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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.

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]

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]

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]

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]

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

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: 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]

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]

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 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]