Toxicogenomics of Five Cytostatics in Fathead Minnow (Pimephales promelas) Larvae.

In this study, the toxicogenomic effects of five cytostatics (tamoxifen, methotrexate, capecitabine, cyclophosphamide, and ifosfamide) on fathead minnow (Pimephales promelas) larvae were evaluated. Post-fertilization eggs were exposed to increasing concentrations of the drugs for six days. The expression levels of two genetic biomarkers for toxicity and four thyroid hormone-related gene pathways were measured. Interestingly, the results showed that all concentrations of the five cytostatics affect the transcription levels of both toxicity biomarker genes. Additionally, the thyroid hormone-related genes had different expression levels than the control, with the most significant changes observed in those larvae exposed to cyclophosphamide and ifosfamide. While a previous study found no effects on fish morphology, this study suggests that the five cytostatics modify subtle molecular responses of P. promelas, highlighting the importance of assessing multibiological level endpoints throughout the lifecycle of animals to understand the full portrait of potential effects of cytostatics and other contaminants.

Postmenopausal women with higher TSH values within the normal range present improved handgrip strength: a pilot study.

OBJECTIVE: To evaluate the possible association between thyroid function within the euthyroid range and musculoskeletal parameters as well as body composition in a sample of postmenopausal women. METHODS: This cross-sectional study included 96 postmenopausal women with serum thyroid-stimulating hormone (TSH) within the normal laboratory reference range. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Bone status and body composition were measured using Dual Energy X-ray absorptiometry (DXA). Physical activity was quantified using the International Physical Activity Questionnaire (IPAQ) index. RESULTS: Serum TSH correlated with handgrip strength (HGS, r-coefficient = 0.233, p = .025), and total body bone mineral density (BMD) T-score values (r-coefficient = 0.321, p = .003). HGS measures were associated with BMD (r-coefficient = 0.415, p < .001), with bone mineral content (BMC, r-coefficient = 0.427, p < .001), and lean mass (r-coefficient = 0.326, p = .003). Women with low muscle strength, defined as HGS < 16 kg, had lower TSH levels than women with normal muscle strength (low vs. normal muscle strength, ANCOVA 1.13 ± 0.49 mU/L vs. 1.60 ± 0.83 mU/L, p = 0.024) independently of age, BMD, percentage of body fat or absolute lean mass. Multivariable linear regression analysis showed that HGS values were associated with TSH measurements (ß-coefficient = 0.246, p = .014) and BMD T-score values (ß-coefficient = 0.306, p = .002). All models were adjusted for age, body mass index (BMI), vitamin D, low-density lipoprotein cholesterol, current smoking, physical activity, and homeostasis model assessment of insulin resistance. CONCLUSIONS: In this sample of postmenopausal women, lower serum TSH values, within normal range, were associated with lower muscle strength compared to higher normal TSH values. Further research is needed to elucidate the significance of our preliminary findings.

Early Serum Markers for Immune Checkpoint Inhibitor Induced Hypophysitis in Melanoma Patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activities and are widely used for the treatment of advanced cancers. However, they may lead to immune-related adverse events (irAEs) and some of them, such as hypophysitis, can be life-threatening. Here, early diagnosis is critical. METHODS: We retrospectively analyzed 40 melanoma patients who developed hypophysitis during ICI treatment with either ipilimumab and/or anti-PD1 therapy and compared them to 40 control patients who did not develop hypophysitis during the ICI treatment, matched for age, gender, type of immunotherapy, and stage. Clinical data and blood values such as LDH, CRP, TSH, T3, T4, and absolute immune cell counts were retrieved from the medical records. Patient characteristics, laboratory values, progression-free survival, and overall survival were compared between the two groups. RESULTS: Patients with ir-hypophysitis had a median age of 59 years, and most of them were male. Clinically, frequent symptoms were fatigue, headache, dizziness, and gastrointestinal symptoms such as nausea or abdominal pain. The onset of ir-hypophysitis differed much between ipilimumab- (median 8 weeks) and anti-PD1 (median 40 weeks)-induced hypophysitis (p < 0.001). At baseline, besides a slightly increased CRP level (p = 0.06), no differences were observed in patients who later developed hypophysitis compared to the control. After treatment started, hypophysitis patients showed a constant and significant decline in T4 levels from the start of therapy until diagnosis (p < 0.05), independent of the ICI treatment regime. However, a decline in T3 and TSH was only noted in patients with ipilimumab-induced ir-hypophysitis. Furthermore, serum sodium levels declined rapidly at the diagnosis of hypophysitis (p < 0.001). In addition, there was a constant increase in the absolute counts of eosinophils and lymphocytes from baseline in hypophysitis patients (p < 0.05). CONCLUSION: Ir-hypophysitis reveals different clinical pictures and onset times depending on the ICI regime used. Whereas a drop in T4 levels was indicative of developing hypophysitis independent of the ICI regime, TSH levels only declined in patients under ipilimumab-based ICI regimes. To best monitor our patients, it is important to recognize these differences.

