Thyroid Hormone Levels Research Articles

Prolonged exposure to NaAsO2 induces thyroid dysfunction and inflammatory injury in Sprague‒Dawley rats, involvement of NLRP3 inflammasome‒mediated pyroptosis.

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.

The Causal Role of Thyroid Hormones in Bipolar Disorders: A Two-Sample Mendelian Randomization Study.

Bipolar disorder is a complex psychiatric condition with distinctions between clinical subtypes including Type 1 and 2 disorders. Several studies have proposed that thyroid hormones may be involved in the aetiology of bipolar disorders. This study employed a two-sample Mendelian randomization (MR) approach to investigate the causal relationships between six thyroid hormone metrics (TSH, FT4, FT3, TT3, FT3/FT4 and TT3/FT4) and bipolar disorder and Type 1 and 2 disorders, separately. Genome-wide association (GWAS) data from the ThyroidOmics Consortium (up to 271,040 individuals of European ancestry) were used for thyroid function metrics. Bipolar disorder GWAS data included 41,917 cases and 371,549 controls (25,060 Type 1 and 6,781 Type 2 cases). We applied inverse variance weighted (IVW) methods for primary MR analysis, with MR Egger, weighted median and weighted mode for sensitivity. Additional tests assessed horizontal pleiotropy and heterogeneity. Higher FT4 levels showed a protective causal effect against bipolar disorder (OR: 0.92, 95% CI: 0.86-0.97, p = 4.58 × 10-3) and a suggestive effect on Type 1 disorders (OR: 0.92, 95% CI: 0.86-0.99, p = 3.21 × 10-2). Elevated FT3 (OR: 1.18, 95% CI: 1.03-1.35, p = 1.55 × 10-2) and FT3/FT4 ratio (OR: 1.97, 95% CI: 1.02-3.82, p = 4.46 × 10-2) had suggestive harmful effects on Type 1 disorders. Sensitivity analyses showed consistent effects, with no significant horizontal pleiotropy or heterogeneity. These findings highlight the protective role of FT4 and the potentially harmful effect of elevated FT3 in Type 1 bipolar disorder, highlighting the need for further research on thyroid hormone levels as a potential treatment strategy for Type 1 bipolar disorder.

Association of thyroid hormones with the severity of chronic kidney disease: a cross-sectional observational study at Tabuk, Saudi Arabia

Background The interplay between chronic kidney disease (CKD) and thyroid dysfunction is becoming more evident in the biomedical community. However, the intricacies of their relationship warrant deeper investigation to understand the clinical implications fully. Objective This study aims to systematically evaluate the correlation between thyroid hormone levels, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and markers of renal disease severity. These markers include serum creatinine, urea, and parathyroid hormone (PTH) levels in individuals diagnosed with CK). Methods We conducted a cross-sectional observational study involving a cohort of 86 participants with CKD recruited from the renal clinic at King Fahad Hospital in Tabuk. Biochemical parameters, encompassing plasma electrolytes and thyroid hormone concentrations, were quantitatively assessed. These measurements were performed with the aid of a Roche Cobas E411 analyzer. The Pearson correlation coefficient was employed to delineate the strength and direction of the associations between the thyroid function markers and renal disease indicators. Results The statistical analysis highlighted a generally weak correlation between the concentrations of thyroid hormones and the indicators of renal disease severity, with Pearson correlation coefficients between −0.319 and 0.815. Critically, no significant correlation was found between creatinine and thyroid hormones (TSH, T3, T4), nor was any substantial correlation between urea and thyroid hormones. Conversely, a robust positive correlation was noted between the levels of parathyroid hormone and serum creatinine (r = 0.718, p < 0.001). Conclusion The data suggests that thyroid hormone levels have a minimal correlation with the severity of renal disease markers. In contrast, the pronounced correlation between PTH and creatinine underscores the importance of considering PTH as a significant factor in managing and therapeutic intervention of CKD complications. These initial findings catalyze further research to thoroughly investigate the pathophysiological relationships and potential therapeutic targets concerning thyroid dysfunction in patients with renal impairment.

