Free Thyroxine Concentrations Research Articles

Stability analysis of a mathematical model for methimazole dosing in graves' hyperthyroidism: A dynamic approach

This study explores a novel mathematical model for analyzing methimazole (MMI) therapy in patients with Graves' disease, a common autoimmune cause of hyperthyroidism. The model leverages a system of ordinary differential equations to capture the interplay between key factors: methimazole concentration, thyroid-stimulating hormone (TSH), free thyroxine (FT4) concentration, thyroid-stimulating hormone receptor antibody (TRAb) concentration, and functional thyroid gland size (V). Thirteen parameters account for the underlying physiological processes. Stability analysis were employedby Lyapunov stability theory and LaSalle's principle, to demonstrate the model's asymptotic stability. This implies the system converges towards a steady state under defined conditions. Additionally, a clinically relevant chart is constructed based on FT4 levels and treatment duration.For model validation, patient data is utilized within SimBiology simulations implemented in MATLAB. These simulations offer valuable insights into the dynamic response of hyperthyroidism to MMI treatment. This approach holds promise for future applications in optimizing treatment strategies and facilitating personalized medicine approaches.

Analysis of Serum Free Thyroxine Concentrations in Healthy Term Neonates Underlines Need for Local and Laboratory-Specific Reference Interval: A Systematic Review and Meta-Analysis of Individual Participant Data.

Background: Initial evaluation of the hypothalamus-pituitary-thyroid axis is done by measuring serum free thyroxine (fT4) and thyrotropin concentrations. For correct interpretation of these measurements, reliable age-specific reference intervals (RIs) are fundamental. Since neonatal fT4 RIs conforming to the Clinical and Laboratory Standards Institute guidelines are not available for all assays, we set out to create literature-based uniform age-specific neonatal fT4 RIs that may be used for every assay. Methods: For meta-analysis of individual participant fT4 concentrations, we systematically searched MEDLINE and Embase (search date December 6, 2023; PROSPERO registration CRD42016041871). We searched for studies reporting fT4 concentrations in healthy term newborns aged 2-27 days, born to mothers without thyroid disease in iodine-sufficient regions. Authors were invited to supply data. Due to standardization differences between assays, data could not be combined for meta-analysis directly, and we attempted to normalize the data using two distinct methods. Results: We obtained 4206 fT4 concentrations from 20 studies that used 13 different assays from 6 manufacturers. First, we set out to normalize fT4 data using the mean and standard deviation of (assay-specific) adult RIs. fT4 concentrations were transformed into Z-scores, assuming a normal distribution. Using a linear mixed-effects model (LMM), we still found a significant difference between fT4 concentration across studies (p < 0.001), after this normalization. As a second approach, we normalized the fT4 concentrations using data from a method/assay comparison study. We used the relationship between the Cobas assay and the other assays as a reference point to convert all values to Cobas values. However, this method also failed to produce consistent results, with significant differences between the normalized data (LMM p < 0.001). Conclusions: We conclude that our attempts at normalizing fT4 assay results were unsuccessful. Confounders related to our unsuccessful analysis may be assay related and/or biological. These findings have significant implications for patient care, since relying on RIs from literature may result in erroneous interpretation of results. Therefore, we strongly recommend to establish local RIs for accurate interpretation of serum fT4 concentrations in neonates.

Calculation of reference intervals for indicators of thyroid hormones and cortisol in horses

The article discusses the results of calculating reference intervals for thyroid hor mones and cortisol in adult horses. The study included the results of a laboratory study of the concentrations of total triiodothyronine, total and free thyroxine and cortisol from 50 horses aged 3 to 29 years, including 17 mares, 13 stallions and 20 geldings. All animals underwent an extensive biochemical blood test, the results of which revealed no pathological changes.To calculate the normative limits of fluctuations for each hormone, calculations were carried out using the Tukey method, which is used to determine the reference limits in the case of a small number of variants in the group and the absence of a normal distribution. Microsoft Excel was used for calculations. The conducted studies made it possible to clarify the reference intervals for thyroid hormones and cortisol in horses, which were: total triiodothyronine (T3) - 1.13-4.04 nmol/l, total thyroxine (T4) - 20.97-57.42 nmol/l, free thyroxine (fT4) 7.38-23.07 pmol/l, cortisol – 39.42-227.02 nmol/l. The results obtained can be recommended for use not only for the clinical and biochemical laboratory of St. Petersburg State University of Medicine, but also for all veterinary laboratories using diagnostic test systems for enzyme immunoassay of Vital Development Corporation.

