Evaluation of systemic inflammation markers in patients with Hashimoto's thyroiditis.

OBJECTIVE: To investigate markers of systemic inflammation and the effect of thyroid dysfunction on these parameters in patients with Hashimoto's thyroiditis (HT). METHODS: Patients with HT and volunteer healthy individuals admitted to the general surgery outpatient clinic between January 2020 and June 2023 were enrolled into the study. Patients with HT were divided into euthyroid, hypothyroid, and hyperthyroid subgroups. All participant data were retrospectively extracted from the hospital database. RESULTS: A total of 268 patients (euthyroid, n = 131; hypothyroid, n = 83; and hyperthyroid, n = 54) and 124 controls were included. The platelet-to-lymphocyte ratio was lower in the euthyroid group versus control group, and the neutrophil-to-lymphocyte ratio was lower in controls than the three patient subgroups. Euthyroid and hypothyroid patients with HT exhibited a higher systemic inflammation index than the control group. The pan-immune inflammation index was lower in controls than in euthyroid, hypothyroid, and hyperthyroid patients with HT. In patients with HT, inflammation markers did not significantly differ between subgroups. CONCLUSIONS: Markers of systemic inflammation provide meaningful and reliable information in patients with HT, but do not differentiate between euthyroid, hypothyroid, or hyperthyroid patients.

The determinants of leptin, angiopoietin like 8, and thyroid hormones levels in Saudi females with type 2 diabetes mellitus: A retrospective study.

This study aimed to assess the prevalence of thyroid dysfunction, as measured by hormone levels, in Saudi women with type 2 diabetes mellitus (T2DM). The study will also assess thyroid hormones and leptin, angiopoietin like 8 (ANGPTL8), obesity, and cardiovascular diseases (CVD) in T2D patients. A total of 250 women aged 40 to 60 years with T2DM were retrospectively studied between 2021 and 2022. This research examined medical records for T2DM patients. In this investigation, no T2DM patients had thyroid autoantibodies in their medical records. These patients were chosen for their FT4 and TSH values. All participants were Saudi females with T2DM, aged 54.5 years. Of the 250 participants, 32% had hypothyroidism, 14.8% had hyperthyroidism, and 40.8% (102) had no thyroid disease. Hypothyroidism (7.8 ±â€…0.67 mmol/L) exhibited greater fasting blood glucose (FBG) levels than hyperthyroidism (7.1 ±â€…0.64 mmol/L) (P < .05). Hypothyroid and hyperthyroid females had significant differences in high density lipoprotein-cholestrol (HDL-C), triglycerides, triglyceride glucose (TyG) index, body mass index (BMI), waist circumstance (WC), high-sensitivity C-reactive protein (hs-CRP), leptin, ANGPTL8, insulin resistance (IR), and insulin levels (P < .05). Pearson's correlation test showed that T2DM patients' HDL-C levels were favorably but negatively correlated with leptin and ANGPTL8 levels. In hypothyroidism, thyroid stimulation hormone (TSH) is favorably linked with glycated hemoglobin (HbA1c), triglyscride (TG), TyG index, BMI, WC, leptin, ANGPTL8, hs-CRP, and IR. T2DM is linked to thyroid malfunction, notably hypothyroidism, which correlates positively with TSH. TSH variations due to increasing leptin, ANGPTL8, and TyG index may enhance the risk of insulin resistance diseases, such as obesity and CVD, in Saudi females with T2DM.

Zinc and Ferritin Levels and Their Associations with Functional Disorders and/or Thyroid Autoimmunity: A Population-Based Case-Control Study.

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case-control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756-9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628-8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1-specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1-14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity.

Meta-Analytical and Meta-Regression Evaluation of Subclinical Hyperthyroidism's Effect on Male Reproductive Health: Hormonal and Seminal Perspectives.

