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.

Association between lifestyle factors and thyroid function in young euthyroid adults

Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:Energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).Energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.

Analysis of the value and safety of thyroid-stimulating hormone in the clinical efficacy of patients with thyroid cancer

BACKGROUND Thyroid cancer(TC)is a common malignant tumor in the endocrine system.In recent years,the incidence and recurrence rates of TC have been raising due to increasing work pressure and irregular lifestyles.Thyroid-stimulating hormone(TSH)is a specific parameter for thyroid function screening.This study aims to explore the clinical value of TSH in regulating the progression of TC,so as to find a breakthrough for the early diagnosis and treatment of TC.AIM To explore the value and safety of TSH in the clinical efficacy of patients with TC.METHODS 75 patients with TC admitted to the Department of Thyroid and Breast Surgery of our hospital from September 2019 to September 2021 were selected as the observation group,and 50 healthy subjects were selected as the control group during the same period.The control group was treated with conventional thyroid replacement therapy,and the observation group was treated with TSH suppression therapy.The soluble interleukin(IL)-2 receptor(sIL-2R),IL-17,IL-35levels,free triiodothyronine(FT3),free tetraiodothyronine(FT4),CD3+,CD4+,CD8+,CD44V6,and tumor supplied group of factor(TSGF)levels were observed in the two groups.The occurrence of adverse reactions was compared between the two groups.RESULTS After treatment with different therapies,the levels of FT3,FT4,CD3+,and CD4+in the observation group and the control group were higher than those before treatment,while the levels of CD8+,CD44V6,and TSGF were lower than those before treatment,and the differences were statistically significant(P<0.05).More importantly,the levels of sIL-2R and IL-17 in the observation group were lower than those in the control group after 4 wk of treatment,while the levels of IL-35 were higher than those in the control group,and the differences were statistically significant(P<0.05).The levels of FT3,FT4,CD3+,and CD4+in the observation group were higher than those in the control group,and the levels of CD8+,CD44V6,and TSGF were lower than those in the control group.There was no significant difference in the overall incidence rate of adverse reactions between the two groups(P>0.05).CONCLUSION TSH suppression therapy can improve the immune function of patients with TC,lower the CD44V6 and TSGF levels,and improve serum FT3 and FT4 levels.It demonstrated excellent clinical efficacy and a good safety profile.

Correlation analysis of serum thyroglobulin,thyroid-stimulating hormone levels,and thyroid-cancer risk in thyroid nodule surgery

BACKGROUND Thyroglobulin(Tg)is one of the markers of thyroid cancer,and its concentration may be elevated in patients with malignant thyroid tumors.Thyroid-stimulating hormone(TSH)is secreted by the pituitary gland,which has a significant impact on thyroid gland function.Excessively high or low TSH levels may be associated with an increased risk of thyroid cancer.Thus,in-depth studies on the association of serum Tg and TSH levels with thyroid cancer risk in patients with thyroid nodules are warranted.This can help determine whether Tg and TSH levels can predict the degree of malignancy of thyroid nodules,which can in turn guide doctors in making accurate diagnoses and treatment decisions.Furthermore,such studies can provide more accurate diagnostic methods for thyroid nodules and help patients become aware of the presence of thyroid cancer as early as possible,thereby improving the success rate of treatment and prognosis.AIM To investigate the association of serum Tg and TSH levels with the risk of thyroid cancer in patients undergoing thyroid nodule surgery.METHODS The clinical data and laboratory examination results of 130 patients who underwent thyroid nodule surgery were retrospectively analyzed.Furthermore,their preoperative serum Tg and TSH levels were recorded.Histopathological examination conducted during follow-up revealed the presence of thyroid cancer.Correlation analysis were used to analyze the association of Tg and TSH levels with the risk of thyroid cancer.RESULTS Of the 130 patients,60 were diagnosed with thyroid cancer.Statistical analysis revealed a significant positive correlation between serum Tg levels and the risk of thyroid cancer(P<0.05).This suggests that high serum Tg levels are associated with an increased risk of thyroid cancer.However,no significant correlation was observed between serum TSH levels and the risk of thyroid cancer(P>0.05).CONCLUSION In patients who underwent thyroid nodule surgery,serum Tg levels exhibited a significant correlation with the risk of thyroid cancer but serum TSH levels did not.These findings suggest that serum Tg can serve as an important biomarker for assessing the risk of thyroid cancer in these patients.