Chronic Excess Iodine Intake Inhibits Bone Reconstruction Leading to Osteoporosis in Rats

BackgroundAlthough iodine modulates bone metabolism in the treatment of thyroid disease, the effect of iodine intake on bone metabolism remains less known. ObjectiveThis study evaluated the effect of excess iodine intake in rats on bone reconstruction in the 6th and 12th month of intervention. MethodRats were treated with different doses of iodinated water: the normal group (NI, 6.15 μg/d), 5-fold high iodine group (5HI, 30.75 μg/d), 10-fold high iodine group (10HI, 61.5 μg/d), 50-fold high iodine group (50HI, 307.5 μg/d), and 100-fold high iodine group (100HI, 615 μg/d). Thyroid hormone concentrations were determined by a chemiluminescent immunoassay. Morphometry and microstructure of bone trabecula were observed by hematoxylin and eosin staining and microcomputed tomography, respectively. Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) staining were performed to evaluate the activity of osteoblasts and osteoclasts, respectively. ResultsThe 24-h urine iodine concentration increased with iodine intake. The rats in the HI groups had higher serum thyroid-stimulating hormone and decreased serum free thyroxine concentrations in the 12th month than the NI group (all P < 0.05). The percentage of the trabecular bone area and osteoblast perimeter in the 100HI group were significantly lower than those in the NI group (P < 0.05). Increased structure model index was observed in the 50HI and 100HI groups compared with the NI group in the 6th month and increased trabecular separation in the 12th month (all P < 0.05). ALP and TRAP staining revealed osteoblastic bone formation was reduced, and the number of TRAP+ multinucleated cells decreased with increasing iodine intake. ConclusionsExcess iodine intake may increase the risk of hypothyroidism in rats. Chronic excess iodine intake can lead to abnormal changes in skeletal structure, resulting in reduced activity of osteoblasts and osteoclasts, which inhibits the process of bone reconstruction and may lead to osteoporosis.

The association between dyslipidaemia in the first trimester and adverse pregnancy outcomes in pregnant women with subclinical hypothyroidism: a cohort study

BackgroundSubclinical hypothyroidism (SCH) is linked to dyslipidaemia and adverse pregnancy outcomes. However, the impact of dyslipidaemia on the outcome of pregnancy in SCH is unclear.MethodsWe enrolled 36,256 pregnant women and evaluated their pregnancy outcomes. The following data was gathered during the first trimester (≤ 13+ 6 weeks of gestation): total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), high-density lipoprotein (HDL-C), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations. The reference ranges for lipids were estimated to range from the 5th to the 95th percentile. Logistic regression assessed the relationships between dyslipidaemia and adverse pregnancy outcomes, including abortion, preeclampsia/eclampsia, low birth weight, foetal growth restriction, premature rupture of foetal membranes, gestational hypertension, preterm birth, macrosomia and gestational diabetes mellitus (GDM). Additionally, the best thresholds for predicting adverse pregnancy outcomes based on TSH, FT4, and lipid levels were determined using receiver operating characteristic curves.ResultsIn the first trimester, LDL-C > 3.24 mmol/L, TG > 1.92 mmol/L, HDL-C < 1.06 mmol/L, and TC > 5.39 mmol/L were used to define dyslipidaemia. In this cohort, 952 (3.56%) patients were diagnosed with SCH, and those who had dyslipidaemia in the first trimester had higher incidences of gestational hypertension (6.59% vs. 3.25%), preeclampsia/eclampsia (7.14% vs. 3.12%), GDM (22.53% vs. 13.77%), and low birth weight (4.95% vs. 2.08%) than did those without dyslipidaemia. However, after adjusting for prepregnancy body mass index (pre-BMI), dyslipidaemia was no longer related to these risks. Furthermore, elevated TG dyslipidaemia in SCH patients was connected to an enhanced potential of gestational hypertension (odds ratio [OR]: 2.687, 95% confidence interval [CI]: 1.074 ~ 6.722), and elevated LDL-C dyslipidaemia correlated with increased preeclampsia/eclampsia risk (OR: 3.172, 95% CI: 1.204 ~ 8.355) after accounting for age, smoking status, alcohol use, pre-BMI, and levothyroxine use. Additionally, the combination of TC, TG, LDL-C, pre-BMI, and TSH exhibited enhanced predictive capabilities for gestational hypertension, preeclampsia/eclampsia, and GDM. Values of 0.767, 0.704, and 0.706 were obtained from the area under the curve.ConclusionsAmong pregnant women with SCH, dyslipidaemia in early pregnancy was related to elevated risks of adverse pregnancy consequences. The combined consideration of age, pre-BMI, TSH, and lipid levels in the first trimester could be beneficial for monitoring patients and implementing interventions to reduce adverse pregnancy outcomes.