Combined effects of ammonia-N exposure and salinity changes on hematological and serum biochemical factors and thyroid hormones in Nile tilapia (Oreochromis niloticus).

The aim of this research was to evaluate the interaction effects of ammonia-N levels and salinity on hematological and serum biochemical parameters in Nile tilapia (Oreochromis niloticus). The fish were randomly divided into 12 treatments including the levels of salinity (0, 4, 8 and 12 ppt) and 0, 50% of LC50-96 h of ammonia-N and 30% of LC50-96 h of ammonia-N in a factorial design (4 salinity levels x 3 ammonia levels). Hemoglobin value in all treatments, except for salinity treatments, namely 2, 3, 4, showed a significant decrease than the control (0 ppt and no poisoning). Also, red blood cells in treatment ammonia-N levels were significantly less than the control. Serum protein concentration, in treatments 9 (50% of LC50-96 h of ammonia-N) and 5 and also with increasing salinity (treatments 2, 3 and 4) had a significant decrease compared to the control. There is a significant increase in serum glucose, cortisol, ammonia and urea levels in 50% and 30% of LC50-96 h of ammonia-N treatments compared to the control, meanwhile these parameters were significantly increased with increasing salinity. Serum thyroid stimulating hormone (TSH), T3 and T4 levels in acute and sub-acute ammonia-N treatments were significantly lower than the control. Moreover, with increasing salinity in 50% and 30% of LC50-96 h of ammonia-N treatments, TSH showed a decreasing pattern. According to the results, fluctuations in blood biochemical factors, increase of stress and decrease of thyroid hormones show that the salinity, ammonia, and their interaction caused adverse effects on fish health during the 96 h of testing.

The Impact of Physical Activity on Thyroid Health: Insights From Representative Data in Korea.

CONTEXT: Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption. OBJECTIVE: This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data. DESIGN/SETTING/PARTICIPANTS: This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study. RESULTS: A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study. CONCLUSION: The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function.

Correlation Between Hypothyroidism and Gallstone Disease in Central India.

Introduction The decreased thyroid-stimulating hormone (TSH) levels affect almost every nucleated cell in our body, which directly affects the basal metabolic rate (BMR). It tends to affect multiple organ systems in the human body. In recent times, there have been changes in lifestyle and the consumption of processed foods has increased. Thus, cholelithiasis and hypothyroidism are being encountered frequently, even in rural populations. In recent times, the overt clinical presentation of hypothyroidism is rare due to early diagnosis and treatment of the subclinical hypothyroidism state itself. Aim The aim is to determine the correlation between cholelithiasis and hypothyroidism. Methods This was a cross-sectional study done on the patients presenting to the surgical department at Acharya Vinoba Bhave Rural Hospital affiliated to Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashtra, India between the duration from December 2020 to December 2022, having gallstone disease or with symptoms suggestive of gall bladder stones. The admitted patients were then evaluated for hypothyroidism by thyroid profile tests, and the results were documented. Using the collected data, factors such as clinical spectrum, correlation between cholelithiasis and hypothyroidism, relation with the demographic data, and body mass index (BMI) were studied. Results A total of 52 gallstone patients were included in the study. A greater number of patients were found to be above the age of 40 years (82.7%), with female preponderance (61.5%). More patients with cholelithiasis were from the group with having BMI more than normal (57.6%). More patients having both cholelithiasis and hypothyroidism were also from the group with having BMI more than normal. Most symptomatic patients complained of pain in the right hypochondriac region (88.5%). Of these 52 patients, nine (17.3%) were found to have hypothyroidism (seven were subclinical, two patients had overt clinical symptoms and signs) and the remaining 43 patients were euthyroid. Conclusions Our study supports that there is a correlation between cholelithiasis and hypothyroidism. Out of all the 52 patients, nine had hypothyroidism, seven were subclinical, and two had overt symptoms. Thus, we conclude that there is a correlation between cholelithiasis and hypothyroidism.