Associations between gestational exposure to perfluoroalkyl substances, fetal growth, and the mediation effect of thyroid hormones

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) may cause adverse birth outcomes. Thyroid hormones may play a key role in mediating the effects of PFAS. We enrolled 374 mother-infant pairs from the Ezhou birth cohort study between 2019 and 2020. Eight PFASs and six thyroid hormones were measured in maternal serum during the first trimester of pregnancy. Neonatal growth metrics, including birth weight, length, head circumference, and gestational age, were acquired. Multivariate linear regression was performed to determine the associations between maternal serum PFAS and thyroid hormone levels and birth outcomes and a mediation analysis was also conducted. Except for perfluoroheptanoic acid (41.2%), the other seven PFAS detection rates were more than 85%, and the highest median concentration was observed for PFOSA with levels of 5.21 ng/mL. After controlling for typical confounders, we observed a decrease in birth length (cm) with increasing serum concentrations of perfluorononanoic acid (PFNA) (β = -0.54; 95% CI = -1.0, -0.08) and perfluorohexane sulfonate (PFHxS) (β = -0.64; 95% CI = -0.86, -0.42). Additionally, a decrease in birth head circumference was observed with increasing concentrations of perfluorooctanote (PFOA) (β = -0.73, 95% CI = -1.19, -0.27) and PFHxS (β = -0.30; 95% CI = -0.53, -0.07). Maternal free triiodothyronine (FT3) mediated 36.7% of the negative association between PFNA and birth length, and free thyroxine (FT4) mediated 30.8% of the effect of PFOA on head circumference. When performing stratified analysis by infant sex, the associations might differ between boys and girls. Our study suggested prenatal exposure to some PFASs was negatively associated with birth length and circumference, and FT3 and FT4 may partly mediate the association.

Effect of electronic smoking (Vaping) on thyroid hormones level and lipid profile in men

In the last period, the market quickly became saturated with vaping devices available in many flavors and forms appealing to youth. Both traditional cigarette and e-cigarette smoking are known to potentially alter metabolic processes, including hormone production and to increase the risk of lung, heart and kidney diseases. The aim of the study was to estimate the level of thyroid hormones and lipids in the blood of young men who smoked traditional or e-cigarettes. A case-control study involved 200 men aged 24-25 years who smoked 5-7 h per day, divided into two groups (100 e-cigarette smokers and 100 cigarette smokers) and 50 healthy men who did not smoke. The levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured using COBAS E411. The levels of total cholesterol, TG, LDL and HDL were estimated spectrophotometrically. No significant changes were found in thyroid hormone levels or lipid profiles, except for an increased TG content in the group of traditional cigarette smokers compared to the control group. Whereas in the blood of e-smokers, the increase in the level of FT3 and FT4 and a significant decrease in that of TSH, as well as the elevated content of total cholesterol, TG, and LDL, were detected compared to the control group. The results obtained indicate that e-smoking affects the function of the thyroid gland and lipid metabolism. Keywords: blood samples, lipid profile, thyroid hormones, vaping

Preclinical thyroid hormone profile studies of an ayurvedic medicine Parthadyarishta after chronic administration to male Sprague-Dawley rats

Background: Parthadyarishta (PRTm) is an Ayurvedic preparation used as a traditional medicine to treat heart disease. This research was designed to study the thyroid hormone profile after chronic administration of this drug. Methods: Twenty healthy Sprague-Dawley male rats (90-110 g) were randomly divided into a control group and an experimental group. The experimental group was assigned to receive the drug at a dose of 40 ml/kg of body weight orally. After 28 days of treatment, blood samples were collected to carry out biochemical tests to determine the thyroid hormone safety profile. Serum circulating levels of total thyroxine (tT4), total triiodothyronine (tT3), free thyroxine (fT4), free triiodothyronine (fT3), thyroid stimulating hormone (TSH) were measured by Chemiluminescent Microparticle Immunoassay (CMIA) method. Results: This study showed statistically significant (p=0.008) [21.93%] decrease in tT3 level and statistically significant (p=0.047) [10.73%] increase in fT3 level in the rats. Also, statistically insignificant decrease in tT4 level and increase in fT4 level were observed. There is a [49.96 %] decrease in TSH level (p=0.371). The results suggested that Parthadyarishta have exerted an opposite effect on both the total and free form of T3 by increasing the free form (fT3) though causing decrease in the total form (tT3). Conclusions: As Parthadyarishta has significant impact on thyroid hormone levels so it is recommended to use it cautiously for chronic use specially in cardiac patients. Further studies are needed to determine the toxicological profile of Parthadyarishta and its effect on cardiovascular system through interference in thyroid function.

