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Introduction: Obesity and mild thyroid failure are common diseases, and the complex relationship between thyroid function and excess weight gain is still being researched. This study analyzes and summarizes the current scientific reports on the intricate correlation between thyroid dysfunction and obesity. Material and methods: We have gathered the available materials and scientific reports, analyzing and summarizing them in a single study. Aim of study: We aimed to summarize the studies conducted so far by analyzing the available scientific reports to answer the question of ‘what comes first’ and to understand the correlation between thyroid dysfunction and excessive weight gain. Discussion: Thyroid dysfunction in the form of hypothyroidism is associated with metabolic abnormalities, which may play a crucial role in the development of metabolic syndrome. On the other hand, excess level of leptin associated with excess adipose tissue is a potential cause of disruptions in the hypothalamic-pituitary-thyroid axis, manifested as elevated TSH levels. Therefore, it is worth considering certain aspects regarding the inclusion of hormone replacement therapy in obese patients presenting laboratory features of subclinical hypothyroidism. Conclusion. Obesity-induced thyroid dysfunction is typically reversible with weight loss and hormone replacement therapy should be considered for obese patients with subclinical hypothyroidism only if thyroid antibodies are present to confirm an autoimmune thyroid disorder. [ABSTRACT FROM AUTHOR]

Objective: Physical activity (PA) plays an important role in human health. However, the relationship between the PA and dysthyreosis was not clear. This study aimed to explore this question. Methods: We performed a population-based study on the basis of the participant's information that was collected from the National Health and Nutrition Examination Survey (NHANES) database. The association of the thyroid hormone and total PA metabolic equivalent task (MET) were assessed via linear regression analysis with adjusting for different covariates. Moreover, we also used path analysis to explore the causality between PA, thyroid hormone index, and dysthyreosis. The restricted cubic spline analysis was used to explore the non-linear relationship between the thyroid hormone index and the PA total MET. Results: A total of 2118 participants aged≥20, including 969 females and 1149 males, were collected from NHANES. The linear regression with multivariate adjustment suggested a linear relationship between the PA total MET and Thyroid-Stimulating Hormone Index (TSHI), and Thyroid Feedback Quantile-Based Index (TFQI), respectively. And TFQI and dysthyresis occurrence were significantly correlated (P<0.05). The path analysis showed that the PA total MET affected dysthyreosis occurrence by TFQI. In addition, we found a non-linear relationship between the total PA met and dysthyreosis via restricted cubic spline analysis. Conclusions: PA was significantly correlated with dysthyreosis via thyroid hormone sensitivity. Therefore, it can be considered to prevent the occurrence of dysthyreosis by regulating thyroid hormone sensitivity through PA in daily life. [ABSTRACT FROM AUTHOR]

Thyroid hormones (TH) influence the processes of cell proliferation and differentiation, but their role in the processes of carcinogenesis is contradictory.The purpose of the study. To study the effect of induced hyperthyroidism in mice of both sexes with intertwined Lewis carcinoma (LLC) on the activity of the hypothalamic-pituitary-thyroid axis (GGT).Materials and methods. The experimental model was mixed-sex mice of the C57BL/6 line with subcutaneously transplanted LLC on the background of induced hyperthyroidism (main group). Two control groups were used: control group I – mice with sodium liothyronine- induced hyperthyroidism and control group II – mice with subcutaneously transplanted LLC. On the 25th day after tumor transplantation, the level of thyrotropin- releasing hormone (TRH), thyroid- stimulating hormone (TSH), triiodothyronine (T3), total and free thyroxine (T4, FT4) was determined in the homogenates of GGT organs and in blood serum.Results. In female mice, hyperthyroidism caused an increase in the level of TRH in the hypothalamus and a decrease in TSH in the pituitary gland; in males, a decrease in TRH only in the hypothalamus. In control group II, euthyroid disorder syndrome developed: In mice of both sexes, serum levels of T4 and FT4 were found to decrease against the background of unchanged T3 levels and an increase in TSH content only in females. In the females of the main group, an increase in the level of TSH in the thyroid gland caused a decrease in T3 content in 73 % of animals against the background of normal T4 and elevated FT4 levels, in 27 % of females the T3 level increased. In males, in 73 % of the observations, the T3 level was increased against the background of high T4 and FT4 values and unchanged TSH levels. In the skin and LLC samples of the mice of the main group, an increase in T3 levels was noted.Conclusion. The growth of LLC against the background of hyperthyroidism is a process with multifactorial effects. High levels of T3 in blood serum and skin stimulated the proliferation of tumor cells, which led to the formation of subcutaneous tumors of a larger volume in the mice of the main group. Sex differences in the GGT response indicate different mechanisms that implement pathological processes.

• Low sleep quality has been associated with hypothalamic-pituitary-thyroid axis disturbances. • Few studies focused on the relationship between subclinical hypothyroidism and poor sleep quality. • This systematic review encompasses data from 8 available observational studies with a total of 2916 patients with subclinical hypothyroidism. • Studies included would indicate an association between subclinical hypothyroidism and sleep disturbances. • Future longitudinal prospective studies and intervention trials appear mandatory to further elucidate the issue. The relationship between subclinical hypothyroidism (SHYPO) and sleep disturbances is still poorly investigated. This systematic review aims to critically appraise the existing literature to provide more insights in understanding whether SHYPO favors sleep disturbances or it is the sleep disturbance per se that affects the hypothalamus-pituitary-thyroid axis regulation. Original studies on sleep quality and duration in patients with SHYPO were searched in the PubMed/MEDLINE, Embase, Web of Science and Scopus databases. Two reviewers independently screened articles for inclusion, extracted data, and assessed the quality of included studies. Eight studies, including 2916 patients with SHYPO and 18,574 healthy controls, were retrieved. An overall agreement (7 out of 8 studies), about a positive correlation between decreased sleep quality and/or duration and SHYPO was observed. Five studies investigated sleep quality through self-reported surveys; only two studies explored both subjective and objective assessment of sleep quality with actigraphy (n = 1) or polysomnography (n = 1); finally, one study assessed subjective evaluation of sleep quality through a single question regarding the number of sleeping hours. A high level of heterogeneity among studies was manifest due to differences in population source, sleep measure assessment and criteria for diagnosing SHYPO. Overall, the existing literature data suggest a link between SHYPO and sleep disturbances, but further studies on larger populations of patients with homogeneous study designs and outcomes are warranted. [ABSTRACT FROM AUTHOR]

This article discusses the importance and complexity of reference intervals for thyroid-stimulating hormone (TSH) levels. Reference intervals are established based on a sample of healthy individuals and are used to determine whether an individual's TSH levels are within the normal range. However, factors such as age, ethnicity, sex, iodine status, and pregnancy can affect the reference intervals for TSH. The article also highlights the impact of genetic factors on TSH reference intervals and suggests that personalized treatment based on more accurate reference intervals may improve patient outcomes. However, further research is needed to explore these possibilities. [Extracted from the article]

Thyroid cancer usually begins with thyroid dysfunction and nodules and has become the most common cancer globally, especially in women. Although the causes of thyroid dysfunction are complex, the presence of environmental pollutants, especially certain pesticides as established mutagens, has been widely accepted. Zebrafish (Danio rerio) have similar toxic reactions and signal transduction pathways to humans and are very similar to humans in physiology, development, and metabolic function. Here, the direct toxicity effects and mechanisms of different insecticides and herbicides on zebrafish thyroid functions and indirect toxicity effects originating from thyroid dysfunction were summarized and compared. The overall toxicity of insecticides on the zebrafish thyroid was greater than that of herbicides based on effective concentrations. Penpropathrin and atrazine were more typical thyroid disruptors than other pesticides. Meanwhile, chiral pesticides showed more sophisticated single/combined toxicity effects on both parental and offspring zebrafish. Besides thyroid hormone levels and HPT axis-related gene expression alteration, developmental toxicity, immunotoxicity, and oxidative damage effects were all observed. These data are necessary for understanding the thyroid interference effect of pesticides on humans and for screening for thyroid disruptors in surface water with zebrafish models for the pre-assessment of human health risks and ecological risk control in the future. [ABSTRACT FROM AUTHOR]