Prevalence of high neonatal thyroid stimulating hormone levels as an indicator of iodine deficiency in the province of La Pampa: An epidemiological analysis. / Prevalencia de hipertirotropinemia neonatal como indicador de deficiencia de yodo en la provincia de La Pampa: un análisis epidemiológico.

Introduction. Iodine plays a key role in human metabolism, growth, and development. During pregnancy and childhood, the demand for this micronutrient increases notably. Increased neonatal thyroid stimulating hormone (nTSH) levels, defined as nTSH ≥ 5 mIU/L, are a marker of iodine deficiency in a population if its prevalence is higher than 3%. Objective. To establish the prevalence of nTSH ≥ 5 in La Pampa in the 2021-2022 period, analyze its correlation with different variables, and compare it with data from a historical cohort. Population and methods. Cross-sectional, descriptive-analytical study in a population of newborn infants born in the 5 health regions of the province of La Pampa in 2021 and 2022. Results. Of the 5778 assessed newborn infants, 9.6% had nTSH levels ≥ 5 mIU/L. It was reported that 70.4% of these measurements were done after the third day of life. No significant differences were observed in the frequency of high nTSH levels by year of birth, birth weight, or days until sample collection. A higher prevalence was observed among male infants (10.6% versus 8.5%; p = 0.007) and term infants (9.8% versus 6.6%; p = 0.02). The prevalence of high TSH levels was superior to that observed in the 2001-2002 cohort. Conclusions. The prevalence of high nTSH levels in La Pampa during 2021 and 2022 was 9.6%, suggesting the presence of mild iodine deficiency in the population of this province, higher that what had been reported 2 decades ago.

Introducción. El yodo desempeña un rol fundamental en el metabolismo, el crecimiento y el desarrollo humano. Durante el embarazo y la infancia, la demanda de este micronutriente aumenta considerablemente. La tirotropinemia neonatal (TSHn) aumentada, definida como TSHn ≥5 mUI/l, es un marcador que señala la deficiencia de yodo en una población cuando su prevalencia supera el 3 %. Objetivo. Determinar la prevalencia de TSHn ≥ 5 en La Pampa durante el período 2021-2022, analizar su correlación con diferentes variables y compararla con datos de una cohorte histórica. Población y métodos. Estudio transversal, de diseño descriptivo-analítico, sobre una población de neonatos nacidos en las cinco zonas sanitarias de la provincia de La Pampa durante los años 2021 y 2022. Resultados. De los 5778 neonatos evaluados, el 9,6 % presentó niveles de TSHn ≥5 mUI/l. El 70,4 % de estas mediciones fueron realizadas después del tercer día de vida. No se observaron diferencias significativas en la frecuencia de niveles elevados de TSHn según el año de nacimiento, peso al nacer o días hasta la extracción. Se registró una mayor prevalencia en el sexo masculino (10,6 % versus 8,5 %; p = 0,007) y entre los neonatos nacidos a término (9,8 % versus 6,6 %; p = 0,02). La prevalencia de hipertirotropinemia fue superior a la observada en una cohorte de 2001-2002. Conclusiones. La prevalencia de hipertirotropinemia neonatal en La Pampa durante los años 2021 y 2022 fue del 9,6 %, lo que indica un estado de deficiencia leve de yodo en la provincia, superior al reportado hace dos décadas.

Evaluation of Age and Gender-Related Patterns in Clinical Features and Hematological Findings Among Hypothyroidism Patients in the Al-Jouf Region of Saudi Arabia: A Hospital-Based Study.

