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Background: As a class of synthetic chemicals, organophosphate esters (OPEs) were shown to have thyroid hormones (THs) disrupting potentials in animal studies, while epidemiological evidence on gestational exposure to OPEs and thyroid disruption is limited. Besides, assessment on the safety threshold of OPEs exposure during gestation is especially scarce., Methods: Based on the Shanghai Minhang Birth Cohort Study, we measured maternal urine concentration of 8 OPE metabolites and THs levels in cord plasma and examined their associations using multiple linear regression and quantile g-computation (QGC) models. The benchmark dose (BMD) and its lower limit (BMDL) of urine OPE metabolites concentrations were further estimated via the Bayesian Benchmark Dose Analysis System (BBMD) to reflect the safety threshold of exposure in pregnant women. The corresponding daily intake (DI) of BMDL was then calculated and compared with the current oral reference dose (RfD)., Results: A total of 309 mother-newborn pairs were included in this study. Gestational bis (2-butoxyethyl) phosphate (BBOEP) exposure was associated with higher total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), and free thyroxine (FT4) in cord plasma, while bis(1,3-dichloro-2-propyl) phosphate (BDCPP) was observed to be associated with lower TT3 and FT3/FT4 but higher thyroid stimulating hormone (TSH). In addition, sex-specific effects were observed for bis (2-chloroethyl) phosphate (BCEP), which was associated with lower TT3 in cord plasma of female newborns, and lower TT4 and FT4 in male newborns. Similar results were obtained through QGC model and BBOEP was identified as the main contributor to the higher levels of TT3 and FT3. With benchmark response (BMR) of 10% and background response (P 0 ) of 97.5% for both TT3 and FT3, the BMDL 10 of urine BBOEP concentration was 0.50 μg/L. Further, the corresponding DI of tris (2-butoxyethyl) phosphate (TBOEP), which is the precursor of BBOEP, was 2.53 μg/kg BW/d., Conclusions: Our findings suggest associations between gestational exposure to OPEs and altered THs biomarkers. According to the estimated BMD 10 (BMDL 10 ) of BBOEP and the corresponding DI, the current RfD of 15 μg/kg BW/d for TBOEP may not protect pregnant women and their newborns from thyroid disruption., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ziliang Wang reports financial support, statistical analysis, and writing assistance were provided by Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies. Jiong Li reports writing assistance was provided by Department of Epidemiology, School of Public Health, Nanjing Medical University. Maohua Miao reports financial support and writing assistance were provided by Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies. Yao Chen reports statistical analysis and writing assistance were provided by Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies. Hong Liang reports writing assistance was provided by Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies. Jiaxian Chen reports writing assistance was provided by Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies. Min Luan reports statistical analysis and writing assistance were provided by Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Wei Yuan reports financial support and writing assistance were provided by Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies. Yinan Liu reports equipment, drugs, or supplies was provided by Minhang Maternal and Child Health Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China. Methods: Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline. Results: The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1 , Q 3 ) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all P nonlinear <0.05). Conclusion: In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

The links between Thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) has received widespread attention, but the causal relationships and mediating factors have not been systematically studied. We used two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between TDFDs and OP. Moreover, we performed mediation MR analyses to explore the role of thyroid-related hormones and OP risk factors in the association between TDFDs and OP. Two sample MR analyses showed that hyperthyroidism increased OP (OR = 1.080, 95% CI 1.026 to 1.137; P = 0.0032) risk. Hypothyroidism increases OP (OR = 1.183, 95% CI 1.125 to 1.244; P < 0.0001) risk. Furthermore, mediation analysis revealed that TSH mediated 5.314% of the relationship between hypothyroidism and OP. In contrast, FT4 mediated 9.670% of the relationship between hyperthyroidism and OP. In European populations, TDFDs may increase OP risk. TSH mediates in the causal association between hypothyroidism and OP, and similarly, FT4 mediates in the causal link between hyperthyroidism and OP. Our findings underscore the significance of improving integrative care for individuals with TDFDs to mitigate the risk of OP. It is essential to maintain stable levels of thyroid hormones and closely monitor bone health to effectively mitigate and prevent OP., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: While metformin is known to regulate thyroid stimulating hormone (TSH) levels, the effects of acarbose on thyroid function remain unreported. Our study was designed to evaluate the impact of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetic patients., Methods: In the MARCH study, 788 patients with type 2 diabetes were randomly assigned to treat with acarbose (300 mg) or metformin (1,500 mg) for 48 weeks. Thyroid function was assessed at baseline, 24 weeks, and 48 weeks, and the thyroid feedback quantile index (TFQI) and parameterized thyroid feedback quantile index (PTFQI) were calculated. Generalized estimating equations adjusted for confounders were used to analyze changes over time., Results: Eighty-four patients with subclinical hypothyroidism (SCH) exhibited a decrease in TSH levels (p = 0.001) with no significant differences between the two treatment groups (p = 0.460). Both TFQI (p = 0.029) and PTFQI (p < 0.001) also decreased over time. Mediation analysis revealed that these change over time were not mediated by BMI (all p < 0.05). Among the 489 euthyroid subjects, no significant changes in TSH levels were observed (p > 0.05). Stratification by baseline TSH levels revealed significant increases in TSH, TFQI, and PTFQI (all p < 0.05) in the normal-low TSH group and significant decreases in PTFQI (all p < 0.05) in the normal-high TSH group after treatment with acarbose and metformin., Conclusions: Acarbose and metformin have similar buffering effects on TSH levels, the TFQI and the PTFQI. In patients with lower TSH levels, acarbose and metformin do not further decrease TSH levels., Clinical Trial Registry Number: ChiCTR-TRC-08000231., Competing Interests: Declarations. Ethical approval: Informed consent was obtained from every patient, and ethical approval was granted by the ethics committees at each clinical site in multiple centres. The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines. Prior presentation: None. Competing interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: Exposure to ionizing radiation is inevitable due to its extensive use in industrial and medical applications. The search for effective and safe natural therapeutic agents as alternatives to chemical drugs is crucial to mitigate their side effects. This study aimed to evaluate the effects of citicoline as a standalone treatment or in combination with the anti-hepatotoxic drug silymarin in protecting against liver injury caused by γ-radiation in rats., Methods and Results: The rats were exposed to γ-radiation (7 Gy) and treated with citicoline (300 mg/kg/day) and/or silymarin (50 mg/kg/day). The results showed that citicoline alleviated liver damage in irradiated rats by reducing hepatic malondialdehyde levels, serum aspartate aminotransferase activity, and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). It also increased acetylcholine (ACh) levels and the gene expression of the anti-inflammatory protein α7 nicotinic acetylcholine receptor (α7nAChR). Additionally, citicoline improved serum triiodothyronine (T3) levels, thyroid hormone receptor beta (TRβ) gene expression, and iodothyronine deiodinase type 1 activity in hepatic tissues of irradiated rats. Furthermore, citicoline enhanced the effects of silymarin on thyroxine (T4), TRβ, ACh, and α7nAChR when co-administered in irradiated rats. Histopathological analysis confirmed these findings, demonstrating improved liver tissue structure., Conclusions: Citicoline mitigates γ-radiation-induced liver damage by reducing oxidative stress, activating the cholinergic anti-inflammatory pathway, and modulating thyroid hormone metabolism. These findings support the use of citicoline as a safe standalone treatment or as an adjuvant with silymarin for managing liver damage and thyroid hormone disturbances caused by γ-irradiation., Competing Interests: Declarations. Ethical approval and consent to participate: All animal procedures were carried out following the NIH (National Research Council) Guide for the Care and Use of Laboratory Animals. The study protocol was approved by the Ethics Committee of the NCCRT, Cairo, Egypt (approval number 73 A/23). Human participants, human data, or human tissues are not applicable Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives : This study aimed to investigate the relationship between excessive postpartum iodine intake and the incidence of thyroid disease in mothers, as well as child growth and development. Methods : Of 1054 participants in the 2019 nationwide survey that assessed maternal postpartum iodine intake, 684 mothers participated in a follow-up study. Data on maternal thyroid disease incidence and child growth and development from infant or toddler health checkups were collected. Iodine and nutrient intake were assessed using three-day dietary records, and serum thyroid hormones (triiodothyronine (T3), thyroid-stimulating hormone (TSH), and free thyroxine (free T4)) were measured. Relative risks (RRs) were estimated using Poisson regression analysis. Results: Among the 684 participants, 23 (3.4%) were diagnosed with thyroid disease by a physician during the follow-up period. The incidence of maternal thyroid disease was not significantly associated with excessive iodine intake, even after adjusting for confounding factors. Additionally, excessive maternal iodine intake was not related to subclinical hypothyroidism in mothers or child growth and development. Conclusions : After a three-year follow-up, no relationship was observed between high postpartum iodine intake and the risk of thyroid disease. Large-scale longitudinal studies are required to evaluate the long-term effects of excessive postpartum iodine intake on maternal health and child growth and development.