The medicinal nature of traditional Chinese medicine (TCM) mainly plays a role in regulating the energy and material metabolism of the body. The energy metabolism of the body is also regulated by the nervous and endocrine systems, and the hormones are an important component of the endocrine system to realize the coordinated action. Therefore, the medicinal nature of TCM is inextricably linked with the metabolism of hormones. Hyperthyroidism, qi-yin deficiency syndrome is regarded as the classic heat syndrome category in Chinese medicine, which can be used as model to reflect the mechanism and difference of qi tonifying of ginseng herbs with different medicinal natures. Steroid hormones are synthesized in the adrenal cortex, mitochondria of placental cells, smooth endoplasmic reticulum, and gonads of the human body by the participation of various metabolic enzymes. Meanwhile, most of the patients with hyperthyroidism have adrenocortical dysfunction in the clinic, and the corresponding clinical symptoms are closely related to the hypothalamic-pituitary-thyroid axis (HPT), the hypothalamic-pituitary-adrenal axis (HPA), and the hypothalamic-pituitary-gonadal axis (HPG). When hyperthyroidism occurs, the production and release of steroid hormones will be affected to a certain extent. To explore the correlation between the level of steroid hormones and hyperthyroidism, and the ameliorative effects of red ginseng and ginseng leaves of different types of the genus Ginseng on hypermetabolism of hyperthyroidism and the changes of related indexes, a method of ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) was established for rapid identification and quantification of chemical components, including adrenaline, androstenedione, testosterone, dehydroepiandrosterone, estriol, progesterone, 17α-hydroxypregnenolone, corticosterone, and cortisol in rat serum. Then, multivariate analysis method, principal component analysis (PCA), and Spearman test were used to analyze the correlation among adrenaline, steroid hormones, and thyroid function. The results showed that the contents of steroid hormone in the serum of the model group of rats decrease to different degrees, compared with the control group, and increase after the administration of different types of ginsengs. Meanwhile, it was proved that the established method has high sensitivity, good reproducibility, high accuracy, and fast analysis, which can screen a large number of steroid hormones in complex samples in a short time, for accurately investigation of the effects of ginsengs on the content of 9 types of steroid hormones in hyperthyroidism rats. The abnormal levels of steroid hormones are related to thyroid hormones. Corticosterone and adrenaline can serve as key indicators for regulating steroid hormone metabolism of TCMs like ginsengs. Testosterone can be used as the biomarker for regulating steroid hormones of the cold nature herbs. Adrenaline and androstenedione can be used as biomarkers for regulating steroid hormones of the warm nature herbs. This method can conveniently, quickly, accurately, and efficiently complete the analysis of target components in samples. The average recoveries of steroid hormones in rat serum range from 88.75% to 106.94%, and the relative standard deviation is less than 1.99%. This can be used for the determination of steroid hormones in rat serum systematically, rapidly, accurately and efficiently, and provides a methodological reference for the analysis and determination of steroid hormones. [ABSTRACT FROM AUTHOR]

The production of thyroid hormones is regulated by the hypothalamic-pituitary-thyroid axis. Thyrotropinreleasing hormone (TRH) is synthesized in the hypothalamus and stimulates the release of thyroid-stimulating hormone (TSH) from the anterior pituitary. Secretion of TRH is stimulated by factors such as exercise, stress, malnutrition, low plasma glucose and sleep. TSH secretion, in turn, is regulated by negative feedback from thyroid hormones thyroxine (T4) and triiodothyronine (T3), acting on both the pituitary gland and possibly the hypothalamus. Increased levels of T3 and T4 decrease TSH secretion and vice versa. TSH binds to the TSH-receptor (TSH-R) on the thyroid cell membrane, a G protein-coupled receptor (GPCR) that activates the Gs-adenylyl cyclase-cyclic AMP pathway. Activation of this pathway increases cAMP formation, which in turn mediates the increased uptake and transport of iodide, iodination of thyroglobulin and synthesis of iodotyrosines. TSH binding to TSH-R also stimulates phospholipase C, leading to thyroid cell hypertrophy. Chronic stimulation by TSH can cause hypertrophy of the entire gland, resulting in a goiter, particularly in cases of iodine deficiency. [ABSTRACT FROM AUTHOR]

Neonatal maternal separation is used to evaluate the effects of early life stress on various systems. The current study evaluated the impact of early life stress exposure on the morphometry and ultrastructure of adult male albino rat testis and clarified its intimate relation with hypothalamic-pituitarythyroid/Adrenal and gonadal axes. Thirty pregnant rats (dams) were divided into groups (i), (ii) and (iii). Neonates(pups) were also divided into; control (I), and neonatal maternal separation II (NMS II): pups were segregated from their dams for 2 hours /day. Group (NMSIII): pups were segregated from their dams for 4 hours/day from postnatal day 0 to postnatal day 14. Histological results revealed distortion affecting the testicular parenchyma in groups (II) and (III). Sections from both groups revealed markedly disrupted seminiferous tubules; decreased height of germinal epithelium; and decreased tubular diameter with widened interstitium. Immunohistochemical results revealed that the number of proliferating cells (ki67 positive cells) and inducible nitric oxide synthetase (iNOS positive cells) were significantly attenuated in both groups II, III. No substantial change was observed in the quantity of apoptotic cells. Degenerative signs were observed by transmission electron microscopy in both groups II and III; but much more extensive in group III. Sertoli cells, spermatogonia and primary spermatocytes showed irregular nuclear membrane, degenerated mitochondria with distorted crista, dilated endoplasmic reticulum and rarified cytoplasm. Extensive drop in sperm density in epididymal tissue was clearly observed in group III. Biochemical analysis revealed increased serum levels of oxidative stress markers and significant attenuation of different hormones of the Hypothalamic-Pituitary axis in groups II and III. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following 1 h of cold head-out water immersion (HOWI), compared with when cold HOWI is completed during normobaric normoxia. In a randomized crossover single-blind design, 12 healthy adults (27 ± 2 yr, 2 women) completed 1 h of cold (22.0 ± 0.1°C) HOWI breathing either normobaric normoxia (F I O 2 = 0.21) or normobaric hypoxia (F I O 2 = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid-stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60 min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared with normoxia (98 ± 1%, P < 0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post-cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, P < 0.001) in both conditions but did not change differently between conditions (condition × time: P = 0.552). Circulating TSH, total T3, free T4, total T3, and free T4 concentrations demonstrated significant main effects of time (all P ≤ 0.024), but these changes did not differ between normoxic and hypoxic conditions (condition × time: all P ≥ 0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during 1 h of cold HOWI. NEW & NOTEWORTHY: Acute head-out cold (22°C) water immersion (HOWI) decreased core temperature and increased thermogenesis. This thermogenic response was paralleled by the activation of the hypothalamic-pituitary-thyroid axis, as evidenced by changes in thyroid hormones. However, cold HOWI in combination with moderate normobaric hypoxia did not modify the thermogenic nor the circulating thyroid hormone response. This finding suggests that hypoxia-induced alterations in thyroid hormone concentrations are unlikely to acutely contribute to adaptations resulting from repeated cold-water exposures. [ABSTRACT FROM AUTHOR]

Background Thyroid-related hormones act to regulate metabolic pathways and blood pressure (BP). However, the relationship of TSH and peripheral thyroid hormones and the role of the hypothalamic-pituitary-thyroid axis on hypertension development is not fully understood. We assessed sex-specific associations of thyroid-related hormones with BP and hypertension in Hispanic/Latino adults followed for 6 years. Methods We studied 1789 adults, ages 45 to 74, free of diabetes at baseline from a subcohort of the Hispanic Community Health Study/Study of Latinos. We assessed TSH, free T4 (FT4), T3, and various indicators of thyroid axis. Using multivariable linear and Poisson regression adjusted for survey design and confounding variables, we estimated a priori sex-specific associations of thyroid-related hormones with changes in BP and hypertension development. Results In men and women, TSH and TSH/FT4 ratios were associated with changes in diastolic BP and T3 with changes in pulse pressure and the development of hypertension from prehypertension. In men, a 1-SD increase in TSH [incident rate ratio (IRR) = 1.42; 95% confidence interval (CI): 1.15, 1.75] and TSH/FT4 ratio (IRR = 1.20; 95% CI: 1.07, 1.35) were positively associated with the development of hypertension from prehypertension while the TSH/FT4 ratio (IRR = 0.85; 95% CI:.72, 1.00) was protective in women. We observed sex-specific differences in associations of the T3/FT4 ratio and indices of pituitary sensitivity to thyroid hormones with changes in pulse pressure and hypertension development. Conclusion Thyroid-related hormones are associated with sex-specific changes in BP and hypertension among Hispanic/Latino adults consistent with selected studies conducted in other populations. Mechanisms underlying associations of pituitary sensitivity to thyroid hormones with BP and hypertension development warrant further study. [ABSTRACT FROM AUTHOR]

Context Previous studies have demonstrated associations of endogenous thyroid hormones with diabetes; less is known about stages of diabetes development at which they are operative, mechanisms of associations, and the role of the hypothalamic-pituitary-thyroid axis. Objective This study examined associations of thyroid hormones with incident prediabetes and diabetes and with changes in glycemic traits in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the largest cohort of Hispanic/Latino adults with diverse backgrounds in the United States. Methods The study includes 592 postmenopausal euthyroid women and 868 euthyroid men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Baseline hormones included thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (T3), and indices calculated from thyroid hormones evaluating pituitary sensitivity to thyroid hormone. Transitions to diabetes and prediabetes, and changes in glycemic traits determined at the 6-year follow-up visit, were examined using multivariable Poisson and linear regressions. Results Among women, T3 (incident rate ratio [IRR] = 1.65; 95% CI, 1.22-2.24; P =.001) and TSH (IRR = 2.09; 95% CI, 1.01-4.33; P =.047) were positively, while FT4 (IRR = 0.59; 95% CI, 0.39-0.88; P =.011) was inversely, associated with transition from prediabetes to diabetes. Among men, the T3/FT4 ratio was positively associated with transition from normoglycemia to prediabetes but not from prediabetes to diabetes. Indices measuring sensitivity of the pituitary to thyroid hormone suggested increased sensitivity in men who transitioned from prediabetes to diabetes. Conclusion Positive associations in women of T3 and TSH and inverse associations of FT4, as well as inverse associations of thyroid indices in men with transition from prediabetes to diabetes, but not from normoglycemia to diabetes, suggest decreased pituitary sensitivity to thyroid hormones in women and increased sensitivity in men later in the development of diabetes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have revealed the sex-specific features of pituitary-thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary-TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQIFT4) and the thyroid feedback quantile-based index by FT3(TFQIFT3) with of TNs in Chinese euthyroid adults. Methods: 8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted. Results: TFQIFT3 among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQIFT4 levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both P for trend < 0.05). Additionally, lower TFQIFT3 and TFQIFT4 levels were significantly associated with a higher prevalence of TNs in women (both P for trend < 0.05), and lower TFQIFT3 levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQIFT3 and TFQIFT4 levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQIFT4 and the prevalence or number of TNs in men were not found. Conclusions: The trends of THs, TSH, TFQIFT4, and TFQIFT3 at different ages were sex-dependent. Both TFQIFT4 and TFQIFT3 levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs. [ABSTRACT FROM AUTHOR]

