Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Exploring the relationship between Hashimoto's thyroiditis and male fertility:A meta-analytic and meta-regression perspective on hormonal and seminal factors

Objective:To explore the relationship between Hashimoto's autoimmune hypothyroidism(HT)and male fertility,focusing on hormonal and seminal factors.Methods:A systematic literature search was conducted across databases such as PubMed,Web of Science,EMBASE,Scopus,Cochrane,and Google Scholar,covering studies published from January 2000 to March 2024.Studies investigating the impact of HT on semen quality parameters and reproductive hormones were included.Pooled effect estimates were calculated using standard mean difference(SMD)and 95%confidence intervals(CI).Results:A total of 8 studies with 8965 participants were included.HT significantly affected semen quality and reproductive hormone levels.Specifically,there was a notable decrease in progressive morphology(SMD=-0.78;95%CI:-1.40 to-0.17;P=0.01)and sperm motility(SMD=-1.151;95%CI:-1.876 to-0.425;P=0.002).In addition,there were no significant changes in reproductive hormones,although there were elevated levels of luteinizing hormone(SMD=0.437;95%CI:0.000 to 0.874;P=0.050)and follicle-stimulating hormone(SMD=0.293;95%CI:-0.171 to 0.758;P=0.216),with a slight impact on testosterone levels(SMD=-1.143;95%CI:-2.487 to 0.200;P=0.095).Conclusions:This systematic review and meta-analysis provides robust evidence of the detrimental effects of HT on semen quality and reproductive hormones,underscoring the necessity for thorough evaluation and management of thyroid function in male infertility assessments.

Thyroid hormones and thyroid hormone receptors: Effects of thyromimetics on reverse cholesterol transport

Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop- ment, and metabolism in almost all tissues. THs exert their actions by binding to thyroid hormone receptors (TRs). There are two major subtypes of TRs, TRα and TRβ, and several isoforms (e.g. TRα1, TRα2, TRβ1, and TRβ2). Activation of TRα1 affects heart rate, whereas activation of TRβ1 has positive effects on lipid and lipoprotein metabolism. Consequently, particular interest has been focused on the development of thyromimetic compounds targeting TRβ1, not only because of their ability to lower plasma cholesterol but also due their ability to stimulate RCT, at least in pre-clinical models. In this review we focus on THs, TRs, and on the effects of TRβ1-modulating thyromimetics on RCT in various animal models and in humans.

Effect of TSH Suppression Therapy on Sex Hormone Levels after Thyroid Cancer Surgery

Objective:To analyze the effect of thyroid-stimulating hormone(TSH)suppression therapy on sex hormone levels in patients undergoing postoperative treatment for thyroid cancer.Methods:A total of 40 patients undergoing postoperative thyroid cancer treatment were selected for data analysis.TSH suppression therapy was implemented during the postoperative period.Patients were grouped according to the TSH level:TSH<0.1,0.1≤TSH<0.5,and TSH≥0.5.Results:Among male patients,there were no significant differences in sex hormone levels at different dosing times and TSH levels(P>0.05).For female patients,testosterone levels at different dosing times showed no significant differences under the same circumstances(P>0.05).The comparison of testosterone levels at different TSH levels over 5 years of TSH suppression therapy did not yield significant differences(P>0.05).However,the comparison of testosterone levels within 5 years of TSH suppression therapy yielded significant differences(P<0.05),with the lowest levels observed at 0.1≤TSH<0.5.Conclusion:The use of TSH suppression therapy in postoperative thyroid cancer treatment minimally affects sex hormone levels in male patients.However,it has a significant impact on female patients.Therefore,preoperative sex hormone testing is recommended,and postoperative monitoring should include regular sex hormone testing.

Stimulating effect of thyroid hormones in peripheral nerve regeneration:research history and future direction toward clinical therapy

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions.Despite extensive investigation,testing various surgical repair techniques and neurotrophic molecules,at present,a satisfactory method to ensuring successful recovery does not exist.For successful molecular therapy in nerve regeneration,it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth.Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination.Therefore,any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration.Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system,so they could be candidates for nervous system regeneration.This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration.Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves.We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves,and accelerates functional recovering.This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves.The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells.