Background: Maternal thyroid hormones play a vital role in fetal development, and imbalances can lead to adverse outcomes. Iron deficiency may impair thyroid function due to iron's essential role in iodine oxidation during thyroid hormone synthesis. This review examines the relationship between various indicators of maternal iron status and thyroid function during pregnancy., Methods: We conducted a systematic search in MEDLINE/PubMed, Web of Science, Embase, Scopus, and the Cochrane Library for studies published up to 2023. Meta-analyses determined pooled thyroid hormone levels in patients with and without iron deficiency, using serum ferritin (cut-off = 30 µg/L) and hemoglobin (cut-off = 11 g/dL). Meta-regression analyses examined linear relationships between iron status indicators and thyroid hormones., Results: Forty-seven studies involving 53,152 pregnant women were included. Meta-analysis showed no significant difference in thyroid-stimulating hormone, free T4, or total T4 when considering serum ferritin levels in iron-deficient versus iron-sufficient individuals. However, regarding hemoglobin levels, iron deficiency was associated with higher thyroid-stimulating hormone (2.31 mIU/L vs. 1.75 mIU/L) and lower free T4 (10.7 pmol/L vs. 13.3 pmol/L), but not total T4. Meta-regression revealed no significant associations between serum ferritin and thyroid hormones. Conversely, maternal hemoglobin levels were inversely associated with thyroid-stimulating hormone (P-value = 0.009) and directly associated with free T4 (P-value < 0.001), with no significant link to total T4., Conclusions: Maternal hemoglobin levels are more strongly correlated with thyroid function than serum ferritin levels. This suggests that monitoring hemoglobin could enhance the early detection and management of thyroid dysfunction during pregnancy., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD4202451820., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Parsaei, Dashtkoohi, Amirkhalili, Chashmyazdan, Korevaar and Nazeri.)

Objective: There is limited epidemiological data regarding the association of blood lipids with thyroid hormones. Thus, the present article aims to explore whether there is an association between non-high-density to high-density lipoprotein cholesterol ratio (NHHR) and thyroid hormones., Methods: We analyzed samples from 3,881 adults aged 20 years and above who took part in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. The study tested for thyroid hormones, including total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), as well as thyroid-stimulating hormone (TSH). Survey-weighted linear regression and restricted cubic spline (RCS) models were employed to investigate the relationship between NHHR and thyroid hormones. Subsequently, subgroup analyses were conducted. In Mendelian randomization (MR), the inverse variance weighting method (IVW) is used as the primary analytical approach., Results: This study finally comprised 3,881 adults aged 20 years and older. After extensive adjustments for covariables, the regression analysis revealed significant negative associations between NHHR and FT4 (β: -0.11, 95% confidence interval [CI]: -0.18, -0.04), FT4/FT3 (β: -0.06, 95% CI: -0.08, -0.04), and TT4/TT3 (β: -0.001, 95% CI: -0.001, 0.000). Both observational and Mendelian randomization studies suggest that high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol may not significantly influence the risk of hyperthyroidism or hypothyroidism., Conclusions: The study indicates negative associations between NHHR and FT4, as well as the ratios of FT4/FT3 and TT4/TT3. This suggests that NHHR may reflect changes in thyroid function, highlighting its potential clinical significance in assessing thyroid function and metabolic health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Tan, Zhang, Wu, Zhu and Gao.)

Background: Exposure to several metal elements has been found to be associated with thyroid hormone homeostasis. However, evidence for combined exposure is inconclusive, especially for children., Objective: To examine the individual and joint effects of blood metal elements on thyroid hormones in children., Methods: A total of 12,470 children aged 0-14 were collected from January 2018 to December 2021 in Hunan Children's Hospital. The concentrations of lead (Pb), iron (Fe), calcium (Ca), copper (Cu), zinc (Zn) and magnesium (Mg) in blood were detected via atomic absorption spectrometry (AAS). The levels of thyroid stimulating hormone (TSH), triiodothyronine (TT3, FT3) and total and free thyroxine (TT4, FT4) were measured by electrochemiluminescence immunoassay (ECLIA). Generalized linear regression (GLR) model and Quantile-based g-computation (QGC) were employed to estimate the association between metal exposure and thyroid hormone homeostasis., Results: GLR model showed that a unit increase in ln-transformed Fe was associated with increases in TT3 (β = 0.163; P FDR < 0.001), TT4 (β = 12.255; P FDR < 0.001) and FT3 (β = 0.615; P FDR < 0.001), as well as decreases in TSH (β = -0.471; P FDR = 0.005) and FT4 (β = -1.938; P FDR < 0.001). The result of QGC analysis indicated a positive relationship of the ln-transformed concentration of metal mixture with the levels of TT3 (β = 0.018; P = 0.012), TT4 (β = 2.251; P < 0.001) and FT3 (β = 0.074; P < 0.001) in children. Fe was the predominant contributor among the metal mixture with positive contributions to TT3 (weight = 0.439), TT4 (weight = 0.502) and FT3 (weight = 0.450)., Conclusions: The combined metal exposure was associated with increased levels of TT3, TT4, and FT3 in children and Fe appeared to be the major contributor. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Cao, Xiang, Du, Chen, Xue, Li, Qiu and Duan.)

Objectives: Numerous studies show that the adipokines play a role in on the thyroid axis. The aim of this study was the evaluation of serum level of CTRP-3 and CTRP-6 as a member of the adipokines family in patients with Hashimoto's., Methods: The levels of CTRP-3 and CTRP-6 were evaluated with enzyme-linked immunosorbent assay in 70 subjects (35 newly diagnosed Hashimoto's thyroiditis and 35 healthy subjects). Their relationship with the thyroid hormone and some biochemical factors was analyzed., Results: The levels of CTRP3 and CTRP6 in patients with Hashimoto's disease were higher than those in the control group (p<0.05). There was a significant positive correlation between CTRP3 and TSH levels (r=0.286 and p=0.017). There was a significant relationship between CTRP3 and Fasting Blood Sugar (r=0.249 and p=0.038). There was a significant inverse negative correlation between CTRP6 levels and T3 (r=-0.269 and p=0.024), and T4 (r=-0.272 and p=0.023). Moreover, there was a significant positive correlation between CTRP6 serum levels and TSH serum levels (r=0.397 and p=0.001). There was a significant positive correlation between CTRP6 levels and Cholesterol (r=0.351 and p=0.003), and LDL (r=-0.244 and p=0.042)., Conclusions: Finally, our results demonstrated that serum levels of CTRP3 and CTRP6 are higher in patients with Hashimoto's compared to the control group and probably play a role in the pathogenesis of Hashimoto's thyroiditis., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Context: Serum thyrotropin and thyroid hormone (TH) levels are routine markers of thyroid function. However, their diagnostic performance is limited under special conditions, such as in amiodarone-induced hyperthyroidism (AIH). Such cases would require the assessment of tissue TH action, which is currently unfeasible., Objective: Development of an approach that determines how well serum parameters are reflected in tissue TH action of patients., Methods: TH-responsive marker genes were identified from human hair follicles (HFs) with next-generation sequencing, validated by quantitative polymerase chain reaction. A classification model was built with these markers to assess tissue TH action and was deployed on amiodarone-treated patients. The impact of amiodarone on tissue TH action was also studied in thyroid hormone action indicator (THAI) mice., Results: The classification model was validated and shown to predict tissue TH status of subjects with good performance. Serum- and HF-based TH statuses were concordant in hypothyroid and euthyroid amiodarone-treated patients. In contrast, amiodarone decreased the coincidence of serum-based and HF-based TH statuses in patients with hyperthyroidism, indicating that AIH is not unequivocally associated with tissue hyperthyroidism. This was confirmed in the THAI model, where amiodarone prevented tissue hyperthyroidism in THAI mice despite high serum free thyroxine., Conclusion: We developed a minimally invasive approach using HF markers to assess tissue TH economy that could complement routine diagnostics in controversial cases. We observed that a substantial proportion of patients with AIH do not develop tissue hyperthyroidism, indicating that amiodarone protects tissues from thyrotoxicosis. Assessing tissue TH action in patients with AIH may be warranted for treatment decisions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Neonicotinoids exposure was found to induce thyroid dysfunction. However, there lack of direct evidence between neonicotinoids exposure and thyroid hormone (TH) disruption in population study, especially in children, which limits the understanding on their health hazard. To fill this knowledge gap, we conducted a cross-sectional study on children of a rural area in South China (n = 88), and analyzed urinary ten neonicotinoids (including metabolites), serum TH, thyroxine-binding globulin (TBG), and thyroid stimulating hormone (TSH) levels. Based on linear regression, generalized additive model, and Bayesian kernel machine regression, neonicotinoids levels were found to be correlated with TH, TBG, and TSH levels, with stronger effects for metabolites than parent compounds in most cases. Mixture exposure of neonicotinoids had significantly positive effect on free triiodothyronine (T 3 ) . N-desmethyl-acetamiprid (N-dm-ACE) was negatively associated with T 3 for female, which corresponded to much lower T 3 levels for female than for male. Also, N-dm-ACE was found to non-monotonic associated with free thyroxine for male. Some neonicotinoids had interactive effects with lead and cadmium on TH disruption. The results provide an evidence on TH disruption of neonicotinoids in children, and highlight the need to explore TH disruption of neonicotinoids and safeguard the health of children., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to metals has been related to alterations in leukocyte telomere length (LTL), an aging marker. However, the evidence regarding this relationship in children and adolescents, as well as the underlying mechanisms, remains unclear. Therefore, we aimed to explore the individual and mixture effects of metals on LTL in children and adolescents and to assess the mediating role of thyroid hormones and the modifying effect of a healthy lifestyle. In a cross-sectional study performed in Liuzhou, China, we assessed 5 serum thyroid hormones, 18 urinary metals, and LTL among 1050 children and adolescents aged 6-18 years. We employed multivariate linear regression and weighted quantile sum (WQS) regression to assess the associations of urinary metals with LTL in children and adolescents. Mediation analyses were conducted to explore the effects of thyroid hormones on these relationships. Urinary cobalt (Co), nickel (Ni), strontium (Sr), mercury (Hg), cadmium (Cd), and thallium (Tl) were related to a shorter LTL in children and adolescents. The WQS regression showed a 6.31% (95% CI: -8.76%, -3.79%) decrease in LTL per quartile increase in the WQS index, and identified Ni (23.3%), Sr (21.7%), and Tl (18.0%) as the major contributors. Mediation analyses showed that triiodothyronine (T3) mediated 14.8% and 8.1% of the associations of urinary Sr and Hg with LTL, respectively, and suppressed 9.3% of the association with urinary Co. Furthermore, the inverse associations of Sr, Cd, and Tl with LTL were attenuated among participants who adopted a healthy lifestyle. Our findings suggested that exposure to Co, Ni, Sr, Cd, Hg, Tl, and their mixture were related to a shorter LTL in children and adolescents, potentially mediated by thyroid hormones. Additionally, adopting a healthy lifestyle may alleviate these adverse effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Free thyroid hormone (FTH) serves as the preferred indicator for the clinical assessment of thyroid function, mainly encompassing free thyroxine and free triiodothyronine. The immunoassay commonly employed in the clinical setting exhibits certain unresolvable deficiencies. The results of over 5,500 clinical laboratories for FTH from China in 2024 demonstrated that the outcomes of immunoassay were not comparable, with robust CVs calculated in accordance with ISO 13528 ranging from 13.82% to 21.42%. Establishing reference methods is an important tool to achieve accurate and comparable results of free hormones. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) holds a distinct advantage in the precise detection of small molecules, and two reference methods for free thyroxine based on LC-MS/MS are included in the JCTLM list. This article conducts a comprehensive review of the detection methods and standardization of FTH. It presents the metabolism of thyroid hormones, the significance of detection, the techniques, and application examples of free thyroid hormone assays, and deliberates on the current status, prospects, and recommendations for the standardization of FTH assays. Immunoassay and LC-MS/MS, as significant techniques for FTH detection, are predominantly emphasized in the case references. Ultrafiltration and equilibrium dialysis, which are utilized to separate FTH, are also addressed. This article aims to discuss the status quo of FTH detection and clarify the advantages of LC-MS/MS in FTH detection, propose that LC-MS/MS can be utilized as an auxiliary validation method or alternative method in clinical applications, and offer suggestions for the standardization of testing results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The existing studies on the association between multi-metal mixture exposure and cognitive function in the older adults are limited and controversial, with no studies considering the mediating effect of thyroid hormones on the connection between them. This study of 441 urban older adults assessed 21 urinary metal levels and cognitive function using the Mini-Mental State Examination (MMSE). Urinary metal levels were measured via inductively coupled plasma mass spectrometry (ICP-MS), and thyroid hormones levels were obtained from medical records. Mediation analysis evaluated the role of thyroid hormones in the link between metals exposure and cognitive function. The General Linear Model (GLM) showed negative correlations between MMSE scores and titanium (Ti), copper (Cu), rubidium (Rb), and molybdenum (Mo), and positive correlations with selenium (Se) and barium (Ba). Nonlinear inverse U-shaped associations between Mo, Rb, and MMSE scores were identified using Restricted Cubic Splines (RCS) and Bayesian Kernel Machine Regression (BKMR). Mediation analysis revealed that Free Thyroxine (FT4) mediated the relationship between Rb and MMSE scores by 29.10 % and between Zinc (Zn) and language performance by 35.00 %. Total thyroxine (TT4) mediated the link between Cu and orientation score by 24.69 %, and Thyroid Stimulating Hormone (TSH) mediated the association between Cu and attention score by 38.96 %. Ti, Se, Rb, Mo, Ba and Cu were significantly associated with cognitive impairment risk. Mixed exposure to Mo and Rb was linked to an increased risk of cognitive impairment. Additionally, levels of TSH, FT4 and TT4 were associated with cognitive function, mediating the effects of Rb, Zn and Cu on cognitive function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