Traditionally, the Amphibian Metamorphosis Assay (AMA; OECD TG 231) is performed by exposing Xenopus laevis tadpoles to test substances dissolved in laboratory water. Recently, the use of dietary administration has been proposed to combat poorly soluble test substances in ecotoxicologically‐based regulatory endocrine disruption (ED) studies, specifically the AMA warranting an investigation into the efficacy of dietary administration. An efficacy study comprised of two phases: 1) evaluation of the physical influence of the loading process via solvent and 10, 1, and 0.1 mg/l test substance or surrogate (sunflower oil, SFO) on the Sera® Micron Nature (SMN) diet, and 2) performance of a modified AMA in which Nieuwkoop and Faber (NF) stage 51 X. laevis larvae were exposed to dechlorinated tap water using one concentration of the SFO in the diet for 21 days, was performed. In phase 1, the addition of acetone or acetone with bis(2‐propylheptyl) phthalate (DPHP) or SFO to SMN with subsequent solvent purge altered the diet reducing the density of the liquified diet and dietary pellet size following centrifugation indicative of alteration of the physical properties of the diet. Treatments used in the modified AMA were acetone alone and 0.1 mg/l SFO dissolved in acetone. These treatments were evaluated against an SMN benchmark using standard AMA endpoints. Both the acetone‐treated SMN and 0.1 mg/l SFO‐treated diets significantly reduced survival rates, 67 and 70% relative to the SMN benchmark (100%), decreased developmental stage distribution and snout‐vent length‐normalized hind limb length relative to the SMN benchmark, and slightly increased the prevalence and severity of thyroid follicular cell hypertrophy. Although the acetone‐treated diets may have impacted the hypothalamo‐pituitary‐thyroid axis, clinical signs of gastrointestinal impaction and tail flexure were also observed in the acetone‐treated diets, but not the SMN diet alone. Ultimately, test substance exposure via the diet in an AMA study can produce results that may confound data interpretation, which suggests that the traditional aqueous exposure route is generally more appropriate. Dietary administration has been proposed to combat poorly soluble test substances in ecotoxicologically based regulatory endocrine disruption (ED) studies warranting an investigation into the efficacy of dietary administration. Acetone‐treated diets significantly reduced survival rates, decreased developmental stage distribution and snout‐vent length‐normalized hind limb length, and slightly increased the prevalence and severity of thyroid follicular cell hypertrophy. Test substance exposure via the diet in an AMA study can confound data interpretation, and traditional aqueous exposure route is generally more appropriate. [ABSTRACT FROM AUTHOR]

Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5‐fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine. [ABSTRACT FROM AUTHOR]

The synthetic retinoid bexarotene (BXT), used in the treatment of cutaneous T-cell lymphoma (CTCL), has been associated with central hypothyroidism due to suppression of thyrotropin (TSH) secretion and upregulation of peripheral thyroxine (T4) and triiodothyronine (T3) metabolism. We present a case of a 41-year-old man with CTCL who developed central hypothyroidism within 1 month of receiving BXT. He required sequential uptitration of levothyroxine (LT4) over 15 months, and free T4 (FT4) and total T3 levels were normalized by a daily regimen of LT4 600 mcg and liothyronine (LT3) 15 mcg. While almost all patients regain normal hypothalamic-pituitary-thyroid axis function after cessation of BXT, there are limited data regarding LT4 and LT3 dosing required to adequately treat central hypothyroidism in patients on BXT. Our patient required an LT4 dose approximately 2.8 times the calculated weight-based dose and LT3 supplementation, demonstrating a large LT4/LT3 combination dose may be required to compensate for BXT-induced central hypothyroidism. [ABSTRACT FROM AUTHOR]

The article discusses the urgent need to adopt age-specific upper reference limits for thyroid-stimulating hormone (TSH) in the elderly. TSH is an important biomarker for thyroid function, and its levels tend to increase in elderly individuals. However, this does not necessarily indicate hypothyroidism, and using a single reference range for TSH in all age groups can lead to misdiagnoses and unnecessary treatment. The article highlights the importance of age-specific reference ranges for accurate diagnosis and management of thyroid disorders in the elderly. [Extracted from the article]

OBJECTIVE: To observe the neuroregulatory effects of Chaihu Shugan powder and Banxia Houpo decoction combined with Wuxing acupuncture on anxiety and depression after stroke and its effects on immune inflammatory response, cognitive function impairment, hypothalamic-pituitary-gonadal axis (HPG) and hypothalamicpituitary-thyroid axis (HPT). METHODS: A total of 102 patients with post-stroke anxiety and depression admitted into the hospital from Mar. 2021 to May 2023 were extracted to be divided into 51 cases in the Wuxing acupuncture group (2 cases were shed and 49 cases were eventually included), and 51 cases in the prescription combination group (2 cases were shed and 49 cases were eventually included) according to the random number table method. Both groups were given conventional Western medicine basic treatment, the Wuxing acupuncture group received Wuxing acupuncture treatment based on the conventional Western medicine basic treatment, and the prescription combination group was treated with Chaihu Shugan powder and Banxia Houpo decoction on the basis of the Wuxing acupuncture group. Clinical efficacy of two groups was compared. Traditional Chinese medicine syndrome score, Mini-Mental State Examination ( MMSE) score, Generalized Anxiety Disorder Scale ( GAD-7) score, Hamilton Depression Scale (HAMD) score and Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF) score of two groups before and after treatment were compared. Serum levels of nerve growth factor ( NGF), interleukin-1β (IL-1β), glial fibrillary acidic protein (GFAP), interleukin-17A (IL-17a), thyroid stimulating hormone (TSH), 5-hydroxytryptamine (5-HT) and estradiol 2 (E2) were measured before and after treatment. RESULTS: The total effective rate of the prescription combination group was 97. 96% (48/49), higher than 81. 63% (40/49) of the Wuxing acupuncture group, the difference was statistically significant (P < 0. 05). After treatment, the scores of anxiety and depression, epigastric fullness, chest and hypochondriac distension, frequent sighing in the prescription combination group were lower than those in the Wuxing acupuncture group, the scores of HAMD and GAD-7 were lower than those in Wuxing acupuncture group, and the scores of MMSE and Q-LES-Q-SF were higher than those in Wuxing acupuncture group, with statistically significant differences (P<0. 05). After treatment, levels of of IL-1β, IL-17a and GFAP in prescription combination group were lower than those in Wuxing acupuncture group, and levels of NGF in prescription combination group were significantly higher than those in Wuxing acupuncture group, levels of 5-HT, E2 and TSH in prescription combination group were higher than those in Wuxing acupuncture group, with statistically significant differences (P<0. 05). CONCLUSIONS: Chaihu Shugan powder and Banxia Houpo decoction combined with Wuxing acupuncture in the treatment of patients with post-stroke anxiety and depression can reduce the immune inflammatory response and neurological and cognitive function damage, regulate HPG and HPT, improve anxiety and depression, relieve the disease, improve quality of life and clinical efficacy. [ABSTRACT FROM AUTHOR]

Aim: To weight the prognostic value of thyroid hormones in catastrophic acute‐on‐chronic liver failure (ACLF). Methods: A retrospective cohort (n = 635) and two prospective cohorts (n = 353, and 198) were enrolled in this study. The performance of a novel developed prognostic score was assessed from aspects of reliability, discrimination, and clinical net benefit. Results: Thyroid‐stimulating hormone (TSH) was identified to have the most potential as a prognostic predictor for hepatitis B virus‐related ACLF among thyroid hormones. The novel score (modified chronic liver failure–organ failure score [mCLIF‐OFs]) was developed with weighted TSH and other scored organs in the CLIF‐OFs using the retrospective cohort (n = 635). The predicted risk and observed probabilities of death were comparable across the deciles of mCLIF‐OFs (Hosmer–Lemeshow χ2 = 4.28, p = 0.83; Brier scaled = 11.9). The C‐index of mCLIF‐OFs (0.885 [0.883–0.887]) for 30‐day mortality was significantly higher than that of the CLIF‐OFs, chronic liver failure–sequential organ failure assessment score (CLIF‐SOFAs), CLIF‐C ACLFs, Model of End‐stage Liver Disease (MELD), and Child–Pugh (all p < 0.001). The absolute improvements of prediction error rates of the mCLIF‐OFs compared to the above five scores were from 19.0% to 61.1%. After the analysis of probability density function, the mCLIF‐OFs showed the least overlapping coefficients (27.9%) among the above prognostic scores. Additionally, the mCLIF‐OFs showed greater net benefit than the above five prognostic scores over a wide range of risk threshold of death. Similar results were validated in two prospective ACLF cohorts with HBV and non‐HBV etiologies. Conclusion: Weighted TSH portended the outcome of ACLF patients, which could be treated as a "damaged organ" of the hypothalamic–pituitary–thyroid axis. The novel mCLIF‐OFs is a reliable prognostic score with better discrimination power and clinical net benefit than CLIF‐OFs, CLIF‐SOFAs, CLIF‐C ACLFs, MELD, and Child–Pugh. [ABSTRACT FROM AUTHOR]

