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Objective: Obstructive sleep apnea (OSA) and thyroid dysfunction frequently overlap clinically and are risk factors for cardiovascular disease. The free triiodothyronine to free thyroxine (FT3/FT4) ratio as a novel biomarker of cardiovascular disease prognosis, but the impact of the FT3/FT4 ratio on the prognosis of OSA in patients with acute coronary syndromes (ACS) remains uncertain. Methods: In this prospective cohort study, 2160 patients with ACS were recruited and underwent portable sleep monitoring at Beijing Anzhen Hospital from June 2015 to January 2020. OSA was diagnosed when apnea-hypopnea index of =15 events/h. Patients were further divided into tertiles according to FT3/FT4 ratio. All patients had scheduled follow-up visits at 1, 3, 6, 9 and 12 months after discharge, with subsequent outpatient visits or telephone follow-up visits every 6 months. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction (MI), stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Results: Among 1,547 euthyroid patients enrolled (mean age, 56.0 ± 10.5 years), 812 patients (52.5%) had OSA. The FT3/FT4 ratio between OSA and non-OSA patients was not significantly different. During 2.8 (1.4, 3.5) years follow up, the risk of MACCE increased with the decreasing FT3/FT4 tertiles in patients with OSA (tertile3 as reference, tertile2: hazard ratio (HR) 1.26, 95% CI: 0.85-1.86, P = 0.255; tertile1: 1.60, 95% CI 1.11-2.32; P = 0.013). After adjustment for confounders, the lowest FT3/FT4 tertile was still independently associated with an increased risk of MACCE (adjusted HR 1.66, 95% CI 1.11-2.50, P = 0.015). Conclusion: Lower FT3/FT4 ratio associated with poor prognosis in patients with ACS and OSA. [ABSTRACT FROM AUTHOR]

Primary congenital hypothyroidism is easily diagnosed on the basis of elevated plasma levels of thyroid-stimulating hormone (TSH). In contrast, in the rare disorders of thyroid hormone resistance, TSH and, in mild cases, also thyroid hormone levels are within the normal range. Thyroid hormone resistance is caused by defects in hormone metabolism, transport, or receptor activation and can have the same serious consequences for child development as congenital hypothyroidism. A total of n = 23,522 data points from a large cohort of children and young adults were used to generate normal values and sex-specific percentiles for the ratio of free triiodothyronine (T3) to free thyroxine (T4), the fT3/fT4 ratio. The aim was to determine whether individuals with developmental delay and genetically confirmed thyroid hormone resistance, carrying defects in Monocarboxylate Transporter 8 (MCT8), Thyroid Hormone Receptor alpha (THRα), and Selenocysteine Insertion Sequence-Binding Protein 2 (SECISBP2), had abnormal fT3/fT4 ratios. Indeed, we were able to demonstrate a clear separation of patient values for the fT3/fT4 ratio from normal and pathological controls (e.g., children with severe cerebral palsy). We therefore recommend using the fT3/fT4 ratio as a readily available screening parameter in children with developmental delay for the identification of thyroid hormone resistance syndromes. The fT3/fT4 ratio can be easily plotted on centile charts using our free online tool, which accepts various SI and non-SI units for fT3, fT4, and TSH. [ABSTRACT FROM AUTHOR]

Background: Despite advancement in technology adverse events after left ventricular assist device(LVAD) implantation continue to be the main barrier to more widespread use of it. Therefore, it is vital to identify prognostic factors to reduce adverse cardiac events after LVAD implatation. Thyroid dysfunction is associated with a poor prognosis in individuals with heart failure. The objective of this study is to examine the correlation between thyroid hormones and adverse cardiovascular events following LVAD implantation. Method and Results: The study included a total of 36 patients, with an average age of 60 ± 9 years, of which 77.7% were male. Although there was no significant relationship between TSH and FT3 levels and post-operative adverse events(p>0.05 for both), there was a significant association between FT3/FT4 and all-cause and cardiovascular mortality(p<0.001 for both). ROC analysis revealed that FT3/FT4 values lower than 1 were significantly associated with adverse events(all p < 0.05). There was no significant difference between the two groups in terms of age, gender, BMI, etiology of heart failure, EF, sPAP, smoking status and the presence of comorbid diseases, BNP, TSH and FT3 levels(p>0.05 for all). All-cause mortality, cardiac mortality, arrhythmia prevelance, vasopressor need(day) and duration of ICU stay were significantly higher in FT3/FT4 < 1 group(all p < 0.05). Conclusion: Our findings suggest that FT3/FT4 ratio might be useful as a biomarker of short-term adverse clinical outcomes in patients who underwent LVAD implantation. [ABSTRACT FROM AUTHOR]

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan–Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05–2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine-to-free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods: The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results: Individuals in fourth quartile (Q4) had lower all-cause mortality than those in first quartile (Q1) of FT3/FT4 ratio (hazard ratio (HR): 0.70, 95% CI: 0.51, 0.94). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (HR: 1.43, 95% CI: 1.05, 1.96) (P < 0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions: Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/ FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.

Objective: Although several studies have examined the relationship between thyroid function and muscle strength, their population primarily derived from Asian areas, and their results were controversial. Thus, this study aimed to explore the association between thyroid function and handgrip strength (HGS) in the U.S. population. Methods: A total of 1,067 participants from NHANES were categorized into three different age groups including young (<45 years), middle (45~64 years), and old (≥65 years) age groups. Thyroid function was measured by the competitive binding immune-enzymatic assays, while HGS was examined by a trained evaluator using a dynamometer. The weighted multiple linear regression models were used to examine the association between thyroid function and handgrip strength. The restricted cubic splines were employed to explore the non-linear relationship between these two variables. All statistical analyses were performed using the SPSS version 20.0 and R software. Results: After adjustment for potential covariates, FT3/FT4, but not TSH was positively associated with HGS in middle age group (b=0.091, t=2.428, P=0.016). The subgroup analysis by sex revealed that the positive association between FT3/ FT4 and HGS was observed in the middle age group for both male and female participants (b=0.163, t=2.121, P=0.035; b=0.157, t=2.180, P=0.031). The RCS analysis showed a statistically significant non-linear association between FT3/FT4 and HGS in overall population (P for non-linear=0.026). After adjustment for covariates, men with low HGS had a significant lower FT3/FT4 than those without low HGS in old age group (P=0.013). There was a significant increase in TSH level for female participants with low HGS in old age group compared to those with normal HGS (P=0.048). Conclusions: This study demonstrated FT3/FT4, but not TSH, was positively associated with HGS in middle age group, and the different association was observed in men in middle age group when participants were stratified by sex. Future longitudinal cohort study should be conducted to reveal the causal relationship between thyroid function and muscle strength. [ABSTRACT FROM AUTHOR]