BACKGROUND: The prevalence of hypothyroidism is high in Saudi Arabia and the contributing factors are iodine deficiency and lack of balanced nutrition. This study aims to correlate the gender, age, and presence of co-morbidities with the laboratory findings and clinical presentation. METHODOLOGY: A cross-sectional study was done in the hospitals of the Al-Jouf region. The files of the patients diagnosed with hypothyroidism from the last two years were retrieved by non-probability consecutive sampling technique. IBM SPSS Statistics for Windows, Version 23, (Released 2015; IBM Corp., Armonk, New York, United States) was used for data entry and analysis. Descriptive statistics were presented as frequencies and proportions (for qualitative variables) and mean and standard deviation (SD) (for continuous data). Associated factors were identified through a chi-square test. A p-value less than 0.05 was considered statistically significant. RESULTS: Most of the patients were females within the age group of 36 to 50 years. Significant differences were observed between male and female patients with respect to the FT4 levels, hemoglobin (Hb) levels, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) values, and RBC counts (p-values of <0.001, <0.001, <0.001, <0.001, <0.001 and <0.001, respectively). However, no significant differences were observed between male and female patients in the TSH levels and hematocrit values. Most of the patients were euthyroid (77.24%). The pattern of thyroid function status did not show significant differences with respect to the gender of participants and the different age groups (p-values of 0.447 and 0.775, respectively). The most common co-morbidities observed were diabetes and hypertension. No significant association between the co-morbidities and the pattern of thyroid function status was observed. The most common symptoms were epigastric pain, fatigue, constipation, drowsiness, altered bowel habits, and weight gain. CONCLUSION: This hospital-based study provides valuable insights into some epidemiological characteristics, clinical features, and hematological findings in hypothyroidism patients of the Al-Jouf region. Significant differences were observed between male and female patients with respect to the FT4 levels, Hb levels, MCV, MCH, MCHC values, and RBC counts. The findings strengthen the existing knowledge base and emphasize the importance of timely detection and management of hypothyroidism in this population. Implementation of salt iodination programs and a timely evaluation of the hematological parameters is recommended. Further research is warranted to delve into the hidden mechanisms and long-term ramifications of hematological changes associated with hypothyroidism.

Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

Overlapping action of T3 and T4 during Xenopus laevis development.

Thyroid hormones are involved in many biological processes such as neurogenesis, metabolism, and development. However, compounds called endocrine disruptors can alter thyroid hormone signaling and induce unwanted effects on human and ecosystems health. Regulatory tests have been developed to detect these compounds but need to be significantly improved by proposing novel endpoints and key events. The Xenopus Eleutheroembryonic Thyroid Assay (XETA, OECD test guideline no. 248) is one such test. It is based on Xenopus laevis tadpoles, a particularly sensitive model system for studying the physiology and disruption of thyroid hormone signaling: amphibian metamorphosis is a spectacular (thus easy to monitor) life cycle transition governed by thyroid hormones. With a long-term objective of providing novel molecular markers under XETA settings, we propose first to describe the differential effects of thyroid hormones on gene expression, which, surprisingly, are not known. After thyroid hormones exposure (T3 or T4), whole tadpole RNAs were subjected to transcriptomic analysis. By using standard approaches coupled to system biology, we found similar effects of the two thyroid hormones. They impact the cell cycle and promote the expression of genes involves in cell proliferation. At the level of the whole tadpole, the immune system is also a prime target of thyroid hormone action.

Gestational thyroid hormones and autism-related traits in the EARLI and HOME studies.

Thyroid hormones are essential for neurodevelopment. Few studies have considered associations with quantitatively measured autism spectrum disorder (ASD)-related traits, which may help elucidate associations for a broader population. Participants were drawn from two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI), enrolling pregnant women who already had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study, following pregnant women from the greater Cincinnati, OH area. Gestational thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured in mid-pregnancy 16 (±3) weeks gestation serum samples. ASD-related traits were measured using the Social Responsiveness Scale (SRS) at ages 3-8 years. The association was examined using quantile regression, adjusting for maternal and sociodemographic factors. 278 participants (132 from EARLI, 146 from HOME) were included. TSH distributions were similar across cohorts, while FT4 levels were higher in EARLI compared to HOME. In pooled analyses, particularly for those in the highest SRS quantile (95th percentile), higher FT4 levels were associated with increasing SRS scores (ß = 5.21, 95% CI = 0.93, 9.48), and higher TSH levels were associated with decreasing SRS scores (ß = -6.94, 95% CI = -11.04, -2.83). The association between TSH and SRS remained significant in HOME for the 95% percentile of SRS scores (ß = -6.48, 95% CI = -12.16, -0.80), but not EARLI. Results for FT4 were attenuated when examined in the individual cohorts. Our results add to evidence that gestational thyroid hormones may be associated with ASD-related outcomes by suggesting that relationships may differ across the distribution of ASD-related traits and by familial likelihood of ASD.

Association between exposure to chemical mixtures and epigenetic ageing biomarkers: Modifying effects of thyroid hormones and physical activity.