Background: Traditional approaches to modeling suicide-related thoughts and behaviors focus on few data types from often-siloed disciplines. While psychosocial aspects of risk for these phenotypes are frequently studied, there is a lack of research assessing their impact in the context of biological factors, which are important in determining an individual's fulsome risk profile. To directly test this biopsychosocial model of suicide and identify the relative importance of predictive measures when considered together, a transdisciplinary, multivariate approach is needed. Here, we systematically review the emerging literature on large-scale studies using machine learning to integrate measures of psychological, social, and biological factors simultaneously in the study of suicide. Methods: We conducted a systematic review of studies that used machine learning to model suicide-related outcomes in human populations including at least one predictor from each of biological, psychological, and sociological data domains. Electronic databases MEDLINE, EMBASE, PsychINFO, PubMed, and Web of Science were searched for reports published between August 2013 and August 30, 2023. We evaluated populations studied, features emerging most consistently as risk or resilience factors, methods used, and strength of evidence for or against the biopsychosocial model of suicide. Results: Out of 518 full-text articles screened, we identified a total of 20 studies meeting our inclusion criteria, including eight studies conducted in general population samples and 12 in clinical populations. Common important features identified included depressive and anxious symptoms, comorbid psychiatric disorders, social behaviors, lifestyle factors such as exercise, alcohol intake, smoking exposure, and marital and vocational status, and biological factors such as hypothalamic-pituitary-thyroid axis activity markers, sleep-related measures, and selected genetic markers. A minority of studies conducted iterative modeling testing each data type for contribution to model performance, instead of reporting basic measures of relative feature importance. Conclusion: Studies combining biopsychosocial measures to predict suicide-related phenotypes are beginning to proliferate. This literature provides some early empirical evidence for the biopsychosocial model of suicide, though it is marred by harmonization challenges. For future studies, more specific definitions of suicide-related outcomes, inclusion of a greater breadth of biological data, and more diversity in study populations will be needed. [ABSTRACT FROM AUTHOR]

Background: Graves' disease has been associated with adverse pregnancy, labor and delivery, and neonatal outcomes. Thyroid function levels, assessed during newborn screening (NBS), can serve as indicators of the adaptation in the hypothalamic–pituitary–thyroid axis. We utilized data from the national thyroid NBS program to investigate the characteristics of the mother–infant dyad of term infants born to mothers with past or active Graves' disease. Methods: The dataset of the Israeli NBS for thyroid function was linked with the electronic records of a tertiary medical center to generate a unified database of mothers and their term infants born between 2011 and 2021. The MDClone big data platform extracted maternal, pregnancy, disease course, labor and delivery, and neonatal characteristics of the mother-infant dyads. Results: Out of 103,899 registered mother–infant dyads, 292 (0.3%) mothers had past or active Graves' disease. A forward multivariate linear regression demonstrated that Graves' disease did not significantly affect NBS total thyroxine (tT4) levels (p = 0.252). NBS tT4 levels in infants born to mothers with active Graves' disease were higher than those observed in the general Israeli population (p < 0.001). Mothers with Graves' disease more frequently used assisted reproductive technology (12.7% vs. 9.0%, respectively, p = 0.012; odds ratio [OR] = 1.46 [CI 1.03–2.07], p = 0.031), and had more gestational hypertension (3.9% vs. 1.1%, p < 0.001; OR = 3.53 [CI 1.92–6.47], p < 0.001), proteinuria (2.5% vs. 0.9%, p < 0.001; OR = 3.03 [CI 1.43–6.45], p = 0.004), cesarean sections (26.4% vs. 19.7%, p = 0.029; OR = 1.46 [CI 1.13–1.90], p = 0.004), prelabor rupture of membranes (15.4% vs. 4.1%, p < 0.001; OR = 4.3 [CI 3.13–5.91], p < 0.001), and placental abnormalities (5.1% vs. 2.0%, p < 0.001; OR = 2.64 [CI 1.57–4.44]; p < 0.001). Their infants had lower adjusted birthweight z-scores (−0.18 ± 0.94 vs. −0.03 ± 0.90, p = 0.007) and were more likely to be small for gestational age (12.0% vs. 8.1%, p = 0.005; OR = 1.54 [CI 1.08–2.19], p = 0.018). Conclusions: Neonatal thyroid function levels were affected by maternal Graves' disease only when the disease was active during gestation. Moreover, maternal Graves' disease was also associated with an increased risk of adverse outcomes for the mother–infant dyad. [ABSTRACT FROM AUTHOR]

Thyroid cancer usually begins with thyroid dysfunction and nodules and has become the most common cancer globally, especially in women. Although the causes of thyroid dysfunction are complex, the presence of environmental pollutants, especially certain pesticides as established mutagens, has been widely accepted. Zebrafish (Danio rerio) have similar toxic reactions and signal transduction pathways to humans and are very similar to humans in physiology, development, and metabolic function. Here, the direct toxicity effects and mechanisms of different insecticides and herbicides on zebrafish thyroid functions and indirect toxicity effects originating from thyroid dysfunction were summarized and compared. The overall toxicity of insecticides on the zebrafish thyroid was greater than that of herbicides based on effective concentrations. Penpropathrin and atrazine were more typical thyroid disruptors than other pesticides. Meanwhile, chiral pesticides showed more sophisticated single/combined toxicity effects on both parental and offspring zebrafish. Besides thyroid hormone levels and HPT axis-related gene expression alteration, developmental toxicity, immunotoxicity, and oxidative damage effects were all observed. These data are necessary for understanding the thyroid interference effect of pesticides on humans and for screening for thyroid disruptors in surface water with zebrafish models for the pre-assessment of human health risks and ecological risk control in the future.

Background: Broilers have a robust metabolism and high body temperature, which make them less tolerant to high-temperature (HT) environments and more susceptible to challenges from elevated temperatures. Gut microbes, functioning as symbionts within the host, possess the capacity to significantly regulate the physiological functions and environmental adaptability of the host. This study aims to investigate the effects of gut microbial intervention on the body temperature and thermogenesis of broilers at different ambient temperatures, as well as the underlying mechanism involving the "gut-brain" axis. Methods: Broilers were subjected to gut microbiota interference with or without antibiotics (control or ABX) starting at 1 day of age. At 21 day of age, they were divided into 4 groups and exposed to different environments for 7 d: The control and ABX groups at room temperature (RT, 24 ± 1 °C, 60% relative humidity (RH), 24 h/d) and the control-HT and ABX-HT groups at high temperature (HT, 32 ± 1 °C, 60% RH, 24 h/d). Results : The results demonstrated that the antibiotic-induced gut microbiota intervention increased body weight and improved feed conversion in broiler chickens (P < 0.05). Under HT conditions, the microbiota intervention reduced the rectal temperature of broiler chickens (P < 0.05), inhibited the expression of avUCP and thermogenesis-related genes in breast muscle and liver (P < 0.05), and thus decreased thermogenesis capacity. Furthermore, the gut microbiota intervention blunted the hypothalamic‒pituitary‒adrenal axis and hypothalamic–pituitary–thyroid axis activation induced by HT conditions. By analyzing the cecal microbiota composition of control and ABX chickens maintained under HT conditions, we found that Alistipes was enriched in control chickens. In contrast, antibiotic-induced gut microbiota intervention resulted in a decrease in the relative abundance of Alistipes (P < 0.05). Moreover, this difference was accompanied by increased hypothalamic 5-hydroxytryptamine (5-HT) content and TPH2 expression (P < 0.05). Conclusions: These findings underscore the critical role of the gut microbiota in regulating broiler thermogenesis via the gut-brain axis and suggest that the hypothalamic 5-HT pathway may be a potential mechanism by which the gut microbiota affects thermoregulation in broilers. [ABSTRACT FROM AUTHOR]