We and other investigators reported that mild TSH suppression with levothyroxine (LT 4 ) was needed to achieve normal free triiodothyronine (FT 3 ) levels and metabolic euthyroid state in athyreotic patients. Consequently, management methods based on thyroid tissue volume have been implemented for patients receiving LT 4 at the Kuma Hospital. This retrospective study examined the composition of the thyroid hormone measurement items (serum-free thyroxine [FT 4 ], FT 3 , and FT 4 + FT 3 ) in patients receiving LT 4 monotherapy. According to the etiology of hypothyroidism, 36% of the 25,523 patients included in this study underwent total thyroidectomy (TT). Thirteen percent and 14% had undergone 131 I treatment for hyperthyroidism (RIT) and partial thyroidectomy (PT), respectively. Moreover, 37% of patients had received non-invasive treatment (NIT). The proportion of patients who underwent only FT 3 measurements was higher (TT, 93%; RIT, 61%) in the first two groups, whereas the proportion of patients who underwent only FT 4 measurements was higher (PT, 50%; NIT, 65%) in the remaining two groups. Only FT 3 measurements were performed in 58% of patients. Only FT 4 measurements were performed in 34% of patients. The serum TSH levels were suppressed in nearly half of the patients (46%). Thus, FT 3 was the major thyroid hormone measured in patients receiving LT 4 treatment, and the serum TSH levels were suppressed in nearly half of the patients. This may be attributed to the management guidelines at our hospital, a specialized facility for thyroid disease, wherein half of the patients present are athyreotic or have atrophic thyroid glands after TT or RIT.

Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The global impact of the novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was significant, including in Spain. The initial outbreak in late January 2020 prompted a frantic effort to comprehend the virus and contain its spread, given the limited knowledge available at the time. The study by Amich et al. (2022) in Frontiers in Endocrinology aimed to investigate the influence of thyroid hormone levels and age on the severity of COVID-19 in euthyroid and levothyroxine-treated patients. Although a direct correlation between thyroid hormone levels and the severity of COVID-19 has not been established, it is known that thyroid dysfunction affects immune function and general health, which may impact the outcomes of COVID-19. The research included patients from the Clinic San Carlos Hospital in Madrid, and a comprehensive range of data was collected from each patient, including demographic information, symptoms, comorbidities, and laboratory test results. This approach was employed in order to accurately match patients and identify factors that may influence the severity of COVID-19 outcomes. Blood samples were analyzed using chemiluminescence on a DXI-800® instrument, with the following hormones quantified: thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). These insights contribute to an understanding of the interplay between thyroid function and the severity of COVID-19, highlighting the need for careful patient management in those with thyroid disorders during the pandemic., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Inflammation and a metabolic shift from oxidative metabolism to glycolysis are common in the ischemic heart, the latter partly controlled by pyruvate kinase (muscle, PKM). We previously identified alternative splicing promoting the PKM2 isoform after myocardial infarction (MI). We examined the role of PKM2 physiological upregulation after MI, modeled by ligation of the left anterior descending coronary artery, using global PKM2 knockout (PKM2 -/- ) mice. Echocardiography showed similar cardiac function between PKM2 -/- and control mice after MI. However, PKM2 -/- infarcted hearts had increased abundances of transcripts associated with oxidative stress and immune responses. Immunohistochemistry revealed greater abundance of macrophages in PKM2 -/- hearts prior to MI, with a small increase in CD86 + macrophages in PKM2 -/- infarcted hearts. Elevated baseline plasma IL-6, IL-1β, and C-reactive protein, and cardiac IL-6, 3 days post-MI, were observed in PKM2 -/- mice. Oxidative lipid products were also elevated in baseline PKM2 -/- hearts, while antioxidant glutathione peroxidase 4 was reduced. Greater fibrosis was seen in PKM2 -/- hearts 28 days after MI. These findings suggest Pkm2 ablation primes the heart for increased oxidative stress, inflammation, and fibrosis post-MI. The natural upregulation of PKM2 may mitigate fibrosis by reducing oxidative stress and inflammation, highlighting its protective role in the infarcted heart., (© 2025 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: Thyroid disorders are common. Serum thyroid stimulating hormone is frequently measured and is the single best initial biomarker to diagnose thyroid disease. Automated immunoassays used to evaluate thyroid function are susceptible to interferences that can affect test results and therefore clinical decisions. In this comprehensive review, our aim is to discuss common assay and drug interferences leading to abnormal thyroid function tests., Methods: Authors conducted a literature review of PubMed to include studies on drug related and laboratory assay interferences leading to primary and secondary thyroid dysfunction in addition to interferences with thyroid hormone replacement and thyroid function tests., Results: Overall, there are several assay interferences as well as drug interferences leading to primary thyroid dysfunction including iodine-containing drugs such as amiodarone, lithium, immune checkpoint inhibitors and tyrosine kinase inhibitors, drug interferences leading to secondary thyroid dysfunction such as glucocorticoids, and drug interferences affecting thyroid hormone absorption, metabolism, and thyroid binding globulin levels. In addition, assay interferences from biotin, heterophile antibodies, macro-thyrotropin or anti-streptavidin antibodies may occur without underlying thyroid dysfunction, leading to abnormal thyroid function tests., Conclusion: For appropriate patient management, it is imperative to identify assay interferences when discrepancies between clinical presentation and thyroid function test results are noted., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

