The impact of environmental factors and contaminants on thyroid function and disease from fetal to adult life: current evidence and future directions.

The thyroid gland regulates most of the physiological processes. Environmental factors, including climate change, pollution, nutritional changes, and exposure to chemicals, have been recognized to impact thyroid function and health. Thyroid disorders and cancer have increased in the last decade, the latter increasing by 1.1% annually, suggesting that environmental contaminants must play a role. This narrative review explores current knowledge on the relationships among environmental factors and thyroid gland anatomy and function, reporting recent data, mechanisms, and gaps through which environmental factors act. Global warming changes thyroid function, and living in both iodine-poor areas and volcanic regions can represent a threat to thyroid function and can favor cancers because of low iodine intake and exposure to heavy metals and radon. Areas with high nitrate and nitrite concentrations in water and soil also negatively affect thyroid function. Air pollution, particularly particulate matter in outdoor air, can worsen thyroid function and can be carcinogenic. Environmental exposure to endocrine-disrupting chemicals can alter thyroid function in many ways, as some chemicals can mimic and/or disrupt thyroid hormone synthesis, release, and action on target tissues, such as bisphenols, phthalates, perchlorate, and per- and poly-fluoroalkyl substances. When discussing diet and nutrition, there is recent evidence of microbiome-associated changes, and an elevated consumption of animal fat would be associated with an increased production of thyroid autoantibodies. There is some evidence of negative effects of microplastics. Finally, infectious diseases can significantly affect thyroid function; recently, lessons have been learned from the SARS-CoV-2 pandemic. Understanding how environmental factors and contaminants influence thyroid function is crucial for developing preventive strategies and policies to guarantee appropriate development and healthy metabolism in the new generations and for preventing thyroid disease and cancer in adults and the elderly. However, there are many gaps in understanding that warrant further research.

A Highly Selective Fluorescent Probe for Monitoring the Thyroid Hormone Transporter Activity in Mammalian Cells.

Monocarboxylate transporter 8 (MCT8) is a trans-membrane transporter, which mediates the cellular delivery of thyroid hormones, L-thyroxine (T4) and 3,5,3 '-triiodo-L-thyronine (T3). In humans, the MCT8 protein is encoded by the SLC16A2 gene and mutations in the transporter cause a genetic neurological disorder known as Allan-Herndon-Dudley syndrome (AHDS). MCT8 deficiency leads to impaired transport of thyroid hormones in the brain. Radiolabelled T4 and T3 or LC/MS-MS methods have been used to monitor the thyroid hormone uptake through MCT8. Herein, we developed a fluorescent based assay to monitor the thyroid hormone uptake through MCT8. A dansyl-based fluorescent probe having L-thyroxine moiety is found to be highly selective towards MCT8 in living cells. The high selectivity of the probe towards MCT8 can be attributed to the halogen bond-mediated recognition by the transporter protein. The presence of a free carboxylic acid group is essential for the specificity of the probe towards MCT8. Additionally, the selectivity of the probe for MCT8 is abolished upon esterification of the carboxylic group. Similarly, MCT8 does not recognize the probe when it contains a free amine group.

Relationship between maternal biological features, environmental factors, and newborn neuromotor development associated with visual fixation abilities.

Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.

Lithium and endocrine disruption: A concern for human health?

Lithium is a key medication for the treatment of psychiatric disorders and is also used in various industrial applications (including battery production and recycling). Here, we review published data on the endocrine-disrupting potential of lithium, with a particular focus on the thyroid hormone system. To this end, we used PubMed and Scopus databases to search for, select and review primary research addressing human and animal health endpoints during or after lithium exposure at non-teratogenic doses. Given the key role of thyroid hormones in neurodevelopmental processes, we focused at studies of the neural effects of developmental exposure to lithium in humans and animals. Our results show that lithium meets the World Health Organization's definition of a thyroid hormone system disruptor - particularly when used at therapeutic doses. When combined with knowledge of adverse outcome pathways linking molecular initiating events targeting thyroid function and neurodevelopmental outcomes, the neurodevelopmental data reported in animal experiments prompt us to suggest that lithium influences neurodevelopment. However, we cannot rule out the involvement of additional modes of action (i.e. unrelated to the thyroid hormone system) in the described neural effects. Given the increasing use of lithium salts in new technologies, attention must be paid to this emerging pollutant - particularly with regard to its potential effects at environmental doses on the thyroid hormone system and potential consequences on the developing nervous system.