Thyroid hormones in male reproduction and infertility

Thyroid hormones have been well studied for its relevance to male reproduction in the last few decades. They are considered as essential regulators of male reproductive functions and play vital roles in male gonadal developments. Hyperthyroidism and hypothyroidism both affect testicular functions and influence neuroendocrine regulations over reproductive functionsvia the crosstalk between the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-gonadal axis. The alterations in the male reproductive hormonal milieu by thyroid hormones may lead to reduced testosterone levels and deterioration of semen quality. However, there are very few reports on the direct effects of thyroid disorders upon testicular functions and semen quality. This article aims to review the available literature to present a concise updated concept on the regulation of male reproductive functions by the thyroid hormones, and the possible mechanism by which thyroid dysfunctions affects testicular functions.

Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose

The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.

Comparison of Thyroid Hormones Levels in Female Ducks Blood and Embryo

[Objeclive] The comparison of levels of thyroid hormones （T3, T4 and FT3） in female ducks serum and embryo of different embryonic age between Gaoyou duck and Jinding duck were made to provide basic data for further research. [Method] The levels of thyroid hormones （T3, T4 and FT3） in female ducks serum, fertilized eggs, and 7, 11,15, 19, 22, 28-days embryo of Gaoyou duck and Jinding duck were analyzed with radioimmunoassay （RIA）. [ Result]The levels of thyroid hormones in fertilized eggs were higher than those in serum of female ducks; different em- bryonic age hormone level of Gaoyou duck and Jinding duck in serum had almost the same variation trend, which was low but relatively stable after 15 days. [Condusion] The result suggested that thyroid hormones play an important role in duck embryonic development, especially in the early peded.

Characteristics of Thyroid Hormones in Hypertensive Hispanic Population

The aim was to characterize thyroid function in Hispanic hypertensive population. Retrospective study of 1,023 individuals was performed, in which 68.23% had hypertension （74.21% women） and 37.25% had thyroid pathology. Age, weight, blood pressure, biochemical measurements were recorded, mean age： 53.02 ± 14.80 yr, mean weight： 83.05 ±16.95 kg, thyrotropin-stimulating hormone （TSH） hypertensive patients： 5.55±1.63 μUI/mL and without hypertension： 3,72 ± 1.60 μUI/mL. TSH range concentration distributed by sex indicates： 1.50-2.49 μUI/mL men, 2.50-5.01 μUI/mL women. TSH categories vs. age were positively associated （r = ＋ 0.114, P = 0.044） and hypertension by age was also correlated （r = ＋ 0.178, P = 0.0001）. Significant positive association we found between TSH and diastolic blood pressure （r = ＋ 0.197, P = 0.008）. Systolic and diastolic blood pressure vs. age were positively increasing （r = ＋ 0.410,p = 0.0001; r = ＋0.285, P = 0.0001, respectively）. Prevalence of thyroid pathology in hypertensive subjects are hyperthyroidism 5.87%; hypothyroidism 20.34% （5.73% subclinic） and autoimmune disease 6.25%. High percentage of hypertensive population has concomitant thyroid diseases, more common in women （50-70 years）. Systematic surveillance for occult thyroid dysfunction in patients with hypertension could prevent future cardiovascular disease.

Association of Serum Ferritin Levels and Thyroid Hormones

Thyroid metabolism is orchestrated by the action of various minerals and trace elements including iron, iodine, selenium, and zinc. Iron deficiency, specifically deficiency in serum ferritin levels, is one of the common causes of thyroid dysfunction. Our objective was to evaluate the relationship between serum ferritin levels and circulating thyroid hormones. For this, a retrospective analysis was performed on 16,512 individuals who tested for serum levels of ferritin and thyroid profile at Vibrant America Clinical Laboratories. Subjects were stratified based on the serum levels of ferritin. Age (p −0.03232, p < 0.0001). Analysis of Linear association by Pearson’s correlation exhibited a considerable correlation between varying serum ferritin levels with all tested thyroid hormones. The study concludes that serum ferritin levels were associated with thyroid hormone synthesis and metabolism in individuals with optimal levels of circulating ferritin.