The thyroid hormone (TH) status is routinely assessed by thyrotropin (TSH) and thyroxine (T4). Both biomarkers are mainly regulated by TH receptor beta, whereas many peripheral organs employ the alpha receptor. Serum cluster of differentiation 5-like molecule (CD5L) is a liver-derived protein under control of both TH receptor isoforms. However, clinical data on its relation to TH status are sparse. An additional biomarker of TH status is needed in particular during pregnancy, where the routine biomarkers become dynamically disturbed. This study aimed to determine possible covariates regulating serum CD5L and to test its potential suitability as additional TH biomarker during pregnancy. A sandwich ELISA for serum CD5L was established using newly raised antibodies. Circadian effects and the impact of liver disease on serum CD5L concentrations were assessed. Serum samples from pregnant women with well-characterized TH and trace element status were analyzed, and CD5L concentrations were correlated with other indicators of TH status including TSH, fT4, fT3, copper, and selenium concentrations. The new quantitative assay for CD5L showed high accuracy. Serum CD5L was stable in dilution and refreezing experiments and did not show strong circadian variance or dependency on liver disease. In serum of pregnant women, CD5L correlated positively to fT3, but not to fT4 or TSH. Significant positive correlations of CD5L were observed with serum levels of the TH-responsive trace elements selenium and copper. The data support the potential suitability of serum CD5L as an additional marker of TH status, with potential value for pregnancy and thyroid disease., (© 2024 The Author(s). BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Objective: Approximately 200 million people have been diagnosed with thyroid disease worldwide. Associations between thyroid disorders and nutritional factors have been established in former studies., Methods: The Web of Science, PubMed, and Scopus databases and Google Scholar were searched without date restriction until June 2023 by using relevant keywords. All original articles written in English that studied the effects of vitamin D supplementation on TSH and thyroid hormones were eligible for the present review., Results: The present review included a total of 16 randomized controlled trials (RCTs) with 1127 participants (intervention group, 630; control group, 497). Based on the findings made, vitamin D supplementation had no significant effects on serum TSH levels in 9 cases (56.2%) reported in the trials. However, TSH levels were elevated in 4 studies (26.6%) and low in 3 (18.7%) cases after vitamin D administration. Four cases reported in 6 RCTs and 4 cases reported in 5 trials indicated no significant effects on thyroxine (T 4 ) and triiodothyronine (T 3 ) levels after vitamin D supplementation, respectively. Moreover, 8 cases of 11 included RCTs reported that vitamin D intake had no significant effects on fT4, and 5 cases of 7 RCTs demonstrated no significant effects on fT3 levels after vitamin D supplementation., Conclusion: Most findings suggest that vitamin D supplementation had no significant effects on thyroid hormones and more than half indicated no significant effect on TSH levels. Nevertheless, high-quality research is further required to prove these achievements and evaluate vitamin D effects on other markers of thyroid function., (Copyright © 2024 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists., Methods: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions"., Results: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91)., Conclusions: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines., Competing Interests: Declarations. Conflict of interest: LH, PP, EP, EVN and JCG received consultancy fees from Institut Biochimique SA. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed concent: For this type of study, formal consent is not required., (© 2024. The Author(s).)

The correlation between thyroid hormone (TH) sensitivity and microvascular complications of type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to explore the association between TH sensitivity and the risk of diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic neuropathy (DNP) in euthyroid T2DM patients. This study included a total of 946 hospitalized T2DM patients and calculated their sensitivity to the TH index, and each patient completed screenings for DKD, DR, and DNP. Multivariate logistic regression, generalized additive modeling, and subgroup analysis were used to assess the association between TH index sensitivity and the risks of DKD, DR, and DNP. After adjusting for confounding factors, a significant linear correlation was observed between the sensitivity of the thyroid feedback quartile index 3 (TFQI3) and DKD risk. However, the sensitivities of thyroid-stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI) and partial thyroid feedback quartile index (PTFQI) exhibited nonlinear correlations with the risk of developing DKD. The effect sizes to the left of the inflection point for TSHI, TT4RI and PTFQI were (odd ratio [OR] = 0.53, 95% confidence interval [CI]: 0.288-0.977), (OR = 0.863, 95%Cl: 0.751-0.992) and (OR = 0.007, 95%Cl: 0-0.724), respectively. However, there was no significant correlation between TH index sensitivity and DR/DNP risk. This study provides valuable insights into the relationship between TH sensitivity and the risks of DKD, DR, and DNP, with substantial clinical implications for individual prediction among T2DM patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent for publication: Not applicable. Ethical approval and consent to participate: Our study protocol was approved by the research committee of the First Affiliated Hospital of Nanchang University (no. 2022–3–031). The ethics committee granted approval for the utilization of anonymized historical data in the study and waived the requirement for informed consent from patients. ., (© 2024. The Author(s).)

Aim: Hypothyroidism is created by disruption of thyroid hormone production, which can destroy the emotional, relational, social, and working life of patients if left untreated. Hypothyroidism has multiple etiologies. We evaluated the relationship of hematological parameters and inflammatory biomarkers with thyroid hormones to find the potential use of these items in patients screening and prognosis., Methods: This is a cross-sectional study, which was done on 88 individuals of both genders (32 male and 56 female), over 18 years old with a mean age of 45 years old. These patients were referred by physicians after examination to our laboratories of Qaem Medical Laboratory of Kuhchenar and Jahrom University of Medical Sciences, Fars, Iran. The patients had recent symptoms and signs of hypothyroidism with increased TSH above the normal range, and negative serum anti-TPO antibody. To determine ABO, Rh, and Lewis (Le) blood groups was used anti-A, anti-B, anti-D, anti-Lea, and anti-Leb monoclonal antibodies. Serum T3, T4, and TSH was measured by direct chemiluminescent immunoassay. Anti-TPO antibody was measured by ELISA. CRP was determined using an immunoturbidimetric assay. CBC count assessment was done via an automated cell counter. Exclusion criteria were patients with acute or chronic inflammatory diseases. Herein, we evaluated the correlation of hematological parameters consisting ABO, Rh, and Le blood groups, RBC and WBC parameters, and platelet count as well as inflammatory biomarkers including ESR, CRP, IL-8, and NLR with T3, T4, and TSH in hypothyroid patients., Results: Our study showed a significant correlation between Lea blood group (non-secretor) in comparison with Leb blood group (secretor) with TSH (P = 0.01). There was no correlation between Leb and Lea blood groups with T3 and T4. We did not observe the correlation between Rh and ABO blood groups with T3, T4, and TSH. We observed significant correlations between Hb, Hct, and MCH with T3 (PHb = 0.012, PHct = 0.021, and PMCH = 0.032) and also, with T4 in hypothyroidism (PHb = 0.023 and PHct = 0.026). We revealed significant correlations between Hb, Hct, and MCH with TSH in hypothyroidism (PHb = 0.017, PHct = 0.019, and PMCH = 0.007). The significant correlations between CRP and IL-8 with T3, T4, and TSH was not explored. The significant correlations between ESR with T3 and TSH was not detected. ESR showed a significant correlation with T4 (PESR = 0.020). There were also no significant correlations between the counts of neutrophils, lymphocytes, monocytes, and eosinophils, as well as NLR with T4. There was only significant correlation between monocyte count with T3 (PMono = 0.029) and also lymphocyte count with TSH (PLymph = 0.041)., Conclusion: In this investigation, we observed a significant relationship between Lea blood group in comparison with Leb blood group with TSH. We demonstrated significant correlations between Hb and Hct with T3, T4, and TSH, and also correlations between MCH with T3 and TSH. In conclusion, the assessment of Hb, Hct, MCH, and Le blood groups as hematological parameters can help physicians in the management of hypothyroidism., Competing Interests: Declarations. Ethics approval and consent to participate: The Research Ethics Committee at the Jahrom University of Medical Sciences gave ethical permission to this research. All authors confirm that all methods were performed according to the relevant guidelines and regulations. Experiments were performed based on the guidelines of the Medical Ethics Committee of the Jahrom University of Medical Sciences (IR.JUMS.REC.1400.093). Consent for publication: Not applicable. Competing interest: The authors declare no competing interests., (© 2024. The Author(s).)

Thyroid function is closely linked to circadian rhythms, but the relationship between the frequency of night eating and thyroid function remains unclear. Our study aimed to investigate the association between night eating frequency and its impact on thyroid function and sensitivity. This study included 6093 participants from the U.S. National Health and Nutrition Examination Survey (2007-2012). Night eating behavior was assessed through 24-hour dietary recall, with night eating frequency calculated on the basis of food intake between 10:00 PM and 4:00 AM. The thyroid hormone indices examined included T3, T4, FT3, FT4, TSH, TGA, Tg, and TPOAb, whereas thyroid hormone sensitivity was assessed via indices such as the FT3/FT4, TSHI, TT4RI, and TFQI. The associations between night eating frequency and thyroid function were analyzed via weighted univariate and multivariate linear regression analyses. Subgroup analyses and interaction test analyses were also employed to test this correlation. Compared with individuals who did not eat at night, those who ate more frequently at night had higher levels of Tg (OR 1.223 [95% CI 1.048, 1.429], p trend=0.015) but lower levels of T3 (OR 0.728 [95% CI 0.611, 0.868], p trend=0.235) and TPOAb (OR 0.728 [95% CI 0.611, 0.868], p trend=0.235). Subgroup analysis indicated that this association between Tg and night eating was stronger in the DM group (Tg: OR 1.49 [95% CI 1.15, 1.93]), p interaction=0.022) and that the association between TPOAb and night eating was stronger in the group without DM (TPOAb: OR 0.9 [95% CI 0.82, 0.97]), p interaction=0.003). Our findings suggest a significant association between night eating frequency and thyroid function. However, no statistically significant differences were found in thyroid sensitivity based on night eating frequency. Despite these findings, the hormone fluctuations observed were within normal clinical ranges. Further rigorously designed studies are needed to establish a causal relationship between night eating frequency and thyroid function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhou, Liu, Wang, Zhou, Wang, Wang and Wang.)

