Altered Thyroid Hormone Levels Research Articles

Associations of per- and polyfluoroalkyl substances and alternatives with subclinical hypothyroidism in children: A cross-sectional study in China

There is growing experimental and epidemiological evidence linking perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure to thyroid dysfunction; however, the association between PFAS and their alternatives to subclinical hypothyroidism in children remains to be elucidated. This study investigated the association between 30 PFASs and thyroid function using serum samples from 194 children (aged 3–17 years) who participated in the Zhejiang Human Biomonitoring Program. Various thyroid function indicators, including free triiodothyronine, free thyroxine (FT4), and thyrotropin, were tested, and subclinical hypothyroidism was diagnosed. Linear regression was employed to examine the associations between individual PFASs and thyroid hormone levels, and logistic regression was applied to assess their associations with subclinical hypothyroidism. The quantile g-computation (qgcomp) method was used to examine the combined and individual effects of PFAS mixtures on thyroid function. Both PFASs and their alternatives were associated with altered thyroid hormone levels and subclinical hypothyroidism. A higher level of perfluorohexanoic acid (PFHpA) was associated with decreased FT4 with a reduction of −0.028 pmol/L (95 % confidence interval [95 % CI]: −0.047, −0.008) per unit increase as well as increased odds of subclinical hypothyroidism (odds ratio [OR] = 1.95; 95 % CI: 1.11, 3.53). Moreover, a higher PFAS mixture was associated with elevated odds of subclinical hypothyroidism (OR = 3.72; 95 % CI: 1.08, 12.85), in which PFHpA, in conjunction with 6:2 chlorinated perfluoroalkyl ether sulfonic acid, accounted for the greatest proportion of the variance. These findings augment our understanding of the adverse effects of PFASs and their alternatives on thyroid homeostasis, underscoring the need for further epidemiological research.

Distribution of Polybrominated Diphenyl Ethers (PBDEs) in Placental Tissues of Maternal and Fetal Origin in Exposed Wistar Rats and Associations with Thyroid Hormone Levels.

In utero exposure to polybrominated diphenyl ethers (PBDEs) is linked to adverse pregnancy and fetal health outcomes, including altered thyroid hormone (TH) levels. Despite their phase out, PBDEs are still commonly detected in newborn cord blood. While PBDEs can cross the placenta, few studies have separately assessed PBDEs or THs in the maternal and fetal placental tissues. Additionally, no studies have separately assessed THs in these tissues across mid- and late gestation, during the onset of fetal TH synthesis. To address these gaps, we conducted a study with Wistar rats and examined PBDE accumulation in the maternal and fetal placenta. Pregnant dams were exposed daily to sesame oil vehicle, a low dose, or high dose PBDE mixture. At GD15 and 20, dams were sacrificed and placental tissues were collected. Tissues were analyzed for PBDEs, T3, rT3, and T4 using mass spectrometry. BDE-47, -99, -100, and -209 were frequently detected in both the fetal and maternal placenta. At GD15, higher concentrations of BDE-99, -100, and -209 were measured in the fetal placenta; however, this trend reversed by GD20, with higher maternal placental concentrations. Placental T3 and T4 were significantly impacted by exposure, tissue, and exposure x tissue at GD15, with significant reductions in both THs following low dose exposure in the maternal placenta. By GD20, maternal placental T3 was only significantly reduced in the high exposure groups and there was no effect on placental T4. Overall, these results highlight the rapid developmental changes that occur throughout gestation between the maternal and fetal placenta, and the differential impacts of gestational PBDE exposure on placental T3 and T4 across mid- and late-gestation.

Psychological aspects of Graves' ophthalmopathy.

This review aims to discuss the psychological aspects of Graves' ophthalmopathy (GO), estimate the prevalence of depression and anxiety disorders in GO, examine whether these psychiatric disorders are more prevalent in GO than in Graves' disease (GD) without eye disease, and evaluate the main contributors for depression and anxiety in GO. A review of the literature. Both depression and anxiety are associated with GO. The prevalence of depression and anxiety disorders specifically in GO patients was estimated at 18-33% and 26-41%, respectively. The reported prevalence in GD patients ranged from 9% to 70% for depression and from 18% to 88% for anxiety disorders. Significantly higher levels of depression and anxiety were found in GD patients compared with patients with non-autoimmune hyperthyroidism. Conflicting results have been reported regarding the association of antithyroid autoantibodies with depression and anxiety disorders. Serum thyroid hormone levels do not correlate with the severity of depression and anxiety. An improvement of psychiatric symptoms is observed in hyperthyroid patients after treatment of thyrotoxicosis. Moreover, depression and anxiety are significantly related to impaired quality of life (QoL) in GO. Exophthalmos and diplopia were not associated with depression nor anxiety, but orbital decompression and strabismus surgery do seem to improve QoL in GO patients. The results of this review suggest that altered thyroid hormone levels and autoimmunity are prognostic factors for depression and anxiety in GO. With regard to the visual and disfiguring aspects of GO as contributing factors for depression and anxiety, no decisive conclusions can be made.