Feeding Supplemental lodine to Adult Mink;Effect on Thyroid Hormones in Adult and offspring

We fed adult mink diets containing supplemental iodine, from 0 to 320 ppm, for one or seven months prior to breeding. Blood samples collected from the adults and their offspring (kits) at 4 wk post-partum were assayed for total thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and T4-binding indices. As expected T4 concentrations of the adult and kit mink varied inversely with the level of supplemental iodine. In addition, T3 and rT3 concentrations decreased gradually in kits from the long-term experiment in response to the increased dietary iodine of the dams. T3 concentrations of kits from dams fed iodine short-term decreased markedly while rTy concentrations were elevated greatly in response to increased dietary iodine of the dam. These decreases in hormone levels are due to serum iodine blocking the thyroid uptake of iodine and subsequent decrease of hormone synthesis. Excess iodine may also block the effect of thyroid stimulating hormone. The T4-binding indices of the adults, in general, were depressed, while the T4-binding indices of the kits were more variable. These effects are probably due to fluctuations in thyroglobulin.

Serum Level of Thyroid Hormones in Patients with Chronic Hepatitis C Virus Infection

Objective: There are clinical and laboratory associations between thyroid and liver diseases. Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. The most frequent and clinically important endocrine extrahepatic diseases are thyroid disorders and type 2 diabetes mellitus. We aim to study the relationship between the serum level of thyroid hormones (THs) and the severity of liver disease in patients with chronic hepatitis C virus (CHC) infection. Methods: 60 patients with CHC infection were selected for the study. They were divided into two groups: with or without liver cirrhosis. Those with liver cirrhosis were further subdivided according to the Child-Turcotte-Pugh scoring system. Serum levels of free T3 (FT3), free T4 (FT4) and TSH were measured to all patients. Results: There was decrease in the FT3 and FT4 levels and increase in the TSH levels in patients with CHC with cirrhosis when compared to patients with CHC without cirrhosis. Conclusion: Thyroid profile abnormalities were seen in cirrhotic HCV patients when compared to non-cirrhotic patients. The abnormalities in the serum level of THs (decreased FT3, FT4, and increased TSH) are strongly associated with the severity of liver damage and advancing of the child score.

Assessment of LLLT systemic effects on thyroid hormones function after dental titanium implant installation:An experimental rabbit model

This study aimed to assess the systemic effect of LLLT on thyroid gland functioning and consequently on calcium regulation through Triiodothyronine (T3) and Thyroxine (T4) measurements in rabbits’ serum. A total of thirty two New Zealand male rabbits were randomly distributed in four groups with eight animals each: control group C (nonirradiated animals), group EI (5 J/cm2 per session), group EII (10 J/cm2 per session) and group EIII (20 J/cm2 per session). All animals underwent lower left incisor extraction followed by immediate insertion of an osseintegrated implant, providing an equality of initial clinical condition between the groups. The experimental groups were irradiated with aluminium gallium arsenide diode laser (GaAlAs, λ = 830 nm, 50 mW, CW), during 13 days at each 48 hours, totalizing 7 sessions. Laboratorial T3 and T4 measurements were done in four distinct moments (before surgical procedure, immediately after surgical procedure, after the first LLLT session and after the last LLLT session) in all animals. The results obtained showed statistically significant differences in Triiodothyronine values between the groups throughout the experiment. It was concluded that the LLLT, in the protocol of irradiation used in this study, promoted a significantly alteration on rabbits’ serum hormonal levels.

Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development

The importance of the thyroid hormone axis in the regulation of skeletal growth and maintenance has been well established from clinical studies involving patients with mutations in proteins that regulate synthesis and/or actions of thyroid hormone. Data from genetic mouse models involving disruption and overexpression of components of the thyroid hormone axis also provide direct support for a key role for thyroid hormone in the regulation of bone metabolism. Thyroid hormone regulates proliferation and/or differentiated actions of multiple cell types in bone including chondrocytes, osteoblasts and osteoclasts. Thyroid hormone effects on the target cells are mediated via ligand-inducible nuclear receptors/transcription factors, thyroid hormone receptor （TR） a and ~, of which TRa seems to be critically important in regulating bone cell functions. In terms of mechanisms for thyroid hormone action, studies suggest that thyroid hormone regulates a number of key growth factor signaling pathways including insulin-like growth factor-I, parathyroid hormone related protein, fibroblast growth factor, Indian hedgehog and Wnt to influence skeletal growth. In this review we describe findings from various genetic mouse models and clinical mutations of thyroid hormone signaling related mutations in humans that pertain to the role and mechanism of action of thyroid hormone in the regulation of skeletal growth and maintenance.