Bioaccumulation of trace element contaminants with endocrine disruptive (ED) potential has been noted in European brown bears, though evidence of their effects is lacking. Generalized linear models were employed to assess circulating levels of reproductive, stress, and thyroid hormones in relation to arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb) and thallium (Tl) in 53 free-ranging brown bears (Ursus arctos) from two European populations (Carpathian and Dinara-Pindos). Other potential drivers of hormone variation, such as essential elements, ecological factors, physiological variables, and capture methods, were included as predictors. The models demonstrated a positive association between cortisol and Cd, and a negative association with Tl. In addition, Tl and Pb were identified as key factors in explaining variation in thyroid hormones (free triiodothyronine, fT3 and free thyroxine, fT4). Trap type was significant in explaining variation in fT3 concentrations, while sex was an important predictor of progesterone levels. The essential elements, cobalt (Co) and copper (Cu) accounted for 41 % of testosterone variation, while Cu and selenium (Se) were negatively associated with fT4. Other notable predictors of investigated hormone variation included body condition index (important for cortisol), age (for fT4), year (for fT3), capture day (for fT4 and fT4:fT3 ratio) and population (fT4:fT3 ratio). This study evidenced trace elements as important factors to consider when studying hormonal variation in terrestrial wildlife (Tl for cortisol and fT3, Cd for cortisol, Cu for testosterone and fT4, Co for testosterone, Pb and Se for fT4). To gain a more definitive understanding of the effects of exposure to element contaminants on endocrine status, it is recommended to include more sensitive and specific endocrine disruption-related endpoints in a larger sample size. Doing so will further enhance our understanding of the potential adverse endocrine effects of environmental pollutants on these bear populations and other large mammalian wildlife species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Thyroid hormone is a known pivotal factor that affects bone metabolism; however, whether bone microarchitecture is associated with thyroid hormone sensitivity is poorly understood. The trabecular bone score (TBS) serves as an essential indicator for assessing bone microarchitecture. This study aimed to investigate the relationship between sensitivity to thyroid hormones and TBS in euthyroid individuals., Methods: This cross-sectional study involved 3320 euthyroid participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2008. Data, including thyroid function, TBS and other related parameters, were extracted and analyzed. The indices of thyroid hormone sensitivity, including the thyrotropin thyroxine resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), thyroid feedback quantile-based index (TFQI) and parametric thyroid feedback quantile-based index (PTFQI), were calculated. Greater values of these indicators indicated a greater degree of impaired thyroid hormone sensitivity., Results: Impaired sensitivity to thyroid hormones was associated with degraded bone microarchitecture following adjustments for confounding variables (TT4RI: P = 0.005, TSHI: P = 0.008, TFQI: P = 0.003 and PTFQI: P = 0.006). The restricted cubic spline model demonstrated a positive relationship between TT4RI, TSHI, TFQI, PTFQI and degraded bone microarchitecture. Similar findings were observed in the analysis of subgroups stratified by age, sex, race, diabetes status, hypertension status and hyperuricemia status., Conclusions: In euthyroid individuals, impaired sensitivity to thyroid hormones is associated with degraded bone microarchitecture. However, further studies are required to confirm this relationship., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki. The data originated from the NHANES, and informed consent was obtained from all of the participants by the NCHS Ethics Review Board. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aims: Acquired resistance to thyroid hormone appears to exist in the general population. We aimed to evaluate the association between indices of thyroid hormone sensitivity and non-alcoholic fatty liver disease (NAFLD), and made stratified analyses by diabetic status., Methods: We included 26,413 participants from a health screening program and 8,246 hospitalized patients with type 2 diabetes. Thyroid Feedback Quantile-based Index (TFQI), thyroid stimulating hormone index (TSHI) and thyrotroph thyroxine resistance index (TT4RI) were calculated. Advanced fibrosis risk was determined using the FIB-4 score. Multivariate logistic regression analysis was performed., Results: TFQI was associated with an increased risk of NAFLD in patients with diabetes (fourth quartile vs. first quartile: odds ratio [OR]=1.39 and 1.82 in hospitalized and non-hospitalized patients, respectively, both P<0.001) but not non-diabetic participants (OR=0.94, P=0.40). Further adjustment for the homeostasis model assessment of insulin resistance generated similar findings in diabetes (OR=1.27, P=0.025). The TFQI-associated NAFLD risk increase in diabetic patients was confined to NAFLD with low probability of advanced fibrosis (OR 1.42, P=0.001), but not those with intermediate-to-high probability (OR=0.86, P=0.23). Also, TFQI was associated with a significantly lower risk for advanced fibrosis in the diabetic at-risk patients (OR=0.62, P=0.005) but not those non-diabetic at-risk participants, independent of the presence of NAFLD. The association was less significant for TT4RI and TSHI., Conclusions: Impaired sensitivity to thyroid hormone was associated with an increased risk of developing NAFLD but a reduced risk of advanced fibrosis limited to diabetic individuals. Our findings suggest stratified studies of NAFLD based on diabetic status are needed in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Liu, Wang, Han, Yan, Xiang, Shen and Feng.)

Chemical monitoring studies in North Carolina, USA and Shandong, China have reported detections of perfluoroalkylether carboxylic acids of increasing chain length with ether bonds between each fluorinated carbon. Despite detection there is limited hazard data available to inform risk assessment. Here, we exposed pregnant Sprague-Dawley rats to two of these compounds, perfluoro-3,5,7,9-butaoxadecanoic acid (PFO4DA) and perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA), from gestation days 18-22 across a series of doses (0.3-62.5 mg/kg/d) via oral gavage. PFO5DoA was acutely toxic to rat dams and fetuses at the top two doses (30 and 62.5 mg/kg), while PFO4DA did not cause acute toxicity at any doses tested. PFO5DoA significantly increased maternal liver weight (≥3 mg/kg; 28% increase at 10 mg/kg) while PFO4DA did not affect maternal liver weight up to 62.5 mg/kg. PFO4DA and PFO5DoA both significantly reduced serum total thyroxine in maternal (≥10 mg/kg for both) and fetal (≥1 mg/kg) rats. Both compounds significantly reduced fetal liver glycogen concentrations, increased fetal serum total bile acids, and altered expression levels of multiple genes associated with glucose metabolism in the fetal liver. Serum concentrations of PFO5DoA were higher than PFO4DA in both rat dams and fetuses at equivalent maternal oral doses indicating greater accumulation. Dose response modelling of several fetal endpoints as a function of serum molar concentration indicates PFO5DoA was ∼3-4-fold more potent than PFO4DA. PFO5DoA and PFO4DA produced maternal and fetal toxicity from short-term oral maternal exposure indicating need for additional toxicity data to evaluate potential human health risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Type 2 diabetes mellitus (T2DM) poses a significant public health challenge, contributing to considerable morbidity and mortality worldwide, which necessitates urgent preventive measures. Thyroid disorders, prevalent in many individuals, are intricately linked to metabolic health, yet studies on their relationship with T2DM yield inconsistent results-some suggesting an increased risk with abnormal thyroid hormone levels, while others indicate potential protective effects. This study investigated the association between changes in serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels and the incidence of type 2 diabetes mellitus., Methods: Data from 1938 individuals aged ≥20 in the Tehran Thyroid Study cohort were used, spanning four examination cycles from 1999 to 2012, with three-year intervals. TSH and FT4 levels were log-transformed and modeled as time-varying exposures to study their association with incident T2DM., Results: During a median follow-up of 9.43 years, 135 new T2DM cases were identified. The multivariable-adjusted joint model (JM) revealed that each unit increase in log-transformed TSH level was associated with a 25% decrease in T2DM incidence [HRs (95% CI): 0.75 (0.64-0.90)]. Conversely, each unit increase in FT4 level showed a marginally significant higher risk [1.06 (0.99-1.13); p-value=0.06]., Conclusion: The findings of this study suggest that dynamic changes in serum thyroid hormones are associated with the development of T2DM. Rising TSH and decreasing FT4 over time are associated with a lower risk of diabetes. These findings suggest a complex interplay between thyroid function and the risk of T2DM, emphasizing the importance of monitoring thyroid hormone levels as a part of T2DM prevention strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amirabadizadeh, Mehran, Amouzegar, Asgari, Khalili and Azizi.)

Introduction: The involvement of thyroid hormone in cardiovascular disease remains debated. The aim of our research was to ascertain whether thyroid hormone sensitivity indices are related to carotid plaque (CAP) risk in the general population., Methods: We recruited 5,360 participants for health examinations to explore the correlation between thyroid hormone sensitivity indices and CAP risk. We then compared baseline characteristics of participants with CAP to those without CAP based on multivariate logistic regression analysis. Additionally, we conducted subgroup analyses stratified by gender and age to further elucidate this relationship., Results: Among the 5,360 participants, 1,055 (19.7%) were diagnosed with CAP. After adjusting for various confounding factors, our results showed a positive association between CAP risk and the indices (TFQI, PTFQI, TSHI, and TT4RI). Conversely, the FT3/FT4 ratio showed a negative correlation with CAP risk. Sex-based subgroup analysis revealed a stronger correlation between thyroid hormone sensitivity and CAP in females compared to males. In the age subgroup, the significant association was observed in older individuals (age >60) compared to middle-aged participants (age ≤60)., Conclusion: Our study suggests a significant correlation between thyroid hormone sensitivity and CAP, particularly in females and participants over the age of 60., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We acknowledge the assistance of ChatGPT version 3.5 in improving the English expression and correcting grammatical errors in our manuscript., (Copyright © 2024 Gong, Wang, Ding, Yu, Xu, Xu and Ling.)

