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.

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.

Sensitive detection of thyroid stimulating hormone by inkjet printed microchip with a double signal amplification strategy

An electrochemical immunosensor for sensitive detection of thyroid stimulating hormone(TSH) has been developed by using an inkjet printed microchip and based on a double signal amplification strategy using magnetic beads(MBs), alkaline phosphatase(ALP) and p-aminophenyl phosphate(pAPP) reaction.Differential pulse voltammetry(DPV), cyclic voltammogram(CV) and amperometric i-t curve(i-t) were employed to characterize the immunosensor. High sensitivity and good selectivity were observed. The detection linear range was from 0.01 μIU/mL to 10 μIU/mL, in which the peak currents increased along with the concentration. The detection limit was 0.005 μIU/mL at S/N = 3. The immunosensor was also applied for TSH detection in human serum with recoveries from 98.0% to 101.8% and relative standard deviations from 1.3% to 3.1%, demonstrating potential value in clinical diagnosis.

Relationship between fibroblast growth factor 21 and thyroid stimulating hormone in healthy subjects without components of metabolic syndrome

Objective:To determine the relationship between human fibroblast growth factor 21(FGF21)and thyroid stimulating hormone(TSH)by testing the level of FGF21,lipid metabolism,and car-bohydrate metabolism-related indices,as well as the level of TSH,among metabolic syndrome-free patients with normal physical examination results.Methods:An enzyme-linked immunosorbent assay(ELISA)was used to test the levels of serum FGF21 and free fatty acids(FFA)in metabolic syndrome-free patients with normal physi-cal examination results,and electrochemiluminescence(ECLIA)was used to measure TSH,thy-roglobulin antibodies(TGAbs),and thyroid peroxidase antibody(TPOAb)levels.Results:Three hundred fifty-six metabolic syndrome-free patients(116 males and 240 females;average age,43±13 years)with normal physical examination results were enrolled.Among the pa-tients with normal physical examination results,FGF21 had a weak relationship with obesity indices,such as the waist circumference(r=0.110,P=0.038),the waist-to-hip ratio(r=0.119,P=0.025),and the triglycerides level(TG;r=0.302,P=0.000),and a weak relationship with blood lipid levels,such as total cholesterol(TCHO;r=0.113,P=0.012)and low-density lipoprotein-cholesterol(LDL-C;r=0.175,P=0.001),but no relationship with TSH(r=-0.023,P=0.666).In addition,the FGF21 levels in thyroid autoantibody-positive and-negative groups were not significantly different.Conclusion:Among the metabolic syndrome-free patients with normal physical examina-tion results,FGF21 has no apparent relationship with TSH or thyroid autoimmunity.

Is there A Link between Serum Thyroid Stimulating Hormone Level and the Results of in vitro Fertilization and Embryo Transfer?

Objective To analyze the clinical features and outcomes in infertile patients with different levels of thyroid stimulating hormone （TSH） undergoing IVF/ICSL and to investigate whether inappropriate level of TSH has the adverse effect on the results of the IVF-ET.Methods A total of 389 patients undergoing IVF/ICSI from January 2009 to December 2011 were divided into 3 groups according to the basal TSH level： group A （TSH〈 2.0 mlU/L）, group B （TSH 2.0-4.5 mlU/L） and group C （TSH〉4.5 mlU/L）. Oocyte retrieved, fertilization rate, cleavage rate, available embryo rate, pregnancy rate and miscarriage rate were analyzed to explore whether serum TSH level was correlated with the results of lVF/ICSI.Results There were no differences in number of oocyte retrieved, fertilization rate, cleavage rate and available embryo rate among 3 groups （P〉0.05）. Clinical pregnancy rate in group B （43.0%） was significantly higher than that in group A （30.2%） and group B （23.5%）, respectively （P〈0.05）. There were no significant differences in miscarriage rate among 3 groups.Conclusion TSH level has no effect on fertility rate or miscarriage rate in patients undergoing IVF/ICSL Inadequacy TSH level would decrease the IVF/ICSI pregnancy rate.

Thyroid Hormone Biomonitoring:A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals

The thyroid is an essential endocrine organ in human body,and thyroid hormones(THs)are pivotal signaling molecules and mediators in various physiological processes.THs,particularly in their free form,play a critical role in regulating body temperature and in the metabolism of lipid and glucose,making the maintenance of TH levels crucial for human health.THs undergo a series of metabolic processes,producing TH metabolites(THMs).THMs are significant in endocrine regulation,such as 3,5-diiothyronine(3,5-T2)and 3-iodothyronamine(3-T1AM),which exhibit activities akin to THs.The production and distribution of THMs are intricately linked to the function of specific organs and tissues,highlighting the need for advanced research into the determination and mechanisms of THMs in body.Exposure to endocrine disrupting chemicals(EDCs)can significantly affect the levels of thyroid stimulating hormone(TSH)and THs.This review utilizes machine learning to analyze epidemiological data,identifying potential EDCs that pose risks of hyperthyroidism and hypothyroidism.Additionally,it delves into the toxicological mechanisms of these EDCs,examining their effects on TH production,binding processes,related proteins,and metabolic enzymes.This approach effectively bridges the gap between epidemiological studies and toxicological researches,laying the groundwork for future research trends.By integrating epidemiological studies with machine learning,this review offers insightful perspectives on the potential risks associated with chemical exposure and underscores the necessity for further research in understanding the impact of EDCs on TH metabolism and TH-related health effects.