Iodothyronine deiodinase gene analysis of the Pacific oyster Crassostrea gigas reveals possible conservation of thyroid hormone feedback regulation mechanism in mollusks

Iodothyronine deiodinase catalyzes the initiation and termination of thyroid hormones(THs) effects, and plays a central role in the regulation of thyroid hormone level in vertebrates. In non-chordate invertebrates, only one deiodinase has been identified in the scallop C hlamys farreri. Here, two deiodinases were cloned in the Pacific oyster C rassostrea gigas( Cg Dx and C g Dy). The characteristic in-frame TGA codons and selenocysteine insertion sequence elements in the oyster deiodinase c DNAs supported the activity of them. Furthermore, seven orthologs of deiodinases were found by a tblastn search in the mollusk Lottia gigantea and the annelid C apitella teleta. A phylogenetic analysis revealed that the deiodinase gene originated from an common ancestor and a clade-specific gene duplication occurred independently during the differentiation of the mollusk, annelid, and vertebrate lineages. The distinct spatiotemporal expression patterns implied functional divergence of the two deiodinases. The expression of C g Dx and Cg Dy was influenced by L-thyroxine T4, and putative thyroid hormone responsive elements were found in their promoters, which suggested that the oyster deiodinases were feedback regulated by TH. Epinephrine stimulated the expression level of C g Dx and Cg Dy, suggesting an interaction effect between different hormones. This study provides the first evidence for the existence of a conserved TH feedback regulation mechanism in mollusks, providing insights into TH evolution.

Recent advances in liver preconditioning: Thyroid hormone, n-3 long-chain polyunsaturated fatty acids and iron

Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver transplantation and major hepatic resection. For these reasons, numerous PC strategies have been evaluated in experimental models of ischemia-reperfusion liver injury, which have not been transferred to clinical application due to side effects, toxicity and difficulties in implementation, with the exception of the controversial ischemic PC. In recent years, our group has undertaken the assessment of alternate experimental liver PC protocols that might have application in the clinical setting. These include thyroid hormone (T3), n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), or iron, which suppressed liver damage due to the 1 h ischemia-20 h reperfusion protocol. T3, n-3 LCPUFA and iron are hormetic agents that trigger biologically beneficial effects in the low-dose range, whose multifactorial mechanisms of action are discussed in the work.

Thyroid hormone analogues and derivatives:Actions in fatty liver

Fatty liver or nonalcoholic fatty liver disease(NAFLD),a problem of increasing clinical significance and prevalence worldwide,is associated with increased risk for the development of cirrhosis and hepatocellular carcinoma.Although several therapeutic approaches can be used in the context of NAFLD,dietary and physical activities are still the most frequently used strategies.Some pharmacological agents show promising results although no conclusions can be drawn from recent clinical trials.Thyroid hormones[THs;thyroxine(T4)and3,3′,5-triiodo-L-thyronine(T3)]coordinate a diverse array of physiological events during development and lipid/energy homeostasis and have some potentially therapeutic actions which include inducing weight loss,and lowering plasma cholesterol levels and tissue adiposity.The thyroid hormones exert their physiological effects by binding to specific nuclear receptors[thyroid hormone receptors(TR)]of which the TRβisoform is liver specific and has been considered a putative target for the treatment of dyslipidemia and fatty liver.In view of this,the aim of the review is(1)to provide an overview of the action of T3 on lipid metabolism with implications for liver steatosis and(2)to provide an update on the current knowledge concerning the administration of TRβselective thyromimetics(GC-1 and MB07811),as well as of 3,5-diiodo-L-thyronine and its novel functional analogue TRC150094 in animal models of overweight and related disorders including primarily fatty liver.