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.

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.

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.

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 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.

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.

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.

Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in a Chinese community-based population of euthyroid people aged 40 years and older

This study investigated whether high-normal thyrotropin（TSH） levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects（40-77 years old） with TSH levels in the normal range（0.35-5.00 mU/L）.Using 2.50 mU/L as the cut-off point of TSH level within the normal range,we divided subjects into the high-TSH（2.50-5.00 mU/L;n= 1,064） and low-TSH（0.35-2.50mU/L;n= 1,292） group.The results showed that the mean levels of body mass index（BMI）,total cholesterol（TC）,low density lipoprotein cholesterol（LDL-C）,and fasting plasma glucose（FPG） were higher in the high-TSH group and TSH levels were significantly positively con-elated with BMI,LDL-C,TC,and FPG.The prevalence of central obesity,hypertriglyceridemia,low high density lipoprotein cholesterol（HDL-C）,and high FPG（〉5.60 mmol/L） was significantly higher in females and subjects with high-TSH levels.Metabolic syndrome was also more prevalent in the high-TSH group.People over the age of 40 years with high-normal TSH levels had a 1.2-fold increased risk of metabolic syndrome,compared with those with low-normal TSII levels,after adjusting for age and gender.In conclusion,high normal TSH is a risk factor for metabolic syndrome in people ≥40 years old.

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.

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.

Effect of parathyroid hormone on apoptosis of human medullary thyroid carcinoma cells

Objective The aim of the study was to investigate the effect of parathyroid hormone(PTH) on the apoptosis of human medullary thyroid carcinoma(MTC) cells.Methods In vitro cultured medullary thyroid carcinoma cell lines were treated with parathyroid hormone and parathyroid hormone receptor-monoclonal antibody,and the apoptosis of cells was detected by flow cytometry.Results The cell morphology changed significantly after treatment based on the observation using the inverted phase-contrast microscope.Various concentrations of parathyroid hormone and parathyroid hormone receptor-monoclonal antibody effectively induced apoptosis in a time-and concentrationdependent manner.When the concentration of parathyroid hormone was 2.0 μmol/L and that of parathyroid hormone receptor-monoclonal antibody was 1.0 μmol/L,the apoptotic rate was 13.24% and 20.78%,respectively,representing a statistically significant difference from that of the control cells(P < 0.05).Conclusion PTH plays a role in inducing apoptosis of human MTC cells.

Changes of serum thyroid hormone and plasma catecholamine of 16 th and 17 th Chinese Expeditioners in Antarctic environment

The serum thyroid hormone and plasma catecholamine were examined in 18 male and 2 female members of the Chinese Antarctic Expedition (who spent the 2000 or 2001 austral winter at the Great Wall Station) . The changes of serum thyroid hormone i. e. total thyroxine (TT4) and free T4 (FT4) , total triodothyronine (TT3) and freeT3 ( FT3 ) , thyroid stimulating hormone ( TSH ) and plasma catecholamine, including norepinephrine (NE) , epinephrine ( E) and dopamine ( DA ) , were investigated by Chemoluminescence Immunoassay (CLIA) and High Performance Liquid Chromatography with electrochemical detection (HPLC-ECD) . Samples were taken at different time; (1)1 day before departure to Antarctica (16th expedition 1999/12/ 09; 17th expedition 2000/12/06). (2) 1 day after returned to China after living 54 weeks in Antarctica ( 16th expedition 2000/12/25 ; 17th expedition 2001/12/25 ). Comparing the data of before departure and returned, results showed that there was a significant decrease in the contents of TT4 (P <0. 01) with no significant change in the content of TT3 , FT3 and FT4. It was also found that the content of TSH increased significantly (P <0. 001) ; No significant changes of plasma NE and DA were found but the content of E decreased significantly ( P < 0. 001) . The results indicated that the special Antarctic environment led to a restrain effect on the thyroid function and the level of plasma E in Antarctic expedition members. Both the thyroid and adrenal medulla system were associated in response to the Antarctic systemic stress.