Effects and phenotypic consequences of transient thyrotoxicosis and hypothyroidism at different stages of zebrafish Danio rerio (Teleostei; Cyprinidae) skeleton development.

The effects and consequences of changes in thyroid hormones (THs) level are among the actively studied topics in teleost developmental and evolutionary biology. In most of the experimental models used, the altered hormonal status (either hypo- or hyperthyroidism) is a stable characteristic of the developing organism, and the observed phenotypic outcomes are the cumulative consequences of multiple TH-induced developmental changes. Meanwhile, the influence of the transient fluctuations of TH content on skeleton development has been much less studied. Here, we present experimental data on the developmental effects and phenotypic consequences of transient, pharmacologically induced thyrotoxicosis and hypothyroidism at different stages of ossified skeleton patterning in zebrafish. According to the results, the skeleton structures differed in TH sensitivity. Some showed a notable shift in the developmental timing and rate, while other demonstrated little or no response to changes in TH content. The developmental stages also differed in TH sensitivity. We identified a relatively short developmental period, during which changes in TH level significantly increased the developmental instability and plasticity, leading to phenotypic consequences comparable to those in fish with a persistent hypo- or hyperthyroidism. These findings allow this period to be considered as a critical developmental window.

Lower Free Thyroxine Levels Are Associated with Diabetic Kidney Disease in Males with Type 2 Diabetes Mellitus: An Observational Cross-Sectional Study.

Objectives: We aimed to explore the correlation between thyroid function and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 7516 T2DM patients were enrolled and grouped according to DKD status. Clinical parameters, including blood glucose parameters, thyroid function, and indicators of renal impairment, were collected and compared between the DKD and Non-DKD groups. Correlation analysis and univariate/multivariate logistic regression analyses were performed. Results: Age, T2DM duration, the use of insulin and lipid-lowering drugs, systolic and diastolic blood pressure, body mass index, and fasting blood glucose levels were greater in the DKD group than in the Non-DKD group (p < 0.001). Notably, compared with those in the Non-DKD group, patients in the DKD group had lower triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) levels and higher thyrotropin levels (p < 0.001). Univariate logistic regression analysis revealed that T3, T4, FT3, and FT4 levels were negatively correlated with the risk of DKD. Spearman correlation analysis confirmed that T3, T4, FT3, and FT4 levels were negatively correlated with blood urea nitrogen levels, blood creatinine levels, and the urinary albumin-to-creatinine ratio (p < 0.05). Multivariate logistic regression analysis revealed that a greater FT4 level was a protective factor against DKD in T2DM patients, especially in males, with a cut-off value of 13.35 pmol/L (area under the curve = 0.604). Conclusions: Thyroid hormone levels, especially FT4 levels, were significantly negatively correlated with DKD in T2DM patients.

Perinatal exposure to environmental chemicals that disrupt thyroid function can perturb testis development

Thyroid hormones (THs) are essential for normal growth and development. Their role in skeletal and brain development is well established, with congenital hypothyroidism causing stunted growth and severe intellectual disability. THs are also important for the development of other tissues and organs, including the testis. Developmental hypothyroidism can manifest as smaller testes in early postnatal life that later develop into macroorchidism in adulthood due to increased proliferation of Sertoli cells. Effects of hypothyroidism on the testes can be modelled in rodents by exposing developing animals to TH-suppressing pharmaceuticals such as propylthiouracil (PTU) and methimazole (MMI). These drugs act by inhibiting the thyroperoxidase (TPO) enzyme in the thyroid gland, inhibiting the synthesis of THs. It is possible that environmental chemicals that inhibit TPO activity can also cause TH-mediated effects on the developing testis, but the extent to which this occurs is not known. Herein, we characterized the effects of perinatal exposure to the herbicide amitrole together with the antithyroid drug MMI. Pregnant Sprague-Dawley rats were exposed by oral gavage to two doses of amitrole (25 or 50 mg/kg body weight/day) or MMI (8 or 16 mg/kg body weight/day) from gestational day 7 until birth. After birth, pup exposure was continued by dosing lactating dams from day of delivery until pup day 16. Both chemicals caused a significant reduction in TH levels on day 16. This perinatal hypothyroidism disrupted both germ and Sertoli cell development, resulting in smaller testes and reduced seminiferous tubule diameter in 16-day old pups. Notably, fetal male blood progesterone levels were increased after exposure to both amitrole and MMI, whereas the amitrole-exposed animals also displayed increased estradiol levels. Our study raises concerns that exposure to environmental chemicals that happen to disrupt TH production may disrupt TH-dependent testis development, with adverse consequences to human reproductive health.