Statistical Associations between Vestibular Pathologies and Hypothyroidism: A Retrospective Study.

The association between vestibular pathologies and thyroid hormone disorders has been known for several decades. However, very little information is available on the types of vestibular symptoms that may be affected by altered thyroid hormone levels. The aim of this study was to provide patient data in order to identify statistical associations between vestibular pathologies and thyroid hormone disorders. A retrospective review of the records of 422 patients seen for physiotherapy treatment of vertigo was carried out. Statistical analysis of the data was performed using logistic regression, providing Chi2 and Odds Ratio statistics. Our results show that hypothyroidism statistically significantly increases the expression of certain symptoms, such as vestibular instability and gait disorders, in vestibular pathologies such as Menière's disease or central vertigo. By analyzing patient data, our study provides new evidence of dependence between altered thyroid status and the expression of vestibular pathologies.

OR06-02 Placental Distribution Of Polybrominated Diphenyl Ethers (Pbdes) And Thyroid Hormones Across Gestation In PBDE-exposed Wistar Rats

Abstract Disclosure: S. Gaballah: None. B. Horman: None. G. St Armour: None. K. Hoffman: None. H.B. Patisaul: None. H. Stapleton: None. In utero exposure to polybrominated diphenyl ethers (PBDEs) has been linked to adverse pregnancy and fetal health outcomes, including altered thyroid hormone (TH) levels. Despite their phase out, PBDEs are still measured in newborn cord blood. While evidence suggests that PBDEs can cross the placental barrier, few studies have assessed differences in PBDE or TH accumulation in the maternally and fetally-derived placental tissue layers or studied fetal sex-differences. To address these gaps, we conducted a controlled exposure study in Wistar rats (n=8 per treatment and gestational day (GD)). From GD2, pregnant dams were exposed daily to sesame oil vehicle, a low dose, or high dose mixture of 10 PBDEs. The low dose represents the 95th percentile of PBDEs measured in U.S. house dust, and the high dose is ∼20X higher. At GD15 and GD20, dams were sacrificed and placental tissues were micro-dissected into maternally and fetally-derived layers. Tissues were analyzed for PBDEs and for T3, rT3, and T4 using mass spectrometry. BDEs 47, 99, 100, and 209 were frequently detected in the fetal and maternal tissues. Higher concentrations of BDEs 99, 100, and 209 were measured in the fetal placenta on GD 15; however, this trend flipped at GD20, with higher maternal concentrations of BDEs 47, 99, and 209. This shift appears to be related to changes in the mass of the maternal and fetal layers during gestation and not to different partioning processes. Only BDE 99 was significantly different between the two layers, in both sexes. At both timepoints, T3 levels were several-fold higher in maternal tissues than fetal, but T3 decreased in maternal tissues by GD20. No sex differences were observed. In general, we observed a significant difference in maternal and fetal T3 levels at GD15 and GD20 in control, low, and high dose-exposed animals. At GD15, there was a significant difference between maternal and fetal female placental T4 levels (p=0.0237) and a suggestive difference in males (p=0.081) in the high dose group, as well as a significant effect of sex between the fetal tissues in the low dose group (p=0.0044). T4 was only detected in the fetal side at GD20, with no significant effects of treatment or sex. These results highlight the rapid developmental changes throughout gestation between the maternal and fetal placenta. Overall, these data highlight that PBDE accumulation in Wistar rats changes across gestation, causing disruption of TH levels in maternal and fetal tissues, and that sex-specific differences may be contributing to differential accumulation patterns in male and female-associated placentas. Coupled with rapid morphological changes in the fetal and maternal layers during placental growth, in utero PBDE exposure may result in adverse impacts on placental TH regulation and fetal health. Presentation: Thursday, June 15, 2023