Inhibited 131I Uptake but Normal Release of Thyroid Hormone by Thyroid Gland in Response to TSH Administration in Subclinical Hypothyroidism

Background: Subclinical hypothyroidism is characterized by normal circulating thyroid hormone levels with super-normal TSH concentrations in absence of clinical manifestations. In majority of subjects, an etiologic factor is often identified. Moreover, therapy with levothyroxine normalizes serum TSH concentration while maintaining normal thyroid hormone concentrations. However, the exact pathophysiology of these thyroid hormone alterations is not well defined. Objective: Major steps in synthesis i.e. iodine uptake and the release of thyroid hormones in response to SC TSH administration were assessed in subjects with subclinical hypothyroidism. Methods: 10 men and 5 women with subclinical hypothyroidism, ages 42 - 76 years and 10 euthyroid men (39 - 70 years) participated. 24 hr 131Iodine thyroid uptake and serum T3, T4 and TSH concentrations were determined prior to and after SC administration of recombinant human TSH, 0.9 mg for two consecutive days. Comparisons were conducted for 24 hour uptake values as well as serum T3, T4 and TSH levels obtained prior to and after TSH administration. Results: In subjects with subclinical hypothyroidism 24 hour 131I thyroidal uptakes were normal (10% - 30%). However, the mean value was significantly lower, (p 3 and T4 concentrations in subjects with subclinical hypothyroidism were not significantly different in comparison to normal subjects. Serum TSH concentrations were supernormal and therefore were significantly higher in subjects with subclinical hypothyroidism in comparison to normal subjects and rose markedly in both groups following TSH administration with no significant difference among groups. Serum T4 and T3 rose significantly from PreTSH levels in both groups (p 131I Thyroid uptake is inhibited prior to as well as following SC TSH administration in comparison to normal subjects with maintenance of normal hormone release.

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease:A population-based study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is currently considered as the most common cause of chronic liver disease worldwide.Risk factors for NAFLD have been well-described,including obesity,type 2 diabetes mellites(T2DM),dyslipidemia(DLP)and metabolic syndrome.Hypothyroidism has been identified as an independent risk factor for the development of NAFLD,although the literature is inconsistent AIM To evaluate the prevalence of hypothyroidism in patients with NAFLD,assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy.METHODS Our cohort’s data was obtained using a validated,large,multicenter database(Explorys Inc,Cleveland,OH,United States)aggregated from pooled outpatient and inpatient records of 26 different healthcare systems,consisting of a total of 360 hospitals in the United States,and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding.We evaluated a cohort of patients with hypothyroidism and NAFLD.Multivariate analysis was performed to adjust for confounding risk factors including hypertension(HTN),T2DM,DLP,obesity and metabolic syndrome.SPSS version 25,IBM Corp was used for statistical analysis,and for all analyses,a 2-sided P value of<0.05 was considered statistically significant.Exclusion criteria were limited to age<18 years.RESULTS Among the 37648180 included individuals in this database who are above the age of 18 years,there were a total of 2320 patients with NAFLD(6.16 per 100000)in the last five years(2015-2020),amongst which 520 patients(22.4%)had hypothyroidism.Baseline characteristics of patients in this database are described in Table 1.Patients with NAFLD were also more likely to have obesity,T2DM,DLP,HTN,and metabolic syndrome(Table 2).While males and females were equally affected,patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk.There was an increased risk of NAFLD among patients with hypothyroidism(OR=1.587).Furthermore,thyroid hormone replacement was not associated with a decreased risk for developing NAFLD(OR=1.106,C=0.952-1.285,P=0.303).CONCLUSION Hypothyroidism seems to be an independent risk factor for the development of NAFLD.Thyroid hormone replacement did not provide a statistically significant risk reduction.Further studies are needed to evaluate the effect of thyroid hormone replacement and assess if being euthyroid while on thyroid replacement therapy affects development and/or progression of NAFLD.

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.