Magnitude of cardiac abnormality and its associated factors among hyperthyroidism patients on follow-up at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

BackgroundThyroid hormones have an effect on every organ system, in particular, the heart responds to minimal changes in serum thyroid hormone level. Thyroid hormone causes a lot of changes in the cardiovascular system, such as increased heart rate, contractility, systolic hypertension, changes in peripheral vascular resistance, atrial fibrillation (AF), and hypercoagulability from the direct effect of thyroid hormone on cardiac myocyte and /or due to increased metabolic state. However, the magnitude of such heart abnormalities and its associated factors were not well studied in Ethiopia.ObjectiveTo determine the magnitude of cardiac abnormality and its associated factors among hyperthyroidism patients on follow-up at Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia, 2022.MethodsAn institution-based cross-sectional study was carried out among 318 hyperthyroid patients who were on follow-up at the endocrine clinic of TASH, Addis Ababa, Ethiopia from June to October 2022. The data were collected using a pretested structured interviewer administered questionnaire. The data were entered into the computer using EpiData version 3.1 and analyzed using SPSS version 25 software. Bivariable and multivariable logistic regression models were fitted to determine the association between the independent and dependent variables. Adjusted odds ratio with its 95% confidence interval and p-value < 0.05 were used to declare the presence and strength of statistically significant associations.ResultIn this study a total of 318 hyperthyroid patients were participated, most (90.9%) of them were females. The overall prevalence of heart failure among hyperthyroid patients was 17.0% (95% CI = 13.0, 21.6). More than half (52.7%) and one third (33.2%) of the participants showed abnormal electrocardiographic and echocardiographic findings respectively. Marital status (not married) [AOR = 2.37, 95% CI (1.03, 5.44)], pattern of hyperthyroidism [AOR = 13.09, 95% CI (4.70, 36.41)], being Asthmatic [AOR = 7.63, 95% CI (1.55, 37.52)], type of medication [AOR = 3.49, 95% CI (1.11, 11.02)] and duration of treatment [AOR = 4.95, 95% CI (2.05,11.99)] were significantly associated with cardiac abnormality.ConclusionA significant portion of hyperthyroid patients overburdened by cardiac abnormalities. Being unmarried, overt hyperthyroid, Asthmatic, long stay on treatment and type of treatment were significantly associated with cardiac abnormality. Hence, attention should be given for cardiac abnormalities while treating hyperthyroid patients.

Effects of 4G Long-Term Evolution Electromagnetic Fields on Thyroid Hormone Dysfunction and Behavioral Changes in Adolescent Male Mice.

Radiofrequency electromagnetic fields (RF-EMFs) can penetrate tissues and potentially influence endocrine and brain development. Despite increased mobile phone use among children and adolescents, the long-term effects of RF-EMF exposure on brain and endocrine development remain unclear. This study investigated the effects of long-term evolution band (LTE) EMF exposure on thyroid hormone levels, crucial for metabolism, growth, and development. Four-week-old male mice (C57BL/6) were exposed to LTE EMF (whole-body average specific absorption rate [SAR] 4 W/kg) or a positive control (lead; Pb, 300 ppm in drinking water) for 4 weeks. Subsequently, the mice underwent behavioral tests including open field, marble burying, and nest building. Blood pituitary and thyroid hormone levels, and thyroid hormone-regulating genes within the hypothalamus-pituitary-thyroid (HPT) axis were analyzed. LTE exposure increased T3 levels, while Pb exposure elevated T3 and T4 and decreased ACTH levels. The LTE EMF group showed no gene expression alterations in the thyroid and pituitary glands, but hypothalamic Dio2 and Dio3 expressions were significantly reduced compared to that in the sham-exposed group. Pb exposure altered the hypothalamic mRNA levels of Oatp1c1 and Trh, pituitary mRNA of Trhr, and Tpo and Tg expression in the thyroid. In conclusion, LTE EMF exposure altered hypothalamic Dio2 and Dio3 expression, potentially impacting the HPT axis function. Further research is needed to explore RF-EMF's impacts on the endocrine system.