Subclinical hyperthyroidism (SCH) is a subtle thyroid dysfunction marked by decreased serum thyroid-stimulating hormone (TSH) levels while maintaining a normal thyroid hormone profile. Despite its mild nature, SCH can significantly impact various physiological functions, including male reproductive health. However, the effects of SCH on reproductive hormones and semen quality are less understood compared to overt thyroid disorders. This study employed extensive search methods across various databases from January 2000 to February 2024 to explore the relationship between SCH and Hormonal and Seminal Perspectives. Effect sizes, estimated using the standardized mean difference (SMD) and pooled with a Random-effect model, provided significant insights from 748 participants. Included studies adhered to the following criteria: Patients (male individuals with SCH), Intervention (assessment of reproductive hormones and semen quality), Comparison (SCH patients versus healthy controls), and Outcome (changes in reproductive factors). Significant alterations in reproductive hormones were observed in SCH patients, including reduced LH levels (SMD = - 0.20; p = 0.007), elevated FSH levels (SMD = 0.25; p = 0.002), and stable testosterone levels (SMD = - 0.05; p = 0.50). Regarding thyroid profile, SCH was associated with increased FT3 (SMD = 0.15; p < 0.001) and FT4 (SMD = 0.08; p = 0.002) levels, along with decreased TSH levels (SMD = - 2.00; p < 0.001). Adverse effects on semen quality were also observed. These findings underscore the need to incorporate thyroid health assessments in the evaluation of male infertility, recognizing the impact of minor thyroid hormone deviations on reproductive outcomes.

Causal validation of the relationship between 35 blood and urine biomarkers and hyperthyroidism: a bidirectional Mendelian randomization study and meta-analysis.

Background: Hyperthyroidism is an endocrine disorder with a relatively low global prevalence but significantly higher incidence among females compared to males. The onset age primarily ranges from 30 to 50, although it is not limited to this age group. Challenges in the treatment of hyperthyroidism include individualized treatment plan formulation, management of side effects, and prediction of disease progression, necessitating comprehensive consideration to achieve more effective therapy and management. Mendelian randomization studies can reveal more precise therapeutic targets between blood and urine biomarkers and hyperthyroidism, providing more decadent treatment options for the condition. Methods: The study will build upon the omics Mendelian randomization (MR) framework by conducting MR analysis using 35 blood and urine biomarkers separately for two distinct databases of hyperthyroidism. Subsequently, the results will undergo meta-analysis and multiple corrections to ensure accuracy and reliability. Finally, positive findings will undergo reverse MR validation to verify causal relationships with hyperthyroidism. Results: In the British database, the MR analysis of Total bilirubin levels about hyperthyroidism yielded an odds ratio (OR) of 1.097 (95% CI: 0.951-1.265, P = 0.205). Conversely, in the Thyroid Omics Association database, the MR analysis revealed an OR of 1.283 (95% CI: 1.122-1.467, P = 0.0002) for the same relationship. Meta-analysis of the MR analysis results from both databases, following multiple corrections, resulted in an OR of 1.192 (95% CI: 1.081-1.314, P = 0.015). Additionally, the direction of beta values in the MR analysis results from both databases was consistent. Conclusion: The urine biomarker total bilirubin levels may contribute to an increased risk of hyperthyroidism and accelerate its progression, thus representing a risk factor for the condition.

Preoperative Thyroid-Stimulating Hormone Levels and Three-Year Mortality in Elderly Hip Fracture Patients: Insights from a Prospective Cohort Study.

BACKGROUND It is unclear whether preoperative thyroid-stimulating hormone (TSH) level is correlated with long-term mortality in the elderly after hip fracture surgery. We aimed to assess the association between TSH levels and 3-year mortality in these patients. MATERIAL AND METHODS We enrolled patients aged 65 and above who had hip fracture surgery and thyroid function tests upon admission from 2018 to 2019. Patients were categorized based on TSH median value, quartiles, or thyroid function status. The median follow-up time was 3.1 years. Cox proportional hazards models were used to examine the correlation between TSH levels and mortality, adjusting for covariates. RESULTS Out of 799 eligible patients, 92.7% (741/799) completed the follow-up, with 20.6% (153/741) of those having died by the end of the follow-up. No statistically significant differences in mortality risks were found when stratified by TSH median value (HR 0.88, 95% CI 0.64-1.22, P=0.448) or quartiles (HR ranging from 0.90 to 1.13, P>0.05). Similarly, when categorized based on admission thyroid function status, patients who presented with hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism upon admission did not demonstrate a statistically significant difference in mortality risk compared to those who were considered euthyroid (HR 1.34, 95% CI 0.72-2.49, P=0.359; HR 0.77, 95% CI 0.38-1.60, P=0.489; HR 1.15, 95% CI 0.16-8.30, P=0.890; HR 1.07, 95% CI 0.34-3.38, P=0.913, respectively). CONCLUSIONS Admission TSH is not significantly associated with 3-year mortality in geriatric patients after hip fracture surgery.