Thyroid disorders have witnessed a surge in prevalence over the last two decades, ranking as the most prevalent endocrine disorders after metabolic syndrome. These encompass hyperthyroidism, hypothyroidism, thyroiditis, and the presence of potentially benign or malignant thyroid nodules. Thyroid hormone, crucial for normal development, growth, and metabolic regulation, undergoes activation from thyroxine to triiodothyronine, influencing a myriad of genes. The cellular signaling pathway is intricately regulated, involving thyroid hormone transporters, receptor isoforms, and interactions with corepressors and coactivators. Non-genomic actions of thyroid hormone have also come to light. The hypothalamic-pituitary-thyroid axis primarily governs thyroid function and hormone levels, complemented by other feedback loops. Thyroid function tests (TFTs) encompass thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels. Evolving evidence suggests that optimal thyroid hormone levels may vary within the normal range, influencing clinical outcomes. There is no universally established optimum, but mid-range levels may best signify euthyroidism. In hypothyroidism, elevated TSH levels and low FT4 and FT3 levels are indicative, while hyperthyroidism manifests with low TSH levels and elevated FT4 and/or FT3 levels. Recent research proposes a paradigm shift towards evaluating and treating hypothyroidism based on thyroxinemia rather than relying solely on TSH levels. Furthermore, metabolic syndrome, characterized by interconnected metabolic abnormalities, exhibits a heightened risk in individuals with thyroid dysfunction, particularly hypothyroidism. Insulin resistance, attributed to thyroid dysfunction, potentially underlies metabolic syndrome. Understanding these intricacies paves the way for more effective clinical management. [ABSTRACT FROM AUTHOR]

Objective: This study employs case data analysis to elucidate alterations in hormone levels pre and post-surgery among patients with pituitary adenoma. Moreover, it investigates the influence of various associated factors on endocrine function. Methods: A retrospective analysis was conducted on clinical data from 428 patients who underwent surgical treatment within a short period at a single center. Statistical methods were employed to examine detailed hormone level fluctuations before and after surgery in patients with pituitary adenoma, along with their interrelations with different factors. Results: Between January 2016 and October 2022, a total of 428 consecutive patients with pituitary adenoma underwent surgical treatment. Of these, 232 were males and 196 were females, with an average age of 45.91 years (range: 16-84, standard deviation: 12.18). Univariate analysis indicated that females exhibited a higher susceptibility to preoperative endocrine dysfunction (p < 0.05). Conversely, males, patients with larger tumor volumes, and older patients were more prone to preoperative pituitary insufficiency. Postoperatively, the most substantial remission rate occurred in prolactin (77.4%), followed by growth hormone (GH) (71.8%) and cortisol (4/6). The highest recovery rate in functions was observed in growth hormone secretion function (80%), followed by pituitary-adrenal axis hormone secretion function (56.3%) and pituitary-thyroid axis hormone secretion function (47.5%). The most noteworthy incidence of newly developed postoperative endocrine deficiencies was found in the pituitary-adrenal axis (31.8%), while the occurrence rates of deficiencies in other axes were relatively low. The elevated postoperative remission rate of growth hormone correlated with a higher surgical resection rate and lower preoperative growth hormone levels. Additionally, lower preoperative prolactin levels corresponded to a higher remission rate of prolactin postoperatively. Furthermore, the restoration of postoperative thyroid hormone secretion function was associated with higher preoperative free thyroxine levels. Reduced postoperative cortisol secretion function was linked to multiple surgeries and an extended interval between hormone retesting and surgery. Conclusion: Surgical intervention effectively ameliorates endocrine disorders in pituitary adenoma patients, thereby mitigating symptoms and enhancing their quality of life. Preoperative management of growth hormone and prolactin levels facilitates an increased remission rate of these hormones post pituitary adenoma surgery. Patients displaying preoperative thyroid hormone secretion dysfunction should be considered for active supplementation therapy. Whenever feasible, complete tumor resection is recommended. For patients undergoing reoperation or multiple surgeries, vigilant postoperative cortisol monitoring and supplementation should be thoughtfully administered. [ABSTRACT FROM AUTHOR]

The relationship between the thyroid gland and reproduction in amphibians and reptiles has been studied for more than 100 years. Most studies suggest a positive involvement of thyroid hormones with some aspects of reproduction, but some studies support a negative role for thyroid hormones at certain life stages. Comprehensive studies of gene activation/suppression by thyroid hormones and their absence at various levels of the hypothalamo–pituitary–gonadal axis coupled with observations of adrenocorticoid activity, reproductive performance, and metabolic involvement are needed to understand this complex relationship. Highlights: Most amphibian and reptilian populations are declining in the face of climate changes, pollution, and habitat destruction. Although the hypothalamo–pituitary–thyroid axis often is positively associated with reproduction in amphibians and reptiles, negative interactions also occur at some life stages and in some species. Comprehensive studies involving thyroid and adrenal activity and gene activation/repression linked with reproductive events are needed [ABSTRACT FROM AUTHOR]

Parabens are classified as endocrine-disrupting chemicals (EDCs) capable of interfering with the normal functioning of the thyroid, affecting the proper regulation of the biosynthesis of thyroid hormones (THs), which is controlled by the hypothalamic–pituitary–thyroid axis (HPT). Given the crucial role of these hormones in health and the growing evidence of diseases related to thyroid dysfunction, this review looks at the effects of paraben exposure on the thyroid. In this study, we considered research carried out in vitro and in vivo and epidemiological studies published between 1951 and 2023, which demonstrated an association between exposure to parabens and dysfunctions of the HPT axis. In humans, exposure to parabens increases thyroid-stimulating hormone (TSH) levels, while exposure decreases TSH levels in rodents. The effects on THs levels are also poorly described, as well as peripheral metabolism. Regardless, recent studies have shown different actions between different subtypes of parabens on the HPT axis, which allows us to speculate that the mechanism of action of these parabens is different. Furthermore, studies of exposure to parabens are more evident in women than in men. Therefore, future studies are needed to clarify the effects of exposure to parabens and their mechanisms of action on this axis. [ABSTRACT FROM AUTHOR]

A study conducted at a hospital in eastern India investigated the levels of iron and Vitamin B12 in patients with primary hypothyroidism. The study found that there was a significant difference in the levels of these nutrients between the patients and a control group. The authors suggest that routine testing of iron and Vitamin B12 levels should be done in patients with hypothyroidism for early detection and intervention. However, more research is needed to determine the exact relationship between these nutrient levels and the disease. [Extracted from the article]

Schizophrenia is a chronic psychiatric disorder with inconsistent behavioral and cognitive abnormalities with profound effects on the individual and the society. Individuals with schizophrenia have altered thyroid function, but results from observational studies are conflicting. To date, it remains unclear whether and in which direction there is a causal relationship between thyroid function and schizophrenia. To investigate causal paths, a bidirectional two-sample Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies including up to 330,132 Europeans. Thyroid function was described by the normal-range thyroid-stimulating hormone (TSH) and free thyroxine levels as well as an increased and decreased TSH status. The iterative radial inverse-variance weighted approach with modified second order weights was used as the main method. Based on a discovery and replication sample for schizophrenia, pooled effect estimates were derived using a fixed-effect meta-analysis. Robustness of results was assessed using both a range of pleiotropy robust methods and a network analysis that clustered genetic instruments potentially responsible for horizontal pleiotropy. Genetic liability for hypothyroidism was inversely associated with schizophrenia ( ; 95% CI: (-0.10; -0.02); ). No notable associations were observed between other thyroid parameters and schizophrenia. Furthermore, no associations could be detected in the reverse direction. Our results suggest that an elevated level of TSH reduce the risk for schizophrenia. The role of thyroid function and the hypothalamic-pituitary-thyroid axis in the development of schizophrenia should be subject of further research. [ABSTRACT FROM AUTHOR]

Heat and cold stress can reduce the production performance, reproductive performance, immune and antioxidant capacity of cattle, and even lead to death. Therefore, in order to reduce the adverse effect of heat and cold stress as much as possible, cattle will activate the hypothalamic-pituitary-adrenal cortical axis (HPA), hypothalamic- pituitary-thyroid axis (HPT) and sympathetic-adrenal-medullary axis (SAM) to regulate body. At present, the methods to relieve heat and cold stress include physical methods, nutrient regulation and gene screening, but there are few researches on nutrient regulation and gene screening. The paper summarizes the concept, criterion and influence of heat and cold stress on cattle, and puts forward methods to regulate heat and cold stress and the breeding of varieties resistant to heat and cold stress, to provide reference for further research on heat and cold stress and improve economic benefits of breeding. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Many members of the American Thyroid Association played prominent roles in discovering the various aspects of the hypothalamic–pituitary–thyroid axis. This axis is fundamental for maintaining the normal serum levels of circulating thyroid hormones (THs) and thus the euthyroid state. The pituitary glycoprotein hormone, thyrotropin (TSH), controls the activity of the thyroid gland. Thyrotropin-releasing hormone and the negative feedback mechanism of circulating TH regulate the synthesis and the secretion of TSH. The dynamic interplay of these two dominant mechanisms has essential effects on TSH release. Therefore, the finding of abnormal serum levels of TSH often indicates the presence of a disorder of thyroid gland function. A summary of key historical discoveries in the understanding of the hypothalamic–pituitary axis is presented. [ABSTRACT FROM AUTHOR]