Impact of polyethylene microplastics exposure on kallikrein-3 levels, steroidal-thyroidal hormones, and antioxidant status in murine model: protective potentials of naringin

The widespread presence of microplastics in the environment has raised significant concerns regarding their potential impact on human and animal health. Among various microplastic types, polyethylene microplastics (PE-MPs) are particularly prevalent due to the extensive use in packaging and consumer products. Exploring the uncharted therapeutic potentials of naringin, this study delves into its mitigating effects on disruptions in kallikrein-3 levels, steroidal-thyroidal hormone balance, and antioxidant defense triggered by PE-MPs exposure, paving the way for novel interventions in environmental toxin-induced endocrine and oxidative stress disorders. Male Wistar rats (n = 24) were randomly grouped into four: Control, PE-MPs (1.5 mg/kg), PE-MPs + NAR (1.5 mg/kg PE-MPs + 100 mg/kg NAR), and NAR (100 mg/kg). Hormonal and antioxidant parameters were assessed after 28 days of exposure. PE-MPs exposure caused a significant increase(p < 0.005) in the level of kallikrein-3 (KLK-3) while it significantly reduces the levels of testosterone (TST), luteinizing hormone, thyroid stimulating hormone (TSH) and Free-triiodothyronine (fT3) and Total cholesterol (TChol) concentration. PE-MPs exposure also disrupted significantly (p < 0.005) antioxidant profile by down-regulating the activities of glutathione-S-transferase, catalase (CAT), superoxide dismutase (SOD) and reducing levels of glutathione (GSH) and ascorbic acid (AA) while concentration of malondialdehyde (MDA) levels were increased relative to control. However, the mitigating potentials of naringin on disruptions in hormonal and antioxidant profiles caused by PE-MPs exposure were demonstrated, as NAR normalized KLK-3, steroid, and thyroid hormone levels, cholesterol concentration, and enhanced antioxidant defense. This suggests that NAR is a promising protective agent against endocrine and oxidative damage induced by environmental contaminants such as microplastics.

Blood levels of zearalenone, thyroid-stimulating hormone, and thyroid hormones in patients with colorectal cancer

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.

Exploring the role of plasmapheresis prior to thyroidectomy in managing thyrotoxicosis: a comprehensive scoping review.

A thyroid storm is the most extreme and life-threatening presentation of thyrotoxicosis. Thyroidectomy can be used for definitive treatment. It should be performed after euthyroidism is accomplished. The use of therapeutic plasma exchange (TPE) is a last resort option in cases where standard pharmacological therapy proves to be ineffective. Due to its rare prevalence, there are limited data evaluating the usefulness and efficacy of TPE as a bridging therapy to thyroidectomy. The absence of relevant literature prompted us to conduct a scoping review. The following bibliographic databases were searched for articles dated 30 November 2023: Medline, EMBASE, Web of Science and Google Scholar. The search identified 1047 records, of which 42 articles were accepted with a total of 234 patients. The dominant indications for TPE were side effects due to conventional treatment. The mean fT4 level decreased 51.9% of baseline after TPE, while the mean fT3 level decreased 66.6% of baseline. The main side effects observed with FFP were allergic reactions, while the use of an albumin solution was associated with perioperative bleeding. Based on the limited data available in the literature, we recognize plasmapheresis as an effective treatment option for reducing thyroid hormone levels prior to thyroidectomy in patients with thyrotoxicosis. Available data suggest that it might be reasonable to limit the number of sessions in favor of an earlier surgical intervention. To reduce the risk of bleeding, FFP may be a better option as a replacement fluid, especially in the session prior to thyroidectomy.

Association between air pollutants, thyroid disorders, and thyroid hormone levels: a scoping review of epidemiological evidence.