Context: It is still not clear how the free triiodothyronine (FT3) to free thyroxine (FT4) ratio affects the prognosis of acute myocardial infarction (AMI), especially the risk of heart failure (HF) subsequent to AMI. Objective: The purpose of this study was to see how peripheral sensitivity to thyroid hormones, as measured by the FT3/FT4 ratio, affected HF and mortality after AMI. Methods: Our study was a retrospective cohort study. The primary endpoint was HF after AMI during and after hospitalization. The secondary endpoints were all-cause death and cardiovascular death after hospitalization. Results: The main sample included 3648 inpatients with AMI with a median age of 61.0 years; 68.9% were male. In the fully adjusted model, compared with patients in the lowest Q1 of the FT3/FT4 ratio, the risk of in-hospital HF in the highest Q4 patients was reduced by 44% (OR 0.56, 95% CI 0.44-0.72, P trend < .001), the risk of out-of-hospital HF was reduced by 37% (HR 0.63, 95% CI 0.48-0.84, P trend < .001), and the risks of all-cause and cardiovascular death were also significantly reduced. The analysis of different subgroups is consistent with the overall results. Furthermore, the sensitivity analysis of the euthyroid sample of 2484 patients was consistent with the main sample. Mediation analysis showed that altered levels of amino-terminal pro-B-type natriuretic peptide were mediators between the FT3/FT4 ratio and all endpoints in our study. Conclusion: The thyroid hormone peripheral sensitivity of the FT3/FT4 ratio is an independent predictor of HF and mortality after AMI. [ABSTRACT FROM AUTHOR]

Context: Impaired sensitivity to thyroid hormones has been demonstrated to be positively associated with the prevalence of metabolic disorders. However, the relationship between sensitivity to thyroid hormones and metabolic dysfunction--associated fatty liver disease (MAFLD) and liver fibrosis remained unclear. Objective: We aimed to determine the associations of thyroid hormone sensitivity indices with MAFLD and its progression to liver fibrosis in Chinese euthyroid adults. Methods: This community-based study included 7906 euthyroid adults. We calculated the thyroid sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, Thyroid Feedback Quantile-based Index by FT4 (TFQIFT4), and Thyroid Feedback Quantile-based Index by FT3 (TFQIFT3), indicating peripheral and central thyroid hormone sensitivity respectively. Liver steatosis and fibrosis were diagnosed by vibration-controlled transient elastography (VCTE). Multivariable logistic/linear regression and restricted cubic spline (RCS) analysis were conducted. Results: Compared with participants in the first quartile (Q1), the prevalence of MAFLD was increased by 62% in the fourth quartile (Q4) of FT3/ FT4 ratio (OR 1.62; 95% CI [1.38, 1.91]) and by 40% in Q4 of TFQIFT3 (OR 1.40; 95% CI [1.18, 1.65]) (both P < .05). No associations between TFQIFT4 and the prevalence of MAFLD were found. In addition, compared with participants in Q1, the prevalence of liver fibrosis was increased by 45% in Q4 of TFQIFT3 (OR 1.45; 95% CI [1.03, 2.06]) (P < .05) in participants with MAFLD. Conclusion: Impaired central sensitivity to FT3 was associated with MAFLD and its progression to liver fibrosis. More prospective and mechanism studies are warranted to confirm these conclusions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between free triiodothyronine (FT3)/free thyroxine (FT4) ratio, Apolipoprotein B (Apo B)/Apolipoprotein A1 (ApoA1) ratio and clinical efficacy and short-term prognosis after discharge in patients with acute ischemic stroke (AIS). Methods: 102 patients with AIS who were admitted to the The Second People's Hospital of Anhui Province from February 2020 to February 2022 were selected. All patients received revascularization, antiplatelet and other treatments after inclusion, and they were divided into an effective group (76 cases) and an ineffective group (26 cases) according to the clinical efficacy. Serum FT3, FT4, Apo B and Apo A1 levels of all patients with AIS were detected after treatment, and FT3/FT4 ratio and Apo B/Apo A1 ratio were calculated. All patients with AIS were followed up for 3 months after discharge. According to the prognosis of patients with AIS during follow-up, patients were divided into poor prognosis group (31 cases) and good prognosis group (71 cases). Serum FT3, FT4, Apo B, Apo A1 levels, FT3/FT4 ratio and Apo B/Apo A1 ratio difference were compared in the different groups, and the factors affecting the short-term prognosis of patients with AIS after discharge were analyzed. Results: The serum FT3 level and FT3/FT4 ratio in the ineffective group were lower than those in the effective group (P<0.05), and the serum Apo B level and Apo B/Apo A1 ratio were higher than those in the effective group (P<0.05). The serum FT3 level and FT3/FT4 ratio in the poor prognosis group were lower than those in the good prognosis group (P<0.05), and the serum Apo B level and Apo B/Apo A1 ratio were higher than those in the good prognosis group (P<0.05). High National Institutes of Health Neurological Deficit Score (NIHSS Score) and increased Apo B/ApoA1 ratio were risk factors for poor short-term prognosis of patients with AIS after discharge(P<0.05), and increased FT3/FT4 ratio was a protective factor (P<0. 05). Conclusion: The decrease of FT3/FT4 ratio and the increase of Apo B/ApoA1 ratio in patients with clinically ineffective treatment and poor prognosis of AIS. The low FT3/FT4 ratio and high Apo B/ApoA1 ratio are related to the poor short-term prognosis of patients with AIS after discharge. [ABSTRACT FROM AUTHOR]

Abstract Background Studies have demonstrated the associations between pre-pregnancy obesity, thyroid dysfunction, dyslipidemia, and increased risk of gestational diabetes mellitus (GDM) in pregnant women. This study was designed to investigate whether and to what extent, the interactions between these factors contribute to the risk of GDM. Methods A case–control study of 232 GDM cases and 696 controls was conducted among pregnant women from Hangzhou, China. Multiple logistic regression analysis was applied to identify independent risk factors of GDM. Crossover analysis was performed to assess the interactive effects of pre-pregnancy body mass index (pBMI), thyroid hormones, and blood lipid profiles on the risk of GDM. The indexes including attributable proportion (AP) to the interaction and the relative excess risk due to interaction (RERI) were calculated. Results Chinese pregnant women with pBMI > 23 kg/m2 (adjusted: OR = 4.162, p 2.30 mmol/L) (adjusted: OR = 1.735, p

Context: It remains unclear whether the thyroid system could regulate the atherogenic remnant cholesterol (RC) levels in euthyroid status. Objective: We aimed to investigate the relationship between sensitivity to thyroid hormones and RC levels in Chinese euthyroid population. Methods: This study included 18 766 euthyroid adults. High RC levels were defined as the upper quartile of RC levels. The thyroid hormone sensitivity indices, including thyroid feedback quantile-based index (TFQI), thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI), and free triiodothyronine to free thyroxine (FT3/FT4) ratio were calculated. Linear and binary logistic regression analysis were applied to determine the associations between those composite indices with RC levels by genders. Results: Both females and males with high RC levels exhibited co-existing higher TSH and FT4 levels. Linear regression analysis revealed that TFQI, TSHI, and TT4RI were positively, while FT3/FT4 ratio levels were negatively associated with serum RC levels. The odds ratios (ORs) (95% CI) for high RC levels were increased with rising TFQI quartiles (Q) [females: Q3 1.41 (1.22-1.63), Q4 1.61 (1.39-1.86); males: Q3 1.25 (1.09-1.45), Q4 1.38 (1.19-1.59), all P for trend < 0.001] after full adjustment, with Q1 as the reference. TSHI and TT4RI yielded similar results. By contrast, the ORs (95% CI) for high RC levels were decreased with increasing FT3/FT4 ratio quartiles in both genders (P for trend < 0.001). Conclusion: In euthyroid adults, reduced sensitivity to thyroid hormones was associated with high RC levels. Our results suggested an additive cardiometabolic risk of euthyroid population with thyroid hormones insensitivity. [ABSTRACT FROM AUTHOR]