Posthemithyroidectomy hypothyroidism. Prevalence and predictive markers. Comparison between patients with euthyroid and hyperthyroid nodular goitre.

BACKGROUND AND OBJECTIVE: Posthemithyroidectomy hypothyroidism (PHH) is a relatively common complication (22%-30%) for which we have no published information from our country. The objective of the study is to determine the prevalence of PHH and evaluate its predictive markers by comparing patients who had euthyroidism with those who had hyperthyroidism before hemithyroidectomy. PATIENTS AND METHOD: Retrospective observational cross-sectional study on 106 patients, 88 euthyroid before hemithyroidectomy and 18 hyperthyroid. RESULTS: Prevalence of PHH in euthyroid patients 42% (89.2% subclinical hypothyroidism; 10.8% manifest hypothyroidism) and in hyperthyroid patients 50% (77.8% subclinical hypothyroidism; 22.2% manifest hypothyroidism). Predictive markers in euthyroid patients: preoperative thyrotropin ≥ 2.2 mIU/L (OR: 4.278, 95% CI: 1.689-10.833; sensitivity: 54.1%, 95% CI: 38%-70.1%; specificity: 78.4%, 95% CI: 67.1%-89.7%), age ≥50 years (OR: 3.509, 95% CI: 1.438-8.563; sensitivity: 64.9%, 95% CI: 49.5%-80.3%; specificity: 64.7%, 95% CI: 51.6%-77.8%) and percentage of remainder lobe ≤ 19.6% (OR: 1.024, 95%: 1.002-1.046; sensitivity: 70.2%, 95% CI: 55.5%-84.9%; specificity: 48.6%, 95% CI: 34.9%-62.3%). Predictive marker in hyperthyroid patients: weight >70 kg (OR: 28, 95% CI: 2.067-379.247; sensitivity: 88.9%, 95% CI: 68.4%-100%; specificity: 88.9%, 95% CI: 68.4%-100%). CONCLUSIONS: This is the first study in our country that demonstrates a prevalence of PHH above the average in euthyroid patients, which is slightly higher and more intense in hyperthyroid patients, and that recognizes the classic predictive markers in euthyroid patients but highlights a novel predictive marker marker in hyperthyroid patients, useful to assess a different risk of PHH when indicating hemithyroidectomy and to establish closer control of postoperative hormonal evolution.

Overall, sex-and race/ethnicity-specific prevalence of thyroid dysfunction in US adolescents aged 12-18 years.

Background: Thyroid dysfunction significantly affects the health and development of adolescents. However, comprehensive studies on its prevalence and characteristics in US adolescents are lacking. Methods: We investigated the prevalence of thyroid dysfunction in US adolescents aged 12-18 years using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and 2007-2012 cycles. Thyroid dysfunction was assessed using serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) measurements. We analyzed the prevalence across demographic subgroups and identified associated risk factors. Results: The study included 2,182 participants, representing an estimated 12.97 million adolescents. The group had a weighted mean age of 15.1 ± 0.06 years, with males constituting 51.4%. Subclinical hyperthyroidism emerged as the most prevalent thyroid dysfunction, affecting 4.4% of the population. From 2001-2002 to 2011-2012, subclinical hyperthyroidism remained consistent at 4.99% vs. 5.13% in the overall cohort. Subclinical and overt hypothyroidism was found in 0.41 and 1.03% of adolescents respectively, and overt hyperthyroidism was rare (0.04%). The prevalence of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) positivity in the overall population were 5.8 and 9.8%, respectively. Positivity for TgAb was risk factors for hypothyroidism, while older age, female and Black Americans were risk factors for hyperthyroidism. Female adolescents and adolescents with an older age were more likely to be positive for TPOAb and TgAb, while Black and Mexican Americans had a lower risk of TPOAb and TgAb positivity. Conclusion: Subclinical hyperthyroidism was the most common form of thyroid dysfunction, and its prevalence remained stable from 2001-2002 to 2011-2012. Notable disparities in the prevalence of hyperthyroidism and antibody positivity were observed among different age, sex and racial/ethnic groups.