The goal of the present study was to examine the effects of environmentally relevant concentrations of the neonicotinoid insecticides thiamethoxam and imidacloprid on the metamorphosis of the toad Rhinella arenarum. Tadpoles were exposed from stage 27 until completion of metamorphosis to concentrations of thiamethoxam ranging between 1.05 and 1050 µg/L and concentrations of imidacloprid varying between 3.4 and 3400 µg/L. The two neonicotinoids were found to act differently at the range of concentrations tested. Thiamethoxam did not markedly alter the final % tadpoles completing metamorphosis but extended by 6–20 days the time needed for tadpoles to complete metamorphosis. The extra number of days required to reach metamorphosis was concentration-dependent between 1.05 and 100.5 µg/L, and then stable at 20 days between 100.5 and 1005 µg/L. In contrast, imidacloprid did not significantly interfere with the overall time needed to complete metamorphosis but decreased success of metamorphosis at 3400 µg/L, the highest concentration tested. Both neonicotinoid concentrations did not markedly alter body size and weight of the newly metamorphosed toads. With a lowest observed effect concentration (LOEC) of 1.05 µg/L, thiamethoxam may be more likely to impact tadpole development in the wild compared to imidacloprid, which was without any apparent effect at concentrations up to 340 µg/L (no-observed effect concentration or NOEC). As the influence of thiamethoxam was triggered after tadpoles had reached Stage 39, when metamorphosis is strictly dependent upon thyroid hormones, this observed effect is attributed to result from actions of this neonicotinoid insecticide on the hypothalamic-pituitary-thyroid axis. [ABSTRACT FROM AUTHOR]

Purpose of the study. Was to analyze changes in pathophysiological parameters of transplantable tumor growth and functional activity of the hypothalamic-pituitary-thyroid axis (HPT) in rats of both sexes with Guerin's carcinoma in presence of induced hypothyroidism.Materials and methods. The dynamics of tumor growth and average life span were assessed in white alley rats of both sexes with Guerins carcinoma transplanted subcutaneously on the background of thyreostatic induced hypothyroidism. RIA (radioimmune assay) and ELISA (enzyme-linked immunosorbent assay) methods were used to determine levels of thyroid hormones in the blood and thyroid and tumor samples, and thyrotropin-releasing hormone (TRH) in the hypothalamus, as well as TSH in the pituitary gland. The experiment included 2 control groups: animals of both sexes with hypothyroidism (control group 1, number of rodents = 15) and animals with subcutaneously transplanted Guerin's carcinoma without hypothyroidism (control group 2, number of rodents = 15).Results. Hypothyroidism in female rats inhibited the tumor growth and improved median survival by 1.8 times (p < 0.05). No such effect was observed in males of the main group. Levels of regulatory peptides of the hypothalamus and pituitary gland declined in females of the main group, while levels of TSH in the pituitary gland in males increased, despite a decrease in TRH by 3.5 times. TSH levels decreased in the thyroid and blood of animals of both sexes; however, a decrease in levels of total and free circulating thyroxine (T4 and FT4) by 1.6 times and by 2.8 times was found in the tumor, respectively; samples of Guerin's carcinoma in males of the main group remained saturated with T4 and FT4 as well as and in control group rodents without induced hypothyroidism.Conclusions. The gender differences in the pathophysiology of the tumor development in presence of hypothyroidism, as well as changes in the functional activity of the HPT axis in experimental animals revealed in this study can probably be associated with sex hormones, which requires further study of the hypothalamic-pituitary-gonadal (HPG) axis and steroid hormones in peripheral organs and tumor samples.

A recent work of our group has shown the significant effects of thyroxine treatment on the restoration of postural balance function in a rodent model of acute peripheral vestibulopathy. Based on these findings, we attempt to shed light in this review on the interaction between the hypothalamic–pituitary–thyroid axis and the vestibular system in normal and pathological situations. Pubmed database and relevant websites were searched from inception through to 4 February 2023. All studies relevant to each subsection of this review have been included. After describing the role of thyroid hormones in the development of the inner ear, we investigated the possible link between the thyroid axis and the vestibular system in normal and pathological conditions. The mechanisms and cellular sites of action of thyroid hormones on animal models of vestibulopathy are postulated and therapeutic options are proposed. In view of their pleiotropic action, thyroid hormones represent a target of choice to promote vestibular compensation at different levels. However, very few studies have investigated the relationship between thyroid hormones and the vestibular system. It seems then important to more extensively investigate the link between the endocrine system and the vestibule in order to better understand the vestibular physiopathology and to find new therapeutic leads. [ABSTRACT FROM AUTHOR]

Hyperactivation of hypothalamic–pituitary–adrenal (HPA) axis and hypothalamic–pituitary–thyroid (HPT) axis were found in acute high altitude challenge, but the role of gut microbiota and metabolites is unknown. We utilized adult male Sprague–Dawley rats at a simulated altitude of 5500 m for 3 days in a hypobaric-hypoxic chamber. ELISA and metabolomic analyses of serum and 16S rRNA and metabolomic analyses of fecal samples were then performed. Compared with the normoxic group, serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and thyroxine (tT4) were increased in the hypoxia group, whereas thyrotropin-releasing hormone (TRH) was decreased. Bacteroides, Lactobacillus,Parabacteroides,Butyricimonas,SMB53,Akkermansia,Phascolarctobacterium, and Aerococcus were enriched in hypoxia group, whereas [Prevotella], Prevotella,Kaistobacter,Salinibacterium, and Vogesella were enriched in normoxic group. Metabolomic analysis indicated that acute hypoxia significantly affected fecal and serum lipid metabolism. In addition, we found five fecal metabolites may mediate the cross-talk between TRH, tT4, and CORT with [Prevotella], Kaistobacter,Parabacteroides, and Aerococcus, and 6 serum metabolites may mediate the effect of TRH and tT4 on [Prevotella] and Kaistobacter by causal mediation analysis. In conclusion, this study provides new evidence that key metabolites mediate the cross-talk between gut microbiota with HPA and HPT axis under acute hypobaric hypoxia challenge. [ABSTRACT FROM AUTHOR]

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are under homeostatic control by the hypothalamic-pituitary-thyroid axis and plasma TH binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB). THBPs buffer free THs against transient perturbations and distribute THs to tissues. TH binding to THBPs can be perturbed by structurally similar endocrine-disrupting chemicals (EDCs), yet their impact on circulating THs and health risks are unclear. In the present study, we constructed a human physiologically based kinetic (PBK) model of THs and explored the potential effects of THBP-binding EDCs. The model describes the production, distribution, and metabolism of T4 and T3 in the Body Blood, Thyroid, Liver, and Rest-of-Body (RB) compartments, with explicit consideration of the reversible binding between plasma THs and THBPs. Rigorously parameterized based on literature data, the model recapitulates key quantitative TH kinetic characteristics, including free, THBP-bound, and total T4 and T3 concentrations, TH productions, distributions, metabolisms, clearance, and half-lives. Moreover, the model produces several novel findings. (1) The blood-tissue TH exchanges are fast and nearly at equilibrium especially for T4, providing intrinsic robustness against local metabolic perturbations. (2) Tissue influx is limiting for transient tissue uptake of THs when THBPs are present. (3) Continuous exposure to THBP-binding EDCs does not alter the steady-state levels of THs, while intermittent daily exposure to rapidly metabolized TBG-binding EDCs can cause much greater disruptions to plasma and tissue THs. In summary, the PBK model provides novel insights into TH kinetics and the homeostatic roles of THBPs against thyroid disrupting chemicals. [ABSTRACT FROM AUTHOR]

Background: Drugs are the mainstay of the clinical management of epilepsy. Carbamazepine (CBZ) is commonly used for treating epilepsy and neuropathic pain. This drug has been reported to have toxic effects on the hematological system due to its induction of oxidative stress. This study aimed to investigate the protective effects of vitamin C against hematological and thyroid toxicities caused by the chronic use of carbamazepine in male Wistar rats. Methods: Thirty-two adult Wistar rats were categorized randomly into four groups of eight rats each and treated as follows: Group 1 received distilled water (2 mL/kg); group 2 was treated with vitamin C (100 mg/kg); group 3 received carbamazepine (20 mg/kg), and group 4 was pre-treated with vitamin C (100 mg/kg) and given carbamazepine (20 mg/kg) 30 min later. All treatments were administered via gavage once per day over fifteen consecutive weeks. The rats' blood samples were tested for changes in hematological parameters while the sera were evaluated for liver biochemical enzymes and thyroid hormone levels. Results: The results revealed that pre-treatment with vitamin C protected against alterations in parameters associated with hematological and thyroid toxicities. Conclusion: Based on the study results, it was concluded that: a) The chronic use of CBZ caused hematological and thyroid toxicities, and b) Vitamin C protected against these toxicities. Therefore, it is highly likely that vitamin C has the potential to protect experimental animals against injuries induced by CBZ to the liver, blood cells, and hypothalamic-pituitary-thyroid axis in a Wistar rat model. [ABSTRACT FROM AUTHOR]

The concept of dual‐adaptive thermogenesis underlying metabolic adaptation to prolonged energy deficit posits that there are two control systems that govern energy sparing: a rapid‐reacting system to energy deficit and a slow‐reacting system to fat store depletion. The latter control system, referred to as the "adipose‐specific" control of thermogenesis, contributes to accelerating fat store replenishment (catch‐up fat) during weight regain. The case is put forward here that, whereas adaptive thermogenesis during weight loss results primarily from central suppression of the sympathetic nervous system and hypothalamic–pituitary–thyroid axis, during weight regain it operates primarily through peripheral tissue resistance to the actions of this neurohormonal network. Emerging evidence that altered deiodination of thyroid hormones within the skeletal muscle and liver is a key determinant of such peripheral resistance therefore offers entry points toward elucidating the molecular mechanisms that underlie the adipose‐specific control of thermogenesis and unraveling tissue‐specific targets to counter obesity recidivism. [ABSTRACT FROM AUTHOR]