Does Retinol-Binding Protein 4 (holo- and apo-RBP4) Increase or Remain Constant in Sera from Patients with Hypothyroidism?

Retinol-binding protein 4 (RBP4) is a retinol transporter in the blood plasma. Many diseases alter the plasma or serum levels of RBP4. Since serum RBP4 concentrations have been reported to decrease in hyperthyroidism, this study investigated whether serum RBP4 concentrations increased or remained constant in hypothyroidism. In sera from patients with hypothyroidism (n=71), hyperthyroidism (n=30), and healthy subjects (n=20), serum concentrations of RBP4 (sum of holo- and apo-RBP4), retinol, albumin, creatinine, and related constituents were measured, and RBP4/retinol molar ratio (as an index of apo-RBP4) and estimated glomerular filtration rate (eGFR) were calculated. The results showed that serum RBP4 concentrations tended to increase with decreasing free thyroxine concentrations, but there were no significant differences among patients with hypothyroidism, hyperthyroidism, and healthy subjects. When patients with hypothyroidism were subdivided by serum RBP4 level using 2.1 μmol/L cut-off value, patients with >2.1 μmol/L were revealed to be patients with older age having lower tri-iodothyronine, higher holo-RBP4, higher apo-RBP4, higher retinol, higher RBP4/retinol molar ratio, and lower eGFR than those in patients with <2.1 μmol/L. Multiple regression analysis showed significant associations between serum RBP4 levels and explanatory variables (retinol and eGFR). Although serum levels of RBP4 prior to the onset of renal dysfunction may affect the present concentrations, we conclude that the increase of serum RBP4 (both holo- and apo-RBP4) in patients with hypothyroidism was attributed to the decline in eGFR. In contrast, serum RBP4 concentration remained constant without renal dysfunction.

Relationship between thyroid function and sex hormones in female German shepherd dogs.

Several variables influence the serum concentration of thyroid hormones in dogs, including breed, age, drugs, and concurrent diseases. However, data regarding the interaction between thyroid function and the estrous stage of female dogs are limited. Estrous stage may influence thyroid function in German Shepherd dogs. Longitudinal, observational, non-randomized cohort study. The dogs were monitored during the complete estrous cycle, and different stages were determined by vaginal cytology. Two blood samples were collected at the beginning and end of each stage to analyze the following: total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3), canine thyrotropin (cTSH), progesterone, 17-β-estradiol, triglycerides, and cholesterol concentrations. Hematological and biochemical evaluations were performed at the beginning and end of the study period. Seventeen German Shepherds were included, of which 7 were bred during the study period. One dog was excluded for estrus interruption and another for suspected hypothyroidism. Serum concentrations of T4, fT4, and fT3 were negatively correlated with age. Total thyroxine demonstrated significant changes in serum concentrations between estrous stages, with higher concentrations in estrus and diestrus. Total thyroxine concentrations were positively correlated with progesterone concentrations and negatively correlated with 17-β-estradiol concentrations. Free thyroxine did not show significant variations but was positively correlated with progesterone concentrations. Canine TSH concentrations were positively correlated with 17-β-estradiol concentrations. No significant differences in thyroid hormones and cTSH concentrations were observed between diestrus during pregnancy and pseudopregnancy. Different stages of estrus can influence the measurement of TT4 in female dogs.

Changes in thyroid function and evolution of subclinical thyroid disease in older men.

Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r = .16, p < .05). Change in FT4 correlated inversely with baseline FT4 (r = -0.35, p < .05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully-adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02-1.17, p = .006; per 2.7-fold increase in TSH OR = 65.4, CI = 31.9-134, p < .001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high-normal TSH.