Reproductive disorders linked to the interaction between sex steroid and thyroid hormonal activities, oxidative stress responses, and the rate of metabolism of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) in zebrafish

The objective of this study was to assess the thyroid hormone disruption and reproductive dysfunction effects of the bioaccumulation and rate of mechanism in zebrafish exposed to tris(1,3-dichloro-2-propyl) phosphate (TDCPP), with stress responsiveness. The fish were exposed to test concentrations of TDCPP (0, 0.06, 0.3, 1.5 µg/mL) for 21 days, in accordance with no observed adverse effect level (i.e., < EC10) for zebrafish embryos. The bioaccumulation of TDCPP was found to be significantly higher in female zebrafish, while the metabolic rate was significantly higher in male zebrafish at all concentrations studied. The thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) levels and sex steroid (i.e., estrogen, androgen, and progesterone) levels were significantly increased only in female zebrafish exposed to TDCPP, and no significant difference was observed in male zebrafish, although their cortisol levels increased. The response to TDCPP can, therefore, be considered sex-specific. The results of this study demonstrate for the first time, that the different response in the bioaccumulation and metabolic rate of TDCPP in males and females. The results also indicate that TDCPP alters thyroid hormone levels, furthermore, as steroidogenesis is related to reproductive function with differing response in males and females. TDCPP can be assumed to exert reproductive toxicity via disruption of thyroid and steroid synthesis through a slow metabolic rate in the whole body after exposure. Consequently, our proposed methodological approach to assess the interactions of thyroid and steroid biosynthesis and metabolic rate of TDCPP with reproductive toxicity will serve a testing strategy to examine the adverse outcomes of emerging environmental chemicals.

Association of exposure to perfluoroalkyl substances (PFAS) and phthalates with thyroid hormones in adolescents from HBM4EU aligned studies

BackgroundPerfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in various types of consumer products. There is epidemiological and experimental evidence that PFAS and phthalates may alter thyroid hormone levels; however, studies in children and adolescents are limited. AimTo investigate the association of exposure to PFAS and phthalate with serum levels of thyroid hormones in European adolescents. MethodsA cross-sectional study was conducted in 406 female and 327 male adolescents (14–17 years) from Belgium, Slovakia, and Spain participating in the Aligned Studies of the HBM4EU Project (FLEHS IV, PCB cohort, and BEA, respectively). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) were measured in sera from study participants, and urinary metabolites of six phthalates (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and the non-phthalate plasticizer DINCH® were quantified in spot urine samples. Associations were assessed with linear regression and g-computational models for mixtures. Effect modification by sex was examined. ResultsIn females, serum PFOA and the PFAS mixture concentrations were associated with lower FT4 and higher FT3 levels; MEP and the sums of DEHP, DiNP, and DINCH® metabolites (∑DEHP, ∑DiNP, and ∑DINCH) were associated with higher FT4; ∑DEHP with lower FT3; and the phthalate/DINCH® metabolite mixture with higher FT4 and lower FT3. In males, PFOA was associated with lower FT4 and the PFAS mixture with higher TSH levels and lower FT4/TSH ratio; MEP and ∑DiNP were associated with higher FT4; and MBzP, ∑DEHP, and the phthalate/DINCH® metabolite mixture with lower TSH and higher FT4/TSH. PFOA, mono-(2-ethyl-5-hydroxyhexyl) phthalate (OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (oxo-MEHP), and monocarboxyoctyl phthalate (MCOP) made the greatest contribution to the mixture effect. ConclusionsResults suggest that exposure to PFAS and phthalates is associated with sex-specific differences in thyroid hormone levels in adolescents.

The Effect of Induced Thyrotoxicosis on Avian Limb Development.