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.

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.

Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

A systematic review of subclinical hyperthyroidism guidelines: a remarkable range of recommendations.

Background: Subclinical thyroid diseases are often the subject of debate concerning their clinical significance, the appropriateness of diagnostic testing, and possible treatment. This systematic review addresses the variation in international guidelines for subclinical hyperthyroidism, focusing on diagnostic workup, treatment, and follow-up recommendations. Methods: Following the PRISMA guidelines, we searched PubMed, Embase, and guideline-specific databases and included clinical practice guidelines with recommendations on subclinical hyperthyroidism. Guideline recommendations were extracted, and quality assessment was performed using selected questions of the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Results: Of the 2624 records screened, 22 guidelines were included, which were published between 2007 and 2021. Guideline quality was generally intermediate to low. Diagnostic approaches differed substantially, particularly in the extent of recommended testing. Treatment initiation depended on TSH levels, age, and comorbidities, but the level of detail regarding defining precise comorbidities varied. Recommendations for monitoring intervals for follow-up ranged from 3 to 12 months. Conclusion: This review underscores the existing variability in (inter)national guidelines concerning subclinical hyperthyroidism. There isa need for clear recommendations in guidelines considering diagnostic workup, treatment, and follow-up of subclinical hyperthyroidism. In order to establish this, future research should focus on determining clear and evidence-based intervention thresholds.

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.

Minor hyperthyroidism with normal levels of thyroid-stimulating hormone receptor antibodies: a case report.

The present report describes for the first time a case of diffuse hyperthyroidism in a 30-year-old female patient who had normal levels of thyroid-stimulating hormone receptor antibodies (TSHR-Ab), slightly elevated plasma levels of thyroid hormones, and slightly increased thyroid blood flow. Seven years before, after severe stress, she had Graves' disease with elevated plasma levels of TSHR-Ab. The patient's recent medical history included mental stress and autonomic dysfunction. This report describes a mild form of hyperthyroidism in terms of elevated plasma levels of thyroid hormones and Doppler ultrasonography data; this condition was first defined as 'minor hyperthyroidism'. The examination data suggest a probable secondary role of the immune system and primary role of the autonomic nervous system in the pathogenesis of Graves' disease.

Thyroid dysfunction in nonvalvular atrial fibrillation and clinical outcomes.

BACKGROUND: Thyroid dysfunction's effects on those who have been diagnosed with atrial fibrillation have not been well investigated. We looked at how thyroid function among patients with pre-existing atrial fibrillation related to thromboembolic risk and clinical outcomes. METHODS: We gathered the medical information of patients diagnosed with nonvalvular atrial fibrillation (NVAF) between 2016 and 2020 at Dongguan People's Hospital. We then assessed the correlation between thyroid dysfunction and thrombotic risk (CHA2DS2-VASc) as well as the occurrence of clinical composite endpoint (all-cause death, heart failure, systemic embolism and hemorrhage events). RESULTS: Of 1329 patients were admitted, 82.6% were euthyroid, 7.4% had subclinical hyperthyroidism, 4.2% had subclinical hypothyroidism, and 6.7% had low triiodothyronine (T3) syndrome. Lower levels of total triiodothyronine (TT3) were linked to an increased risk of thromboembolism (P < 0.005). During a median follow-up period of 1.84 years, there were 608 clinical composite endpoint occurrences. In the adjusted model, Low T3 syndrome was linked to a higher risk of the clinical composite endpoint (HR, 1.68; 95% CI, 1.20-2.37; P < 0.05) in comparison to euthyroidism. Specifically, low T3 syndrome was linked to a higher risk of heart failure (HR, 1.52; 95%CI, 1.01-2.30; P < 0.05) and all-cause death (HR, 3.34; 95% CI, 1.76-6.36; P < 0.001). CONCLUSION: Low T3 syndrome are linked to an increased risk of heart failure and all-cause death in individuals with NVAF. And Patients with NVAF and low TT3 levels have a higher risk of thromboembolism.