The effects of swimming training at different temperatures along with cinnamon supplementation on liver enzymes and thyroid hormones in diabetic rats.

Objective: The aim of this study was to investigate the effects of swimming (S) training in water at 5°C (S5C) and 35°C (S35C) along with cinnamon (Cin) supplementationon liver enzymes and thyroid hormones in streptozotocin (STZ(-induced diabetic rats. Materials and Methods: In this experimental trial, 48 diabetic rats (55 mg/kg STZ) were divided into (1) diabetic control (CD), (2) S5C, (3) S5C+Cin, (4) S35C, (5) S35C+Cin and (6) Cin groups.Eight rats were placed in the healthy control (HC) group to evaluate the effects of diabetes induction on the research variables. Swimming training was performed at 5±2°C and 35±2°C for eight weeks, 3 days a week.For Cin supplementation, 200 mg/kg/day of the aqueous extract of cinnamon was dissolved in the animals drinking water. One-way analysis of variance with Tukey's post- hoc test in Graphpad Prism software was used to analyze the findings. Results: S5C and S35C significantly increased thyroid-stimulating hormone (TSH), and decreased alkaline phosphatase (ALP) and alanine aminotransferase (ALT)(p≤0.05). TSH levels in the S35C group were higher than the S5C group (p≥0.05); ALT levels in the S5C group were lower than the S35C group (p≥0.05). Also, Cin decreased AST and ALT levels (p≥0.05), while S35C+Cin decreased T3, ALP and ALT and S5C+Cin decreased ALP (p≥0.05). Conclusion: It seems that training at different temperatures and consumption of cinnamon synergistically lead to improvement of liver enzymes and modulation of thyroid hormones. However, the effect of training in cold water and its impact on thyroid hormones is still unknown and needs further research.

Delta check limits for thyroid function tests adjusted for clinical settings.

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.

Exposure to thiourea during the early stages of development impedes the formation of the swim bladder in zebrafish larvae.

Thiourea, a widely used agrochemical, is known to inhibit the activity of thyroid peroxidase, a key enzyme in the biosynthetic pathway of thyroid hormones. Thyroid insufficiency compromises the basal metabolic rate in warm-blooded organisms and embryonic development in vertebrates. In this study, we looked for developmental defects by exposing the zebrafish embryos to an environmentally relevant dose of thiourea (3 mg/mL). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to validate thiourea's presence in the treated zebrafish embryos. Structural anomalies like bent tail and pericardial edema were noticed in 96-h post-fertilization (hpf) larvae. On histological examination, underdeveloped swim bladder was noticed in 96 hpf larvae exposed to 3 mg/mL thiourea. The treated larvae also failed to follow the characteristic swimming behavior in response to stimuli due to defective swim bladder. Swim bladder being homologous to the lung of tetrapod, the role of Bmp4, a major regulator of lung development, was studied along with the associated regulatory genes. Gene expression analysis revealed that thiourea administration led to the downregulation of bmp4, shh, pcna, anxa5, acta2, and the downstream effector snail3 but the upregulation of caspase3. The protein expression showed a similar trend, wherein Bmp4, Shh, and Pcna were downregulated, but Cleaved Caspase3 showed an increased expression in the treated group. Therefore, it is prudent to presume that exposure to thiourea significantly reduces the expression of Bmp4 and other key regulators; hence, the larvae fail to develop a swim bladder, a vital organ that regulates buoyancy.

Thyroid and parathyroid function disorders induced by short-term exposure of microplastics and nanoplastics: Exploration of toxic mechanisms and early warning biomarkers.