Objective. Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impaired social interaction and communication, restrictive and repetitive patterns of behavior, interests and activities. The aim of this study was to determine the postnatal levels of thyroid hor-mones and investigate their association with the severity of ASD symptoms. Methods. The study included 56 children (46 boys and 10 girls) with ASD aged 24-42 months. For ASD diagnostics the Autism Diagnostic Observation Schedule - second version (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) - interview with the child's parents or guard-ians were used. Venous blood was drawn right after the diagnostic procedures to analyze serum thyroid-stimulating hormone (s-TSH), free triiodothyronine (s-fT3), and free thyroxine (s-fT4) levels. Linear regression analysis was conducted to assess the relationship between the concentra-tions of thyroid hormones and ASD symptoms severity. Results. Serum concentrations of measured hormones were within normal reference ranges in almost all children. Decline of s-TSH was significantly associated with an increase in the severity of impaired social interaction and impaired communication as rated by parents (ADI-R) and with a higher prevalence of stereotyped behavior as observed in the diagnostic examination (ADOS-2). A decrease in s-fT3 was associated with higher frequency of stereotyped behavior as assessed by parents (ADI-R). Neither sex nor age were significant predictors. Conclusion. Although thyroid hormone levels were normal, we demonstrated an association of thyroid hormones with ASD symptoms., (© 2024 Maria Kopcikova et al., published by Sciendo.)

Background: Thyroid hormones (THs) are essential for brain development. Numerous studies have identified significant links between thyroid dysfunction and cognitive function. However, research on the significance and necessity of thyroid function tests in diagnosis of neurological disorders is limited and subject to controversy., Methods: Our study employed a combination of meta-analysis and case-control design. For the meta-analysis, we conducted a systematic search of online databases for studies that compared thyroid function tests in children with neurological disorders to controls. In our case-control study, we recruited a total of 11836 children, comprising 7035 cases and 4801 healthy controls. Wilcoxon Rank Sum Test was used to determine characteristics of thyroid function between the cases and healthy controls. In order to exclude the false discovery rate (FDR), the Benjamini-Hochberg (BH) procedure is applied., Results: A total of 12 relevant literature sources were included in the meta-analysis. Compared with controls, free thyroxine (FT4) levels were significantly decreased in neurological disorders in meta-analysis (MD = -0.29, 95% CI: -0.50 to -0.09), whereas thyroid-stimulating hormone (TSH) levels showed no significant difference (MD = -0.07, 95% CI: -0.36 to 0.21). In our case-control study, levels of free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and anti-thyroglobulin antibodies (TG-Ab) were notably reduced among individuals with neurological disorders, compared with healthy controls ( P <0.001, P< 0.001, P =0.036, P =0.006). However, thyroid-stimulating hormone (TSH) levels did not show any statistically significant differences among the cases and controls., Conclusions: Our research demonstrates that, in comparison to controls, children with neurological disorders exhibited a significant decrease in FT4 levels, while TSH levels remained unchanged. This finding provides a reference for potential serum marker of neurological disorders in children. Replication in future studies with the assessment of THs is needed to determine whether thyroid function should be included as a routine screening in these children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Meng, Bigambo, Gu, Wang and Li.)

Background: Diabetic nephropathy (DN) is one of the most common and severe complications in patients with type 2 diabetes mellitus (T2DM). Thyroid dysfunction has been associated with diabetes and its complications but the relationship between thyroid autoantibodies and T2DM-DN remains unclear., Objective: The study aims to investigate the association between thyroid autoantibodies and diabetic nephropathy in patients with T2DM and analyze the expression of serum thyroid hormone levels in T2DM-DN patients and its prognostic value., Methods: 117 patients with T2DM who visited our hospital from December 2020 to December 2022 were recruited and assigned to group A (65 patients with T2DM-DN) and group B (52 patients with T2DM without DN). Serum TH levels of patients with DN and normal diabetic patients were analyzed, and the prognosis of patients was evaluated., Results: The results demonstrated that compared to group B, group A had higher serum cystatin C (cysC), serum creatinine (SCr), thyroglobulin antibody (TgAb), and urinary microalbumin/creatinine (UACR) levels, while the levels of free triiodothyronine (FT3), albumin (ALB), and estimated glomerular filtration rate (eGFR) were lower (P < .05). FT3 in group A2 was inferior to that in group A0 and group A1 (P < .05). After correction, the results demonstrated that the level of thyroid peroxidase antibody (TPOAb) in group A1 was superior to that in group A0 (P < .05). The positive rates of TPOAb (20%) and TgAb (23.08%) in patients with T2DM-DN were drastically superior to those in patients with T2DM without DN. Among the independent risk factors for DN, the OR of positive TPOAb was 8.125., Conclusion: The level and positive rate of thyroid autoantibodies in patients with T2DM-DN were high and TPOAb positivity might be a risk factor for the occurrence of T2DM-DN.

Objectives: This study aimed to employ big data analysis to harmonize reference intervals (RI) for thyroid function tests, with refinement to the TSH upper reference limit, and to optimize the TSH reflex algorithm to improve clinical management and test utilization., Design & Methods: TSH, free T4, and free T3 results tested in Alberta, Canada, on Roche Cobas and Siemens Atellica were extracted from the laboratory information system (N = 1,144,155 for TSH, N = 183,354 for free T4 and N = 92,632 for free T3). Results from specialists, inpatients, or repeat testing, as well as from positive thyroid disease, autoimmune disease, and pregnancy biomarkers were excluded. RIs were derived using statistical models (Bhattacharya, refineR, and simple non-parametric) followed by endocrinology and laboratory review., Results: The TSH RIs for 0 to 7 days, 8 days to 1 year, and ≥1 year were 1.23 to 25.0 mIU/L, 1.00 to 6.80 mIU/L and 0.20 to 6.50 mIU/L, respectively. The free T4 RIs for 0 to 14 days, 15 to 29 days, and ≥30 days were 13.5 to 50.0 pmol/L, 8.7 to 32.5 pmol/L, and 10.0 to 25.0 pmol/L, respectively. An updated TSH reflex algorithm was developed based on the optimized TSH and free T4 RIs, with free T4 reflexed only at a TSH of <0.1 mIU/L., Conclusions: The collaboration of a multidisciplinary team and the utilization of big data analysis led to the enhancement of thyroid function RIs, specifically resulting in the widening of the upper TSH reference limit to 6.50. Application of these optimized RIs with the TSH reflex algorithm will serve as a guide for improvement in interpretation of thyroid function tests., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background & Aims: We have recently demonstrated that subcutaneous adipose tissue (SAT) expression of genes associated with thyroid hormone (TH) action is altered in obesity and insulin resistance. The aim of the present study was to examine the effect of diet-induced weight-loss on SAT expression of genes associated with TH action., Methods: The study group comprised 38 individuals with overweight/obesity, which completed 12-week dietary intervention program. Hyperinsulinemic-euglycemic clamp and SAT biopsy were performed before and after the program. Fifteen normal-weight individuals were examined at baseline only., Results: Overweight/obese individuals had lower free thyroxine (fT4) and higher free triiodothyronine (fT3)/fT4 ratio, lower SAT TH receptor isoforms (TRα and TRβ, encoded by THRA and THRB, respectively) and peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) mRNA expression and higher SAT type II and type III iodothyronine deiodinase (encoded by DIO2 and DIO3, respectively) and nuclear receptor corepressor (NCOR1) mRNA expression in comparison with normal-weight individuals. Diet-induced weight loss resulted in a decrease in fT3 and fT3/fT4 ratio and an increase in SAT THRA, THRB and PPARGC1A. SAT NCOR1 and forkhead box protein O1 (FOXO1) decreased only in individuals, who lost at least 10 kg (n = 20). Higher increase in insulin sensitivity after weight loss was associated with a lower decrease in fT3/fT4 ratio., Conclusions: Diet-induced weight loss partly reverses alterations in SAT expression of genes associated with TH action. Responses of circulating TH and SAT expression of genes associated with TH action to diet-induced weight loss are related to body weight and insulin sensitivity., Competing Interests: Conflict of interest No conflict of interest exists regarding this study., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Recent unusual mortality events involving skin pathology in bearded ( Erignathus barbatus ), ringed ( Pusa hispida ), and spotted seals ( Phoca largha ) in Alaska highlight the potential sensitivity of ice-associated species to the complex effects of climate change. The regulation of thyroid hormones, cortisol, and vitamin A have been shown to play essential roles in skin health and seasonal molt in some pinnipeds. Unfortunately, the lack of available reference data for healthy Alaskan ice seals has prevented the adequate evaluation of these factors in cases associated with mortality events. To improve understanding of blood analytes that may serve as useful markers of skin health, we compiled diagnostic information for individuals in long-term managed care following short-term rehabilitation. Thyroid hormones (TT4, TT3, and FT4d), cortisol, and vitamin A levels are reported for four ringed seals, four spotted seals, and three bearded seals at the Alaska SeaLife Center in Seward, Alaska, with serial samples obtained when possible and referenced to time of year. For ringed and spotted seals, the thyroid hormones and vitamin A showed a strong seasonal pattern with peak values obtained during the annual molt in spring, whereas cortisol values did not vary predictably between molting and non-molting periods. Trends were similar for individuals across both sex and species. Bearded seals had fewer available data for younger individuals only, but observed analyte values are provided for this understudied species. Collectively, these measurements can be used to support veterinary management of ice seals under human care and to provide initial baselines for skin health monitoring in wild populations and in stranded individuals with known skin lesions or pathology.