Thyroid hormone (TH) is essential for bone development. Altered TH levels such as hyperthyroidism, or thyrotoxicosis, results in the early maturation of the cartilaginous scaffold for long bone development, which can cause improper ossification. Maternal hyperthyroidism during embryonic development causes neonatal thyrotoxicosis and can therefore lead to stunted growth in infants. In our avian model of induced thyrotoxicosis, we injected saline (control) or 25ng thyroxine (T4) in 0.1 mL dose into fertilized chicken eggs on embryonic (E) days E11 and E15. On E19, chicken embryo length was measured and limbs were collected. The left limbs were whole-mount stained with Alizarin Red (bone) and Alcian Blue (cartilage). Limbs were then imaged and tibias were measured using ImageJ. The tibias from the right limbs were further dissected, embedded in paraffin, cut (5μM), and stained with Safranin O (cartilage) and Fast Green (bone). Sections were examined to determine morphological changes in the cartilaginous long bone scaffold. Body length was 4.8% shorter following thyroxine exposure (p&lt;0.01). Tibias were 2.4% shorter, though not statistically significant (p=0.36). Paraffin-embedded sections suggested increased chondrocyte hypertrophy, although further quantification is required. In conclusion, our data support thyroxine-induced changes in long bone morphology. Understanding how thyrotoxicosis can alter bone development in utero is important for developing potential targeted therapies for improving ossification in cases of neonatal thyrotoxicosis.&#x0D; &#x0D; Acknowledgment of NASA West Virginia Space Grant Consortium (Grant #80NSSC20M0055) and the Genomics Core Facility and WV-INBRE (NIH grant P20GM103434).

Salivary Alterations in Autoimmune Thyroid Diseases: A Systematic Review

Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's thyroiditis and Graves' disease. Saliva performs many functions and, importantly, has the potential for easy, non-invasive diagnostics of several systemic disorders. This systematic review was designed to answer the question whether salivary alterations are reliable for the diagnosis of autoimmune thyroid diseases. Following the inclusion and exclusion criteria, fifteen studies were included. Due to their heterogeneity, saliva analysis was divided into two subgroups: quantitative assessment analysing salivation and qualitative assessment concerning potential salivary biomarkers for AITD. In addition to detecting altered levels of thyroid hormones and antibodies, salivary changes were also observed in the concentrations of total protein, cytokines and chemokines, as well as markers of oxidative status. According to the saliva flow rate values, significantly reduced saliva secretion was observed in patients with HT. In conclusion, it is not possible to unequivocally state if salivary biomarkers can potentially be used in autoimmune thyroid disease diagnosis. Therefore, further investigations, including salivation disorders, are necessary to validate these findings.

Hormonal Crosstalk Between Thyroid and Breast Cancer.

Differentiated thyroid cancer and breast cancer account for a significant portion of endocrine-related malignancies and predominately affect women. As hormonally responsive tissues, the breast and thyroid share endocrine signaling. Breast cells are responsive to thyroid hormone signaling and are affected by altered thyroid hormone levels. Thyroid cells are responsive to sex hormones, particularly estrogen, and undergo protumorigenic processes upon estrogen stimulation. Thyroid and sex hormones also display significant transcriptional crosstalk that influences oncogenesis and treatment sensitivity. Obesity-related adipocyte alterations-adipocyte estrogen production, inflammation, feeding hormone dysregulation, and metabolic syndromes-promote hormonal alterations in breast and thyroid tissues. Environmental toxicants disrupt endocrine systems, including breast and thyroid homeostasis, and influence pathologic processes in both organs through hormone mimetic action. In this brief review, we discuss the hormonal connections between the breast and thyroid and perspectives on hormonal therapies for breast and thyroid cancer. Future research efforts should acknowledge and further explore the hormonal crosstalk of these tissues in an effort to further understand the prevalence of thyroid and breast cancer in women and to identify potential therapeutic options.

Exposure to diclofenac alters thyroid hormone levels and transcription of genes involved in the hypothalamic–pituitary–thyroid axis in zebrafish embryos/larvae

Diclofenac (DCF), one of typical non-steroidal anti-inflammatory drugs (NSAIDs), has been frequently detected in various environmental media. Nevertheless，the potential endocrine disrupting effects of DCF on fish were poorly understood. In the present study, zebrafish embryos/larvae were used as a model to evaluate the adverse effects of DCF on development and thyroid system. The results demonstrated that DCF only significantly decreased the heart rate at 72 h post-fertilization (hpf), exhibiting limited influence on the embryonic development of zebrafish. Treatment with DCF significantly reduced whole-body thyroxine (T4) levels, and changed transcriptional levels of several genes related to the hypothalamic-pituitary-thyroid (HPT) axis. These findings provide important information regarding to the mechanisms of DCF-induced developmental toxicity and thyroid disruption in fish.

Urinary phthalate metabolites in pregnant women: occurrences, related factors, and association with maternal hormones.