Evidence on the effects of internal chemical mixture exposures on biological age is limited. It also remains unclear whether hormone homeostasis and lifestyle factors can modify such a relationship. Based on the Biomarkers for Air Pollutants Exposure (BAPE) study, which involved healthy older adults aged 60-69 years in China, we found that chemical mixture exposures, including metals, polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFASs), phthalates (PAEs), and organophosphate esters (OPEs), were significantly associated with shortened DNAmTL and accelerated SkinBloodClock, in which PFASs and OPEs in blood were the primary contributors to DNAmTL, while metals and PAEs had relatively higher contributions in urine. Furthermore, lower levels of thyroxin appeared to exacerbate the adverse effects of environmental chemicals on epigenetic ageing but relatively higher levels of physical activity had the beneficial impact. These findings may have important implications for the development of healthy ageing strategy and aged care policy, particularly in light of the global acceleration of population ageing.

Thyroid hormone action in adult neurogliogenic niches: the known and unknown.

Over the last decades, thyroid hormones (THs) signaling has been established as a key signaling cue for the proper maintenance of brain functions in adult mammals, including humans. One of the most fascinating roles of THs in the mature mammalian brain is their ability to regulate adult neurogliogenic processes. In this respect, THs control the generation of new neuronal and glial progenitors from neural stem cells (NSCs) as well as their final differentiation and maturation programs. In this review, we summarize current knowledge on the cellular organization of adult rodent neurogliogenic niches encompassing well-established niches in the subventricular zone (SVZ) lining the lateral ventricles, the hippocampal subgranular zone (SGZ), and the hypothalamus, but also less characterized niches in the striatum and the cerebral cortex. We then discuss critical questions regarding how THs availability is regulated in the respective niches in rodents and larger mammals as well as how modulating THs availability in those niches interferes with lineage decision and progression at the molecular, cellular, and functional levels. Based on those alterations, we explore the novel therapeutic avenues aiming at harnessing THs regulatory influences on neurogliogenic output to stimulate repair processes by influencing the generation of either new neurons (i.e. Alzheimer's, Parkinson's diseases), oligodendrocytes (multiple sclerosis) or both (stroke). Finally, we point out future challenges, which will shape research in this exciting field in the upcoming years.

Long-term fasting induced basal thermogenesis flexibility in female Japanese quails.

Male Japanese quails (Coturnix japonica) have been found to exhibit a three-phase metabolic change when subjected to prolonged fasting, during which basal thermogenesis is significantly reduced. A study had shown that there is a significant difference in the body temperature between male and female Japanese quails. However, whether female Japanese quails also show the same characteristic three-phase metabolic change during prolonged fasting and the underlying thermogenesis mechanisms associated with such changes are still unclear. In this study, female Japanese quails were subjected to prolonged starvation, and the body mass, basal metabolic rate (BMR), body temperature, mass of tissues and organs, body fat content, the state-4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the muscle and liver of these birds were measured to determine the status of metabolic changes triggered by the starvation. In addition, the levels of glucose, triglyceride (TG) and uric acid, and thyroid hormones (T3 and T4) in the serum and the mRNA levels of myostatin (MSTN) and avian uncoupling protein (av-UCP) in the muscle were also measured. The results revealed the existence of a three-phase stage similar to that found in male Japanese quails undergoing prolonged starvation. Fasting resulted in significantly lower body mass, BMR, body temperature, tissues masses and most organs masses, as well as S4R and CCO activity in the muscle and liver. The mRNA level of av-UCP decreased during fasting, while that of MSTN increased but only during Phase I and II and decreased significantly during Phase III. Fasting also significantly lowered the T3 level and the ratio of T3/T4 in the serum. These results indicated that female Japanese quails showed an adaptive response in basal thermogenesis at multiple hierarchical levels, from organismal to biochemical, enzyme and cellular level, gene and endocrine levels and this integrated adjustment could be a part of the adaptation used by female quails to survive long-term fasting.

Sensitivity to thyroid hormones is associated with sleep duration in the euthyroid population with depression degree lower than moderate.

