Long-term prognostic value of thyroid hormones in left ventricular noncompaction.

PURPOSE: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC). METHODS: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated. RESULTS: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance. CONCLUSION: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.

Comparison of pathophysiology in subclinical hyperthyroidism with different etiologies.

Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.

Elevation of free triiodothyronine (fT3) levels by Plasmodium falciparum independent of thyroid stimulating hormone (TSH) in children with uncomplicated malaria.

BACKGROUND: Malaria parasites have a devastating effect on the infected host. However, there is a paucity of data on the effect of Plasmodium falciparum on thyroid hormones. METHODS: This case-control study (1:1) involved children <16 years of age with uncomplicated malaria. Hematological parameters were determined using the URIT-5380 hematology analyzer (China). Later, levels of thyroid hormones, namely free triiodothyronine (fT3), free tetraiodothyronine (fT4), and thyroid-stimulating hormone (TSH), were determined using human ELISA kits (DiaSino ELISA kit, Zhengzhou, China). RESULTS: Ninety children with malaria and ninety matched control group were studied. Overall, compared to the control group, lower TSH (3.43 ± 1.25 vs. 3.84 ± 1.34, p = 0.035) and elevated levels of fT3 levels (5.85 ± 1.79 vs. 3.89 ± 1.19, p < 0.001) were observed in patients with malaria. However, fT4 levels were comparable between cases and control group (16.37 ± 2.81 vs 17.06 ± 3.5, p = 0.150). Free T3 levels were significantly higher in children <10 years (p < 0.001) and higher among male children with malaria (p < 0.001). Overall, there was a significant positive relationship between parasite counts and fT3 (R = 0.95, p < 0.001). Furthermore, body temperature was positively correlated with fT3 (R = 0.97, p < 0.001). CONCLUSIONS: Isolated fT3 thyrotoxicosis was observed in falciparum malaria, especially in children <10 years and male malaria patients, independent of TSH. This observation could explain the severity of malaria in children.

Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort.

BACKGROUND: Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of free T4 (FT4) into free T3 (FT3) is thought to occur in these patients, decreasing the availability of FT3 and contributing to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (THs) are associated with clinical status and outcomes. OBJECTIVES: The objective of this study was to evaluate the association of FT3/FT4 ratio and TH with clinical, analytical, and echocardiographic parameters, as well as their prognostic impact in individuals with stable HFpEF. METHODS: We evaluated 74 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modeling to study the associations of TH and FT3/FT4 ratio with clinical, anthropometric, analytical, and echocardiographic parameters, and survival analysis to evaluate associations with the composite of diuretic intensification, urgent HF visit, HF hospitalization, or cardiovascular death over a median follow-up of 2.8 years. RESULTS: The mean age was 73.7 years and 62% were men. The mean FT3/FT4 ratio was 2.63 (standard deviation: 0.43). Subjects with lower FT3/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3/FT4 ratio was associated with higher body fat (ß = -5.60 kg per FT3/FT4 unit, p = 0.034), higher pulmonary arterial systolic pressure (PASP) (ß = -10.26 mm Hg per FT3/FT4 unit, p = 0.002), and lower left ventricular ejection fraction (LVEF) (ß = 3.60% per FT3/FT4 unit, p = 0.008). Lower FT3/FT4 ratio was associated with higher risk for the composite HF outcome (HR = 2.50, 95% CI: 1.04-5.88, per 1-unit decrease in FT3/FT4, p = 0.041). CONCLUSIONS: In patients with HFpEF, lower FT3/FT4 ratio was associated with higher body fat, higher PASP, and lower LVEF. Lower FT3/FT4 predicted a higher risk of diuretic intensification, urgent HF visits, HF hospitalization, or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion might be a mechanism associated with HFpEF progression.

Free triiodothyronine predicts the risk of developing diabetic kidney disease.

BACKGROUND: Low levels of Free Triiodothyronine (FT3) are associated with poor survival in chronic kidney disease, and the aim of this study was to further assess the relationship between changes in FT3 levels and renal damage in patients with type 2 diabetes based on glomerular and tubular markers. METHODS: We retrospectively studied 452 type 2 diabetic patients, measured glomerular damage markers (UACR, eGFR) and tubular damage markers (NAG/Cr,ß2-MG), analyzed the relationship between FT3 and renal damage by logistic regression models, and plotted restrictive cubic splines. RESULTS: 41.6% of subjects had diabetic kidney disease (DKD), and the prevalence of DKD decreased progressively with increasing FT3 levels in the third quartile. Spearman correlation analysis showed that FT3 was negatively associated with UACR, NAG/Cr and ß2-MG, while eGFR was positively associated with FT3. Multifactorial analysis, after adjusting for relevant confounders, revealed that compared with the lowest quartile of FT3, the highest quartile reduced the risk of developing urinary albumin (OR = 0.499,95% CI:0.289-0.856), moderate to severe impairment of glomerular filtration rate (OR = 0.106,95% CI:0.032-0.354), renal tubular marker ß2 -MG positive (OR = 0.516,95% CI:0.299 to 0.883) and the risk of DKD occurrence (OR = 0.450,95% CI:0.260 to 0.774). In the sample model, FT3 levels below 4.39 pmol/L were associated with an increased risk of glomerular tubule injury and DKD occurrence. CONCLUSIONS: FT3 is closely associated with glomerular tubular injury and is a protective factor. As FT3 levels (< 4.39 pmol/L) decrease, the risk of developing DKD becomes higher, and FT3 can be used as an independent predictor of developing DKD.

Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum.

As previously demonstrated, serum beta-human chorionic gonadotropin (ß-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum ß-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum ß-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum ß-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between ß-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and ß-hCG levels for HG. Versus those in the control group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum ß-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that ß-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum ß-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, ß-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.

A Systematic Review and Meta-Analysis of Free Triiodothyronine (FT3) Levels in Humans Depending on Seasonal Air Temperature Changes: Is the Variation in FT3 Levels Related to Nonshivering Thermogenesis?

Thyroid hormones play a crucial role in regulating normal development, growth, and metabolic function. However, the controversy surrounding seasonal changes in free triiodothyronine (FT3) levels remains unresolved. Therefore, the aim of this study was to conduct a systematic review and meta-analysis of variations in FT3 levels in relation to seasonal air temperatures in the context of current knowledge about its role in nonshivering thermogenesis. Ten eligible articles with a total of 336,755 participants were included in the meta-analysis. The studies were categorized into two groups based on the air temperature: "Cold winter", where the winter temperature fell below 0 °C, and "Warm winter", where the winter temperature was above 0 °C. The analysis revealed that in cold regions, FT3 levels decreased in winter compared to summer (I2 = 57%, p < 0.001), whereas in warm regions, FT3 levels increased during winter (I2 = 28%, p < 0.001). These findings suggest that seasonal variations in FT3 levels are likely to be influenced by the winter temperature. Considering the important role of the FT3 in the nonshivering thermogenesis process, we assume that this observed pattern is probably related to the differences in use of thyroid hormones in the brown adipose tissue during adaptive thermogenesis, which may depend on intensity of cold exposure.

Predictive Value of Free Triiodothyronine in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background: Homeostasis of thyroid hormones has significant effects on the cardiovascular system. The aim of this study was to investigate the association between free triiodothyronine (FT3) and adverse cardiovascular events in patients with acute coronary syndrome (ACS) who were undergoing percutaneous coronary intervention (PCI). Methods: A total of 1701 patients with ACS undergoing PCI were included in this study. All patients were divided into three groups according to the tertiles of FT3 level: the lowest tertile (FT3 < 4.51 pmol/L), the middle tertile (4.51 pmol/L ≤ FT3 < 4.89 pmol/L) and the highest tertile group (FT3 ≥ 4.89 pmol/L). The primary study endpoint was a composite of major adverse cardiovascular events (MACE), which included all-cause death, ischemic stroke, myocardial infarction, or unplanned repeat revascularization. Results: During a median follow-up period of 927 days, 349 patients had at least one event. Compared with patients with the highest tertile, those with the lowest tertile had a significantly higher incidence of MACE, all-cause death, MI, ischemic stroke and repeat revascularization (all p values < 0.05). In the multivariate Cox regression analysis, the middle tertile had similar risk of MACE (HR = 0.986, 95% CI 0.728-1.336, p = 0.929) as the highest tertile, but the patients with the lowest tertile had a 92.9% higher risk of MACE (HR = 1.929, 95% CI 1.467-2.535, p < 0.001). There was a non-linear relationship between FT3 and MACE and unplanned repeat revascularization (all p values for non-linear association < 0.001). Adding the tertiles of FT3 level into the baseline model yielded a significant improvement in discrimination for predicting MACE ( Δ AUC = 0.013, p = 0.025). Conclusions: A significantly reduced FT3 level was independently associated with a worse prognosis in patients with ACS undergoing PCI.

Serum thyroid-stimulating hormone is an independent risk factor of recurrent Guillain-Barré syndrome.

INTRODUCTION/AIMS: Guillain-Barré syndrome (GBS) is generally considered to be monophasic, but some patients have recurrences. The purpose of this study was to clarify the possible link between thyroid parameters and recurrent GBS (RGBS) patients in China. METHODS: In this retrospective study we enrolled patients who were admitted to the Department of Neurology of The First Affiliated Hospital of Zhengzhou University from 2014 to 2020 and fulfilled the diagnostic criteria of GBS or Miller Fisher syndrome. We evaluated clinical characteristics; cerebrospinal fluid parameters; and serum levels of thyroid-stimulating hormone (TSH), free thyroxine, and free triiodothyronine in 320 individuals, including 302 with monophasic GBS and 18 with recurrent GBS. RESULTS: Serum levels of TSH in monophasic GBS patients were significantly lower than those in RGBS patients (P < .001), whereas FT3 levels were higher in the monophasic GBS group (P = .022). Age at onset, incidence of antecedent illness, time from onset to nadir, proportion with acute inflammatory demyelinating polyradiculoneuropathy, and Hughes Functional Grading Scale score at nadir were statistically significant between monophasic GBS patients and RGBS patients (P < .05). The multivariate regression analysis revealed that antecedent illness, AIDP, and high TSH were independent risk factors for RGBS. Our receiver-operating characteristic curve analysis showed that the risk of recurrence in GBS patients increases when the TSH concentration is higher than 3.87 µIU/mL. DISCUSSION: Our results demonstrate an association between TSH and RGBS. Oxidative stress is one of the possible interpretations for this association.