Jing Hong,1,&ast; Wen-Yue Liu,1,&ast; Xiang Hu,1 Wen-Wen Chen,2 Fei-Fei Jiang,1 Ze-Ru Xu,1 Fei-Xia Shen,1 Hong Zhu1 1Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Geriatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhu, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 577-55579622, Fax +86 577-55578522, Email zhuhong@wmu.edu.cnPurpose: Free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio have been associated with mortality in various diseases. However, no study to date has identified a link between FT3, FT3/FT4 ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). This study aimed to investigate this relationship.Methods: This retrospective cohort study included 726 patients diagnosed with DFUs in a public hospital from January 2015 to October 2019. Patients were classified by the optimal cut-off values of the FT3 and FT3/FT4 ratio, respectively. The association of FT3 and FT3/FT4 ratio with all-cause mortality was evaluated in a multivariable cox regression model. Directed acyclic graphs were used to assess the minimally sufficient sets of confounding variables.Results: Log rank tests indicated that patients with low FT3 and FT3/FT4 ratio had lower overall survival rates (all p < 0.001). The adjusted HRs for all-cause mortality were 0.48 (95% CI: 0.32– 0.73, P = 0.001) when comparing high versus low FT3 and 0.47 (95% CI: 0.32– 0.70, P < 0.001) when comparing high versus low FT3/FT4 ratio. Subgroup analyses showed that these associations existed only in elderly patients (≥ 65 years) and women, after adjustment. In men, only high FT3/FT4 ratio was associated with low all-cause mortality, after adjustment.Conclusion: Routine assessment of FT3 and FT3/FT4 ratio may be a simple and effective way to identify high-risk patients with DFUs, especially in elderly patients and women.Keywords: FT3, FT3/FT4 ratio, mortality, diabetic foot ulcer

Background: Crescent formation indicates severe glomerular pathology, and hypothyroidism usually predicts poor prognosis for severe diseases. However, the relationship between thyroid function and the progression of chronic kidney disease (CKD) is unclear. This study analysed the prognostic predictive value of the serum free triiodothyronine (FT3) to free thyroxine (FT4) ratio and its correlation with renal function in patients with CKD with crescent formation. Methods: This single-centre study included 162 CKD patients with glomerular crescents confirmed by renal pathology between March 2012 and December 2014. According to the first tertile (0.284) of FT3/FT4 ratio, the patients were divided into high and low FT3/FT4 ratio groups. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of the FT3/FT4 ratio. Results: The age, haemoglobin, eGFR, urinary albumin-to-creatinine ratio, cardiac troponin T, N-terminal brain natriuretic peptide precursor, FT3, FT4, percentage of total crescents in non-globally sclerotic glomeruli, prevalences of hypertension, moderate to severe renal tubulopathy and crescentic nephritis, and proportion of patients receiving glucocorticoids and immunosuppressants were significantly different between high and low FT3/FT4 ratio groups (P < 0.05). Multivariate Cox regression analysis showed that when compared with patients with a high FT3/FT4 ratio (>0.284), those with intermediate and low FT3/FT4 ratios (=0.284) had an increased risk of the longterm composite endpoint (P < 0.05 for various adjustment models). Conclusions: A low FT3/FT4 ratio is associated with increased mortality and worse outcome risk in CKD patients with crescent pathology. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population. Methods: This retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015. Results: During a median of 87 months of follow-up, we observed 699 allcause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results. Conclusions: FT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated the associations between pre-pregnancy obesity, thyroid dysfunction, dyslipidemia, and increased risk of gestational diabetes mellitus (GDM) in pregnant women. This study was designed to investigate whether and to what extent, the interactions between these factors contribute to the risk of GDM.Methods: A case-control study of 232 GDM cases and 696 controls was conducted among pregnant women from Hangzhou, China. Multiple logistic regression analysis was applied to identify independent risk factors of GDM. Crossover analysis was performed to assess the interactive effects of pre-pregnancy body mass index (pBMI), thyroid hormones, and blood lipid profiles on the risk of GDM. The indexes including attributable proportion (AP) to the interaction and the relative excess risk due to interaction (RERI) were calculated.Results: Chinese pregnant women with pBMI > 23 kg/m2 (adjusted: OR = 4.162, p < 0.001), high triglyceride levels (> 2.30 mmol/L) (adjusted: OR = 1.735, p < 0.001), and the free triiodothyronine/free thyroxine (FT3/FT4) ratio ≥ 0.502 (OR = 4.162, p < 0.001) have significantly increased risk of GDM. Crossover analysis indicated that there were significant interactions between pre-pregnancy overweight/obesity and FT3/FT4 ≥ 0.502 (AP = 0.550, p < 0.001; RERI = 7.586, p = 0.009), high TG levels and FT3/FT4 ≥ 0.502 (AP = 0.348, 95%CI = 0.081-0.614, P = 0.010; RERI = 2.021, 95%CI = 0.064-3.978, p = 0.043) on the risk of GDM.Conclusion: The interactions between pBMI and FT3/FT4 ratio, TG level and FT3/FT4 ratio may have significant impacts on the risk of GDM in pregnant women. Such findings may help improve our understanding of the pathogenesis of GDM as well as develop comprehensive strategies for the management of GDM. [ABSTRACT FROM AUTHOR]

Thyroglobulin gene abnormalities cause thyroid dyshormonogenesis. A 6-yr-old boy of consanguineous parents presented with a large goiter and mild hypothyroidism (thyroid-stimulating hormone [TSH] 7.2 μIU/mL, free T3 [FT3] 3.4 pg/mL, free T4 [FT4] 0.6 ng/dL). Despite levothyroxine (LT4) administration and normal TSH levels, the goiter progressed slowly and increased rapidly in size at the onset of puberty. Thyroid scintigraphy revealed a remarkably high 123I uptake of 75.2%, with a serum thyroglobulin level of 13 ng/ml, which was disproportionately low for the goiter size. DNA sequencing revealed a novel homozygous missense variant, c.434G>A [p.Gly145Glu], in the thyroglobulin gene. Goiter growth was suppressed by increasing the LT4 dose. Thyroidectomy was performed at 17-yr-of-age. Thyroglobulin analysis of the thyroid tissue detected mutant thyroglobulin present in the endoplasmic reticulum, demonstrating that thyroglobulin transport from the endoplasmic reticulum to the Golgi apparatus was impaired by the Gly145Glu variant. During the clinical course, an elevated FT3/FT4 ratio was observed along with thyroid enlargement. A high FT3/FT4 ratio and goiter seemed to be compensatory responses to impaired hormone synthesis. Thyroglobulin defects with goiter should be treated with LT4, even if TSH levels are normal. [ABSTRACT FROM AUTHOR]

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Context: Establishing the etiology of thyrotoxicosis is of utmost importance to plan the appropriate line of therapy. However, certain scenarios such as absence of pathognomonic clinical features of Graves' disease in some patients, or non-availability of radionuclide scanning and newer generation TRAb assays especially in resource-poor settings, necessitates utilization of other, simple and effective measures to differentiate between the two common causes of thyrotoxicosis, Graves' disease (GD) and Destructive thyroiditis (DT). Aims: The aim of this work was to study the role of FT3/FT4 ratio, T3/T4 ratio and color flow Doppler ultrasound in treatment-naïve patients with thyrotoxicosis, in comparison to Tc-99m pertechnetate thyroid scanning in the differentiation of thyrotoxicosis due to GD and DT. Materials and Methods: Clinical data was collected from all study subjects. Thyroid function tests including FT3, FT4, T3, T4 and TSH, TSH Receptor Antibody (TRAb), Technetium Tc 99m pertechnetate scan and the mean peak systolic velocity in inferior thyroid artery (mean PSV-ITA) by color Doppler ultrasonography of thyroid gland was done in all patients. Results: A total of 83 treatment-naïve patients with thyrotoxicosis (61 with GD and 22 with DT) were studied. Mean PSV-ITA, T3/T4 ratio and FT3/FT4 ratio showed a sensitivity of 85.2%, 73.8%, and 77.04%, and a specificity of 90.9%, 72.7%, and 59.09%, respectively. The three parameters in combination yielded a positive predictive value of 100% in the diagnosis of Graves' disease. Conclusion: Results of this study show that inferior thyroid artery blood flow, T3/T4 ratio and FT3/FT4 ratio are useful parameters in the differentiation between GD and DT.