Thyroid hormones influence mammary gland differentiation and lactation by binding to thyroid hormone receptors. Hyperthyroidism disrupts pregnancy and lactation, affecting offspring growth and milk production. Despite maternal milk is a vital source of bioactive compounds and nutrients for newborns, it is unclear whether hyperthyroidism alters its composition, mainly immune factors. Therefore, our work aimed to evaluate the influence of hyperthyroidism on milk quality and immunological parameters during early lactation. Twelve-week-old female Wistar rats received daily injections of 0,25 mg/kg T 4 (HyperT, n = 20) or vehicle (control, n = 19) starting 8 days before mating and continuing throughout pregnancy. Rats were euthanized on day 2 of lactation for analyzing the impact of hyperthyroidism on mammary gland, serum and milk samples. HyperT pups exhibited reduced weight, length and head circumference with altered serum hormones, glucose and albumin levels. HyperT mammary gland analysis revealed structural changes, including decreased alveolar area, adipose tissue, increased connective tissue and reduced epithelial elongation, accompanied by decreased TRβ1 RNA expression. HyperT milk displayed lower caloric value and fat concentration. HyperT animals exhibited altered milk immune cell counts, displaying increased numbers of CD45 + and CD3 + cells and decreased CD11b/c + cells without changes on milk and serum IgA, IgG and IgG2a levels. In summary, we have demonstrated that hyperthyroidism affects mammary gland morphology, disrupts pup development and alters biochemical and immunological parameters. Our findings highlight the impact of maternal hyperthyroidism on offspring early development and milk immune composition, underscoring the importance of thyroid function in maternal and neonatal immune health., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Resistance to thyroid hormone shows underlying mechanical link with chronic kidney disease (CKD) and is prevalent in CKD population. However, whether it attributes to mortality risk among CKD population is unknown. This study aimed to examine the association of thyroid hormone resistance (THR) with all-cause and cause-specific mortality among CKD individuals., Methods: This study extracted CKD population from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI) for mortality from all causes, cardiovascular disease (CVD)., Results: A total of 1,634 adults with CKD were included in the cohort, in which 663 deaths were recorded during an average follow-up of 8.72 years. After multivariate adjustment, resistance to thyroid hormone was significantly associated with higher all-cause and CVD mortality. There was an 18% and 31% increase in risks of all-cause and CVD mortality per-standard deviation (SD) increment in Parametric Thyroid Feedback Quantile-based Index (PTFQI) respectively. When PTFQI was analyzed as categorical variable (classified according to PTFQI percentiles), after adjusted for potential confounders and taking PTFQI ≤ P 5 as reference, the HRs and 95% CIs in category with PTFQI > P 95 for all-cause mortality and CVD mortality were 2.12 [1.10, 4.09] ( p for trend 0.026) and 5.14 [1.81, 14.60] for ( p for trend 0.018), respectively., Conclusions: Resistance to thyroid hormone, centered on variations in the typical pituitary response to thyroid hormones, may independently correlate with all-cause and CVD mortality in CKD patients.

Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited., Methods: Genetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive., Results: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in 2 cases. Thyroid hormone treatment improved motor development, whereas speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20 years because SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted antithyroid treatment instead., Conclusion: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in 4 patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy., Competing Interests: Conflict of Interest The authors declare no conflicts of interest, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Resting energy expenditure (REE) may fluctuate during the menstrual cycle (MC), due to the physiological effects of estradiol (E2) and progesterone. This study examined changes in REE and metabolic hormones (leptin, ghrelin, thyroid hormones), and dietary intake in two hormonally distinct groups, naturally menstruating women (NoOC) and women using monophasic combined oral contraceptives (COC)., Methods: Measurements included REE by indirect calorimetry, body composition by bioimpedance, and blood samples for hormone analysis in the early follicular and midluteal phases of the MC in the NoOC group ( n = 38) or the active and inactive phases of the COC cycle (COC; n = 19). Participants recorded their food intake for 3 d after measurements. A secondary analysis was completed for the NoOC group without REE outliers (difference between measurements >1.5 × interquartile range, n = 4)., Results: In the NoOC group, luteal phase REE was 40 kcal higher than follicular phase REE (95% confidence interval (CI), -2 to 82 kcal·d -1 , d = 0.20, P = 0.061). Leptin ( d = 0.35, P < 0.001), triiodothyronine (T3; d = 0.26, P = 0.05), and fat intake ( d = 0.48, P = 0.027) were higher, and thyroxine ( d = 0.21, P = 0.041) was lower in the luteal phase. After excluding outliers, REE was 44 kcal higher in the luteal phase than in the follicular phase (95% CI, 12-76 kcal·d -1 , d = 0.22, P = 0.007). In the COC group, the mean difference in REE was -2 kcal (95% CI, -82 to 79 kcal·d -1 ) between active and inactive phases, whereas T3 was higher in the inactive phase ( d = 0.01, P = 0.037)., Conclusions: REE increases only slightly from the follicular to the luteal phase but remains unchanged between COC phases. Increases in T3, leptin, and fat intake during the luteal phase might echo metabolic fluctuations that parallel female sex hormones during the MC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

While previous studies suggested that phthalate exposure poses a risk to cardiovascular health, the results are mixed and indicated variability based on population characteristics and health outcomes assessed. Research that simultaneously investigates the association between urinary phthalate metabolites and multiple cardiovascular risk factors within a single study is relatively scarce. This study assessed human exposure to phthalates by determining urinary metabolite concentrations, and applied multiple statistical techniques to systematically evaluate the individual dose-response relationships and joint effects of phthalate exposure on blood lipids, blood pressure, and fasting blood glucose. The results revealed significant negative associations between urinary phthalate metabolites and low-density lipoprotein cholesterol, triglycerides, total cholesterol, diastolic blood pressure, systolic blood pressure, and fasting blood glucose. Significant nonlinear associations were obtained between specific individual metabolites and diastolic blood pressure. The oxidative stress biomarker 8-hydroxydeoxyguanosine levels in urine and thyroid hormone levels in paired serum were measured simultaneously. Then, we examined the indirect roles of thyroid hormones and oxidative stress in the association between urinary phthalate metabolites and cardiovascular risk factors by mediation and moderation analysis. While the mediation effect was not statistically significant, the negative associations of urinary phthalate metabolites with fasting blood glucose, triglyceride, and lipoprotein cholesterol were statistically significant at lower levels of thyroid hormones by moderation analysis. The association was also significant under certain levels of oxidative stress. The results demonstrated that phthalate exposure is associated with several cardiovascular risk factors, and maintaining appropriate oxidative stress levels and ensuring sufficient thyroid hormone levels may attenuate these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The aim of this study was to compare the levels of thyroid hormones in children with ADHD and ADHD-NOS and to assess the relationship between ADHD symptom severity, anxiety symptom severity and thyroid hormone levels. The study was planned as a cross-sectional, retrospective study. The records of patients who applied to the study center in between January 2012 and January 2013 were screened and 205 ADHD and ADHD-NOS cases' records were evaluated. Both groups were compared according to thyroid hormon levels. The diagnosis of 205 patients' records and their comorbid psychiatric disorders was made clinically. ADHD symptom severity was assessed by Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S). Anxiety symptom severity was assessed by The Screen for Anxiety Related Emotional Disorders (SCARED). Groups were compared with parametric or non-parametric methods according to assumptions of normality. P was set at 0.05 (two-tailed). Among the whole sample, 99 (48.3 %) patients were ADHD, and 106 (51.7 %) patients were ADHD- NOS. The average age of the children in the ADHD group was 10.88 ± 3.02 years, and the average age of the children in the NOS-ADHD group 9.93 ± 2.49 years. Thyroid hormone levels were detected in 81 of 205 patients participating in the study. We found statistically significantly higher T4 levels in the ADHD group compared to the ADHD-NOS group (p=0.006). A statistically significant negative correlation between the total number of diagnoses and T4 level was noted (p=0.001). TSH levels correlated significantly with T-DSM-IV-S total score and symptom counts in the Hyperactivity subscale of this measure. Thyroid hormone levels may be affected in children with impairing ADHD symptoms and increased comorbidities. Our results should be supported with future studies.

