Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants

This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease （PAD） among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine （FT3）, free thyroxin （FT4）, thyroid-stimulating hormone （TSH）, and thyroid antibodies were measured.

Free triiodothyronine level correlates with statin responsiveness in acute myocardial infarction

Background Although thyroid hormone （TH） has important effects on lipid metabolism, the relationship between TH and statin responsiveness has never been investigated. We hypothesize that TH plays an important role in statin responsiveness in patients with acute myocardial infarction （AMI）. Methods Consecutive 1091 hospitalized AMI patients in Fuwai hospital （Beijing, China） were enrolled into this current study. The study population was divided into three groups based on the intensity of statin treatment： low-intensity （n = 221）, moderate-intensity （n = 712） and high-intensity （n = 158）. Lipid levels were measured after statin therapy lasting for 10-14 days. The association between TH, lipid profile levels and achievement of low-density lipoprotein cholesterol （LDL-C） lowering goals was explored in patients with AMI on statin therapy. Results By general linear analysis, a significant linear trend between free triiodothyronine （FT3） and LDL-C level （linear coefficient r = -0.082, P = 0.001） and FT3 and total cholesterol （TC） level （r = -0.105, P = 0.031） was observed in the moderate-intensity statin group. A more apparent linear trend was detected in the high-intensity statin group （for LDL-C： r = -0.113, P = 0.005; for TC： r = -0.172, P = 0.029, respectively）. However, no significant correlation was observed in the low-intensity statin group. Compared with the low-FT3 group （defined as FT3 〈 1.79 pg/mL）, the OR （95% CI） for attaining a LDL-C 〈 3.0mmol/L was found to be 2.217 （1.001–4.839） in the higher FT3 group （〉 2.95 pg/mL）. The OR （95% CI） for attaining the more intensive goal （LDL-C 〈 1.8mmol/L） was 2.836 （1.014–5.182）. Conclusions Our study reveals that variation in FT3 levels is related to the cholesterol-lowering responsiveness of statins in AMI patients. These findings suggest that low FT3 may be a factor responsible for lack of LDL-C goal attainment and patients’ poor responsiveness to statin treatment.

Free triiodothyronine in relation to coronary severity at different ages： Gensini score assessment in 4206 euthyroid patients

Objective To study whether free triiodothyronine （FT3） within normal range has effects on the presence and severity of coronary ar- tery disease （CAD） in different gender and age groups. Methods A total of 4206 euthyroid patients were consecutively enrolled and di- vided into CAD group （n = 3306） and non-CAD group （n = 900）. All patients underwent coronary angiography （CAG）. Gensini score （GS） was used to determine the severity of coronary artery stenosis. Severe CAD was defined as GS 〉 32 and mild CAD was defined as GS 〈 32. Logistic regression analysis and linear regression analysis were conducted to determine the association of FT3 with CAD in patients with different gender and ages. Results Concentration of FT3 was lower in patients with CAD than that in angiography-normal control group （P 〈 0.05）. In addition, concentration of FT3 was lower in severe CAD than that in mild CAD. After adjusting for traditional cardiovascular risk factors and potential confounders, FT3 was negatively correlated with the presence of CAD, but not in the old patients （〉 65 years old）. Mul- tivariable linear regression analysis showed that FT3 was negatively associated with GS in male and young patients with stable CAD, but not in the old patients. Conclusions Low FT3 within normal range was negatively associated with the presence and severity of CAD in young patients, but not in the old ones. Further studies are needed to confirm our findings.

Free triiodothyronine level indicates the degree of myocardial injury in patients with acute ST-elevation myocardial infarction

Background Previous studies have suggested that hypothyroidism correlated with coronary heart diseases （CHD） mortality in long-term cohort, but whether the thyroid function status is associated with myocardial injury in acute ST- elevation myocardial infarction （STEMI） has not been investigated sufficiently.