AimsAbnormal thyroid hormone secretions can alter the manifestation and prognosis of cardiovascular disease. To assess the effect of the free triiodothyronine (FT3)/free thyroxine (FT4) ratio on the prognosis of patients with heart failure (HF), we performed a propensity-matched study on patients with well-balanced baseline characteristics.MethodsOverall, 8,887 patients with HF were divided into two groups according to the FT3/FT4 ratio. Propensity scores were calculated from each patient. A cohort comprising 2,164 pairs with high or low ratios and with 34 well-balanced baseline characteristics was then assembled. The endpoints were Cardiovascular (CV) mortality and all-cause mortality. The correlation between FT3/FT4 ratio and prognosis was assessed using matched Cox regression analyses. The mean follow-up was 3.3 years.ResultsIn the full pre-match cohort, 3,710 (41.7%) patients died, with 2,581 (29.0%) cases of CV mortality. In the matched-pair cohort, all-cause mortality occurred in 923 (1,238/10,000 person-years of follow-up) patients with a high ratio and 1,036 (1,484/10,000 person-years) patients with a low ratio, resulting in a matched HR of 0.841 (95% CI: 0.769–0.919; P < 0.001). For CV mortality, the result was 638 (856/10,000 person-years) and 714 (1,023/10,000 person-years) patients, respectively, resulting in a matched HR of 0.844 (95% CI: 0.759–0.940; P < 0.001). Subgroup analysis revealed that a low FT3/FT4 ratio had a greater predictive value for all-cause and CV mortality in elderly or male patients and in patients with coronary artery disease (CAD), hypertension, diabetes mellitus, HFmrEF, or HFpEF.ConclusionsA low FT3/FT4 ratio is valuable for predicting CV mortality and all-cause mortality in patients with HF.

The aim of the work was to explore the correlation between thyroid hormones and coronary atherosclerotic severity. This cross-sectional study included 340 euthyroid patients who underwent diagnostic coronary artery angiography (CAG). Gensini Score (GS) was applied to assess the severity of coronary atherosclerosis. Thyroid hormones and routine biochemical parameters were measured. The associations between thyroid hormones and coronary atherosclerosis severity were analyzed. Thyroid hormones levels or parameters were taken as both continuous variables and tertiles into analysis, and the lowest tertile was usually used as the reference (OR=1) for medium and highest tertiles. Free triiodothyronine (FT3) level was associated with GS≥22 (Median GS) in Model I adjusted for age and sex [Continuous: OR=0.46, 95% CI (0.23, 0.92), p=0.029; Tertile 3: OR=0.54, 95% CI (0.30, 0.97), p=0.038], and Model II adjusted for all known risk factors of coronary artery disease (CAD) [Continuous: OR=0.44, 95% CI (0.20, 0.95), p=0.036; Tertile 3: OR=0.49, 95% CI (0.25, 0.96), p=0.039]. Subjects with highest tertile of FT3 to free thyroxine (FT4) ratio (FT3/FT4 ratio) appeared to have the remarkably decreased risk of CAD in both Non-adjusted Model [OR=0.49, 95% CI (0.24, 0.98), p=0.044] and Model I [OR=0.45, 95% CI (0.22, 0.93), p=0.031]. Higher FT3 level within normal range was independently and negatively associated with severity of coronary atherosclerosis. Besides, FT3/FT4 ratio was remarkably correlated with the prevalence of CAD in euthyroid population. [ABSTRACT FROM AUTHOR]

Objective: Obstructive sleep apnea (OSA) and thyroid dysfunction frequently overlap clinically and are risk factors for cardiovascular disease. The free triiodothyronine to free thyroxine (FT3/FT4) ratio as a novel biomarker of cardiovascular disease prognosis, but the impact of the FT3/FT4 ratio on the prognosis of OSA in patients with acute coronary syndromes (ACS) remains uncertain., Methods: In this prospective cohort study, 2160 patients with ACS were recruited and underwent portable sleep monitoring at Beijing Anzhen Hospital from June 2015 to January 2020. OSA was diagnosed when apnea-hypopnea index of ≥15 events/h. Patients were further divided into tertiles according to FT3/FT4 ratio. All patients had scheduled follow-up visits at 1, 3, 6, 9 and 12 months after discharge, with subsequent outpatient visits or telephone follow-up visits every 6 months. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction (MI), stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure., Results: Among 1,547 euthyroid patients enrolled (mean age, 56.0 ± 10.5 years), 812 patients (52.5%) had OSA. The FT3/FT4 ratio between OSA and non-OSA patients was not significantly different. During 2.8 (1.4, 3.5) years follow up, the risk of MACCE increased with the decreasing FT3/FT4 tertiles in patients with OSA (tertile3 as reference, tertile2: hazard ratio (HR) 1.26, 95% CI: 0.85-1.86, P = 0.255; tertile1: 1.60, 95% CI 1.11-2.32; P = 0.013). After adjustment for confounders, the lowest FT3/FT4 tertile was still independently associated with an increased risk of MACCE (adjusted HR 1.66, 95% CI 1.11-2.50, P = 0.015)., Conclusion: Lower FT3/FT4 ratio associated with poor prognosis in patients with ACS and OSA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, He, Ai, Zhao, Chen, Li, Zhang, Fan, Gong and Nie.)

BackgroundIn euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether free triiodothyronine to free thyroxine (FT3/FT4) ratio can predict the recurrence of cardiovascular events (CVEs). We aim to investigate its association with recurrent long-term adverse events in this population.Methods3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T12.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death.ResultsThe median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P

BackgroundThyroid function is closely involved in cardiovascular diseases. The free triiodothyronine (fT3) to free thyroxine (fT4) ratio has been reported as a risk factor for coronary artery disease, but its prognostic value in euthyroid patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear.MethodsA total of 1162 euthyroid patients with MINOCA were enrolled and divided according to decreased tertiles of fT3/fT4 ratio. The study endpoint was major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were performed.ResultsPatients with lower fT3/fT4 tertile levels had a significantly higher incidence of MACE (10.0%, 13.9%, 18.2%; p=0.005) over the median follow-up of 41.7 months. The risk of MACE increased with the decreasing fT3/fT4 tertiles even after multivariate adjustment (tertile1 as reference, tertile2: HR 1.58, 95% CI: 1.05-2.39, p=0.030; tertile3: HR 2.06, 95% CI: 1.17-3.11, p=0.006). Lower level of fT3/fT4 ratio remained a robust predictor of MACE in overall (HR 1.64, 95% CI: 1.18-2.29, p=0.003) and in subgroups. When adding fT3/fT4 ratio [area under the curve (AUC) 0.61] into the thrombolysis in myocardial infarction (TIMI) risk score (AUC 0.69), the combined model (AUC 0.74) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p=0.023).ConclusionsLow level of fT3/fT4 ratio was strongly associated with a poor prognosis in euthyroid patients with MINOCA. Routine assessment of fT3/fT4 ratio may facilitate risk stratification in this specific population.