Over the past two decades, the incidence of thyroid disorders has been steadily increasing. There is evidence to suggest that air pollution may be one of the etiological factors of thyroid diseases. This comprehensive review aimed to examine the evidence related to air pollutants and thyroid disorders and thyroid hormones levels from an epidemiological perspective. The scoping review adopted a systematic approach to search for, identify, and include peer-reviewed articles published in English. We performed a comprehensive search of three databases-PubMed, Embase, and Web of Science to identify relevant literature on the relationship between air pollution [particulate matter, nitrogen oxide, carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2)] exposure and thyroid disorders, including hypothyroidism, congenital hypothyroidism (CH), thyroid nodules, thyroid cancer, autoimmune thyroid diseases, as well as thyroid hormone levels, such as thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4). Articles published until August 1, 2023, were included. A total of 3,373 studies were retrieved, and among them, 25 studies covering eight different air pollutants were relevant. The most frequently studied air pollutants in this review included fine particulate matter (with fine particulate matter (PM2.5), n=21; inhalable particles (PM10), n=10; PM10-2.5, n=1) and nitrogen oxides (with NO2, n=13; NOx, n=3). The thyroid disorders and thyroid hormone levels most commonly associated with evidence of air pollution exposure were hypothyroidism (n=7) and TSH (n=12). Despite variations in study designs and exposure assessments, the findings consistently highlight the substantial health risks that air pollution, particularly PM2.5, poses to thyroid health, especially among vulnerable populations. Given that our study was limited to epidemiological investigations and the increasing prevalence of toxic substances in the environment, there is an urgent need for further research to elucidate the mechanisms by which these pollutants disrupt thyroid function and contribute to the development of thyroid diseases.

The Downregulation of the Liver Lipid Metabolism Induced by Hypothyroidism in Male Mice: Metabolic Flexibility Favors Compensatory Mechanisms in White Adipose Tissue

In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (THs), through their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, which leads to a reduction in energy expenditure as well as in lipid and glucose metabolism. The objective of this study was to evaluate whether the metabolic deregulations induced by hypothyroidism could be avoided through regulatory mechanisms involved in metabolic flexibility. To this end, the response to induced hypothyroidism was compared in males from two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and C57BL/6J mice, which are prone to DIO. The results show that propylthiouracil (PTU)-induced hypothyroidism led to metabolic deregulations, particularly a reduction in hepatic lipid synthesis in both strains. Furthermore, in contrast to the C57BL/6J mice, the WSB/EiJ mice were resistant to the metabolic dysregulations induced by hypothyroidism, mainly through enhanced lipid metabolism in their adipose tissue. Indeed, WSB/EiJ mice compensated for the decrease in hepatic lipid synthesis by mobilizing lipid reserves from white adipose tissue. Gene expression analysis revealed that hypothyroidism stimulated the hypothalamic orexigenic circuit in both strains, but there was unchanged melanocortin 4 receptor (Mc4r) and leptin receptor (LepR) expression in the hypothyroid WSB/EiJ mice strain, which reflects their adaptability to maintain their body weight, in contrast to C57BL/6J mice. Thus, this study showed that WSB/EiJ male mice displayed a resistance to the metabolic dysregulations induced by hypothyroidism through compensatory mechanisms. This highlights the importance of metabolic flexibility in the ability to adapt to disturbed circulating TH levels.

Correlation analysis of FT3/FT4 and frailty in elderly patients with coronary heart disease.

In previous studies on thyroid hormones and frailty, most of the target population were elderly, and there were relatively few studies on elderly patients with coronary heart disease (CHD). Inflammation, oxidative stress, and haemodynamic instability in cardiovascular disease (CVD) can influence fluctuations in thyroid hormone (TH) levels and increase the incidence of frailty. The purpose of the present study was to explore the effect of TH on the risk of frailty in elderly patients with CHD. The Fried scale was used to assess the frailty of participants. The predictive value of TH for frailty was determined using the patient's operating characteristic curve. Multivariate logistic regression model was utilised to analyse the relationship between TH and frailty. A total of 277 elderly patients with CHD were included in the study, of whom 29.96% were in a state of frailty. Free triiodothyronine (FT3)/free thyroxine (FT4) predicted frailty with the largest area under the curve of 0.634. Unordered multinomial logistic regression analysis showed that a lower T3 level was a risk factor for pre-frailty (p < 0.05). Lower levels of T3, FT3, and FT3/FT4 were risk factors for frailty (p < 0.05) after adjusting for demographic variables and blood indexes. The predictive value of FT3/FT4 for frailty was more accurate than that of a single index. Moreover, T3 ≤ 1.095 nmol/L, FT3 ≤ 4.085 pmol/L, and FT3/FT4 ≤ 0.336 were shown to be the influencing factors of frailty, while T3 ≤ 1.095 nmol/L is an independent risk factor pre-frailty. Clinicians should focus on timely identification of the risk of frailty in order to improve patient quality of life and to reduce the risk of complications.