Deuterium, a stable isotope of hydrogen, is abundant in organisms. It is known to produce various biological effects. However, its impact in thyroid hormone synthesis and secretion is poorly studied. The aim of this investigation was to evaluate the dynamics of thyroid hormones and pituitary thyroid-stimulating hormone secretion during bilateral shifts in deuterium supply and assess a possible role of the Na+/I− symporter (NIS), the main iodide transporter, in altered thyroid function. The experiment was performed on adult male Wistar rats, which consumed deuterium-depleted ([D] = 10 ppm) and deuterium-enriched ([D] = 500,000 ppm) water for 21 days. The assessment of total thyroxine and triiodothyronine and their free fractions, as well as thyroid-stimulating hormone in blood serum, revealed the rapid response of the thyroid gland to shifts in the deuterium/protium balance. The present investigation shows that the bilateral changes in the deuterium body content similarly modulate thyroid hormone production and functional activity of the pituitary gland, but the responses of the thyroid and pituitary glands differ. The response of the thyroid cells was to increase the synthesis of the hormones and the pituitary thyrotropes, in order to reduce the production of the thyroid-stimulating hormone. The evaluation of NIS serum levels found a gradual increase in the rats that consumed deuterium-enriched water and no differences in the group exposed to deuterium depletion. NIS levels in both groups did not correlate with thyroid hormones and pituitary thyroid-stimulating hormone production. The data obtained show that thyroid gland has a higher sensitivity to shifts in the deuterium body content than the hypothalamic–pituitary complex, which responded later but similarly in the case of deuteration or deuterium depletion. It indicates a different sensitivity of the endocrine glands to alterations in deuterium content. It suggests that thyroid hormone production rate may depend on deuterium blood/tissue and cytosol/organelle gradients, which possibly disturb the secretory process independently of the NIS. [ABSTRACT FROM AUTHOR]

BackgroundThe genetic code does not fully explain individual variability and inheritance of susceptibility to endocrine conditions, suggesting the contribution of epigenetic factors acting across generations.MethodsWe used a mouse model of developmental thyrotoxicosis (Dio3-/- mouse) to analyze endocrine outcomes in the adult offspring of Dio3-/- males using standard methods for body composition, and baseline and fasting hormonal and gene expression determinations in serum and tissues of relevance to the control of energy balance.ResultsCompared to controls, adult females with an exposed father (EF females) exhibited higher body weight and fat mass, but not lean mass, a phenotype that was much milder in EF males. After fasting, both EF females and males exhibited a more pronounced decrease in body weight than controls. EF females also showed markedly elevated serum leptin, increased white adipose tissue mRNA expression of leptin and mesoderm-specific transcript but decreased expression of type 2 deiodinase. EF females exhibited decreased serum ghrelin, which showed more pronounced post-fasting changes in EF females than in control females. EF female hypothalami also revealed significant decreases in the expression of pro-opiomelanocortin, agouti-related peptide, neuropeptide Y and melanocortin receptor 4. These markers also showed larger changes in response to fasting in EF females than in control females. Adult EF females showed no abnormalities in serum thyroid hormones, but pituitary expression of thyrotropin-releasing hormone receptor 1 and thyroid gland expression of thyroid-stimulating hormone receptor, thyroid peroxidase and iodotyrosine deiodinase were increased at baseline and showed differential regulation after fasting, with no increase in Trhr1 expression and more pronounced reductions in Tshr, Tpo and Iyd. In EF males, these abnormalities were generally milder. In addition, postnatal day 14 (P14) serum leptin was markedly reduced in EF pups.DiscussionA paternal excess of thyroid hormone during development modifies the endocrine programming and energy balance in the offspring in a sexually dimorphic manner, with baseline and dynamic range alterations in the leptin-melanocortin system and thyroid gland, and consequences for adiposity phenotypes. We conclude that thyroid hormone overexposure may have important implications for the non-genetic, inherited etiology of endocrine and metabolic pathologies.

The renin-angiotensin system (RAS) is an essential endocrine system with roles in electrolyte balance, blood volume, and blood pressure. While the canonical RAS exerts systemic vasoregulatory effects through steps involving hepatic, renal, and pulmonaryderived compounds, there is also evidence of localized, independently acting RAS in organs such as the liver and kidney. Further, modulations in RAS resulting from fetal hypothyroidism have previously been documented, although the temporal specificity of this endocrine interaction is not well-characterized. Thus, the objective of the current study was to examine the timedependency of modulations in local hepatic and renal RAS in a porcine model of fetal hypothyroidism. To achieve this, pregnant gilts (n = 24) were divided evenly into either a control (CON) or methimazole (MMI) treatment group, with the MMI group receiving 5 mg kg-1 d-1 of oral MMI treatment and the CON group receiving an equivalent sham carrier. Each group was further divided into four timepoints (n = 3/treatment at each timepoint), with treatment beginning on d 34, 45, 55, or 65 of gestation. After 21 d of treatment, and at d 55, 66, 76, and 86, respectively, the gilts were humanely euthanized, blood samples taken from all fetuses (n = 340), and thyroid, liver (LVR), and kidney (KID) collected from a subset of four fetuses per litter (n = 96). Confirmation of fetal hypothyroidism in the MMI group was accomplished via histological assessment of the thyroid and measurement of circulating thyroxine (T4) concentrations. Each MMI-treated fetus (n = 96) subset showed evidence of goitrous thyroid histology, with the absence of healthy eosinophilic colloid indicating successful disruption of the fetal hypothalamic-pituitary-thyroid axis. T4 assays performed on a similar subset of n = 96 fetuses showed that MMI treatment significantly reduced T4 concentrations within each timepoint relative to CON (P < 0.001 at all timepoints). Following confirmation of hypothyroidism, RNA was extracted from the fetal LVR and KID samples to allow for gene expression analysis by qPCR. Ct values were normalized, fold changes calculated using the 2-ΔΔCt method, and differences within timepoint determined using a Wilcoxon signed-rank test. AGT, the precursor to all bioactive RAS peptides, was significantly downregulated in LVR at d 66 (P = 0.014) and 76 (P < 0.001). ACE was significantly upregulated at d 76 in both LVR (P = 0.037) and KID (P = 0.005). No significant changes were observed for ACE2 in either tissue, or for renal REN. Finally, AGTR1, the receptor that mediates RAS effects, was significantly downregulated at d 55 in KID (P < 0.001) and d 76 in LVR (P = 0.023), while also being upregulated at d 86 in LVR (P = 0.033). Collectively, these results show that fetal hypothyroidism modulates RAS function in a gestational age-dependent manner, which may alter fetal development and subsequent postnatal physiology. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones play a key role in differentiation and metabolism and are known regulators of gene expression through both genomic and epigenetic processes including DNA methylation. The aim of this study was to examine associations between thyroid hormones and DNA methylation. Methods: We carried out a fixed-effect meta-analysis of epigenome-wide association study (EWAS) of blood DNA methylation sites from 8 cohorts from the ThyroidOmics Consortium, incorporating up to 7073 participants of both European and African ancestry, implementing a discovery and replication stage. Statistical analyses were conducted using normalized beta CpG values as dependent and log-transformed thyrotropin (TSH), free thyroxine, and free triiodothyronine levels, respectively, as independent variable in a linear model. The replicated findings were correlated with gene expression levels in whole blood and tested for causal influence of TSH and free thyroxine by two-sample Mendelian randomization (MR). Results: Epigenome-wide significant associations (p-value <1.1E-7) of three CpGs for free thyroxine, five for free triiodothyronine, and two for TSH concentrations were discovered and replicated (combined p-values = 1.5E-9 to 4.3E-28). The associations included CpG sites annotated to KLF9 (cg00049440) and DOT1L (cg04173586) that overlap with all three traits, consistent with hypothalamic–pituitary–thyroid axis physiology. Significant associations were also found for CpGs in FKBP5 for free thyroxine, and at CSNK1D/LINCO1970 and LRRC8D for free triiodothyronine. MR analyses supported a causal effect of thyroid status on DNA methylation of KLF9. DNA methylation of cg00049440 in KLF9 was inversely correlated with KLF9 gene expression in blood. The CpG at CSNK1D/LINC01970 overlapped with thyroid hormone receptor alpha binding peaks in liver cells. The total additive heritability of the methylation levels of the six significant CpG sites was between 25% and 57%. Significant methylation QTLs were identified for CpGs at KLF9, FKBP5, LRRC8D, and CSNK1D/LINC01970. Conclusions: We report novel associations between TSH, thyroid hormones, and blood-based DNA methylation. This study advances our understanding of thyroid hormone action particularly related to KLF9 and serves as a proof-of-concept that integrations of EWAS with other -omics data can provide a valuable tool for unraveling thyroid hormone signaling in humans by complementing and feeding classical in vitro and animal studies. [ABSTRACT FROM AUTHOR]