Objective: The variations of thyroid hormones within normal ranges are observed in different metabolic conditions. Considering available data, levels of thyroid hormones change in obesity and type 2 diabetes mellitus (DM) in opposite ways. This study aimed to evaluate thyroid hormone levels and free triiodothyronine-to-free thyroxine (fT3/fT4) ratios in different glucose metabolism statuses of euthyroid patients with obesity. Material and Methods: This retrospective study evaluated thyroid hormones and the fT3/fT4 ratio of 209 patients with obesity who were grouped according to their glucose metabolism statuses. Results: One hundred and thirty-one (62.7%) patients had normal glucose tolerance, 41 (19.6%) patients had prediabetes, and 37 (17.7%) patients had DM. Serum fT4 level was found to be higher in patients with DM compared to patients with normal glucose tolerance (p=0.009), although no difference was observed in serum thyroid-stimulating hormone and fT3 levels among groups. FT3/fT4 ratio was determined to be lower in patients with DM than patients with normal glucose tolerance (p=0.012). Hemoglobin A1c was independently and positively associated with fT4 (β=0.345, r²=0.119, p=0.003) and negatively associated with fT3/fT4 ratio (β=-0.371, r²=0.138, p=0.001). Conclusion: Serum fT4 level increased, and fT3/fT4 ratio decreased in patients with type 2 DM independent of the degree of obesity. The interaction of DM with thyroid hormones in our cohort seemed to overcome obesity-related changes in thyroid functions. [ABSTRACT FROM AUTHOR]

Background: Thyroid function is closely involved in cardiovascular diseases. The free triiodothyronine (fT3) to free thyroxine (fT4) ratio has been reported as a risk factor for coronary artery disease, but its prognostic value in euthyroid patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear. Methods: A total of 1162 euthyroid patients with MINOCA were enrolled and divided according to decreased tertiles of fT3/fT4 ratio. The study endpoint was major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were performed. Results: Patients with lower fT3/fT4 tertile levels had a significantly higher incidence of MACE (10.0%, 13.9%, 18.2%; p=0.005) over the median follow-up of 41.7 months. The risk of MACE increased with the decreasing fT3/fT4 tertiles even after multivariate adjustment (tertile1 as reference, tertile2: HR 1.58, 95% CI: 1.05-2.39, p=0.030; tertile3: HR 2.06, 95% CI: 1.17-3.11, p=0.006). Lower level of fT3/fT4 ratio remained a robust predictor of MACE in overall (HR 1.64, 95% CI: 1.18-2.29, p=0.003) and in subgroups. When adding fT3/fT4 ratio [area under the curve (AUC) 0.61] into the thrombolysis in myocardial infarction (TIMI) risk score (AUC 0.69), the combined model (AUC 0.74) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p=0.023). Conclusions: Low level of fT3/fT4 ratio was strongly associated with a poor prognosis in euthyroid patients with MINOCA. Routine assessment of fT3/fT4 ratio may facilitate risk stratification in this specific population. [ABSTRACT FROM AUTHOR]

Background: In euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether free triiodothyronine to free thyroxine (FT3/FT4) ratio can predict the recurrence of cardiovascular events (CVEs). We aim to investigate its association with recurrent long-term adverse events in this population. Methods: 3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T1<2.41, n=1170; 2.41≤T2<2.75, n=1198; T3>2.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death. Results: The median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P<0.05). After adjustment of confounding factors, decreased FT3/FT4 ratio was independently associated with an increased risk of all-cause death (HR 1.82, 95% CI 1.13-2.93, P=0.014), cardiac death (HR 1.90, 95% CI 1.04-3.46, P=0.036) and MACCE (HR 1.33, 95% CI 1.10-1.60, P=0.003) which was driven mainly by all-cause death. Conclusions: In euthyroid patients with prior cardiovascular events undergoing PCI, FT3/FT4 ratio might be a potential predictor of all-cause and cardiac mortality. Routine assessment of FT3/FT4 ratio might be a simple and effective tool for risk stratification in this specific patient population. [ABSTRACT FROM AUTHOR]

Context: Establishing the etiology of thyrotoxicosis is of utmost importance to plan the appropriate line of therapy. However, certain scenarios such as absence of pathognomonic clinical features of Graves' disease in some patients, or non-availability of radionuclide scanning and newer generation TRAb assays especially in resource-poor settings, necessitates utilization of other, simple and effective measures to differentiate between the two common causes of thyrotoxicosis, Graves' disease (GD) and Destructive thyroiditis (DT). Aims: The aim of this work was to study the role of FT3/FT4 ratio, T3/T4 ratio and color flow Doppler ultrasound in treatment-naïve patients with thyrotoxicosis, in comparison to Tc-99m pertechnetate thyroid scanning in the differentiation of thyrotoxicosis due to GD and DT. Materials and Methods: Clinical data was collected from all study subjects. Thyroid function tests including FT3, FT4, T3, T4 and TSH, TSH Receptor Antibody (TRAb), Technetium Tc 99m pertechnetate scan and the mean peak systolic velocity in inferior thyroid artery (mean PSV-ITA) by color Doppler ultrasonography of thyroid gland was done in all patients. Results: A total of 83 treatment-naïve patients with thyrotoxicosis (61 with GD and 22 with DT) were studied. Mean PSV-ITA, T3/T4 ratio and FT3/FT4 ratio showed a sensitivity of 85.2%, 73.8%, and 77.04%, and a specificity of 90.9%, 72.7%, and 59.09%, respectively. The three parameters in combination yielded a positive predictive value of 100% in the diagnosis of Graves' disease. Conclusion: Results of this study show that inferior thyroid artery blood flow, T3/T4 ratio and FT3/FT4 ratio are useful parameters in the differentiation between GD and DT. [ABSTRACT FROM AUTHOR]

Background and Aims: Whether routine assessment of FT3/FT4 ratio in euthyroid patients with three-vessel disease (3VD) could help identify high-risk individuals remains unclear. This study evaluated the relationship between FT3/FT4 ratio and long-term clinical outcomes in this specific population.Methods and Results: This study included 2106 euthyroid patients with 3VD (stenoses of ≥50% in right coronary artery, left circumflex and left anterior descending). Patients were categorized into three groups according to tertiles of FT3/FT4 ratio (Q1>2.58,n = 704; 2.2 ≤ Q2<2.58, n = 706; Q3<2.22, n = 696). The median follow-up time was 5.3 years, during which 206 deaths and 332 MACCEs (consisting of all-cause death, myocardial infarction, and stroke) occurred. Compared with the other two groups, patients with low level of FT3/FT4 ratio tended to be female, older, diabetic, and had significantly higher incidences of all-cause death, cardiac death and MACCE (all P < 0.05). Cox regression analysis showed that patients with low level of FT3/FT4 ratio had higher risks of long-term cardiac death (adjusted HR = 1.87, 95% CI 1.06-3.28, P = 0.030) and MACCE (adjusted HR = 1.43, 95% CI 1.07-1.93, P = 0.017) than those with high level of FT3/FT4 ratio. Subgroup analysis showed there was a significant interaction between FT3/FT4 ratio and age (≥65 years vs.<65 years) for MACCE (P = 0.029).Conclusion: Low level of FT3/FT4 ratio is independently associated with an increased risk of long-term cardiac death and MACCE in euthyroid patients with 3VD. Routine assessment of FT3/FT4 ratio might be helpful to identify high-risk individuals in this specific population. [ABSTRACT FROM AUTHOR]

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear., Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI., Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]., Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Sun, Li, Zhao, Li, Ye, Niu and Wu.)