Human exposure to micro- and nano-plastics (MNPs) primarily occurs through respiration and diet in the environment. However, the early effects and warning signs of MNPs exposure on vertebrates are unclear. Here we used intratracheal instillation and intragastric infusion to establish mouse models for MNPs exposure to systematically investigate the toxic mechanisms of MNPs on endocrine organs. Results showed that MNPs induced endocrine disruptions in short-term exposure by both dietary and respiratory pathways. Microplastics (MPs) exposed through dietary route were more toxic to thyroid gland, whereas nanoplastics (NPs) exhibited the highest level of toxicity to parathyroid gland through respiration. The transcriptome and validation of related functional genes revealed that MNPs affected the synthesis of thyroglobulin by interfering with the expressions of PAX8 and CREB. MNPs also impacted the levels of thyroid stimulating hormone, further mediating the secretion of thyroid hormones. Moreover, MNPs modulate the expression of Mafb, thereby exerting regulatory effects on parathyroid hormone (PTH) synthesis and growth development in parathyroid cells. Meanwhile, MNPs interfered with the expression of IP3R in the calcium signaling pathway, indirectly affecting the secretion of PTH. This study reveals the effects and mechanisms of MNPs on thyroid and parathyroid and highlights the significance of early warning of MNPs exposure.

Developmental exposure to the Fox River PCB mixture modulates behavior in juvenile mice.

Developmental exposures to PCBs are implicated in the etiology of neurodevelopmental disorders (NDDs). This observation is concerning given the continued presence of PCBs in the human environment and the increasing incidence of NDDs. Previous studies reported that developmental exposure to legacy commercial PCB mixtures (Aroclors) or single PCB congeners found in Aroclors caused NDD-relevant behavioral phenotypes in animal models. However, the PCB congener profile in contemporary human samples is dissimilar to that of the legacy Aroclors, raising the question of whether human-relevant PCB mixtures similarly interfere with normal brain development. To address this question, we assessed the developmental neurotoxicity of the Fox River Mixture (FRM), which was designed to mimic the congener profile identified in fish from the PCB-contaminated Fox River that constitute a primary protein source in the diet of surrounding communities. Adult female C57BL/6 J mouse dams (8-10 weeks old) were exposed to vehicle (peanut oil) or FRM at 0.1, 1.0, or 6.0 mg/kg/d in their diet throughout gestation and lactation, and neurodevelopmental outcomes were assessed in their pups. Ultrasonic vocalizations (USVs) and measures of general development were quantified at postnatal day (P) 7, while performance in the spontaneous alternation task and the 3-chambered social approach/social novelty task was assessed on P35. Triiodothyronine (T3) and thyroxine (T4) were quantified in serum collected from the dams when pups were weaned and from pups on P28 and P35. Developmental exposure to FRM did not alter pup weight or body temperature on P7, but USVs were significantly decreased in litters exposed to FRM at 0.1 or 6.0 mg/kg/d in the maternal diet. FRM also impaired male and female pups' performance in the social novelty task. Compared to sex-matched vehicles, significantly decreased social novelty was observed in male and female pups in the 0.1 and 6.0 mg/kg/d dose groups. FRM did not alter performance in the spontaneous alternation or social approach tasks. FRM increased serum T3 levels but decreased serum T4 levels in P28 male pups in the 1.0 and 6.0 mg/kg/d dose groups. In P35 female pups and dams, serum T3 levels decreased in the 6.0 mg/kg/d dose group while T4 levels were not altered. Collectively, these findings suggest that FRM interferes with the development of social communication and social novelty, but not memory, supporting the hypothesis that contemporary PCB exposures pose a risk to the developing brain. FRM had sex, age, and dose-dependent effects on serum thyroid hormone levels that overlapped but did not perfectly align with the FRM effects on behavioral outcomes. These observations suggest that changes in thyroid hormone levels are not likely the major factor underlying the behavioral deficits observed in FRM-exposed animals.

The Effect of Mediterranean Diet on Thyroid Gland Activity.

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korcula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients.

Thyroid Density in CT Imaging as a Potential Marker of Lung Involvement in COVID-19: A Retrospective Analysis.