12611 The Thyroid Adapts Remarkably to Overnutrition to Mitigate Hypothyroidism

Abstract Disclosure: J. Rampy: None. A. Torres Manzo: None. K. Hoffsmith: None. M.A. Loberg: None. H. Wang: None. V.L. Weiss: None. N. Carrasco: None. Obesity affects &amp;gt;40% of the U.S. population and is one of today’s biggest public health concerns. Losing weight is challenging, and maintaining weight loss even more so, owing to the many biochemical and hormonal changes that occur in the pathogenesis of obesity, some of which do not reverse after weight loss. Thyroid hormones (THs) have far-reaching effects on whole-body energy balance. Their synthesis and release by the thyroid are finely regulated by central mechanisms to control serum TH levels. THs are also regulated by nutrient sensing, so that their levels modulate energy expenditure to match energy intake. Given the reciprocal and fine-tuned relationship between THs and energy balance, one would expect strong upregulation of TH levels to counteract diet-induced weight gain, but this is not consistently reported in obesity studies. Thus, we hypothesized that overnutrition impairs thyroid function, preventing a sustained increase in TH levels. We tested this hypothesis in male C57Bl/6J mice fed a high-fat diet and sucrose water. Strikingly, overnutrition decreased T4 levels after just 5 days—and within 3 weeks, we observed mild hypothyroidism, with increased thyroid stimulating hormone (TSH) levels and goiter. After 6 weeks, intrathyroidal T4 levels were significantly decreased, whereas the expression of the TH precursor thyroglobulin (TG) was unchanged, despite high TSH stimulation. Furthermore, we found increased expression of several ER stress-related proteins, including BiP, p-eIF2α, and PDI. These results suggest that TG was not upregulated because overnutrition-induced ER stress impaired protein translation. Remarkably, even though T4 levels were low, the thyroid maintained normal T3 levels, likely due to the pronounced histological and vascular changes we observed, which should promote TH availability. Some changes were consistent with the classical growth effects of TSH stimulation, while others were likely due to upregulation of adrenomedullin 2, a TSH-responsive angiogenic vasodilator. Preliminary studies in female mice showed similar results. Notably, we have observed similar histological changes in human thyroids, which strongly correlate with BMI. Collectively, our results, despite the unchanged T3 levels, are consistent with a struggling thyroid and a mildly hypothyroid state. Existing data suggest that low T4 can itself be problematic, particularly in metabolic tissues that generate T3, the more biologically active form, from T4 to levels beyond those of the T3 available from the bloodstream. Reversibility of this state is being investigated in ongoing experiments. The causal role that overnutrition plays in thyroid impairment and decreased TH availability in the pathogenesis of obesity has scarcely begun to be elucidated. Our work sheds new light on how overnutrition changes thyroid function and highlights the remarkable adaptability of the thyroid. Presentation: 6/1/2024