Abstract Background Thyroid hormones deeply influence the cardiovascular system; however, the association between the fT3/fT4 ratio and the clinical outcome in euthyroid patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) is not well defined. Therefore, the present study aimed to assess the prognostic performance of the fT3/fT4 ratio in predicting the long-term prognosis in euthyroid patients with AMI undergoing PCI. Methods In a prospective cohort study with a 1-year follow-up, according to the clinical end point, 953 euthyroid individuals (61.0 ± 11.6; female, 25.8%) were divided into two groups: (1) the survival group (n = 915) and (2) the death group (n = 38). Results According to Cox regression multivariate analysis, fT4 (HR: 1.249, 95% CI: 1.053–1.480, p = 0.010) and the fT3/fT4 ratio (HR: 3.546, 95% CI: 1.705–7.377, p = 0.001) were associated with an increased risk of 1-year all-cause mortality. The prognostic performance of the fT3/fT4 ratio was similar to the Global Registry of Acute Coronary Events (GRACE) score in predicting 1-year all-cause mortality (C-statistic: z = 0.261, p = 0.794; IDI: -0.017, p = 0.452; NRI: -0.049, p = 0.766), but better than fT4 (C-statistic: z = 2.438, p = 0.015; IDI: 0.053, p = 0.002; NRI: 0.656, p

To assess the effects of thyroid hormones on appendicular skeletal muscle index (SMI) and hand grip strength (HGS) in people with diabetes. This cross-sectional cohort included 1,135 participants with diabetes admitted to 3 hospitals in Japan. Multiple regression analysis was performed to determine the associations among thyroid hormone levels, SMI, and HGS. Of the 1,135 participants, 480 were female. Their median (interquartile range) age, body mass index, durations of diabetes, and glycated haemoglobin levels were 68 years, 24.3 kg/m2, 10 years, and 7.6 %, respectively. The median (interquartile range) SMI (kg/m2) and hand grip strength of the cohort were 7.1 kg/m2 and 28.2 kg, respectively. Positive correlations between FT3 and the FT3/FT4 ratio with SMI and HGS was observed after adjusting for covariates in males. A negative correlation was found between the FT3/FT4 ratio and sarcopenia as a result of low SMI and low HGS in the male participants but not in females (p for interaction = 0.02). FT3/FT4 ratios may impact skeletal muscles in people with diabetes—particularly in males. Assessments of FT3/FT4 ratios may represent key indicators of muscle mass and strength in males. [ABSTRACT FROM AUTHOR]

Objective: Although several studies have examined the relationship between thyroid function and muscle strength, their population primarily derived from Asian areas, and their results were controversial. Thus, this study aimed to explore the association between thyroid function and handgrip strength (HGS) in the U.S. population., Methods: A total of 1,067 participants from NHANES were categorized into three different age groups including young (<45 years), middle (45~64 years), and old (≥65 years) age groups. Thyroid function was measured by the competitive binding immune-enzymatic assays, while HGS was examined by a trained evaluator using a dynamometer. The weighted multiple linear regression models were used to examine the association between thyroid function and handgrip strength. The restricted cubic splines were employed to explore the non-linear relationship between these two variables. All statistical analyses were performed using the SPSS version 20.0 and R software., Results: After adjustment for potential covariates, FT3/FT4, but not TSH was positively associated with HGS in middle age group (β=0.091, t=2.428, P=0.016). The subgroup analysis by sex revealed that the positive association between FT3/FT4 and HGS was observed in the middle age group for both male and female participants (β=0.163, t=2.121, P=0.035; β=0.157, t=2.180, P=0.031). The RCS analysis showed a statistically significant non-linear association between FT3/FT4 and HGS in overall population (P for non-linear=0.026). After adjustment for covariates, men with low HGS had a significant lower FT3/FT4 than those without low HGS in old age group (P=0.013). There was a significant increase in TSH level for female participants with low HGS in old age group compared to those with normal HGS (P=0.048)., Conclusions: This study demonstrated FT3/FT4, but not TSH, was positively associated with HGS in middle age group, and the different association was observed in men in middle age group when participants were stratified by sex. Future longitudinal cohort study should be conducted to reveal the causal relationship between thyroid function and muscle strength., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wu, Yang, Jiang, Wang and Lin.)

OBJECTIVE: This study was performed to evaluate the effects of metabolic parameters and thyroid dysfunction on the development of non-alcoholic fatty liver disease (NAFLD). METHODS: The current study evaluated a total of 115 patients, 75 female and 40 male. Physical examination and anthropometric measurements were applied to all participants. Hypothyroidism was considered at a thyroid stimulating hormone level ≥ 4.1 mIU/L. Patients with euthyroidism and patients with hypothyroidism were compared. Abdominal ultrasonography was used to diagnose non-alcoholic fatty liver disease. The participants were further compared with regard to the presence of non-alcoholic fatty liver disease. Logistic regression modeling was performed to identify the relationship between non-alcoholic fatty liver disease and independent variables, such as metabolic parameters and insulin resistance. RESULTS: Non-alcoholic fatty liver disease was identified in 69 patients. The mean waist circumference, body mass index, fasting plasma insulin, HOMA-IR (p

Context: It is still not clear how the free triiodothyronine (FT3) to free thyroxine (FT4) ratio affects the prognosis of acute myocardial infarction (AMI), especially the risk of heart failure (HF) subsequent to AMI., Objective: The purpose of this study was to see how peripheral sensitivity to thyroid hormones, as measured by the FT3/FT4 ratio, affected HF and mortality after AMI., Methods: Our study was a retrospective cohort study. The primary endpoint was HF after AMI during and after hospitalization. The secondary endpoints were all-cause death and cardiovascular death after hospitalization., Results: The main sample included 3648 inpatients with AMI with a median age of 61.0 years; 68.9% were male. In the fully adjusted model, compared with patients in the lowest Q1 of the FT3/FT4 ratio, the risk of in-hospital HF in the highest Q4 patients was reduced by 44% (OR 0.56, 95% CI 0.44-0.72, P trend < .001), the risk of out-of-hospital HF was reduced by 37% (HR 0.63, 95% CI 0.48-0.84, P trend < .001), and the risks of all-cause and cardiovascular death were also significantly reduced. The analysis of different subgroups is consistent with the overall results. Furthermore, the sensitivity analysis of the euthyroid sample of 2484 patients was consistent with the main sample. Mediation analysis showed that altered levels of amino-terminal pro-B-type natriuretic peptide were mediators between the FT3/FT4 ratio and all endpoints in our study., Conclusion: The thyroid hormone peripheral sensitivity of the FT3/FT4 ratio is an independent predictor of HF and mortality after AMI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Thyroid hormones deeply influence the cardiovascular system; however, the association between the fT3/fT4 ratio and the clinical outcome in euthyroid patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) is not well defined. Therefore, the present study aimed to assess the prognostic performance of the fT3/fT4 ratio in predicting the long-term prognosis in euthyroid patients with AMI undergoing PCI.Methods: In a prospective cohort study with a 1-year follow-up, according to the clinical end point, 953 euthyroid individuals (61.0 ± 11.6; female, 25.8%) were divided into two groups: (1) the survival group (n = 915) and (2) the death group (n = 38).Results: According to Cox regression multivariate analysis, fT4 (HR: 1.249, 95% CI: 1.053-1.480, p = 0.010) and the fT3/fT4 ratio (HR: 3.546, 95% CI: 1.705-7.377, p = 0.001) were associated with an increased risk of 1-year all-cause mortality. The prognostic performance of the fT3/fT4 ratio was similar to the Global Registry of Acute Coronary Events (GRACE) score in predicting 1-year all-cause mortality (C-statistic: z = 0.261, p = 0.794; IDI: -0.017, p = 0.452; NRI: -0.049, p = 0.766), but better than fT4 (C-statistic: z = 2.438, p = 0.015; IDI: 0.053, p = 0.002; NRI: 0.656, p < 0.001). The fT3/fT4 ratio also significantly improved the prognostic performance of the GRACE score (GRACE score vs GRACE score + fT3/fT4 ratio: C-statistic: z = 2.116, p = 0.034; IDI: 0.0415, p = 0.007; NRI: 0.614, p < 0.001).Conclusions: In euthyroid patients with AMI undergoing PCI, the fT3/fT4 ratio was an independent predictor of 1-year all-cause mortality. Its prognostic performance was similar to the GRACE score, and also improved its prognostic performance (GRACE score vs GRACE score + fT3/fT4 ratio). [ABSTRACT FROM AUTHOR]