A machine learning-assisted system to predict thyrotoxicosis using patients’ heart rate monitoring data: a retrospective cohort study

Previous studies have shown a correlation between resting heart rate (HR) measured by wearable devices and serum free thyroxine concentration in patients with thyroid dysfunction. We have developed a machine learning (ML)-assisted system that uses HR data collected from wearable devices to predict the occurrence of thyrotoxicosis in patients. HR monitoring data were collected using a wearable device for a period of 4 months in 175 patients with thyroid dysfunction. During this period, 3 or 4 thyroid function tests (TFTs) were performed on each patient at intervals of at least one month. The HR data collected during the 10 days prior to each TFT were paired with the corresponding TFT results, resulting in a total of 662 pairs of data. Our ML-assisted system predicted thyrotoxicosis of a patient at a given time point based on HR data and their HR-TFT data pair at another time point. Our ML-assisted system divided the 662 cases into either thyrotoxicosis and non-thyrotoxicosis and the performance was calculated based on the TFT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of our system for predicting thyrotoxicosis were 86.14%, 85.92%, 52.41%, and 97.18%, respectively. When subclinical thyrotoxicosis was excluded from the analysis, the sensitivity, specificity, PPV, and NPV of our system for predicting thyrotoxicosis were 86.14%, 98.28%, 94.57%, and 95.32%, respectively. Our ML-assisted system used the change in mean, relative standard deviation, skewness, and kurtosis of HR while sleeping, and the Jensen–Shannon divergence of sleep HR and TFT distribution as major parameters for predicting thyrotoxicosis. Our ML-assisted system has demonstrated reasonably accurate predictions of thyrotoxicosis in patients with thyroid dysfunction, and the accuracy could be further improved by gathering more data. This predictive system has the potential to monitor the thyroid function status of patients with thyroid dysfunction by collecting heart rate data, and to determine the optimal timing for blood tests and treatment intervention.

Changes in thyroid function levels in female patients with first-episode bipolar disorder.

The identification of molecular biomarkers for bipolar disorder is anticipated to greatly improve the diagnosis and treatment of this disease. The objective of this case-control study is to determine whether the blood thyroid hormone levels in bipolar disorder patients are associated with different types of first onset. From August 1, 2020 to July 31, 2021 a total of 120 female patients diagnosed with bipolar disorder and hospitalized at Qingdao Mental Health Center were recruited as the case group, including 60 patients with depression as their first onset (depression first-episode group, DF) and 60 with mania/hypomania as their first onset (mania/hypomania first-episode group, M/HF). A group of 60 healthy adult females matching general demographic data, such as race and age, were selected as the control group. Blood samples were taken from both groups to measure serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) concentrations. The duration of current onset in the M/HF group was significantly less than that in the DF group (23.1 ± 20.2 vs. 125.2 ± 41.0 days). About 27% of patients in the M/HF group had thyroid abnormalities, in contrast to 60% in the DF group. The blood T3 and T4 levels in both the M/HF group and the DF group, as well as the TF3 levels in the DF group, were significantly lower as compared to control. The M/HF group had significantly higher T3 and FT3 levels than the DF group. The blood T3 levels were inversely correlated with the Young's Mania Scale score and the Hamilton Depression Scale score in both the M/HF and DF groups. Thyroid dysfunction resulting in reduced levels of blood thyroid levels may be involved in the disease progression of bipolar disorder, and correlated with the clinical symptoms in patients with depression or mania as the first episode.

The effect of metformin therapy on serum thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis

Type 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges’s g:1.55, 95%CI 0.93–2.16, p-value < 0.001); FT4 level increased slightly after taking metformin, but the increase was not significant (Heddges’s g: − 0.30, 95%CI − 0.90,0.31, p-value = 0.34). In euthyroid subjects, the slight decrease found in TSH and FT4 concentrations was not statistically significant. Metformin reduces TSH levels in hypothyroid patients; however, it has no effect on TSH levels in euthyroid patients. Metformin does not affect serum FT4 levels in euthyroid and hypothyroid patients.

Stress-Mediated Abnormalities in Regional Myocardial Wall Motion in Young Women with a History of Psychological Trauma.

