The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78-1.85 ng/dL) and triiodothyronine (T3, 76-190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e' ratio > 15, or (b) E/e' ratio of 8-15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01-1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

[A panel study on the association of organophosphate ester flame retardant exposure with thyroid function related hormones in healthy older adults].

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M (Q1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M (Q1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M (Q1, Q3) for TSH, T3, and T4 was 3.74 (2.55, 5.69) µIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%CI:-15.17%, -4.36%) and 11.14% (95%CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

[Investigation of influencing factors and reference ranges for thyroid function in hospitalized preterm infants at the age of 7 days]. / 7æ—¥é¾„ä½é™¢æ—©äº§å„¿ç”²çŠ¶è ºåŠŸèƒ½å½±å“å› ç´ åŠå‚è€ƒå€¼èŒƒå›´æŽ¢è®¨.

OBJECTIVES: To investigate the influencing factors and reference ranges for thyroid function in preterm infants at the age of 7 days, with the aim of avoiding unnecessary clinical reexamination and intervention. METHODS: A retrospective analysis was performed for the data of 685 preterm infants from January 2020 to January 2023. According to gestational age and birth weight, they were divided into a high-risk group (gestational age <34 weeks or birth weight<2 000 g; 228 infants) and a low-risk group (gestational age ≥34 weeks and birth weight ≥2 000 g;457 infants). The influencing factors for thyroid function were analyzed, and 95% reference range was calculated. RESULTS: Gestational age, birth weight, birth season, sex, and assisted reproduction were the influencing factors for thyroid function (P<0.05). For the preterm infants in the high-risk group, the reference ranges of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH) were 2.79-5.40 pmol/L, 8.80-25.64 pmol/L, 0.80-2.15 nmol/L, 50.06-165.09 nmol/L, and 0.80-18.57 µIU/mL, respectively. For those in the low-risk group, the reference ranges of these indicators were 3.08-5.93 pmol/L, 11.17-26.24 pmol/L, 1.02-2.27 nmol/L, 62.90-168.95 nmol/L, and 0.69-13.70 µIU/mL, respectively. FT3, FT4, TT3, and TT4 were positively correlated with gestational age (P<0.05); FT3, FT4, TT3, and TT4 were positively correlated with birth weight (P<0.05); TSH was negatively correlated with birth weight (P<0.05). CONCLUSIONS: Thyroid function in preterm infants at the age of 7 days is affected by the factors such as gestational age and birth weight, and the reference ranges of thyroid function in preterm infants at the age of 7 days should be established based on gestational age and birth weight.

Association between maternal age and sex-based neonatal free triiodothyronine levels.

BACKGROUND: Advanced maternal age may affect the intrauterine environment and increase the risk of neurodevelopmental disorders in offspring. Thyroid hormones are critical for fetal neurological development but whether maternal age influences fetal thyroid hormone levels in euthyroid mothers is unknown. OBJECTIVE: This study evaluated the association between cord blood thyroid hormones and maternal age, fetal sex, maternal thyroid function, and other perinatal factors. METHODS: The study population consisted of 203 healthy women with term singleton pregnancies who underwent elective cesarean section. Maternal levels of free T3 (fT3), free T4 (fT4) and TSH before delivery, and cord levels of fT3, fT4 and TSH were measured. Spearman's correlation coefficient and multiple linear regression analyses were performed to determine the correlation between cord thyroid hormone parameters and maternal characteristics. RESULTS: There were no significant differences in maternal serum or cord blood thyroid hormone levels between male and female births. In multivariate linear regression analysis, maternal age and maternal TSH values were negatively associated with the cord blood levels of fT3 in all births, after adjusting for confounding factors. Maternal age was more closely associated with the cord blood levels of fT3 in female than in male births. CONCLUSION: The inverse association between maternal age and cord blood levels of fT3 in euthyroid pregnant women suggested an impact of maternal aging on offspring thyroid function.

Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis.

BACKGROUND: Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics. METHODS: We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid extract," OR "Natural desiccated thyroid," OR "Nature-Throid," "desiccated thyroid," OR "np thyroid," OR "Synthroid," OR "levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs and excluded non-RCT, case-control studies, and non-English articles. RESULTS: From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score. Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score. CONCLUSIONS: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended.

Low triiodothyronine (T3) levels predict worse outcomes in autoimmune encephalitis-A meta-analysis of current literature.