Background The SARS-CoV-2 pandemic has underscored the multifaceted impact of the virus on human health, extending beyond the respiratory system to involve other organ systems, including the endocrine system. Emerging evidence suggests a notable interaction between COVID-19 and thyroid function, characterized by alterations in thyroid hormone levels and structural changes within the gland. This study aims to explore the association between thyroid density on CT imaging and lung involvement in patients with COVID-19, potentially offering new insights into the systemic effects of the virus. Methodology A retrospective cross-sectional analysis was conducted on 1,066 patients with COVID-19 who underwent chest CT scans without contrast at Government Medical College, Omandurar Government Estate, Chennai, which was designated as the COVID-19 care center from April to June 2021. Thyroid density and lung involvement were quantitatively assessed, and their correlation was analyzed using descriptive and inferential statistics, including the Kruskal-Wallis H test and Shapiro-Wilk test for normality. Results The study population predominantly exhibited normal thyroid density (749, 70.3%), followed by altered (212, 19.9%), nodular (104, 9.8%), and a single instance (0.1%) of absent thyroid density. Despite variability in lung involvement across different thyroid density categories, statistical analysis revealed no significant association between thyroid density and the extent of lung involvement in patients with COVID-19. Conclusions This study found no significant correlation between thyroid density and lung involvement in patients with COVID-19, suggesting that thyroid density on CT imaging may not serve as a reliable marker for lung involvement in this population. Further research is warranted to explore the complex interactions between COVID-19 and thyroid function, as well as the potential implications for patient management and prognosis.

Association between maternal age and sex-based neonatal free triiodothyronine levels.

BACKGROUND: Advanced maternal age may affect the intrauterine environment and increase the risk of neurodevelopmental disorders in offspring. Thyroid hormones are critical for fetal neurological development but whether maternal age influences fetal thyroid hormone levels in euthyroid mothers is unknown. OBJECTIVE: This study evaluated the association between cord blood thyroid hormones and maternal age, fetal sex, maternal thyroid function, and other perinatal factors. METHODS: The study population consisted of 203 healthy women with term singleton pregnancies who underwent elective cesarean section. Maternal levels of free T3 (fT3), free T4 (fT4) and TSH before delivery, and cord levels of fT3, fT4 and TSH were measured. Spearman's correlation coefficient and multiple linear regression analyses were performed to determine the correlation between cord thyroid hormone parameters and maternal characteristics. RESULTS: There were no significant differences in maternal serum or cord blood thyroid hormone levels between male and female births. In multivariate linear regression analysis, maternal age and maternal TSH values were negatively associated with the cord blood levels of fT3 in all births, after adjusting for confounding factors. Maternal age was more closely associated with the cord blood levels of fT3 in female than in male births. CONCLUSION: The inverse association between maternal age and cord blood levels of fT3 in euthyroid pregnant women suggested an impact of maternal aging on offspring thyroid function.

Effect of Sleeve Gastric Surgery on Body Weight and Hypothalamic-Pituitary Axis Hormone Levels in Patients with Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in women of reproductive age. It is difficult for patients with PCOS to achieve weight loss with conventional treatment. The aim of this study was to investigate weight loss and changes in hypothalamic-pituitary axis hormone levels in patients with PCOS combined with obesity after sleeve gastrectomy. METHODS: A retrospective analysis of 12 patients without PCOS and 24 patients with PCOS who underwent bariatric surgery at Beijing Luhe hospital from 2020 to 2022 was performed. The study assessed the changes in body weight and hormonal indexes of the hypothalamic-pituitary axis before and six months after the surgery. RESULTS: Patients with PCOS experienced greater weight loss compared to those without the condition. Following surgery, individuals with PCOS showed lower levels of postoperative testosterone, prolactin, and free testosterone indices compared to preoperative levels. Additionally, postoperative LH and FSH levels were higher than preoperative levels. Analysis of thyroid axis hormone levels revealed that FT3 and TSH levels were notably reduced in patients with PCOS postoperatively. Furthermore, growth hormone levels were found to be elevated in patients with PCOS following surgery. CONCLUSION: Bariatric surgery enhances hormone levels in the hypothalamic-pituitary axis in women with PCOS, leading to greater improvements in patients with PCOS compared to those with simple obesity.

Hypothyroidism and metabolic cardiovascular disease.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) on CV risk, CVD, and mortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH.

Changes in thyroid hormones predict weight regain in patients with obesity who undergo metabolic surgery.

AIM: To investigate the relationship between thyroid function and weight regain in patients with obesity after metabolic surgery. METHODS: This retrospective study enrolled 162 patients who underwent metabolic surgery. Correlations between decreases in thyroid hormone levels and changes in weight, waist circumference (WC) and the Chinese visceral adiposity index (CVAI) were assessed. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cut-off values, respectively. RESULTS: The levels of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) decreased markedly at 1 year after surgery, as did weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, WC and CVAI. Decreases in TSH and FT3 after metabolic surgery were associated with changes in weight, BMI and CVAI. Binary logistic regression and ROC curve analyses confirmed that decreases in TSH can predict good weight loss after metabolic surgery to some extent. Finally, binary logistic regression and ROC curve analyses confirmed that changes in TSH can predict weight regain after metabolic surgery. CONCLUSIONS: Changes in TSH and FT3 after metabolic surgery were correlated with changes in weight and CVAI. Changes in thyroid hormones can predict weight regain in patients with obesity who underwent metabolic surgery.