Psychosocial stress has been associated with the development and progression of atherosclerotic cardiovascular disease (CVD). Previously, we reported subtle differences in global longitudinal strain in somatically healthy women with a psychiatric diagnosis of borderline personality disorder (BPD). This study aimed to investigate the impact of BPD on segmental myocardial wall motion using speckle tracking echocardiography (STE) analysis. A total of 100 women aged between 18 and 38 years were included in this study. Fifty patients meeting the diagnostic criteria for BPD were recruited from the Department of Psychiatry (LWL-University Hospital Bochum) and compared with fifty age-matched healthy control subjects without previous cardiac disease. Laboratory tests and STE were performed with segmental wall motion analysis. The BPD group had a higher prevalence of risk factors for CVD, with smoking and obesity being predominant, when compared with the control group. Other cardiovascular parameters such as blood pressure, glucose, and cholesterol levels were also elevated, even though not to pathological values. Moreover, in the STE analysis, the BPD group consistently exhibited decreased deformation in nine myocardial wall regions compared with the control group, along with a shift toward higher values in the distribution of peak pathological segments. Additionally, significantly higher values of free thyroxine concentration and thyroid's secretory capacity were observed in the BPD group, despite falling within the (high-) normal range. BPD is associated with chronic stress, classical risk factors, and myocardial wall motion abnormalities. Further exploration is warranted to investigate the relationship between high-normal thyroid metabolism, these risk factors, and myocardial function in BPD patients. Long-term follow-up studies would be valuable in confirming the potential for predicting adverse events.

Hyperthyroidism: A Review.

Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

Features of the natural course of subclinical hypothyroidism in young athletes

Objective: to assess the natural course of subclinical hypothyroidism in young athletes.Methods: In the prospective single-center uncontrolled study, data from 3,062 outpatient records of young athletes (members of the Russian national team) of both sexes (middle age — 15 [14; 16] years) and underwent medical examination in the period from January 2021 to September 2022 were studied. All athletes were divided into 2 groups according to the presence of subclinical hypothyroidism (an increase in the level of thyroid-stimulating hormone from 5 to 10 mUn/l with a normal level of T4 free). During a dynamic follow-up (1 year), athletes with subclinical hypothyroidism underwent a repeated study of the concentration of thyroid-stimulating hormone, free thyroxine and antibodies to thyroperoxidase.Results: Signs of subclinical hyperthyroidism were found in 58 young athletes (30 boys (51.7 %) and 28 (48.3 %) girls). During dynamic observation with continued habitual physical activity, spontaneous normalization of the level of thyroid-stimulating hormone was observed in 74 % of young athletes. At the same time, normalization of thyroid-stimulating hormone in girls was observed less often compared to boys (p = 0,272). In no case did clinically pronounced hypothyroidism develop.Conclusion: The majority of young male and female athletes with subclinical hypothyroidism have spontaneous normalization of hormonal profile against the background of persistent physical and psycho-emotional stress. The data obtained make it possible, subject to the possibility of dynamic observation, to recommend doctors working with young elite athletes not to prescribe hormonal replacement therapy and not to modify the usual lifestyle.

Effects of the abdominal fat distribution on the relationship between exposure to air pollutants and thyroid hormones among Korean adult males

BackgroundSeveral significant associations between air pollution and thyroid function have been reported, but few studies have identified whether these associations differ by obesity, particularly its regional distribution. We assessed the relationship between ambient air pollution and thyroid hormone, and whether this relationship is modified by abdominal adiposity, as indicated by the waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral-to-subcutaneous fat ratio (VSR) in Korean men.MethodsWe included 2440 male adults in the final analysis and used each person’s annual average exposure to four air pollutants: particulate matter with an aerodynamic diameter ≤ 10 μm (PM10), nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). Abdominal fat deposition was quantified by computed tomography. Serum thyrotropin (TSH) and free thyroxine (FT4) concentrations were measured for thyroid hormone. To evaluate the relationship between air pollution and thyroid hormone according to adiposity, we performed multiple linear regression analysis on the two subgroups stratified by abdominal fat level.ResultsAbdominal adiposity was significantly related to FT4 concentration. The exposures to air pollutants were associated with increased TSH and decreased FT4 concentrations. In stratified analysis using abdominal fat traits, ambient air pollution except for SO2 was significantly related to increased TSH and decreased FT4 concentrations in the high adiposity group (all p < 0.05), but not in the normal adiposity group. Among the air pollutants, PM10 showed an association with an increase of TSH concentration in all group with high adiposity, including high VAT, high SAT, and high VSR groups (all p < 0.05). In case of FT4, CO showed a similar pattern. Among the abdominal fat-related traits, the VSR in the high adiposity group had the largest effect on the relationship between exposure to air pollutants and thyroid hormone.ConclusionsThis study suggests the first clue that the relationship between air pollution exposure and thyroid hormone differs according to abdominal fat distribution among Korean adult males.