Amphibian metamorphosis as a model for studying the developmental actions of thyroid hormone

The thyroid hormones L-thyroxine and triiodo-L-thyronine have profound effects on postembryonic development of most vertebrates. Analysis of their action in mammals is vitiated by the exposure of the developing foetus to a number of maternal factors which do not allow one to specifically define the role of thyroid hormone (TH)or that of other hormones and factors that modulate its action. Amphibian metamorphosis is obligatorily dependent on TH which can initiate all the diverse physiological manifestations of this postembryonic developmental process(morphogenesis, cell death, re-structuring, etc.) in free-living embryos and larvae of most anurans. This article will first describe the salient features of metamorphosis and its control by TH and other hormones. Emphasis will be laid on the key role played by TH receptor (TR), in particular the phenomenon of TR gene autoinduction, in initiating the developmental action of TH. Finally, it will be argued that the findings on the control of amphibian metamorphosis enhance our understanding of the regulation of postembryonic development by TH in other vertebrate species.

The transcription of iodothyronine deiodinase genes is regulated by thyroid hormone receptor in the Pacific oyster Crassostrea gigas

Thyroid hormones (THs) are indispensable for each phyla in Chordata, while their functions in the non-chordate invertebrates are indistinct. Studies on the TH system in non-chordate invertebrates are important for understanding the evolution of TH system and may be applied in aquaculture or biofouling control at the same time. Iodothyronine deiodinases are keys to studying the TH system, as they are critical enzymes in maintaining TH homeostasis by catalyzing the initiation and termination of the effects of thyroid hormone in vertebrates. Here, we report the primary physiological effects of T4, the outer ring deiodinase activity, and a similar transcription regulation of two oyster deiodinases by TH receptor (CgTR) in an invertebrate, Pacific oyster Crassostrea gigas. L-thyroxine (T4) may have an important physiological function in the oyster, suggested by the growth retardation effect of excessive T4 in umbo larvae stage. The outer ring deiodinase activity transforming T4 to T3 (3, 3', 5-triiodothyronine) was then detected in the Pacific oyster in vivo, which may be conducted by two oyster deiodinases (CgDx and CgDy). Transcription regulation of CgTR onto these two deiodinase genes was also verified by electrophoretic mobility shift assay and dual luciferase reporter assay in mammalian cells. These results contribute to a better understanding of the evolution of the TH system.

The roles of thyroid hormone receptor and T3 in metamorphosis of Haliotis diversicolor

Thyroid hormone is a kind of important hormone which regulates metamorphosis. Its role is well described in amphibian metamorphosis. Thyroid hormones (T3 and T4) have also been demonstrated to play a role in metamorphosis of marine invertebrates. However, the mechanism of thyroid hormone in metamorphosis of marine invertebrates remains unknown. A homolog of vertebrate thyroid hormone receptor (TR) was cloned and identified in abalone Haliotis diversicolor and was named HdTR . The mRNA expressions of HdTR , thyroid peroxidase ( TPO ), thyroid peroxidase 1 ( TPO1 ), idothyronine deiodinase Ⅲ( IDⅢ) and integrin alpha-V ( ITGAV ) had significant diff erence in metamorphosis of H . diversicolor . Metamorphosis rate and mortality rate were significantly diff erent in HdTR RNAi experiment and T3 inducing experiment. In RNAi experiment, ITGAV and CCND1 (cyclin D1) expression of dsRNA HdTR exposing group were significantly lower than those of blank control and negative control. But CTNNB (catenin beta) expression of dsRNA HdTR exposing group was higher than that those of blank control and negative control. ERK (extracellular signal regulated kinases) and PI3K (phosphoinositide-3-kinase) had no significant diff erence in RNAi experiment. Moreover, ITGAV of 1 μmol/L T3 group was significantly lower than that of 0 μmol/L T3 group, PI3K expression of 10 μmol/L T3 group was higher than that of 0 μmol/L T3 group, and the other genes expression had no significant diff erence in T3 inducing experiment. The data of genes expression suggested that CCND1 might be an eff ector gene of TR genomic action, while CTNNB might be regulated by unliganded TR. CCND1 and CTNNB may be involved in cell proliferation of metamorphosis. T3 might regulate the expression level of PI3K via nongenomic way. These results shed light on the mechanism of thyroid hormone in abalone metamorphosis.