INTRODUCTION: An unusual association between thyroid dysfunction and autoimmune encephalitis (AE) was noticed when patients presented with low free triiodothyronine (fT3) levels and antithyroid antibodies. We conducted a meta-analysis to investigate whether thyroid dysfunction, that is, lower fT3 levels are associated with worsening clinical manifestations and prognosis in patients with AE. METHODS: Literature search of five electronic databases was performed till April 5, 2023. Inclusion criteria were as follows: Observational studies reporting patients with all subtypes of AE and assessing thyroid dysfunction categorized as low fT3 and non-low fT3. Primary endpoints included modified Rankin scale (mRS) at admission, abnormal magnetic resonance imaging, length of stay, seizures, and consciousness declination. RESULTS: Comprehensive literature search resulted in 5127 studies. After duplicate removal and full-text screening, six observational studies were included in this analysis. Patients with low fT3 were 2.95 times more likely to experience consciousness declination (p = .0003), had higher mRS at admission (p < .00001), had 3.14 times increased chances of having a tumor (p = .003), were 3.88 times more likely to experience central hypoventilation, and were 2.36 times more likely to have positivity for antithyroid antibodies (p = .009) as compared to patients with non-low fT3. CONCLUSION: The findings of our study suggest that low fT3 levels might be related to a more severe disease state, implying the significance of thyroid hormones in AE pathogenesis. This finding is crucial in not only improving the early diagnosis of severe AE but also in the efficient management of the disease.

Vitamin D and thyroid function: A mendelian randomization study.

BACKGROUND: Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function. METHODS: We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis. RESULTS: The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02). CONCLUSIONS: Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration.

Therapeutical Potential of T3 as Adjuvant Therapy in Male Alloxan-induced Diabetic Rats.

Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in controlling glycemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6 U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB expression, TSH levels, and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.

[Related factors of euthyroid sick syndrome in patients with sepsis].

OBJECTIVE: To evaluate the prevalence of euthyroid sick syndrome (ESS) in sepsis patients and to explore its influencing factors. METHODS: In the study, 365 patients diagnosed with sepsis in the emergency critical care department of Shanghai First People's Hospital from January 2017 to January 2023 were retrospectively enrolled. The patients were divided into ESS and non-ESS groups based on whether the patients were complicated with ESS.Baseline variables and relevant clinical data of the enrolled patients were collected. The prevalence of ESS in sepsis patients and its influencing factors were evaluated by multivariate Logistic regression analysis, and the 30-day survival rates were compared between the two groups. The optimal cutoff value for free triiodothyronine (FT3) was explored to predict death in the patients with sepsis. RESULTS: There were 103 sepsis patients with ESS, accounting for 28.2% of the total cases. The severity of sepsis in ESS group was significantly higher than that in non-ESS group (P < 0.05). The acute physiology and chronic health evaluationⅡ(APACHEⅡ)score and sequential organ failure assessment (SOFA) score of ESS group were significantly higher than those of non-ESS group (P < 0.05). C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA) and interleukin-6 (IL-6) in ESS group were higher than those in non-ESS group. total cholesterol(TC)and high-density liptein cholesterol(HDL-C)in ESS group were lower than those in non-ESS group, and the differences were statistically significant (P < 0.05).Multivariate Logistic regression analysis showed that PCT, IL-6, CRP, SAA and activated partial thromboplatin time (APTT) were independent risk factors for ESS in the sepsis patients (OR values were 1.105, 1.006, 1.005, 1.009 and 1.033, respectively; 95% CI were 1.044-1.170, 1.001-1.012, 1.001-1.009, 1.005-1.014, 1.004-1.062, respectively, P < 0.05).The 30-day survival rate in ESS group was significantly lower than that in non-ESS group, the Long-rank chi-square test value was 16.611, and the difference was statistically significant (P < 0.05).The receiver operation characteristic area under the curve (AUCROC)of FT3 predicted death in the patients with sepsis was 0.924 (95% CI 0.894-0.954). The serum FT3 cutoff point was 3.705 pmol/L, the specificity was 0.868, and the sensitivity was 0.950. CONCLUSION: In this study, the incidence of ESS in sepsis patients was determined to be 28.2% with poor prognosis. The results showed that PCT, IL-6, CRP, SAA and APTT were independent risk factors for ESS in sepsis patients, while HDL-C was a protective factor (P < 0.05). FT3 is a novel potential biomarker for predicting death in patients with sepsis.

The Effect of Mediterranean Diet on Thyroid Gland Activity.

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korcula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients.

Reduced serum CLCF1 levels in hyperthyroidism patients and T3-treated mice.

