and ZAP1) and upregulating detoxification-related genes (COT1 and ZRC1), thus altering thyroid toxicity. These results provide comprehensive insights into the influence and mechanism of DOM on bioavailability and thyroid toxicity of Zn and suggest that the influence is associated with complex physical, chemical and biological processes, indicating that more refined medium constraints along with subtle biological reactions should be considered when predicting the bioavailability and toxicity of Zn in environmental water samples.

Parathyroid hormone in situ measurement in patients with hyperparathyroidism: single-centre experience of 179 patients.

Context: The measurement of parathyroid hormone(PTH) in situ (PTHis) by fine-needle aspiration (FNA) has been proposed as a tool to preoperatively help localize parathyroid glands detected on ultrasound. However, the accuracy of PTHis is highly variable according to the few available studies. Aim: We aimed to develop and validate the PTHis procedure and assessed the performance of PTHis in a large series of patients with hyperparathyroidism and/or undetermined cervical lesions. Patients and methods: The technique set-up consisted of PTHis measurement in thyroid samples from patients with thyroid nodules and patients with high circulating PTH levels (tertiary hyperparathyroidism). Consecutive patients were recruited at one tertiary referral centre from 2017 to 2020 and submitted to ultrasound-guided FNA-PTHis determination. Results: During the method set-up, we obtained undetectable PTHis levels in all non-parathyroid tissues after sample dilutions. PTHis was higher in patients with hyperparathyroidism (n = 145; 1817 ± 3739 ng/L; range: <4.6-31 140) than in those with thyroid or undetermined cervical lesions (n= 34; <4.6 ng/mL; P < 0.0001). When evaluating PTHis performance in histologically proven samples (158 lesions from 121 patients), PTHis was detectable in 85/97 parathyroid lesions (87%; range: 22-31;140 ng/L) and undetectable in all non-parathyroid lesions (n = 61; P < 0.0001). The specificity and positive predictive value were 100%, and the sensitivity was 87.6%. False-negative lesions (n= 12) were smaller (9.4 ± 5.9 mm) and more often consisted of hyperplasias (75%) than true-positive lesions (16.1 ± 8.4 mm and 33%, P = 0.009 and P = 0.0089, respectively). The method was safe and well tolerated. Four educational cases are also provided. Conclusions: PTHis determination is a safe and well-tolerated procedure that enhances the specificity of ultrasound-detected lesions. If accurately set-up, it confirms the parathyroid origin of uncharacterized cervical lesions.

Thyroid dysfunction and insulin resistance in end-stage renal disease patients before and 1 year after starting maintenance hemodialysis: A prospective multicenter study.

BACKGROUND: Thyroid dysfunction and insulin resistance (IR) are common findings in patients with ESRD. We aimed to evaluate thyroid dysfunction and IR in ESRD before and after 1 year of starting hemodialysis (HD). METHODS: This was a prospective study that recruited newly starting HD patients who fulfilled the inclusion criteria. Patients were evaluated for TSH, free T4, free T3, fasting insulin, fasting glucose, HOMA-IR, serum ferritin, and hs-CRP levels before starting their first dialysis session and after 1 year of regular HD. RESULTS: Eighty-one patients have completed the 1-year follow-up period. After 1 year of regular HD, there were statistically significant increments of hs-CRP, serum ferritin, and TSH levels. On the other hand, fasting insulin level and HOMA-IR showed statistically significant increments after 1 year of starting HD. After 1 year of regular HD, TSH level showed a positive correlation with hs-CRP and serum ferritin level, while free T3 was negatively correlated with HOMA-IR. On the other hand, there was a significant positive correlation between HOMA-IR, hs-CRP, and serum ferritin levels, while HOMA-IR was negatively correlated with Kt/V. CONCLUSIONS: This study suggests overlapping complex pathogenesis of thyroid dysfunction, chronic inflammation, and IR in chronic HD patients.

Urinary levels of phthalate esters and heavy metals in adolescents with thyroid colloid cysts.

We aimed to evaluate 14 urinary phthalate metabolites and 4 toxic metals in adolescents having thyroid colloid cyst (TCC) and compare with age and sex-matched others without TCC. Phthalate metabolites were analysed with UPLC-MS/MS and heavy metals with ICP-MS. TCC ratios in tertile subgroups of pollutants were compared with multiple logistic regression analysis after adjusting for age, sex, z-scores for body mass index and urinary creatinine values. Adolescents having the highest tertile of mono (2-ethylhexyl) phthalic acid and mercury had increased odds and those with the highest tertiles of monocarboxy-isononyl phthalate, mono (3-carboxypropyl) phthalate, monoisobutyl phthalate had lower odds for TCC than counterparts. The odds of TCC were lower for those in the second and the third tertiles. No differences in TCC ratios were detected with other pollutants. Given phthalate esters' and toxic metals' specific interactions on TCC, further studies were necessary to assess the influence of chemicals on TCC.