In this study, we aimed to evaluate phthalate metabolite levels in pregnant women, to explore the factors influencing exposure, and to assess phthalate metabolite levels in relation to thyroid hormone synthesis. We recruited 463 pregnant women and collected urine, blood, and questionnaire data at participant's first prenatal examination. Ten phthalate metabolites were analyzed: mono-isobutyl phthalate (MiBP); mono-methyl phthalate (MMP); mono-ethyl phthalate (MEP); mono-n-butyl phthalate (MnBP); mono-n-octyl phthalate (MOP); mono-benzyl phthalate (MBzP); and the metabolite of di-2-ethylhexyl phthalate (DEHP), which were mono (2-ethylhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-carboxypentyl) phthalate. Multivariable generalized estimating equation models and linear mixed models were used to predict urinary biomarker concentrations and to assess the associations between phthalate exposure and thyroid hormones. Positive associations were found between phthalate metabolites and lower education (MEP and MOP), living near the road (MEP, MnBP, and ∑DEHP), and consuming more puffed food (MEP and MBzP). In addition, MnBP (percent change [%△] = 4.25; 95% confidence interval [CI] = 0.32, 8.18) and ∑DEHP (%△ = 5.12; 95% CI = 1.25, 8.99) were positively associated with thyroid-stimulating hormones, although MEP and MnBP were inversely associated with free thyroxine and total triiodothyronine. Our findings suggest that certain habits and behaviors were predictive of the positive presence of phthalate metabolites and that certain phthalate esters are associated with altered thyroid hormone levels.

Impact of brominated flame retardants on lipid metabolism: An in vitro approach

Brominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.

Exposure of adult zebrafish to androstenedione alters thyroid hormone levels and the transcriptional expression of genes related to the hypothalamus-pituitary-thyroid axis

Androstenedione (AED) is a naturally occurring androgen that is released into the environment through human and animal excretion. Several studies have shown that AED can interfere with the normal growth, development, and reproduction of organisms. However, studies examining the thyroid system, an important part of endocrine system of fish, are still lacking. This study examines thyroid hormone levels including T3 and T4, and transcriptional expression levels of genes associated with the hypothalamic-pituitary-thyroid axis (HPT axis) in adult zebrafish. Fish were exposed to a solvent control and three other concentrations of AED (0.2, 2.3, and 23.7 μg/L) for 60 days. Results indicated that AED significantly increased T4 levels but inhibited transcription of some HPT axis-related genes (nis, tpo, tg, dio1, dio2, sult1 st5, pax8, and nkx2.1) in female zebrafish. The adverse effects of AED on the thyroid system in males were very low, only affecting down-regulation of the tshb gene and up-regulation of the thrb gene. The overall results demonstrated that AED interferes with the thyroid endocrine system in fish.

Evaluation of Thyroid Hormone Levels in Full-Term Neonates Presented with Septic Shock

Introduction: The incidence of neonatal sepsis in India is 38 per 1000 live births. Many authorsfound an association between altered thyroid hormone levels and septic shock in neonates and itmay be of prognostic importance in septic shock treatment. This study has been conducted to findthe relationship between thyroid profile and septic shock in neonates and also to compare thethyroid profile in survivor and non-survivor groups of septic shock patients. Methods: Thisanalytical prospective cohort study was conducted in the NICU of a tertiary care teaching institutionin central India. Full-term neonates with late-onset sepsis were included in this study and estimationof thyroid hormones (TSH, T3, T4, fT3, and fT4) was performed. These neonates were divided intothose with and without septic shock patients and levels of thyroid hormones were correlatedbetween these patients to find significant relations. The Vasoactive-Inotropic Score (VIS) score wascalculated. Results: A total of 195 full-term neonates were included in the study. The mean value ofTSH, T3, T4, fT3, and fT4 among neonates with septic shock were 5.27 μg/ml, 80.01 ng/dl, 6.36μg/dl, 1.40 pg/ml, and 1.40 μg/dl, respectively while the values were 5.29 μg/ml, 94.4 ng/dl, 7.25μg/dl, 1.84 pg/ml, and 1.43 μg/dl, respectively in septic neonates without shock. This difference wasstatistically significant except for TSH (p&gt;0.05). The mean value of TSH, T3, T4, fT3, and fT4 amongseptic shock survivors were 5.27 μg/ml, 80.01 ng/dl, 6.36 μg/dl, 1.40 pg/ml, and 1.40 μg/dl and inseptic shock non-survivors were 2.40 μg/ml, 37.33 ng/dl, 3.86 μg/dl, 0.99 pg/ml, and 0.84 μg/dl,respectively (p&lt;0.0001). Only T3 was found to be significantly co-related with VIS in septic shock inall the groups (&lt;0.001). Conclusion: Our study suggests that TSH, T3, T4, fT3, and fT4 levels aresignificantly low in patients suffering from the septic shock which may vary in the case of TSH. Also,there is a significant decrease in thyroid profile among septic shock non-survivors as compared tosurvivors.