Purpose The aim of this study is to discuss the value of ultrasound-based shear wave™ elastography (SWE) in diffuse thyroid disease (DTD). Method Thyroid stiffness in 154 patients with DTD and 30 normal subjects was measured by SWE. The serum indicators of all subjects were detected. Results The area under the receiver operating characteristic (AUROC) curve for DTD by SWE was 0.852. The AUROCs of SWE for differentiating chronic autoimmune thyroiditis (CAT) from Graves' disease (GD) and subacute thyroiditis (SAT) were 0.549 and 0.989, respectively. The AUROCs for distinguishing GD from SAT by SWE and the fT3/fT4 ratio were 0.975 and 0.713, respectively. Conclusion SWE aids in the diagnosis of DTD, and SWE is superior to the fT3/fT4 ratio for distinguishing GD from SAT. However, SWE was unsuitable for differentiating CAT from GD. [ABSTRACT FROM AUTHOR]

Objective The interrelation between TSH, thyroid hormones and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. Design This is a cross-sectional study that included subjects in a medical health check-up programme at a single institution. Patients The study included 132 346 participants (66 991 men and 65 355 women) aged over 18 years who had TSH, free T4 ( FT4) and free T3 ( FT3) levels within the institutional reference ranges. Measurements Thyrotropin, FT4, FT3 and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin and glucose were measured. Results There was a positive association between FT3/ FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status and menopausal status (in women). The FT3/ FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/ FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women. Conclusions Thyrotropin levels were positively associated with FT3/ FT4 ratio within the euthyroid range. The higher FT3/ FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/ FT4 ratio has a better predictive power for metabolic syndrome than TSH. [ABSTRACT FROM AUTHOR]

Context: Impaired sensitivity to thyroid hormones has been demonstrated to be positively associated with the prevalence of metabolic disorders. However, the relationship between sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis remained unclear., Objective: We aimed to determine the associations of thyroid hormone sensitivity indices with MAFLD and its progression to liver fibrosis in Chinese euthyroid adults., Methods: This community-based study included 7906 euthyroid adults. We calculated the thyroid sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, Thyroid Feedback Quantile-based Index by FT4 (TFQIFT4), and Thyroid Feedback Quantile-based Index by FT3 (TFQIFT3), indicating peripheral and central thyroid hormone sensitivity respectively. Liver steatosis and fibrosis were diagnosed by vibration-controlled transient elastography (VCTE). Multivariable logistic/linear regression and restricted cubic spline (RCS) analysis were conducted., Results: Compared with participants in the first quartile (Q1), the prevalence of MAFLD was increased by 62% in the fourth quartile (Q4) of FT3/FT4 ratio (OR 1.62; 95% CI [1.38, 1.91]) and by 40% in Q4 of TFQIFT3 (OR 1.40; 95% CI [1.18, 1.65]) (both P < .05). No associations between TFQIFT4 and the prevalence of MAFLD were found. In addition, compared with participants in Q1, the prevalence of liver fibrosis was increased by 45% in Q4 of TFQIFT3 (OR 1.45; 95% CI [1.03, 2.06]) (P < .05) in participants with MAFLD., Conclusion: Impaired central sensitivity to FT3 was associated with MAFLD and its progression to liver fibrosis. More prospective and mechanism studies are warranted to confirm these conclusions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: It remains unclear whether the thyroid system could regulate the atherogenic remnant cholesterol (RC) levels in euthyroid status., Objective: We aimed to investigate the relationship between sensitivity to thyroid hormones and RC levels in Chinese euthyroid population., Methods: This study included 18 766 euthyroid adults. High RC levels were defined as the upper quartile of RC levels. The thyroid hormone sensitivity indices, including thyroid feedback quantile-based index (TFQI), thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI), and free triiodothyronine to free thyroxine (FT3/FT4) ratio were calculated. Linear and binary logistic regression analysis were applied to determine the associations between those composite indices with RC levels by genders., Results: Both females and males with high RC levels exhibited co-existing higher TSH and FT4 levels. Linear regression analysis revealed that TFQI, TSHI, and TT4RI were positively, while FT3/FT4 ratio levels were negatively associated with serum RC levels. The odds ratios (ORs) (95% CI) for high RC levels were increased with rising TFQI quartiles (Q) [females: Q3 1.41 (1.22-1.63), Q4 1.61 (1.39-1.86); males: Q3 1.25 (1.09-1.45), Q4 1.38 (1.19-1.59), all P for trend < 0.001] after full adjustment, with Q1 as the reference. TSHI and TT4RI yielded similar results. By contrast, the ORs (95% CI) for high RC levels were decreased with increasing FT3/FT4 ratio quartiles in both genders (P for trend < 0.001)., Conclusion: In euthyroid adults, reduced sensitivity to thyroid hormones was associated with high RC levels. Our results suggested an additive cardiometabolic risk of euthyroid population with thyroid hormones insensitivity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Crescent formation indicates severe glomerular pathology, and hypothyroidism usually predicts poor prognosis for severe diseases. However, the relationship between thyroid function and the progression of chronic kidney disease (CKD) is unclear. This study analysed the prognostic predictive value of the serum free triiodothyronine (FT3) to free thyroxine (FT4) ratio and its correlation with renal function in patients with CKD with crescent formation., Methods: This single-centre study included 162 CKD patients with glomerular crescents confirmed by renal pathology between March 2012 and December 2014. According to the first tertile (0.284) of FT3/FT4 ratio, the patients were divided into high and low FT3/FT4 ratio groups. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of the FT3/FT4 ratio., Results: The age, haemoglobin, eGFR, urinary albumin-to-creatinine ratio, cardiac troponin T, N-terminal brain natriuretic peptide precursor, FT3, FT4, percentage of total crescents in non-globally sclerotic glomeruli, prevalences of hypertension, moderate to severe renal tubulopathy and crescentic nephritis, and proportion of patients receiving glucocorticoids and immunosuppressants were significantly different between high and low FT3/FT4 ratio groups (P < 0.05). Multivariate Cox regression analysis showed that when compared with patients with a high FT3/FT4 ratio (>0.284), those with intermediate and low FT3/FT4 ratios (≤0.284) had an increased risk of the long-term composite endpoint (P < 0.05 for various adjustment models)., Conclusions: A low FT3/FT4 ratio is associated with increased mortality and worse outcome risk in CKD patients with crescent pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wu, Nie, Lv, Li, Zhu, Jin, Shen, Li, Liu, Fang and Ding.)