Prognostic value of free triiodothyronine in patients with dilated cardiomyopathy

Background:The association between free triiodothyronine(FT3)and long-term prognosis in dilated cardiomyopathy(DCM)patients has not been evaluated.The purpose of this study was to determine whether the level of FT3 could provide prognostic value in patients with DCM.Methods:Data of consecutive patients diagnosed with DCM were collected from October 2009 to December 2014.FT3 was measured by fluoroimmunoassay.Other biochemical markers,such as free thyroxin(FT4),thyroid-stimulating hormone,red blood cell,hemoglobin,blood urea nitrogen,and serum creatinine,were tested at the same time.Follow-up was performed every 3 months.The primary endpoint was all-cause mortality.Pearson analysis was used to evaluate the correlation of FT3 and other lab metrics with DCM patients’prognosis.The association of long-term mortality in DCM and FT3 was compared using Cox hazards model.Results:Data of 176 patients diagnosed with DCM were collected.Of them,24 patients missed FT3 values and six patients were lost to follow-up.Altogether,data of 146 patients were analyzed.During the median follow-up time of 79.9(53.5-159.6)months,nine patients lost,61 patients died(non-survival group),and 85 patients survived(survival group).FT3 was significantly lower in non-survival group than that in survival group(3.65±0.83 pmol/L vs.4.36±1.91 pmol/L;P=0.003).FT3 also showed a significantly positive correlation with red blood cell and hemoglobin,negatively correlated with age,blood urea nitrogen and serum creatinine(P<0.05),respectively.Patients in the group of lower FT3 levels(FT3≤3.49 pmol/L)suffered from a higher risk of all-cause mortality(P for log-rank=0.001).In multivariate Cox regression analysis,FT3 level was significantly associated with all-cause mortality(hazard ratio:0.70,95%confidence interval 0.52-0.95,P for trend=0.021).Conclusion:Low levels of FT3 were associated with increased all-cause mortality in patients with DCM.

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.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

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.

Changes in thyroid function in patients with liver failure and their clinical significance:A clinical study of non-thyroidal illness syndrome in patients with liver failure

Background:Non-thyroidal illness syndrome(NTIS)develops in a large proportion of critically ill patients and is associated with high risk for death.We aimed to investigate the correlation between NTIS and liver failure,and the short-term mortality of patients with these conditions.Methods:The clinical data of 87 patients with liver failure were collected retrospectively,73 of them were randomly selected for an observational study and to establish prognostic models,and 14 for model validation.Another 73 sex-and age-matched patients with mild chronic hepatitis were randomly selected as a control group.Serum free triiodothyronine(FT3),free thyroxine(FT4),and thyroid-stimulating hormone(TSH)were measured.The clinical characteristics of patients with liver failure and NTIS were analyzed.The follow-up of patients lasted for 3 months.Additionally,the values for predicting short-term mortality of model for end-stage liver disease(MELD),Child-Turcotte-Pugh(CTP),chronic liver failure-sequential organ failure assessment(CLIF-SOFA)scores,FT3-MELD model,and FT3 were evaluated.Results:The observation group had significantly lower FT3(2.79±0.71 vs.4.43±0.75 pmol/L,P<0.001)and TSH[0.618(0.186-1.185)vs.1.800(1.570-2.590)mIU/L,P<0.001],and higher FT4(19.51±6.26 vs.14.47±2.19 pmol/L,P<0.001)than the control group.NTIS was diagnosed in 49 of the patients with liver failure(67.12%).In the observation group,patients with NTIS had a higher mortality rate than those without(63.27%vs.25.00%,P=0.002).Across the whole cohort,the 3-month mortality was 50.68%.The international normalized ratios(INR)were 2.40±1.41 in survivors and 3.53±1.81 in deaths(P=0.004),the creatinine(Cr)concentrations were 73.27±36.94μmol/L and 117.08±87.98μmol/L(P=0.008),the FT3 concentrations were 3.13±0.59 pmol/L and 2.47±0.68 pmol/L(P<0.001),the MELD scores were 22.19±6.64 and 29.57±7.99(P<0.001),the CTP scores were 10.67±1.53 and 11.78±1.25(P=0.001),and the CLIF-SOFA scores were 8.42±1.68 and 10.16±2.03(P<0.001),respectively.FT3 was negatively correlated with MELD score(r=−0.430,P<0.001).An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula:Logit(P)=−1.337×FT3+0.114×MELD+0.880.The area under the receiver operating characteristic(ROC)curve was 0.827 and the optimal cut-off value was 0.4523.The corresponding sensitivity and specificity were 67.6%and 91.7%.The areas under the ROC curve for FT3 concentration,MELD score,CTP score,and CLIF-SOFA score were 0.809,0.779,0.699,and 0.737,respectively.Conclusions:Patients with liver failure often develop NTIS.FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure.Thus,the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.