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings. (1) Contrary to postulations that TTR and/or ALB are the major local T4 contributors, the three THBPs may unload comparable amounts of T4 in Liver, a rapidly perfused organ; however, their contributions in slowly perfused tissues follow the order of abundances of T4TBG, T4TTR, and T4ALB. The T3 amounts unloaded from or loaded onto THBPs in a tissue acting as a T3 sink or source respectively follow the order of abundance of T3TBG, T3ALB, and T3TTR regardless of perfusion rate. (2) Any THBP alone is sufficient to maintain spatially uniform TH tissue distributions. (3) The TH amounts unloaded by each THBP species are spatially dependent and nonlinear in a tissue, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end. (4) Spatial gradients of TH transporters and metabolic enzymes may modulate these contributions, producing spatially invariant or heterogeneous TH tissue concentrations depending on whether the blood-tissue TH exchange operates in near-equilibrium mode. In summary, our modeling provides novel insights into the differential roles of THBPs in local TH tissue distribution., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Perchlorate, nitrate, and thiocyanate are well-known sodium/iodide symporter (NIS) inhibitors that disturb iodide uptake at the thyroid, affecting thyroid function. However, the associations between NIS inhibitor exposure and thyroid function are not well summarized in humans., Objective: We aimed to summarize associations between NIS inhibitor exposure and thyroid function markers and to identify key information gaps for future studies., Methods: From four databases (Embase, Web of Science, PubMed, CINAHL plus) up to May 31, 2024, we systematically searched studies that examined associations between levels of the three NIS inhibitors and thyroid hormones, including free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), and total triiodothyronine (TT3) as well as thyroid-stimulating hormone (TSH). We also conducted a random-effects meta-analysis to estimate the pooled effect size of the associations between NIS inhibitor levels and thyroid function marker levels., Results: Of 2,588 identified studies, we selected 9 studies for full-text review and 4 studies for a meta-analysis. The association between perchlorate and TSH was primarily studied and only three studies considered iodine concentrations. As a result of a meta-analysis, TSH levels were positively associated with levels of combined NIS inhibitors [β: 0.105; 95% confidence interval (CI): 0.046, 0.160] and perchlorate [β = 0.133; 95% CI: 0.056, 0.211]. We found negative trends between NIS inhibitors and FT3 and TT4 and positive but nonsignificant trends between FT3 and perchlorate and between TT4 and thiocyanate., Conclusions: Our study provided comprehensive evidence on the association between exposure to NIS inhibitors and thyroid function markers in humans, aligning with the mechanisms observed in in vivo studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Mycotoxins are secondary metabolites produced by various species of mold fungi commonly found in plant materials. Zearalenone (ZEN) adversely affects the endocrine system. This study aimed to determine whether thyroid-stimulating hormone (TSH), procalcitonin (PCT), free triiodothyronine (fT3), and free thyroxine (fT4) levels are altered during natural zearalenone mycotoxicosis in patients diagnosed with sigmoid colon cancer (SCC) or colorectal cancer (CRC). A study was conducted on women and men diagnosed with SCC or CRC accompanied by the presence or absence (Patients Without ZEN - PWZ group) of ZEN in the blood. The PWZ group consisted of 17 patients with symptoms of SCC and CRC in whom ZEN and its metabolites were not detected in peripheral blood. The experimental (empirical) groups included a total of 16 SCC and CRC patients who tested positive for ZEN, but not its metabolites. TSH values in both sexes were within the upper limit of the reference range (0.27-4.2 μIU/mL) adopted by the hospital laboratory and corresponded to the upper second tertile and the lower third tertile. PCT values demonstrated that SCC and CRC were accompanied by a systemic or local bacterial infection. All mean values of fT3 were in the middle of the reference range, and the mean values of fT4 were within the upper reference limit. The fT3/fT4 prognostic marker was somewhat above the cut-off point of 0.22. These results indicate that in postmenopausal women and andropausal men who were diagnosed with SCC and CRC and were exposed to food-borne ZEN, higher values of the prognostic marker (fT3/fT4) were associated with an unfavorable prognosis. The study also revealed that the more distal the neoplastic lesions in the colon, the higher the percentage of both thyroid hormones, regardless of the patient's sex. The presence of ZEN in the diet alters thyroid activity in patients diagnosed with SCC and CRC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A burgeoning body of epidemiological and toxicological evidence suggests that thyroid health may be significantly impacted by exposure to both long- and short-chain perfluoroalkyl substances (PFAS) compounds. We conducted a meta-analysis to examine the association between 16 PFAS compounds and five thyroid hormones (TSH, TT3, TT4, FT3, and FT4) in the serum of a pregnant women, adolescents, and adults. The dose-response relationship between some PFAS and thyroid hormones in different population subpopulation was found and the model was fitted. We also amalgamated data from 18 animal experiments with previously published in vitro studies to elucidate the toxicological mechanisms underlying the impact of PFAS on the thyroid gland. The results of the study showed that (a) both conventional and emerging PFAS compounds were identified in human samples and exhibited associations with thyroid health outcomes; (b) in animal studies, PFAS have been found to impact thyroid gland health through two primary mechanisms: by influencing the hypothalamic-pituitary-thyroid axis and by binding to thyroid receptors. This study provides a systematic description of the health effects and risk assessment associated with PFAS exposure on the thyroid gland. Furthermore, dose-response relationships were established through the Hill model in python., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Currently, nothing is known about the connection between muscle mass and thyroid hormone levels in middle-aged and elderly Chinese with normal thyroid function. The purpose of this study was to determine the potential association between muscle mass and thyroid function status in middle-aged and elderly Chinese subjects with normal thyroid function., Methods: A cohort of 1868 participants in China were included in this retrospective study; their mean age was 53.97 years, and their skeletal muscle mass index was 7.44 kg/m 2 . Of them, 60.97% were men. Thyroid hormone concentrations, standard biochemical indices, and the frequency of chronic illnesses were among the many factors that were evaluated. Bioelectrical impedance analysis (BIA) was used to assess the patients' body composition. The skeletal muscle index (SMI) was calculated using the following formula: SMI = ASM (kg)/height 2 (m 2 ), where ASM stands for appendicular skeletal muscle mass. To identify the correlations between the variables, the Spearman correlation coefficient was used. Binary logistic regression analysis was conducted to investigate the potential linkages between thyroid hormone levels and diminished muscle mass., Results: In this investigation, a significant correlation was observed between low muscle mass and FT3/FT4 (OR=0.044, 95% CI: 0.004-0.440, P=0.008), as well as FT3 (OR=0.697, 95% CI: 0.508-0.957, P=0.025). Conversely, no discernible correlation trend was detected with TSH (OR=0.972, 95% CI: 0.814-1.160, P=0.753) and FT4 (OR=1.97, 95% CI=0.983-1.224, P=0.1). Following adjustment for various confounding factors, including age, vitamin D levels, triglycerides, HDL-C, LDL-C, total protein, hypertension, diabetes, hyperuricemia, and overweight/obesity, across the entire study population, a positive correlation between SMI and FT3/FT4 was identified. Subsequent gender, age, and weight-stratified analyses revealed consistent correlation trends between SMI and FT3/FT4, with all interactions yielding P-values > 0.05., Conclusion: Our study has revealed that among middle-aged and elderly Chinese individuals exhibiting normal thyroid function, a reduction in the free T3 to free T4 ratio is associated with a decline in muscle mass., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Qian, Ding, Jin, Chen, Fu, Zhao, Chen and Chen.)

Background: Thyroid hormones are essential for cognitive function and can impact cognitive performance even in euthyroid individuals. This study investigates how thyroid hormones influence cognitive performance in the elderly and whether body composition biomarkers moderate this relationship. The aim is to determine if lifestyle interventions should prioritize weight loss, overall body fat reduction, or abdominal fat loss., Methods: We analyzed data from the NHANES 2011-2012 dataset, focusing on thyroid hormone levels, cognitive performance, and body composition metrics in euthyroid individuals aged 60 to 80 years. A total of 573 participants were included in the analysis. Pearson correlation analyses were conducted to evaluate the associations between thyroid hormone indicators and cognitive performance metrics. Ordinal logistic regression and linear regression analyses were used to determine the predictive capacity of thyroid hormones on cognitive functions, adjusting for potential confounders such as age, gender, and education level. Statistical analyses were performed using R Studio and Stata, utilizing Pearson correlation, ordinal logistic regression, and linear regression methods., Results: Significant correlations were observed between short-term memory and TT3 ( r = 0.111, p = 0.018), TSHI ( r = -0.121, p = 0.010), and TFQI ( r = -0.107, p = 0.023); delayed memory and FT3 ( r = 0.143, p = 0.003), TT3 ( r = 0.146, p = 0.002), and TSHI ( r = -0.125, p = 0.009); and executive function with FT4 ( r = -0.141, p = 0.003) and the FT3/FT4 ratio ( r = 0.137, p = 0.004). Although thyroid indicators did not independently predict short-term memory (OR = 0.006, p = 0.116), they were statistically significant for delayed memory with FT3 (OR = 0.642, p = 0.017) and TT3 (OR = 0.010, p = 0.015). Linear regression analysis indicated that FT4 (t = -2.99, p = 0.003) and the FT3/FT4 ratio (t = 2.91, p = 0.004) were significant predictors of executive function. Hierarchical regression analyses revealed that BMI and waist circumference (WWI) significantly moderated the relationship between thyroid function and short-term memory (BMI: z = 2.44, p = 0.015; WWI: z = -2.19, p = 0.029). BMI also moderated the models for delayed memory (z = 2.11, p = 0.035), while RFM and C-index did not exhibit significant moderating effects. No moderators were identified in the relationship between executive function and thyroid hormones., Conclusion: This study underscores the significant influence of higher BMI and waist circumference on the relationship between thyroid function and memory performance. In contrast, body composition indicators such as RFM and C-index do not appear to significantly affect cognitive function related to thyroid levels, highlighting the importance of fat distribution in cognitive health assessments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Duan, Liu, Li and Zhang.)