Background: Thyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population., Methods: This retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015., Results: During a median of 87 months of follow-up, we observed 699 all-cause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results., Conclusions: FT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lang, Li, Zhang, Zhang, Wu and Zhang.)

Abstract: Objective: To investigate the relationship of thyroid hormones in glucose homeostasis in impaired glucose-tolerant subjects with normal thyroid functions. Methods: Cross-sectional analysis was carried out in (n =260) impaired glucose-tolerant (IGT) and normal glucose-tolerant (NGT) subjects. Thyrotropin (TSH), total triiodothyronine (TT3), total thyroxin (TT4) free T3 (fT3), free T4 (fT4), and insulin were assessed by enzyme-linked immunoassays (ELISA). Fasting plasma glucose (FPG) and HbA1c were measured by glucose oxidase and low-pressure cation exchange chromatography. Homeostasis model of assessment (HOMA-IR) was employed to assess the level of insulin resistance; fT3/fT4 ratio was calculated. Anthropometric measurement and habits were recorded. Results: Marked hyperinsulinemia and insulin resistance were observed in IGT subjects. Serum TT3 and fT3 levels were significantly low in the IGT as compared to normal glucose-tolerant (NGT) controls. TT4 and TSH were higher in IGT subjects as compared to control subjects. There was a significant positive correlation of TSH with BMI only in the control group (r =0.351; P <0.05). Correlation of insulin with TT3, fT3,and TSH was significant (P <0.05) in IGT subjects. A significant low fT3/fT4 ratio was observed in IGT subjects as compared to NGT subjects (P <0.01). In multiple regression analysis, TSH, TT4 and fT3 contributed significantly to the variance of fasting insulin and insulin resistance in IGT subjects. Conclusion: Hyperinsulinemia and insulin resistance are associated with low T 3 /T 4 ratio in pre-diabetic euthyroid Pakistani subjects. [Copyright &y& Elsevier]

Aims: Abnormal thyroid hormone secretions can alter the manifestation and prognosis of cardiovascular disease. To assess the effect of the free triiodothyronine (FT3)/free thyroxine (FT4) ratio on the prognosis of patients with heart failure (HF), we performed a propensity-matched study on patients with well-balanced baseline characteristics., Methods: Overall, 8,887 patients with HF were divided into two groups according to the FT3/FT4 ratio. Propensity scores were calculated from each patient. A cohort comprising 2,164 pairs with high or low ratios and with 34 well-balanced baseline characteristics was then assembled. The endpoints were Cardiovascular (CV) mortality and all-cause mortality. The correlation between FT3/FT4 ratio and prognosis was assessed using matched Cox regression analyses. The mean follow-up was 3.3 years., Results: In the full pre-match cohort, 3,710 (41.7%) patients died, with 2,581 (29.0%) cases of CV mortality. In the matched-pair cohort, all-cause mortality occurred in 923 (1,238/10,000 person-years of follow-up) patients with a high ratio and 1,036 (1,484/10,000 person-years) patients with a low ratio, resulting in a matched HR of 0.841 (95% CI: 0.769-0.919; P < 0.001). For CV mortality, the result was 638 (856/10,000 person-years) and 714 (1,023/10,000 person-years) patients, respectively, resulting in a matched HR of 0.844 (95% CI: 0.759-0.940; P < 0.001). Subgroup analysis revealed that a low FT3/FT4 ratio had a greater predictive value for all-cause and CV mortality in elderly or male patients and in patients with coronary artery disease (CAD), hypertension, diabetes mellitus, HFmrEF, or HFpEF., Conclusions: A low FT3/FT4 ratio is valuable for predicting CV mortality and all-cause mortality in patients with HF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Han, Li, Tong, Li and Sun.)

Introduction: Insulin resistance (IR) is a key and early pathogenetic mechanism of cardiometabolic diseases with huge potential if detected early and mitigated, for lowering the burden of the disease. Available data are conflicting to what extent adult thyroid dysfunction is associated with IR. Therefore, we aimed to investigate the association and to identify which thyroid parameters are predictors of IR., Material and Methods: After undergoing basic anthropometric and biochemical studies including thyroid hormones, oral glucose tolerance test (OGTT), and insulin, 1425 middle-aged individuals were divided into three groups according to thyroid parameters: overt hypothyroidism (OH), subclinical hypothyroidism (SH), and euthyroidism (EU)., Results: The homeostasis model assessment of IR (HOMA-IR), fasting insulin, and two-hour glucose levels of OGTT showed a steady, yet insignificant, increase from EU through SH to OH. The strongest noted correlations were those of insulin levels with free triiodothyronine/free thyroxine (FT3/FT4) ratio (r = 0.206, p < 0.001) and FT3 (r = 0.205, p < 0.001). Also in the case of HOMA-IR, the only statistically significant correlations were observed for FT3 (r = 0.181, p < 0.001) and the FT3/FT4 ratio (r = 0.165, p < 0.001). Among other thyroid hormones, linear logistic regression proved the FT3/FT4 ratio as the only significant predictor of HOMA-IR (linear coefficient = 5.26, p = 0.027) and insulin levels (linear coefficient = 18.01, p = 0.023), respectively. Thyroid-stimulating hormone was not associated with IR in either correlation or regression analysis., Conclusions: The FT3/FT4 ratio should be more emphasised in the diagnosis and treatment of thyroid disorders. Patients could benefit from a pharmacological reduction of the FT3/FT4 ratio, potentially leading to a decrease in insulin resistance, and thus a corresponding decrease in the risk of the cardiometabolic diseases.

While patients with large goitrous thyroid diseases often have a relatively high serum free triiodothyronine (FT 3 )/free thyroxine (FT 4 ) ratio, athyreotic patients have a relatively low FT 3 /FT 4 ratio. Here we investigated the relationship between thyroid hormone status and thyroid volume (TV) among a large number of euthyroid Hashimoto thyroiditis (HT) patients. We retrospectively enrolled 2,603 untreated HT patients who visited the Kuma hospital from 2012 to 2016, and divided them into four groups as per the TV: normal TV (<20 mL), slight goiter (20 ≤ TV < 50 mL), moderate goiter (50 ≤ TV < 80 mL), and the large goiter group (≥80 mL). Baseline characteristics and laboratory data of each group were compared to those of 1,554 control subjects. The association between FT 3 /FT 4 ratio and TV among HT patients was then analyzed. We observed a change in laboratory parameters among 13 patients in the large goiter group who were prescribed levothyroxine (LT 4 ) for reducing TV. Compared to normal subjects, the moderate and large goiter groups exhibited significantly higher serum FT 3 levels, while all HT groups exhibited lower serum FT 4 levels. Serum FT 3 /FT 4 ratios showed a positive correlation with TV (r = 0.35, p < 0.01), which was independent of age, sex, body mass index, and TgAb and TSH levels. LT 4 treatment lowered serum FT 3 levels and FT 3 /FT 4 ratios significantly. Our results indicated that HT patients with increased TV tended to present with high serum FT 3 , low FT 4 , and high FT 3 /FT 4 ratios. The elevation of deiodinase activity may be an important factor affecting thyroid hormonal balance in such patients.