The Consumption of Food-Based Iodine in the Immediate Pre-Pregnancy Period in Madrid Is Insufficient. San Carlos and Pregnancy Cohort Study.

A pre-gestational thyroid reserve of iodine is crucial to guarantee the increased demand for thyroid hormone production of early pregnancy. An iodine intake ≥150 µg/day is currently recommended. The objective of this study was to assess average pre-gestational food-based iodine consumption in pregnant women at their first prenatal visit (<12 gestational weeks), and its association with adverse materno-fetal events (history of miscarriages, early fetal losses, Gestational Diabetes, prematurity, caesarean sections, and new-borns large/small for gestational age). Between 2015-2017, 2523 normoglycemic women out of 3026 eligible had data in the modified Diabetes Nutrition and Complication Trial (DNCT) questionnaire permitting assessment of pre-gestational food-based iodine consumption, and were included in this study. Daily food-based iodine intake was 123 ± 48 µg, with 1922 (76.1%) not reaching 150 µg/day. Attaining this amount was associated with consuming 8 weekly servings of vegetables (3.84; 3.16-4.65), 1 of shellfish (8.72; 6.96-10.93) and/or 2 daily dairy products (6.43; 5.27-7.86). Women who reached a pre-gestational intake ≥150 µg had lower rates of hypothyroxinemia (104 (17.3%)/384 (21.4%); p = 0.026), a lower miscarriage rate, and a decrease in the composite of materno-fetal adverse events (0.81; 0.67-0.98). Reaching the recommended iodine pre-pregnancy intake with foods could benefit the progression of pregnancy.

Thyroid function and immune status in perch (Perca fluviatilis) from lakes contaminated with PFASs or PCBs.

The environment contains a multitude of man-made chemicals, some of which can act as endocrine disruptors (EDCs), while others can be immunotoxic. We evaluated thyroid disruption and immunotoxic effects in wild female perch (Perca fluviatilis) collected from two contaminated areas in Sweden; one site contaminated with per- and polyfluoroalkyl substances (PFASs) and two sites contaminated with polychlorinated biphenyls (PCBs), with one reference site included for each area. The hepatic mRNA expression of thyroid receptors α and ß, and the thyroid hormone metabolising iodothyronine deiodinases (dio1, dio2 and dio3) were measured using real-time PCR, while the levels of thyroid hormone T3 in plasma was analysed using a radioimmunoassay. In addition, lymphocytes, granulocytes, and thrombocytes were counted microscopically. Our results showed lower levels of T3 as well as lower amounts of lymphocytes and granulocytes in perch collected from the PFAS-contaminated site compared to reference sites. In addition, expressions of mRNA coding for thyroid hormone metabolising enzymes (dio2 and dio3) and thyroid receptor α (thra) were significantly different in these fish compared to their reference site. For perch collected at the two PCB-contaminated sites, there were no significant differences in T3 levels or in expression levels of the thyroid-related genes, compared to the reference fish. Fish from one of the PCB-contaminated sites had higher levels of thrombocytes compared with both the second PCB lake and their reference lake; hence PCBs are unlikely to be the cause of this effect. The current study suggests that lifelong exposure to PFASs could affect both the thyroid hormone status and immune defence of perch in the wild.

The changes of essential trace elements in residents from an e-waste site and the relationships between elements and hormones of the hypothalamic-pituitary-thyroid (HPT) axis.

The heavy metals pollution and related health issues were widely reported in e-waste sites, while the impacts of e-waste exposure on the essential trace elements have been neglected. The aim of this study was focused on the internal Cu, Fe, Mn and Zn levels in the residents from an e-waste site and the potential endocrine disrupting effects of these essential trace elements on the hypothalamic-pituitary-thyroid (HPT) axis. This was a cross-sectional study that 87 subjects were recruited from the e-waste site and 81 from the reference site. The results indicated that the e-waste exposed group had significantly lower Fe, Mn level when compared with the reference group (p < 0.05). Cu and Zn were also lower in the exposed group but the differences were not statistically significant. The exposed group had significantly higher TSH level and Fe was significantly associated with TSH in the females (ß (95% CI): - 1.892 (-3.309, -0.475), p = 0.009), rather than in males or all subjects. The exposed group also showed oxidative stress which was indicated by the increased concentrations of MDA and 8-iso-PG. It was further indicated the elevated MDA was mediated by the increase of TSH in the females but not directly related to Fe. In conclusion, the e-waste exposed group showed a decrease of essential trace elements, an increase of TSH and oxidative stress. The decreased Fe was related to the elevated TSH in the females, which further indirectly mediated the increase of oxidative stress. The results suggested that the internal exposure levels and the potential health effects of the essential trace elements in populations from e-waste sites should be of more concern. And the women might be more vulnerable and they need more protection to against the adverse health effects from e-waste.