Association between serum TSH concentration and bone mineral density: an umbrella review.

INTRODUCTION: The aim of this study was to summarize the results of previous studies, standardize the data, and present new statistical results in order to provide physicians with clinically significant outcomes regarding the association between serum TSH concentration and bone mineral density (BMD). METHODS: To perform this umbrella review, a systematic search was conducted in which major online medical databases, such as PubMed, Web of Science, Embase, Scopus, Cochrane Library, and Google Scholar, were searched for meta-analyses and systematic reviews regarding the effect of TSH on BMD. Furthermore, all primary studies were screened for statistical analysis. RESULTS: The statistical outcomes of the present study were based on the data of 75,898 patients. The pooled risk ratio of any kind of fracture in patients with subclinical hyperthyroidism was estimated to be 1.36 (95% CI: 1.18-1.56; p < 0.001). The SMD for BMD in the distal radius in male patients receiving L-thyroxine suppression therapy was estimated to be -0.61 (95% CI: -1.10-(-0.11); p = 0.02). Furthermore, the pooled risk ratio of any fracture in patients receiving L-thyroxine suppression therapy was estimated to be 1.98 (95% CI: 0.98 - 3.98; p = 0.06). In these patients, the BMD may significantly differ from that in non-treated patients. However, the difference depends on the type of bone. CONCLUSIONS: Our data confirmed that subclinical hyperthyroidism has a detrimental effect on bones, causing decreased BMD. Based on the obtained results, the authors suggest that a reduced TSH serum level itself may be an individual factor associated with decreased BMD and, thus, with a greater risk of bone fracture. Nevertheless, it should be noted that the effects of TSH suppression therapy differ between areas of interest for assessing BMD. Furthermore, the results have shown that this issue may, in specific areas, concern not only postmenopausal women but also male patients. These conclusions should contribute to a careful consideration of the application of TSH suppressive therapy in all patients. Particular attention should be given to patients after DTC, while all the advantages and disadvantages of implementing L-thyroxine therapy should be individually considered.

Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a multivariable mendelian randomization and mediation analysis.

Background: Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC. Methods: Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis. Results: The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC). Conclusion: The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.

Assessment of hemostasis in hyperthyroid and euthyroid cats using two viscoelastic assays and platelet aggregometry.

BACKGROUND: Hyperthyroidism in humans is associated with a hypercoagulable state and an increased risk of thromboembolism. OBJECTIVE: To evaluate hemostatic variables in hyperthyroid and euthyroid cats with the hypothesis that hyperthyroid cats will have evidence of altered hemostasis consistent with a potential hypercoagulable state. ANIMALS: Client-owned hyperthyroid (n = 16) and euthyroid (n = 15) cats over 8 years of age. METHODS: Prospective observational study. Hyperthyroid and euthyroid cats were enrolled. Rotational thromboelastometry (ROTEM), whole-blood platelet impedance aggregometry (WBPIA) and a point-of-care viscoelastic coagulation monitor (VCM-Vet) were performed immediately after minimally traumatic venipuncture under sedation. RESULTS: Hyperthyroid cats had significantly higher values for variables as assessed by VCM-Vet: A10 (34 [17-47] vs 25 [17-38], P = .003); A20 (39.5 [23-55] vs 31 [21-45], P = .003); and MCF (41 [24-58] vs 35 [22-49], P = .03). Hyperthyroid cats had significantly different values versus the euthyroid cohort as assessed by different ROTEM channels: increased A10, INTEM (61.5 [39-75] vs 54 [23-66], P = .007) and FIBTEM (18 [10-35] vs 13 [2-27], P = .01); increased A20, INTEM (68 [45-78] vs 61 [30-70], P = .006) and FIBTEM (17 [10-34] vs 11 [2-25], P = .002); increased MCF, EXTEM (72 [65-81] vs 69 [34-78], P = .04), INTEM (70 [45-85] vs 62 [35-71], P = .01) and FIBTEM (18 [13-37] vs 14 [3-27], P = .02); increased alpha angle, EXTEM (80 [68-85] vs 76 [41-84], P = .01); shortened CT, EXTEM (52.5 [29-73] vs 60 [52-92], P = .003) and FIBTEM (52.5 [16-75] vs 65 [53-165], P = .001); and decreased ML, FIBTEM (20 [1-36] vs 33 [19-59], P <.001). No significant differences were found with WBPIA. CONCLUSIONS AND CLINICAL IMPORTANCE: The hyperthyroid cats in this study had evidence of altered hemostasis as assessed by 2 viscoelastic methodologies, and characterized by increased clot amplitude, firmness, and faster coagulation times vs euthyroid controls.