Cardamom seed (Elettaria cardamomum (L.) Maton; EC) is consumed in several countries worldwide and is considered a nutraceutical spice since it exerts antioxidant, anti-inflammatory, and metabolic activities. In obese individuals, EC intake also favors weight loss. However, the mechanism for these effects has not been studied. Here, we identified that EC modulates the neuroendocrine axis that regulates food intake, body weight, mitochondrial activity, and energy expenditure in mice. We fed C57BL/6 mice with diets containing 3%, 6%, or 12% EC or a control diet for 14 weeks. Mice fed the EC-containing diets gained less weight than control, despite slightly higher food intake. The lower final weight of EC-fed mice was due to lesser fat content but increased lean mass than control. EC intake increased lipolysis in subcutaneous adipose tissue, and reduced adipocyte size in subcutaneous, visceral, and brown adipose tissues. EC intake also prevented lipid droplet accumulation and increased mitochondrial content in skeletal muscle and liver. Accordingly, fasting and postprandial oxygen consumption, as well as fasting fat oxidation and postprandial glucose utilization were higher in mice fed with EC than in control. EC intake reduced proopiomelanocortin (POMC) mRNA content in the hypothalamic arcuate nucleus, without an impact on neuropeptide Y (NPY) mRNA. These neuropeptides control food intake but also influence the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes. Thyrotropin-releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and circulating triiodothyronine (T3) were lower in EC-fed mice than in control. This effect was linked with decreased circulating corticosterone and weight of adrenal glands. Our results indicate that EC modulates appetite, increases lipolysis in adipose tissue and mitochondrial oxidative metabolism in liver and skeletal muscle, leading to increased energy expenditure and lower body fat mass. These metabolic effects were ascribable to the modulation of the HPT and HPA axes. LC-MS profiling of EC found 11 phenolic compounds among which protocatechuic acid (23.8%), caffeic acid (21.06%) and syringic acid (29.25%) were the most abundant, while GC-MS profiling showed 16 terpenoids among which costunolide (68.11%), ambrial (5.3%) and cis-α-terpineol (7.99%) were identified. Extrapolation of mice-to-human EC intake was performed using the body surface area normalization equation which gave a conversion equivalent daily human intake dose of 76.9–308.4 mg bioactives for an adult of 60 kg that can be obtained from 14.5–58.3 g of cardamom seeds (18.5–74.2 g cardamom pods). These results support further exploration of EC as a coadjuvant in clinical practice. [ABSTRACT FROM AUTHOR]

Background: ISL LIM homeobox 2, also known as insulin gene enhancer protein ISL-2 (ISL2), is a transcription factor gene that participates in a wide range of developmental events. However, the role of ISL2 in the hypothalamus-pituitary-thyroid axis is largely unknown. In the present study, we characterized the expression patterns of ISL2 and revealed its regulative role during embryogenesis using zebrafish. Methods: We used the CRISPR/Cas9 system to successfully establish homozygous ISL2-orthologue (isl2a and isl2b) knockout zebrafish. Moreover, we utilized these knockout zebrafish to analyze the pituitary and thyroid phenotypes in vivo. For further molecular characterization, in situ hybridization and immunofluorescence were performed. Results: The isl2a mutant zebrafish presented with thyroid hypoplasia, reduced whole-body levels of thyroid hormones, increased early mortality, gender imbalance, and morphological retardation during maturity. Additionally, thyrotropes, a pituitary cell type, was notably decreased during development. Importantly, the transcriptional levels of pituitary-thyroid axis hormones-encoding genes, such as tshba, cga, and tg, were significantly decreased in isl2a mutants. Finally, the thyroid dysplasia in isl2a mutant larvae may be attributed to a reduction in proliferation rather than changes in apoptosis. Conclusions: In summary, isl2a regulates the transcriptional levels of marker genes in hypothalamus-pituitary-thyroid axis, and isl2a knockout causing low thyroid hormone levels in zebrafish. Thus, isl2a identified by the present study, is a novel regulator for pituitary cell differentiation in zebrafish, resulting in thyroid gland hypoplasia and phenotypes of hypothyroidism. [ABSTRACT FROM AUTHOR]

It is well established that decreases in plasma leptin levels, as with fasting, signal starvation and elicit appropriate physiological responses, such as increasing the drive to eat and decreasing energy expenditure. These responses are mediated largely by suppression of the actions of leptin in the hypothalamus, most notably on arcuate nucleus (ArcN) orexigenic neuropeptide Y neurons and anorexic pro-opiomelanocortin neurons. However, the question addressed in this review is whether the effects of increased leptin levels are also significant on the long-term control of energy balance, despite conventional wisdom to the contrary. We focus on leptin's actions (in both lean and obese individuals) to decrease food intake, increase sympathetic nerve activity, and support the hypothalamic–pituitary–thyroid axis, with particular attention to sex differences. We also elaborate on obesity-induced inflammation and its role in the altered actions of leptin during obesity. [ABSTRACT FROM AUTHOR]

Objective: To understand differences in thyroid hormone replacement therapy with levo‐thyroxine (l‐T4) between acquired and congenital hypothyroid (CH) patients. Design: We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy. Patients and Measurements: A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18−58). Serum TSH, FT3, FT4, l‐T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups. Results: The daily weight‐based l‐T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p =.03). FT3/FT4 ratio was significantly higher in the EU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in the TP group, but not in the EU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects. Conclusions: Adult CH patients require a higher daily l‐T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic−pituitary−thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH. [ABSTRACT FROM AUTHOR]

[Display omitted] • The hypothalamic-pituitary-thyroid axis was studied in Seriola rivoliana early larvae. • Larvae at 22 °C increased more trh expression than larvae at higher temperatures. • tsh was highly expressed at hatching, and then, downregulated at any temperature. • tsh -binding occurred before hatching, and further upregulating larval thyroglobulin. • On day six after hatching, all HPT axis genes were significantly upregulated. We analyzed the expression of genes involved in the hypothalamic-pituitary-thyroid axis (HPT-axis) in the longfin yellowtail Seriola rivoliana early larva, including temperature effects (22, 26 and 28 °C) and days of development (day one, day two, and day six after hatching). We aimed to determine if egg and larval incubation at different temperatures could disrupt this critical endocrine axis, which, in an aquaculture context, it could provoke mortality during early metamorphosis. There was a significant interaction between temperature and developmental timing on the relative expression of thyrotropin releasing hormone (trh). Larvae at 22 °C was the longest and increased more trh expression than larvae at higher temperatures. Interestingly, thyrotropin stimulating hormone (tsh) was highly expressed after hatching. Subsequently, it was downregulated at any temperature at least until day four, suggesting a temporal inhibition of the HPT axis. Therefore, we suggest that tsh -binding (tshr) to follicles should have occurred from hatching, creating a further "cascade effect" of upregulation of larval thyroglobulin (tg) from day two in a temperature-dependent manner. Consequently, new thyroid hormones should have been produced after yolk sac absorption. The above may indicate a narrow window of larval survival, where the larval transition from endogenous to exogenous feeding would depend on the correct timing to synthesize tg. Temperature significantly affected the expressions of deiodinase 1 (dio1 -downregulated) and deiodinase 2 (dio2 -upregulated) after hatching. The expressions of thyroid receptors alpha (trα) and beta (trβ) remained constant after hatching without significant effects of temperature and days of development. Then, the differential expression on day six showed that all HPT-axis transcripts increased their expressions as larvae developed, which suggested a functional HPT. Finally, there was no evidence that any temperature would disrupt the endocrine's larval axis, which indicated that the longfin yellowtail has a wide temperature adaption. Nevertheless, based on tg upregulation, we suggest that larvae should be maintained around 25–26 °C after hatching for a better chance of survival and development. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were (1) to compare TSH levels between inpatients with critical versus non-critical coronavirus disease 19 (COVID-19), and (2) to describe the status of TSH levels three months after hospitalization. Methods: We collected data on adult patients hospitalized with COVID-19 at Amiens University Hospital. We compared TSH levels between inpatients with critical (intensive care unit admission and/or death) versus non-critical COVID-19. Thereafter, survivors were invited to return for a three-month post-discharge visit where thyroid function tests were performed, regardless of the availability of TSH measurement during hospitalization. Results: Among 448 inpatients with COVID-19, TSH assay data during hospitalization were available for 139 patients without prior thyroid disease. Patients with critical and non-critical forms of COVID-19 did not differ significantly with regard to the median (interquartile range) TSH level (0.96 (0.68–1.71) vs. 1.27 mIU/L (0.75–1.79), p = 0.40). Abnormal TSH level was encountered in 17 patients (12.2%); most of them had subclinical thyroid disease. TSH assay data at the three-month post-discharge visit were available for 151 patients without prior thyroid disease. Only seven of them (4.6%) had abnormal TSH levels. Median TSH level at the post-discharge visit was significantly higher than median TSH level during hospitalization. Conclusions: Our findings suggest that COVID-19 is associated with a transient suppression of TSH in a minority of patients regardless of the clinical form. The higher TSH levels three months after COVID-19 might suggest recovery from non-thyroidal illness syndrome. [ABSTRACT FROM AUTHOR]