Circadian Gating of Thyroid Hormone Action in Hepatocytes.

Thyroid hormones, thyroxin (T4) and the biologically active triiodothyronine (T3), play important roles in liver metabolic regulation, including fatty acid biosynthesis, beta-oxidation, and cholesterol homeostasis. These functions position TH signaling as a potential target for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated T3 levels in the circulation are associated with increased hepatic lipid turnover, which is also under the control of the circadian clock system. In this study, we developed a cell system to study the impact of hepatocyte circadian rhythms on the metabolic response to T3 treatment under control and steatotic conditions. Synchronized AML-12 circadian reporter hepatocytes were treated with T3 at different circadian phases and metabolic conditions. T3 treatment increased metabolic activity in a dose-independent fashion and had no significant effect on circadian rhythms in AML-12 cells. T3 had marked time-of-treatment-dependent effects on metabolic transcript expression. Steatosis induction altered metabolic transcript expression in AML-12 cells. In this condition, the circadian rhythm period was lengthened, and this effect was independent of T3. Under steatotic conditions, T3 had marked time-of-treatment dependent effects on metabolic transcript expression, which differed from those observed under control conditions. These findings reveal a time-of-day-dependent response of hepatocytes to T3, which is further modulated by the metabolic state. Our data suggest that time has a strong influence on liver TH action, which might be considered when treating MASLD.

Adaptive Effects of Endocrine Hormones on Metabolism of Macronutrients during Fasting and Starvation: A Scoping Review.

Food deprivation can occur for different reasons. Fasting (<24 h duration) occurs to meet religious or well-being goals. Starvation (>1-day duration) occurs when there is intentional (hunger strike or treatment of a medical condition) or unintentional (anorexia nervosa, drought, epidemic famine, war, or natural disaster) food deprivation. A scoping review was undertaken using the PubMed database to explore 1805 abstracts and review 88 eligible full-text articles to explore the adaptive relationships that emerge between cortisol, insulin, glucagon, and thyroid hormones on the metabolic pathways of macronutrients in humans during fasting and starvation. The collected data indicate that fasting and starvation prime the human body to increase cortisol levels and decrease the insulin/glucagon ratio and triiodothyronine (T3) levels. During fasting, increased levels of cortisol and a decreased insulin/glucagon ratio enhance glycogenolysis and reduce the peripheral uptake of glucose and glycogenesis, whereas decreased T3 levels potentially reduce glycogenolysis. During starvation, increased levels of cortisol and a decreased insulin/glucagon ratio enhance lipolysis, proteolysis, fatty acid and amino acid oxidation, ketogenesis, and ureagenesis, and decreased T3 levels reduce thermogenesis. We present a potential crosstalk between T3 and the above hormones, including between T3 and leptin, to extend their adaptive roles in the metabolism of endogenous macronutrients during food deprivation.

Visceral Fat Area and Subcutaneous Fat Area Increase in Hyperthyroidism Patients After Treatment-A Single-Group Repeated-Measures Trial.