Characteristic symptoms of hyperthyroidism include weight loss, heart palpitation, and sweating. Thyroid hormones (TH) can stimulate thermogenesis through central and peripheral mechanisms. Previous studies have shown an association between dysfunction of cardiotrophin-like cytokine factor 1 (CLCF1) and cold-induced sweating syndrome, with recent research also indicating a link between CLCF1 and brown adipose tissue thermogenesis. However, it remains unclear whether CLCF1 and TH have synergistic or antagonistic effects on thermogenesis. This study aims to investigate the influence of thyroid hormone on circulating CLCF1 levels in humans and explore the potential possibilities of thyroid hormone in regulating energy metabolism by modulating Clcf1 in mice. By recruiting hyperthyroid patients and healthy subjects, we observed significantly lower serum CLCF1 levels in hyperthyroid patients compared to healthy subjects, with serum CLCF1 levels independently associated with hyperthyroidism after adjusting for potential confounders. Tissue analysis from mice treated with T3 revealed a decrease in CLCF1 expression in BAT and iWAT of C57BL/6 mice. These findings suggest that TH may play a role in regulating CLCF1 expression in adipose tissue.

Relationship between thyroid hormone levels and metabolic dysfunction associated steatotic liver disease in patients with type 2 diabetes: A clinical study.

BACKGROUND: This study investigates the correlation between thyroid hormone levels and metabolic dysfunction in patients with type 2 diabetes mellitus (T2DM) who exhibit normal thyroid function and metabolic dysfunction associated with steatotic liver disease (MASLD). OBJECTIVE: The objective is to identify a scientific basis for the management of T2DM complicated by MASLD, aiming to refine clinical strategies and enhance patient well-being. METHODS: Statistical analysis was conducted using SPSS 26.0, employing independent sample t-tests for normally distributed data and logarithmic transformations for non-normal data to meet analysis prerequisites. Multifactorial logistic regression analysis elucidated the impact of various factors on the risk of MASLD in T2DM patients. RESULTS: Elevated levels of FT3 may be associated with an increased risk of nonalcoholic fatty liver disease. Additionally, the FT3/FT4 ratio has been validated as an effective serological marker for predicting the risk of MASLD. In patients with DM2 and normal thyroid function, changes in thyroid hormone levels are closely related to the occurrence of MASLD. Elevated levels of FT3, total triiodothyronine (TT3), and thyroid-stimulating hormone are associated with an increased risk of MASLD. CONCLUSION: FT3, TT3, and thyroid-stimulating hormone have important clinical value in the diagnosis of patients with T2DM complicated with MASLD.

Thyroid hormones and stroke, the gap between clinical and experimental studies.

Despite plenty of human studies on changes in thyroid hormones after stroke and some animal studies that assessed the effects of thyroid hormone administration on stroke, conclusive evidence for clinical application is lacking. This review aimed to determine the consistency of the results between clinical and preclinical studies. This article reviewed the PubMed, Embase, web of Knowledge, and Google Scholar databases up to June 2023 using the MeSH terms "stroke, cerebral ischemia, cerebral infarction, brain ischemia, brain infarction, triiodothyronine (T3), tetraiodothyronine (T4), thyroxine (T4), and thyroid hormone". The results of clinical and preclinical studies related to T3 substantially confirm each other. That is, in most human studies lower T3 was associated with poor outcomes, and in experimental studies, T3 administration also had therapeutic effects. However, the results of experimental studies related to T4 could not support those of clinical studies. There seem to be some conflicts between experimental and human studies, especially regarding changes and effects of T4 after stroke. The gap between experimental and clinical studies may lead to non-applicable results, wasting time and money, and unnecessary killing of animals.

The effect of bisphenols on sex and thyroid hormone concentrations in cord blood among newborns.

This study aims to investigate the associations of bisphenols with sex and thyroid hormones in cord blood among newborns. Four bisphenols, three hormones related to gonadal function, and four parameters related to thyroid function were measured in umbilical cord blood in 378 mother-newborn pairs. Multivariable linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression were used. In the multivariable linear regression, bisphenol A (BPA) was associated with increased testosterone (TT) (regression coefficient, ß = 0.049, 95% confidence interval, CI: 0.013,0.085; p = 0.007) and free tri-iodothyronine (FT3) levels (ß = 0.019, 95% CI: 0.003, 0.035; p = 0.023), and decreased thyroid peroxidase antibody (TPOAb) (ß = -0.053, 95% CI: 0.098, -0.008; p = 0.021). Consistently associations were observed in males, except TT, which was observed in females, and bisphenol AF (BPAF) was associated with decreased follicle-stimulating hormone (FSH) in females. These associations were also observed in a mixture of bisphenols. Moreover, we observed maternal prepregnancy body mass index (BMI) and delivery mode disparity in the relationship between bisphenols and sex and thyroid hormones. This study suggests that bisphenols may exert effects on sex and thyroid hormones in newborns, the effect may vary with sex differences, maternal prepregnancy BMI, and delivery mode.