We collected thyroid-related hormone index levels, sleep duration, and other basic characteristics of the population with depression from the NHANES 2009-2012 cycles and evaluated the association of Thyroid-Stimulating Hormone Index (TSHI) with sleep duration in the euthyroid population with depression via different analysis methods. We found that the association between TSHI and sleep duration was only found in patients with depression degree < Moderate (score: 1-14) rather than > Moderate group. Among the populations with degree < Moderate (N = 1918), only 4 indexes (parametric Thyroid Feedback Quantile Index, PTFQI, Thyrotroph Thyroxine Resistance Index, TT4RI, Thyroid-Stimulating Hormone TSH, and TSHI) reflecting the sensitivity to thyroid hormones were related to the sleep duration, with a significant non-linear relationship after adjusting for potential confounders (all P < 0.05). Trend analysis indicated that with the level increase of these 4 indexes, the sleep duration increased (all P for trend < 0.001). Further, we found that TSHI was relatively more important among the 4 indexes. Sum up, sensitivity to thyroid hormones is associated with sleep duration in the euthyroid population with depression degree lower than Moderate. Poor sensitivity referred to a longer sleep duration.

Association between multipollutant exposure and thyroid hormones in elderly people: A cross-sectional study in China.

Environmental chemicals have been indicated to cause disruption of thyroid homeostasis in human populations. However, previous studies mostly focused on single group of chemicals. Herein, we investigate the independent and combined effects of multiple pollutants on thyroid homeostasis, including thyroid-stimulating hormone (TSH), total and free thyroxine (tT4 and fT4) and total and free triiodothyronine (tT3 and fT3) in elderly people. These environmental pollutants (n = 144) are from ten categories, including phenols, parabens, perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), phthalate esters (PAEs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), synthetic pyrethroids (SPs), herbicides, and metals. Few studies have evaluated the health risks of these 144 chemicals, especially their joint effects. In single-pollutant evaluations, multiple linear regression (MLR) models were used to estimate the independent associations between multiple exposures and thyroid biomarkers. In multi-pollutant evaluations, elastic net regression and Bayesian kernel machine regression (BKMR) models were used to estimate the combined associations. The MLR models showed that 41 chemicals were significantly related to THs levels. BKMR models revealed the most important chemical groups: metals for TSH, PAHs, SPs and PCBs for tT4, herbicides and SPs for tT3. This study will contribute to the understanding of multipollutant exposure and help prioritize specific chemical groups related to thyroid hormone disruption.

Investigating the connection among thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents affected by type 1 diabetes.

OBJECTIVES: A connection between thyroid hormones (THs) and diverse metabolic pathways has been reported. We evaluated thyroid function and tissue sensitivity to THs in children and adolescents with T1D in comparison to euthyroid controls. Additionally, we investigate whether a relationship exists between sensitivity indices and metabolic parameters. METHODS: A retrospective analysis was conducted on 80 pediatric patients diagnosed with T1D. Clinical parameters, TSH, FT3, FT4, and the presence of MS were documented. Additionally, indices of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were assessed. Thirty healthy subjects were considered as controls. RESULTS: The overall prevalence of MS was 7.27 %, with MS identified in 8 out of 80 (10 %) T1D subjects; none of the controls manifested MS (p<0.01). No significant differences were observed in indexes of tissue sensitivity to THs between subjects with or without MS (all p>0.05). Correlations between THs and indexes of THs tissue sensitivity and metabolic parameters in controls and T1D patients were noted. CONCLUSIONS: This study affirms a heightened prevalence of MS in children with T1D compared to controls and underscores the potential role of THs in maintaining metabolic equilibrium.

The Hormonal Background of Hair Loss in Non-Scarring Alopecias.

Hair loss is a common clinical condition connected with serious psychological distress and reduced quality of life. Hormones play an essential role in the regulation of the hair growth cycle. This review focuses on the hormonal background of hair loss, including pathophysiology, underlying endocrine disorders, and possible treatment options for alopecia. In particular, the role of androgens, including dihydrotestosterone (DHT), testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), has been studied in the context of androgenetic alopecia. Androgen excess may cause miniaturization of hair follicles (HFs) in the scalp. Moreover, hair loss may occur in the case of estrogen deficiency, appearing naturally during menopause. Also, thyroid hormones and thyroid dysfunctions are linked with the most common types of alopecia, including telogen effluvium (TE), alopecia areata (AA), and androgenetic alopecia. Particular emphasis is placed on the role of the hypothalamic-pituitary-adrenal axis hormones (corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol) in stress-induced alopecia. This article also briefly discusses hormonal therapies, including 5-alpha-reductase inhibitors (finasteride, dutasteride), spironolactone, bicalutamide, estrogens, and others.

Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study.

Background: Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. Methods: We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. Results: A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. Conclusion: High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.