Wavelength-dependent three-dimensional single-molecule superlocalization imaging for yoctomole detection of thyroid-stimulating hormone on a quantum dot nanobiosensor

A wavelength-dependent three-dimensional(3D)superlocalization imaging method on gold nanoislands(GNIs)chip was developed as a supersensitive single-molecule thyroid-stimulating hormone(TSH)nanobiosensor.Scattered and fluorescent signals from gold nanoislands on the substrate and quantum dots(QDs)nanoprobes were simultaneously isolated and acquired within an evanescent field layer generated by total internal reflection(TIR)of incident light using a dual-view device.The 3D TIR fluorescence images of TSH-bound QDs on the GNIs were obtained using z-axis optical sectioning at 10nm intervals before/after immunoreaction to identify the optimal conditions for detection.The localized centroid position of QD nanoprobes and GNI were distinguished at a subdiffraction limit resolution using 3D Gaussian fitting to the point spread function.The QD TSH nanobiosensor using wavelength-dependent 3D TIR fluorescence-based single-molecule localization microscopy(3D TIRF-SLM)imaging technique showed an excellent detection limit of 90 yoctomoles(~54 molecules)and a wide linear dynamic range of 1.14 zmol/L-100 pmol/L for TSH.The detection sensitivity was about 4.4×10^(9)times higher than conventional enzyme-linked immunosorbent assay and could successfully quantify TSH in human serum.The wavelength-dependent 3D TIRF-SLM technique may emerge as a reliable platform for ultrahigh-sensitive nanobiosensors at the single-molecule level and early diagnosis with quantification of disease-related ultra-tracebiomolecules.

Relationship between Serum TSH Level with Obesity and NAFLD in Euthyroid Subjects

To explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects,1322 subjects were sub-jected to a questionnaire survey and physical examination.Fasting blood samples were collected to test serum TSH,plasma glucose and lipids.Fatty liver was diagnosed by type B ultrasonography.The rela-tionship between serum TSH level and body mass index (BMI),percentage of body fat and NAFLD was analyzed.The results showed that serum TSH level was significantly higher in females than in males at the same group,and it was significantly higher in overweight group than in control group.Levels of body weight,BMI,waist circumference and percentage of body fat were increased in TSH >2.5 group compared to TSH ≤2.5 group in women.However,plasma lipids showed no significant differences.In males all the parameters showed no significant differences between two groups.Serum TSH was sig-nificantly correlated with body weight,BMI,waist circumference and percentage of body fat after ad-justment for age in females.Multiple linear regression analysis revealed that percentage of body fat and BMI contributed significantly to the variance of TSH.Serum TSH level was significantly higher in non-alcoholic fatty liver group than in normal group in females.Multiple logistic regression analysis showed that TSH level was not the independent risk factor of NAFLD.Taken together the data suggest that se-rum TSH in normal range is significantly correlated with BMI and percentage of body fat in females.And the change of TSH level would not influence the prevalence of NAFLD.

Suicide attempt of an overt hypothyroid patient with levothyroxine:A case report

Rationale: Levothyroxine is the most commonly used agent in thyroid hormone replacement therapy. Although there are many hypothyroid patients who use levothyroxine as a treatment, high level of thyroid stimulating hormone is found in a limited number of levothyroxine overdose cases worldwide.Patient concern: A 34-year-old male patient taking 4.5 mg levothyroxine for suicide. Diagnosis: Overdose of levothyroxine. Interventions: The patient was admitted to the intensive care unit for follow-up treatment. Cardiac rithym and vital parameters of patient were closely monitored. Outcomes: The patient discharged without any life-threatening complications. Lessons: Patient with initial high thyroid stimulating hormone levels may not be in hyperthyroidism crisis by levothyroxine poisoning.