Complex environmental contaminant mixtures and their associations with thyroid hormones using supervised and unsupervised machine learning techniques

Evaluating complex mixtures and their associated health effects poses a challenge in human populations. Herein, we assess the association between 17 organic and metal contaminants in blood with thyroid hormones in a remote Indigenous (First Nations) region from Quebec, Canada (n=526). Using principal component analysis (PCA) to reduce the number of variables, we generated varimax rotated principal component (PC) loadings of contaminants on these uncorrelated synthetic axes. Associations with levels of thyroid hormones (TSH, free T4, and total T3) were conducted using multivariable linear regression methods with the participant PC loadings and adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) analysis was used to evaluate the univariate contaminant exposure effect as well as the contaminant mixture effects on levels of thyroid hormones. Significant and positive associations were found between total T3 and PC-2 (high positive nickel and cadmium loadings), total T3 and PC-3 (negative association with negative loading for nickel and positive loading for cadmium) and TSH and PC-1 (high positive loadings for organic contaminants). No significant observations were observed for free T4. BKMR provided additional insight into the PCA results and suggested that nickel, and not cadmium, was responsible for driving the observed effects with this effect remaining when evaluating the entire mixture. BKMR analysis did not support the association of TSH with organic contaminants that were found in the PCA regression. Our findings reinforced other studies which showed that metals such as nickel may alter thyroid hormone levels and highlighted how complex environmental mixtures interact with each other. These observations represent an important step to determining how complex mixtures of contaminants can be assessed in human populations, especially those living a subsistence lifestyle who may have high body burdens of contaminants, and to help understand the resultant net effect of exposures on endogenous thyroid hormones utilizing novel machine learning statistical methods.

Subclinical hypothyroidism: treat or watch?

Manifest hypothyroidism occurs in more than 5 % of the population, while prevalence of subclinical hypothyroidism is much higher and reaches 15 %. In the practice of an endocrinologist, in most cases, the diagnosis and treatment of manifest hypothyroidism does not raise questions, while subclinical changes in thyroid hormones quite often generate a lot of discussions. The generally accepted reference range for TSH up to 4.50 μIU / ml is in conflict with data showing that more than 95 % of healthy people with euthyroidism have serum TSH levels up to 2.5 μIU / ml. At the same time, a lot of data has been accumulated on the effect of even slightly altered levels of thyroid hormones and TSH on various tissues, organs and systems of the body, especially on the cardiovascular, nervous and reproductive systems. This review analyzes the results of studies aimed at studying the relationship of subclinical hypothyroidism with cardiovascular and metabolic disorders, cognitive disorders, pathology of pregnant women.

Acetylcholinesterase activity and thyroid hormone levels in Ecuadorian adolescents living in agricultural settings where organophosphate pesticides are used.

Organophosphates are frequently applied insecticides that inhibit acetylcholinesterase (AChE) activity resulting in cholinergic overstimulation. Limited evidence suggests that organophosphates may alter thyroid hormone levels, although studies have yielded inconsistent findings. We aimed to test the associations between AChE activity, a physiological marker of organophosphate exposure, and thyroid function in adolescents. We included information of 80 adolescent participants (ages 12-17y in 2016, 53% male) growing up in agricultural settings in Ecuador. We measured fingerstick erythrocytic AChE activity and hemoglobin concentration, and concurrent serum thyroid stimulating hormone (TSH) and free-T4 (fT4) concentrations. General linear models were used to test associations which adjusted for demographic and anthropometric variables. TSH associations were further adjusted for fT4. The mean (SD) AChE, TSH and fT4 levels were 3.77 U/mL (0.55), 2.82 μIU/ml (1.49) and 1.11ng/dl (0.13), respectively. Lower AChE activity, indicating greater organophosphate exposure, was marginally associated with greater fT4 concentrations (difference per SD decrease in AChE activity (β)=0.03ng/dL, [90% CI: 0.00, 0.06]) but not with TSH (β=-0.01 μIU/ml, [-0.38, 0.36]). Gender modified the AChE-TSH association (p=0.03). In girls, lower AChE activity was associated with higher fT4 levels (β=0.05ng/dL [0.01, 0.10]) and lower TSH concentrations (β=-0.51 μIU/ml, [-1.00, -0.023]). No associations were observed in boys. These cross-sectional findings suggest that alterations in the cholinergic system from organophosphate exposures can increase fT4 levels coupled with a beyond-compensatory downregulation of TSH in female adolescents. This is the first study to characterize these associations in adolescents.