Thyroid-Related Hormones Changes Predict Changes in Anthropometric Measures and Incidence of Obesity in Chinese Euthyroid Persons.

The purpose of this study was to investigate the correlation of thyroid-related hormones changes within the reference range with the changes in anthropometric measures and incidence of obesity. The study included 4850 subjects with normal thyroid-related hormones at baseline and at follow-up. We evaluated the relationship of changes in thyroid-related biomarkers with anthropometric measures changes and incidence of obesity. In euthyroid persons, changes in serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) concentrations and FT3/FT4 ratio were independent predictors of changes in body mass index (BMI) and waist circumference (WC) in men, changes in serum FT3 and FT4 concentrations and FT3/FT4 ratio were independent predictors of changes in BMI and WC in women. Every single unit increment in ΔFT3/FT4 was accompanied by a 7.144 and 7.572 times risk of having obesity in men and women, respectively. Every single unit decrement in ΔFT4 was accompanied by a 21.0% and 26.9% lower risk of having obesity in men and women, respectively. In conclusion, in euthyroid individuals, changes in thyroid-related hormones were associated with anthropometric measures changes and incidence of obesity.

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.

Genetic determinants of thyroid function in children.

Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children. We selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects. In childhood, 30/60 SNPs were associated with TSH and 11/31 SNPs with FT4 after multiple testing correction. The effect sizes for AADAT, GLIS3, TM4SF4, and VEGFA were notably larger than in adults. The TSH PRS explained 5.3%-8.4% of the variability in TSH concentrations; the FT4 PRS explained 1.5%-4.2% of the variability in FT4 concentrations. Five TSH SNPs and no FT4 SNPs were associated with thyroid function in neonates. The effects of many known thyroid function SNPs are already apparent in childhood and some might be notably larger in children as compared to adults. These findings provide new knowledge about genetic regulation of thyroid function in early life.

Individual Features of the Hypothalamic-Pituitary-Thyroid Axis Functioning during Aging in Non-Human Primates.

Individual features of age-related changes in the function of the neuroendocrine systems are an important problem as the basic component of a personalized approach to predicting and treating age-related pathologies. We studied the age-related features of the function of the hypothalamic-pituitary-thyroid axis in laboratory primates with depression- and anxiety-like behavior (DAB). It was found that in young female rhesus monkeys with DAB, the basal and thyrotropin-releasing hormone-stimulated levels of thyroid-stimulating hormone were significantly lower than in young animals with standard behavior (control). During aging, the levels of thyroid-stimulating hormone increased in DAB animals and free thyroxine concentrations decreased both at baseline (fasting) and in response to the thyrotropin-releasing hormone test, while in animals with standard behavior, only a trend towards similar hormonal changes was revealed.

Comparative assessment of the functional state of the thyroid gland and the adrenal cortex in cats of different ages

The study of the secretory activity of the endocrine glands is one of the main methods for assessing their functional state and the health of animals in general. In the experiment, we studied the activity of thyroid and corticosteroid hormones in 20 healthy cats aged 1 to 14 years of different breeds and sexes. In the blood serum of the experimental animals, the concentration of total and free thyroxine, total and free triiodothyronine, adrenocorticotropic hormone and cortisol was determined by the enzyme immunoassay. The results of the study showed that the concentration of thyroid and corticosteroid hormones in the blood serum of cats differs markedly depending on age. the functional activity of the adrenal cortex is maximal in cats aged 5 months to 1 year (first group). Thus, in comparison with this group, the level of ACTH in the blood serum of cats of the second group (1-3 years old) significantly decreased by 15.8% (p≤0.05), the third (3-6 years old) and the fourth (animals over 6 years old). ) by 37.7 and 22.1%, respectively (p≤0.01). Also revealed a significant decrease in the concentration of cortisol in animals in the third and fourth groups by 22.1 and 26.8%, respectively, compared with the first group (p≤0.01). The least functional activity of the thyroid gland and adrenal cortex is observed in cats aged 6 years and older. The greatest functional activity of the adrenal cortex is observed in cats aged from 5 months to 1 year. The data obtained make it possible to more effectively detect disorders in the functioning of the thyroid and adrenal glands in animals, taking into account age-related changes.