Association between thyroid hormone levels and frailty in the community-dwelling oldest-old: a cross-sectional study

Background:Changes in thyroid hormone levels are commonly recognized characters among the elderly,which were reported to potentially influence incident frailty.Therefore,we examined the cross-sectional associations of thyroid hormones(THs)with frailty as well as the five components characterizing frailty(fatigue,resistance,ambulation,number ofillnesses,and loss of weight)among the oldest-old.Methods:Four hundred and eighty-seven community-dwelling oldest-old from a local community in Haidian District,Beijing,participated in our recruitment campaign between April 2019 and May 2020.The primary outcomes were a definitive diagnosis of frailty according to the FRAIL scale(Fatigue,Resistance,Ambulation,Illnesses,Loss of weight)and a positive score for each frailty subdomain.Demographic information(age,sex,marital status,and educational status),comorbidities,and details on the participants lifestyles were recorded.Serum THs including free triodothyronin(fT3),triiodothyronine(T3),free thyroxine(fT4),and thyroxine(T4)and thyroid stimulating hormone(TSH)levels were also measured at the beginning of our study.Logistic regressions were conducted to screen for potential risk factors for frailty and its subdomains.Results:Among the total 487 subjects at enrollment,60(12.23%)of them were diagnosed with subclinical hypothyroidism and 110(22.59%)of the total population scored positive for frailty.Logistic regression analyses adjusted for all potential confounders,showed that frailty was significantly associated with the serum TSH concentration(odds ratio[OR]:1.06),fT3 concentration(OR:0.54),and subclinical hypothyroidism score(OR:2.18).The association between fT4 and frailty was absent in our observational study.The fT3/fT4 ratio characterizing peripheral hormone conversion was also tested to be correlated with frailty.Conclusion:Subclinical hypothyroidism,higher TSH level,lower fT3 level,and decreased fT3/fT4 ratio were all associated with frailty assessed by the FRAIL scale among the community-dwelling oldest-old,suggesting a relevant role of thyroid function in aging.Future longitudinal studies are warranted to determine the casual relationship between thyroid dysfunction and frailty in the oldest-old.

Association between TSHR gene polymorphism and the risk of Graves' disease:a meta-analysis

Thyroid stimulating hormone receptor（TSHR） is thought to be a significant candidate for genetic susceptibility to Graves＇ disease（GD）.However,the association between TSHR gene polymorphism and the risk of GD remains controversial.In this study,we investigated the relationship between the two conditions by meta-analysis.We searched all relevant case-control studies in PubMed,Web of Science,CNKI and Wanfang for literature available until May2015,and chose studies on two single nucleotide polymorphisms（SNPs）：rs 179247 and rsl2101255,within TSHR intron-1.Bias of heterogeneity test among studies was determined by the fixed or random effect pooled measure,and publication bias was examined by modified Begg＇s and Egger＇s test.Eight eligible studies with 15 outcomes were involved in this meta-analysis,including 6,976 GD cases and 7,089 controls from China,Japan,Poland,UK and Brazil.Pooled odds ratios（ORs） for allelic comparisons showed that both TSHR rsl79247A/G and rsl2101255T/C polymorphism had significant association with GD（OR=1.422,95%CI=1.353—1.495,P〈0.001,P_（heterogeneity）=0.448;OR= 1.502,95%CI：1.410-1.600,P〈0.001,P_（heterogeneity）=0.642）,and the associations were the same under dominant,recessive and co-dominant models.In subgroup analyses,the conclusions are also consistent with all those in Asian,European and South America subgroups（P〈0.001）.Our meta-analysis revealed a significant association between TSHR rsl79247A/G and rsl2101255T/C polymorphism with GD in five different populations from Asia,Europe and South America.Further studies are needed in other ethnic backgrounds to independently confirm our findings.

New fluorimetric assay of horseradish peroxidase using sesamol as substrate and its application to EIA

Horseradish peroxidase (HRP) is generally used as a label enzyme in enzyme immunoassay (EIA).The procedure used for HRP detection in EIA is critical for sensitivity and precision.This paper describes a novel fluorimetric assay for horseradish peroxidase (HRP) using sesamol as substrate.The principle of the assay is as follow:sesamol (3,4-methylenedioxy phenol) is reacted enzymatically in the presence of hydrogen peroxide to produce dimeric sesamol.The dimer is fluorescent and can be detected sensitively at ex.347 nm,em.427 nm.The measurable range of HRP was 1.0×10-18 to 1.0×10-15 mol/assay,with a detection limit of 1.0×10-18 mol/assay.The coefficient of variation (CV,n=8) was examined at each point on the standard curve,with a mean CV percentage of 3.8%.This assay system was applied to thyroid stimulating hormone (TSH) EIA using HRP as the label enzyme.

INTRAUTERINE GROWTH RETARDATION AT FULL TERM PREGNANCIES WITH ENDOCRINE FACTORS

Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone(GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum.Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants’ weight were taken as control. Growth hormone and insulin were measured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentrations of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH4. 63μ/L vs 7. o1μg/L, insulin 1o. 68μIU/ml vs 31. 44μIU/ml, T487. 39nmol/L vs 138. 1onmol/L. P <o. o5, o. o5 and o. o5, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (1o. 84μmIU/L vs 5. 75μmIU/L, P <o. o1 ). The concentration of growth hormone in maternal serum and the concentration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1. 77μg/L vs 2. 74μg/L,P <o. o1, insulin 5. 84μIU/ml vs 15. 64μIU/ml, P <o. o1). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relatlve scarcity of growth hormone and insulin seems to be a factor to compromise the fetus’ metabolism. Besides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.