8183 An Unusual Cause of Fluctuating Thyroid Hormone Levels

Abstract Disclosure: V. Taqi: None. W. Akhter: None. J.L. Gilden: None. Background: Thyroid disease, especially congenital hypothyroidism is a common endocrine problem with an estimated global prevalence of 4.25%. Since every organ system is affected by thyroid hormones, untreated hypothyroidism can lead to profound adverse outcomes. Many drugs, hormones, and dietary supplements have been noted to affect the efficacy of thyroid hormones, yet there was always concern about the effect of the excessive growth of intestinal flora in the small intestine on thyroid supplement absorption. Drugs, malabsorption, celiac disease and increased excretion are common causes of fluctuating thyroid hormones. In this case, we present a young male patient with congenital hypothyroidism, who required fluctuating doses of levothyroxine due to abnormal thyroid hormone levels, despite compliance with proper administration, and dramatic improvement of thyroid hormone levels after starting probiotic therapy. Case : An 18-year-old Caucasian male with congenital hypothyroidism had been treated with varying doses of thyroid hormone replacement by a Pediatric Endocrine Center. Due to his recall that TSH=4.13 mIU/L and he was “tired of taking medication”, he stopped taking 125 mcg of levothyroxine. Four months later, TSH was &amp;gt; 200 mIU/L (nl=0.48-4.17). Levothyroxine 137 mcg was then started. However, 11 months later, TSH=14.2 mIU/L, Free T4=1.6 ng/dL (nl=1.03-1.64). He was then referred to our Endocrine Clinic. He denied symptoms of hypo or hyperthyroidism or other medical issues. His grandfather was known to have hypothyroidism and diabetes mellitus (details unknown). On exam: Wt. was 149 Ib, Ht= 67 Inch. VS: BP 98/46, P 69, R:16,temp: 97.9F, Physical exam showed normal findings without thyromegaly, but there was a delay in tendon reflexes. Laboratory-unremarkable CBC, CMP panels with normal thyroid antibodies, and Celiac titers. TSH initially improved from 14.2 to 8.4 mIU/L after increasing the thyroxine dosage from 137 to 150 mcg for 2 weeks, then to 175 mcg after 4 weeks, but TSH increased to 12.1 mIu/L, despite being compliant with medication and ensuring proper way of administration. He continued to deny symptoms of hypo or hyperthyroidism, or any other medical issues, including lactose intolerance or malabsorption. However, probiotics were then added to his regimen, and continuation of the current dose resulted in a suppressed TSH=0.15 mIU/L. The levothyroxine was then decreased to 150 mcg with continuation of probiotics. One month later, TSH was 1.31 mIU/L with Free T4 of 1.5 ng/dL. Conclusion : Common causes for fluctuating thyroid hormone levels include intestinal malabsorption, celiac disease, nephrotic syndrome, drugs, and food interaction. This case demonstrates that despite proper administration, fluctuating thyroid hormone levels can result from some uncommon causes, such as lactose intolerance, which can be unmasked by co-administration of probiotics. Presentation: 6/2/2024

8490 The mRNA for the Nonsyndromic Deafness Gene Atp2b2 Is Reduced Following Developmental Hypothyroidism

Abstract Disclosure: E.A. Gregersen: None. R.P. Peeters: None. D. Forrest: None. D.S. Sharlin: None. Thyroid hormone (TH) is essential for auditory system development. In rodent models, low levels of TH during the early postnatal period delay cochlear tissue remodeling and alter ion channel function required for normal auditory function. TH receptors are ligand-dependent transcription factors that regulate gene expression. Considering this, auditory deficits observed in hypothyroidism are thought to be largely the result of altered expression of specific TH target genes. However, few TH-regulated genes in the developing cochlea have been reported. TH is reported to impact calcium signaling in several tissues, but whether regulators of calcium signaling are altered following developmental hypothyroidism in the cochlea is largely unexplored. In this report, we investigated the spatial and temporal expression of the ATPase, Ca++ transporting, plasma membrane 2 (Atp2b2) gene in a mouse model of developmental hypothyroidism. Timed-pregnant dams were treated with thyroid gland inhibitors to induce developmental TH insufficiency from embryonic day 12.5 (E12.5) through post-natal day 15 (P15). Untreated timed-pregnant dams served as euthyroid controls. Control and experimental cochleae were collected over a developmental period ranging from embryonic day 18.5 (E18.5) through P15. Cochleae were then processed to detect Atp2b2 mRNA by in situ hybridization or quantitative real-time PCR. In situ hybridization showed that Atp2b2 localizes to inner and outer hair cells as expected, but Atp2b2 was also observed at lower levels in the greater epithelial ridge and spiral ganglion. Quantification of Atp2b2 mRNA revealed an effect of postnatal day and treatment on Atp2b2. In euthyroid animals, Atp2b2 expression gradually increased until P10, then decreased slightly by P15. In hypothyroid animals, Atp2b2 mRNA was consistently decreased (2-2.5 fold). Hypothyroidism similarly impacted expression regardless of sex. The reduction in Atp2b2 mRNA expression in the hypothyroid animals suggests that Atp2b2 is developmentally regulated in part by thyroid hormone signaling. This study characterizes the relationship between TH and Atp2b2 expression during early cochlear development while providing insight into abnormal cochlear development due to hypothyroidism. Presentation: 6/3/2024