The impact of thyroid function on total spine bone mineral density in postmenopausal women.

PURPOSE: Osteoporosis has been a widespread concern for older women, especially postmenopausal women. Thyroid function is crucial for bone metabolism. However, the relationship between thyroid function variation within thyroxine reference range and bone mineral density (BMD) remains ambiguous. The objective of this study was to evaluate the effect of subclinical hypothyroidism or hyperthyroidism on total spinal BMD in postmenopausal women. METHODS: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010, multivariable weighted logistic regression was used to evaluate the relationships between total spine BMD and TSH among postmenopausal women aged ≥50. RESULTS: After accounting for a number of variables, this study discovered that the middle TSH tertile was associated with a decreased probability of osteoporosis. Additionally, the subgroup analysis revealed that postmenopausal women over the age of 65 or people with an overweight BMI had a clearer relationship between total spine BMD and TSH. CONCLUSION: The total spinal BMD had a positive relationship with thyroid stimulating hormone in postmenopausal women, and that appropriate TSH level (1.38-2.32 mIU/L) was accompanied by higher total spinal BMD.

Evaluation of a novel, sensitive thyroid-stimulating hormone assay as a diagnostic test for thyroid disease in cats.

OBJECTIVE: Clinicians commonly use thyroid-stimulating hormone (TSH) concentrations to diagnose thyroid disorders in humans and dogs. In cats, canine TSH chemiluminescent immunoassays (CLIA) assays are commonly used to measure TSH, but these TSH-CLIAs cannot measure low TSH concentrations (< 0.03 ng/mL) and therefore cannot distinguish between low-normal concentrations and truly low TSH concentrations (characteristic of hyperthyroidism). Our aim was to evaluate a novel TSH assay based on bulk acoustic wave (BAW) technology that has lower functional sensitivity (0.008 ng/mL) than TSH-CLIAs. ANIMALS: 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. METHODS: Serum concentrations of T4, TSH-CLIA, and TSH-BAW were measured in all cats. Untreated hyperthyroid cats were divided into 4 severity groups (subclinical, mild, moderate, and severe), whereas 131I-treated cats were divided into euthyroid and hypothyroid groups. RESULTS: Test sensitivity, specificity, and positive predictive value for identifying hyperthyroidism were higher for TSH-BAW (90.5%, 98.9%, and 86.9%) than TSH-CLIA (79.9%, 76.7%, and 21.7%; P < .001). Test sensitivity for identifying 131I-induced hypothyroidism was only 45.5% for T4 versus 100.0% for both TSH-CLIA and TSH-BAW (P = .03), whereas TSH-BAW had a higher positive predictive value (100%) than did either TSH-CLIA (81.2%) or T4 (71.9%). CLINICAL RELEVANCE: Serum TSH-BAW alone or together with T4 is a highly sensitive and specific diagnostic test for evaluating feline hyperthyroidism and iatrogenic hypothyroidism. Finding low serum TSH-BAW concentrations is most useful for diagnosing subclinical and mild hyperthyroidism, in which serum T4 remains within or only slightly above the reference interval.