Local TSH/TSHR signaling promotes CD8^(+) T cell exhaustion and immune evasion in colorectal carcinoma

Dysfunction of CD8^(+)T cells in the tumor microenvironment(TME)contributes to tumor immune escape and immunotherapy tolerance.The effects of hormones such as leptin,steroid hormones,and glucocorticoids on T cell function have been reported previously.However,the mechanism underlying thyroid-stimulating hormone(TSH)/thyroid-stimulating hormone receptor(TSHR)signaling in CD8^(+)T cell exhaustion and tumor immune evasion remain poorly understood.This study was aimed at investigating the effects of TSH/TSHR signaling on the function of CD8^(+)T cells and immune evasion in colorectal cancer(CRC).Methods:TSHR expression levels in CD8^(+)T cells were assessed with immunofluorescence and flow cytometry.Functional investigations involved manipulation of TSHR expression in cellular and mouse models to study its role in CD8^(+)T cells.Mechanistic insights were mainly gained through RNAsequencing,Western blotting,chromatin immunoprecipitation and luciferase activity assay.Immunofluorescence,flow cytometry and Western blotting were used to investigate the source of TSH and TSHR in CRC tissues.Results:TSHR was highly expressed in cancer cells and CD8^(+)T cells in CRC tissues.TSH/TSHR signaling was identified as the intrinsic pathway promoting CD8^(+)T cell exhaustion.Conditional deletion of TSHR in CD8^(+)tumorinfiltrating lymphocytes(TILs)improved effector differentiation and suppressed the expression of immune checkpoint receptors such as programmed cell death 1(PD-1)and hepatitis A virus cellular receptor 2(HAVCR2 or TIM3)through the protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway.CRC cells secreted TSHR via exosomes to increase the TSHR level in CD8^(+)T cells,resulting in immunosuppression in the TME.Myeloid-derived suppressor cells(MDSCs)was the main source of TSH within the TME.Low expression of TSHR in CRC was a predictor of immunotherapy response.Conclusions:The present findings highlighted the role of endogenous TSH/TSHR signaling in CD8^(+)T cell exhaustion and immune evasion in CRC.TSHR may be suitable as a predictive and therapeutic biomarker in CRC immunotherapy.

The incidence of adverse clinical outcome in acute coronary syndrome patients with subclinical hypothyroidism

Background Subclinical hypothyroidism is associated with adverse cardiovascular outcomes.But less is known about its prognostic role in patients with acute coronary syndrome(ACS).Methods 538 ACS patients with normal serum concentrations of T3 and T4 underwent coronary angiography in our hospital from January 2015 to January 2019 were retrospectively enrolled.They were divided into normal thyroid stimulating hormone(TSH)group(0.27-4.2 uIU/mL)(n=385)and high TSH group(>4.2 uIU/mL)(n=135).The study endpoints were the major adverse cardiovascular events(MACEs).The univariate and multivariate regression analysis including significant covariables were performed to test for the association between subclinical hypothyroidism and MACEs.Results The mean concentration of TSH were 8.72(6.37-11.02)uIU/mL in the high TSH group and 1.94(1.34-2.45)uIU/mL in the normal TSH group.Multivariate logistic regression analysis found that subclinical hypothyroidism[Odds ratio(OR):1.94,95%confidence interval(CI):1.23-2.65,P=0.030]was associated independently with MACE rate in ACS patients.The area under the receiver operating characteristic curve showed that the subclinical hypothyroidism had good predictable value for MACEs in patients with ACS(area under the curve:0.713,95%CI:0.668-0.802,P<0.001).Conclusions Subclinical hypothyroidism is associated with worse clinical prognosis in ACS patients.Clinicians need to pay more attention to subclinical hypothyroidism in ACS patients.[S Chin J Cardiol 2021;22(1):1-6]

A Study on Neonatal Tolerance Against Graves＇ Disease in BALB/c Mice

INTRODUCTION Autoimmunity is defined as, a condition characterized by a specific humoral or cell-mediated immune response against the constituents of the body＇s own tissues （autoantigens）. In numerous autoimmune diseases, such an immune response is well recognized that causes damage to the self-constituents of body tissues by the products of the immune system. Graves＇ hyperthyroidism occurs after the loss of tolerance to the thyroid stimulating hormone receptor （TSHR） and the generation of thyroid stimulatory antibodies that mimic the action of thyroid-stimulating hormone （TSH）.