Endocrine Disrupting Chemical Mixtures Alter Maternal Thyroid Hormones - A Potential Pathway for Altered Fetal Programming?

Background: During early pregnancy the fetus wholly depends on maternal thyroid hormone (TH) for normal growth and development. Even sub-clinical changes can elicit adverse pregnancy and child-health outcomes. Individually, numerous endocrine disrupting chemicals (EDCs) have been linked to altered TH levels, but the combined effect of multiple EDCs remains understudied. Aim: To evaluate the cross-sectional association between 26 suspected or confirmed EDCs measured in urine and blood on maternal TH status during the first trimester of pregnancy. Methods: Within the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study, we assessed EDCs in relation to thyroid function markers, including thyroxine and free and total triiodothyronine (fT3, tT3), among 1240 pregnant women (median 10 weeks gestation) using Weighted Quantile Sum (WQS) regression. We tested bi-directional constraints, adjusting for maternal age, ethnicity, education, parity, smoking, gestational age, thyroglobulin and thyroid-peroxidase antibodies, and urinary creatinine. Based on prior literature, we assessed interactions by gestational age. Results: The EDC mixture was related to lower fT3 levels (WQS=-0.21 95%CI=-0.29, -0.13); the largest chemical weights included total polychlorinated biphenyls (PCBs) (25%), trans-nonachlor (17%), and dichlorodiphenyltrichloroethane (DDT) (10%). The EDC mixture was related to altered fT3, with different chemicals eliciting positive and negative effects. The negatively constrained estimate (WQS=-0.12 95%CI=-0.19, -0.04) was driven by PCBs (17%), DDT (13%), and perfluorooctane sulfonate (PFOS) (13%), whereas the positively constrained estimate (WQS=0.08 95%CI=0.01, 0.15) was driven by 2-4-methyl-7-oxyooctyl-oxycarbonyl-cyclohexane-carboxylic-acid (MOiNCH) (13%), 2-hydroxyphenanthrene (12%), and monoethyl and monobutyl phthalates (MEP, MBP) (11%, 11%). With a negative constraint, there was a significant interaction between the EDC mixture and gestational age for fT3 (WQSxAge=-0.03 95%CI=-0.01, -0.05). Conclusions: During pregnancy, mixtures of persistent chlorinated and perfluoroalkyl compounds were related to lower tT3 and fT3, whereas short-lived pollutants (plasticizers, polycyclic aromatic hydrocarbon) were related to higher fT3. Detected associations may depend on gestational age.

Altered thyroid hormone levels affect the capacity for temperature-induced developmental plasticity in larvae of Rana temporaria and Xenopus laevis.

Anuran larvae show phenotypic plasticity in age and size at metamorphosis as a response to temperature variation. The capacity for temperature-induced developmental plasticity is determined by the thermal adaptation of a population. Multiple factors such as physiological responses to changing environmental conditions, however, might influence this capacity as well. In anuran larvae, thyroid hormone (TH) levels control growth and developmental rate and changes in TH status are a well-known stress response to sub-optimal environmental conditions. We investigated how chemically altered TH levels affect the capacity to exhibit temperature-induced developmental plasticity in larvae of the African clawed frog (Xenopus laevis) and the common frog (Rana temporaria). In both species, TH level influenced growth and developmental rate and modified the capacity for temperature-induced developmental plasticity. High TH levels reduced thermal sensitivity of metamorphic traits up to 57% (R. temporaria) and 36% (X. laevis). Rates of growth and development were more plastic in response to temperature in X. laevis (+30%) than in R. temporaria (+6%). Plasticity in rates of growth and development is beneficial to larvae in heterogeneous habitats as it allows a more rapid transition into the juvenile stage where rates of mortality are lower. Therefore, environmental stressors that increase endogenous TH levels and reduce temperature-dependent plasticity may increase risks and the vulnerability of anuran larvae. As TH status also influences metabolism, future studies should investigate whether reductions in physiological plasticity also increases the vulnerability of tadpoles to global change.