Purpose: There is evidence that long-term vascular risk remains increased in patients with hyperthyroidism even after normalization of thyroid function, and the mechanisms that regulate this risk are unclear. The aim of this study was to assess how visceral fat area and subcutaneous fat area change after hyperthyroidism treatment, and to further explore the relationship between thyroid hormones, abdominal fat area (visceral fat area and subcutaneous fat area), and lipids. Patients and Methods: 50 patients with newly diagnosed Graves' disease were selected. Anthropometric parameters (weight, height, body mass index, waist circumference, neck circumference), laboratory parameters (thyroid hormones, lipid metabolism indices), abdominal fat area (visceral fat area and subcutaneous fat area), and drug dose were collected. Measurements were made at baseline, 6 and 12 months after treatment. We used linear mixed-effects models for analysis. Results: The results showed that the following indexes changed significantly at different time points: visceral fat area, subcutaneous fat area, free triiodothyronine, free thyroxine, thyroid stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, body weight, neck circumference, body mass index, waist circumference, and drug dose (All P<0.001). We found that free triiodothyronine and free thyroxine were significantly negatively associated with abdominal fat area (P<0.01). There was no significant correlation between drug dose and abdominal fat area (P>0.05). Total cholesterol and low-density lipoprotein were significantly positively associated with abdominal fat area (P<0.01). However, high-density lipoprotein (P=0.06) was not correlated with abdominal fat area. Moreover, the results showed a significant negative correlation between thyroid hormones and lipids (P<0.001). Conclusion: After anti-thyroid medicine treatment, patients had elevated visceral fat area and subcutaneous fat area and altered lipid profiles. These changes may be one of the reasons why metabolic and cardiovascular diseases remain increased after thyroid function is restored.

Urinary haloacetic acid concentrations in relation to sex and thyroid hormones among reproductive-aged men.

Sex and thyroid hormones are critical for male reproductive health. However, the associations between haloacetic acid (HAA) exposure - a known endocrine disruptor - and sex and thyroid hormones in humans remains unclear. We thus recruited 502 male participants seeking fertility evaluation from a reproductive center. We measured concentrations of sex and thyroid hormones in a single blood sample and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in repeated urine samples. Multivariable linear regression models were constructed to evaluate the associations between HAA concentrations and hormone measurements. After adjusting for potential confounders and urinary creatinine concentrations, urinary concentrations of TCAA were inversely associated with serum levels of sex hormone-binding globulin (SHBG), testosterone (T), T/luteinizing hormone ratio (T/LH), and thyroid stimulating hormone (TSH) (all P for trend < 0.10). Compared with participants in the lowest quartile of TCAA concentrations, those in the highest quartile had reduced serum levels of SHGB by 14.2 % (95% CI: -26.7, -3.0 %), T by 11.1 % (95% CI: -21.7, -1.3 %), T/LH by 21.0 % (95% CI: -36.7, -7.1 %), and TSH by 19.1 % (95% CI: -39.7, -1.5 %). Additionally, we observed inverse associations between continuous measurements of urinary HAAs and serum levels of free T, bioactive T, and estradiol. Our findings suggest that male HAA exposure may be associated with disrupted sex and thyroid function.

Thyroid hormone enhances efficacy of cisplatin in lung cancer patients via down-regulating GLUT1 expression and reversing the Warburg effect.

Cisplatin (CDDP) is a standard non-small cell lung cancer (NSCLC) chemotherapy, but its efficacy is hampered by resistance, partly due to the Warburg effect. This study investigates how thyroid hormones enhance the Warburg effect, increasing sensitivity to cisplatin in lung cancer. Clinical data from advanced NSCLC patients were analyzed based on thyroid hormone levels, categorizing patients into high and low groups. Cellular experiments involved Control, 10uM CDDP, 10uM CDDP + 0.1uM T3, and 10uM CDDP + 0.1uM T4 categories. Parameters were measured in A549 and PC9 lung cancer cells, including proliferation, apoptosis, mitochondrial membrane potential, ROS production, glycolysis enzyme activity, lactic acid level, and ATP content. Gene and protein expressions were assessed using qPCR and Western Blot. Analysis revealed higher FT3 levels correlated with prolonged progression-free survival before chemotherapy (median PFS: high FT3 group = 12.67 months, low FT3 group = 7.03 months, p = 0.01). Cellular experiments demonstrated that thyroid hormones increase lung cancer cell sensitivity to cisplatin, inhibiting proliferation and enhancing efficacy. The mechanism involves thyroid hormones and cisplatin jointly down-regulating MSI1/AKT/GLUT1 expression, reducing lactic acid and glycolysis. This Warburg effect reversal boosts ATP levels, elevates ROS, and decreases MMP, enhancing cisplatin effectiveness in A549 and PC9 cells. In conclusion, elevated free T3 levels in advanced NSCLC patients correlate with prolonged progression-free survival under cisplatin chemotherapy. Cellular experiments reveal that thyroid hormones enhance lung cancer cell sensitivity to cisplatin by reversing the Warburg effect, providing a mechanistic basis for improved therapeutic outcomes.