Characterization of Glycosphingolipids in the Human Parathyroid and Thyroid Glands.

As part of a systematic investigation of the glycosphingolipids in human tissues, acid and non-acid glycosphingolipids from human thyroid and parathyroid glands were isolated and characterized with mass spectrometry and binding of carbohydrate-recognizing ligands, with a focus on complex compounds. The glycosphingolipid patterns of the human parathyroid and thyroid glands were very similar. The major acid glycosphingolipids were sulfatide and the gangliosides GM3, GD3, GD1a, GD1b, GT1b and Neu5Ac-neolactotetraosylceramide, and the major non-acid glycosphingolipids were globotriaosylceramide and globoside. We also found neolactotetra- and neolactohexaosylceramide, the x2 glycosphingolipid, and complex glycosphingolipids with terminal blood group O and A determinants in both tissues. A glycosphingolipid with blood group Leb determinant was identified in the thyroid gland, and the parathyroid sample had a glycosphingolipid with terminal blood group B determinant. Immunohistochemistry demonstrated the expression of blood group A antigens in both the thyroid and parathyroid glands. A weak cytoplasmatic expression of the GD1a ganglioside was present in the thyroid, while the parathyroid gland had a strong GD1a expression on the cell surface. Thus, the glycosylation of human thyroid and parathyroid glands is more complex than previously appreciated. Our findings provide a platform for further studies of alterations of cell surface glycosphingolipids in thyroid and parathyroid cancers.

Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism.

INTRODUCTION: Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients. METHODOLOGY: Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS: Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS: As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.

Proteomic analysis of thyroid tissue reveals enhanced catabolic activity in Graves' disease compared to toxic multinodular goitre.

Graves' disease (GD) and toxic multinodular goitre (TMNG) are the most common thyroid diseases which mainly lead to thyrotoxicosis, however, the underlying mechanism of distinct clinical presentations remains unclear. Protein extracts from the thyroid tissue specimens of the patients with GD and TMNG were subjected to Difference Gel Electrophoresis (DIGE). Differentially regulated protein spots were determined by image analysis, and the spots displaying statistically significant differences were identified by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometer (MALDI-TOF) followed by MASCOT search. Western blot analysis was used to verify changes occurring at the protein levels. The identified proteins were classified based on their functions in metabolic pathways using bioinformatics algorithms. Fifteen proteins showed significant alterations in abundance between the two disease groups. Bioinformatic analysis revealed the differentially regulated proteins were particularly related to catabolism, oxidative stress and especially energy utilization pathways, including glycolysis, proteolysis, ketone body catabolism and other energy metabolism-related pathways. SIGNIFICANCE OF THE STUDY: Previously, GD has been the subject of many studies that performed the proteomics approaches in the orbital tissue samples or tear. This is one of the very few studies that investigate the changes in the proteome of thyroid tissue in GD. We demonstrated mainly the upregulation of catabolic activity-related proteins in patients with GD compared to TMNG. Although it remains to be elucidated, some of these proteins can be used as markers for GD or have a role in the pathogenesis of the disease. Our study contributes the increasing data over time by providing new biomarker candidates for GD.

Molecular docking and dynamics simulation to screen interactive potency and stability of fungicide tebuconazole with thyroid and sex hormone-binding globulin: Implications of endocrine and reproductive interruptions.

Tebuconazole is a widely used fungicide in agriculture, and it may easily enter in the human food chain. In addition, tebuconzaol skin permeation coefficient (Log Kp) is -5.55 cm/s and it does not violate Lipinski's rule. It may mimic as a ligand for various endocrine and reproductive receptor leading to toxicological response or disease manifestation. We studied interactive potential of tebuconazole with thyroid and sex hormone-binding globulin. The main methods for this in silico analyses are molecular docking and molecular dynamic (MD) simulation. This paper explores how agriculture fungicide tebuconzaol exposure can be a risk for endocrine and reprotoxicity due to its stable interactive potency with thyroid and sex hormone-binding globulin (2CEO and 1D2S). Thyroid impairment is one of the most common endocrine issues in human health. In molecular docking analyses, tebuconazole exhibited binding potency of -6.28 kcal/mol with 2CEO compared to its native ligand thyroxin and inhibitor propylthiouracil which had the binding potency of -9.9 and -4.49 kcal/mol, respectively. The binding score of tebuconzaol with 1D2S was found to be -7.54 kcal/mol compared to native ligand dihydrotestosteron and inhibitor aminoglutethimide which exhibited the binding score of -6.84 and -11.41 kcal/mol, respectively. Therefore, each complex was subjected to MD simulation for comparative assessment of physical movement. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), Radius of Gyration and hydrogen bonding exhibited that fluconazole had stable binding pattern with 2CEO and 1D2S which was almost similar to native ligand and its inhibitor. Study revealed that tebuconazole may lead to potent endocrine and reproductive disruptions.