Low TSH and low T3 hormone levels as a prognostic for mortality in COVID-19 intensive care patients.

Introduction: Coronavirus diasease 2019 (COVID-19) can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. The thyroid gland is a neuroendocrine organ that plays an important role in regulating immunity and metabolism. Low serum levels of thyroid hormones are common in critical disease situations. The association between low thyroid hormone levels and mortality in COVID-19 intensive care patients has yet to be studied. Aim: The aim of this study is to compare thyroid hormone levels between patients in the general intensive care unit (ICU) to patients in the COVID-19 ICU. Methods: This was a retrospective comparative study of 210 patients who were hospitalized at Ziv Medical Center in the general ICU and in the COVID-19 ICU. Clinical and demographic data were collected from patient's electronic medical records. Results: Serum thyroid hormone levels of Thyroid Simulating Hormone (TSH), T4, and T3 were significantly lower in COVID-19 intensive care unit patients compared to the patients from the general intensive care unit (p < 0.05). The mortality rate in the COVID-19 ICU (44.4%) was higher compared to that in the general ICU (27.3%) (p < 0.05). No significant statistical difference was observed between the two groups in terms of gender and recorded comorbidities of diabetes mellitus, cerebral vascular accident, kidney disease, and cancer. Conclusions: Low serum thyroid hormone levels-T3, T4, and TSH-in COVID-19 ICU patients are associated with higher mortality and could possibly be used as a prognostic factor for mortality among COVID-19 ICU patients. Thyroid hormone levels should be a part in the routine evaluation of COVID-19 ICU patients.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study.

Background and Aims: This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects. Methods: Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free thyroxine (fT4)/free triiodothyronine (fT3) ratio. These indices were then categorized into quartiles for analysis. The outcomes were the change rates in VFA, SFA, and BMI among the participants. Result: The present study included 921 patients, with a median follow-up of 2.2 years. In multivariate linear regression, when compared to the first quartile, SFA demonstrated a notable decline in the fourth quartile of TFQI, TSHI, and TT4RI (ß coefficient = -5.78, -7.83, and - 6.84 cm2 per year), while it significantly increased in the fourth quartile of fT4/fT3 ratio (ß coefficient = 6.13 cm2 per year). Similarly, in the fourth quartile of TFQI, TSHI, and TT4RI, VFA decreased significantly, evidenced by ß coefficients of -5.14, -4.80, and -4.08 cm2 per year. Yet, among the quartiles of the fT4/fT3 ratio, no discernible trend in VFA was observed. There was no significant association between indices of thyroid hormone sensitivity and change in BMI. Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy.

Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.

Elevated thyroid stimulating hormone and metabolic syndrome risk in patients with first-episode and drug-naïve major depressive disorder: a large-scale cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is common in major depressive disorder (MDD), but its relationship with thyroid hormones remains unclear. We aimed to examine the association of thyroid hormones and MetS in first-episode drug-naïve (FEDN) MDD patients. METHODS: We recruited 1718 unmedicated MDD patients in this cross-sectional study. MetS was defined based on the 2004 Chinese Diabetes Society Criteria. Serum thyroid hormones including free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin (TGAb) were examined. We used the logistic regression model to determine risk factors for MetS and examined the performance of the regression model by using the Area Under the Curve (AUC). In addition, we performed the trend test to test whether the results were robust. RESULTS: The prevalence of MetS in unmedicated MDD patients was 34.4%. MDD patients with MetS had higher levels of serum TSH, TGAb, and TPOAb (all P < 0.001). Concurrently, serum TSH levels were independent risk factors for MetS in MDD patients (OR:1.49, 95%CI: 1.40-1.58), which could also distinguish MDD patients with and without MetS (AUC was 0.77). Additionally, in the trend test, the results also indicated a similar trend when TSH was used as a categorical variable (P for trend < 0.001). CONCLUSIONS: This study suggests that TSH levels were independent risk factors for MetS in FEDN MDD patients (OR:1.49). The examination of thyroid function may contribute to the early detection of MetS.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.