The correlation between triiodothyronine and the severity of liver fibrosis.

BACKGROUND: The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis. METHODS: We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms. RESULTS: Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2+CD9+ macrophage, which had been identified an important player in the progression of liver fibrosis. CONCLUSION: The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.

The prediction effects of thyroid function in the severity of Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated inflammatory disorder affecting the peripheral nervous system (PNS), is usually complicated with autoimmune diseases including thyroid diseases. Herein, we explored roles of thyroid function and thyroid autoantibodies in the disease severity and its short-term prognosis of GBS. In addition, we further investigated the predictive value of thyroid function for GBS respiratory insufficiency. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 219 GBS patients. According to the thyroid function, the enrolled subjects were divided into 2 groups, that is, patients with abnormal thyroid function (case group) and those with normal thyroid function (control group). The clinical characteristics, disease severity, and short-term prognosis of the patients in 2 groups were compared. In addition, we also divided the 219 GBS patients into mechanical ventilation (MV) group and non-MV group according to whether MV was performed within 1 week after admission. The clinical characteristics, disease severity, short-term prognosis, Erasmus GBS respiratory insufficiency score (EGRIS), and the thyroid function were compared in the two groups. RESULTS: We found that GBS patients with abnormal thyroid function had longer duration of hospitalization, higher frequency of cranial nerve damage, and higher incidence of weakened tendon reflexes. Medical Research Council (MRC) scores on admission, at nadir, and at discharge were lower, and Hughes Functional Grading Scale (HFGS) scores on admission and at discharge were higher in GBS patients with abnormal thyroid function group. More patients in the abnormal thyroid function group had myelin, axonal, and myelin-axonal injuries. In the MV group, the time from onset to admission, MRC scores on admission, and the levels of free triiodothyronine (FT3) were lower; the levels of thyroglobulin antibody (TgAb) and EGRIS were significantly higher than those in the non-MV group. The combination of EGRIS and FT3 serum levels to predict GBS patients with MV, the area under the curve (AUC) was 0.905 (95% CI: 0.861 to 0.948, P < 0.05), sensitivity was 88.9%, and specificity was 84.7%. CONCLUSION: Our results suggest that the serum FT3 levels are negatively correlated with disease severity; the serum FT3 might be a biomarker for the incidence and severity of GBS. Both EGRIS and serum FT3 have a predictive value for the occurrence of acute respiratory insufficiency in GBS patients, and the combination of these two indicators can more accurately predict the risk of acute respiratory insufficiency in GBS patients.

Associations among FT4 level, FT3/FT4 ratio, and non-alcoholic fatty liver disease in Chinese patients with hypopituitarism.

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic metabolic disorder. Thyroid function is associated with NAFLD in different populations; however, little attention has been paid in patients with hypopituitarism. To analyze the association between thyroid function and NAFLD, we included 134 patients with hypopituitarism admitted to the Tianjin Medical University General Hospital between June 2013 and May 2019. Participants were divided into the NAFLD(-) and NAFLD(+) groups based on abdominal ultrasonography findings. We evaluated 68 male and 66 female patients with hypopituitarism. The prevalence of NAFLD was 52.24%. The NAFLD(+) group had a significantly higher free triiodothyronine/free thyroxine (FT3/FT4) ratio than the NAFLD(-) group (p = 0.003). The NAFLD(+) group showed significantly lower levels of FT4 and the growth hormone (GH) than the NAFLD(-) group (p = 0.003 and 0.016, respectively). We observed an association of the FT4 level and FT3/FT4 ratio with NAFLD in the univariate model, which was non-significant after adjustment for metabolic parameters (BMI, HDL-C, triglycerides, serum uric acid, blood pressure, fasting glucose). To better understand the role of each metabolic parameters, we performed additional models for each of those predictors individually after adjustment for age and gender, the association between FT4 level and FT3/FT4 ratio lost significance after adjustment for HDL-C and TG, but not for other predictors. Our findings suggest that thyroid dysfunction may be crucially involved in NAFLD by regulating whole-body metabolism, especially lipid utilization. Therefore, sufficient thyroid hormone replacement therapy for patients with hypopituitarism is recommended from the early stage.

Decreased circulating levels of free triiodothyronine in Sepsis children and correlation analysis.

BACKGROUND: Intensive physical stress in sepsis can induce the disorder of endocrine function and impact the clinical course and prognosis. Low T3 syndrome has been verified to be the predictive indicator of poor prognosis in several researches. Reports on the influence factors of thyroid hormonal levels in children with severe sepsis are rare. We aim to investigate the thyroid hormonal variations in the course of sepsis and analyze that how to be affected by clinical data and inflammatory biomarkers. METHODS: In the case-control study, 184 children with sepsis and 323 controls were included in Tongji Hospital, Wuhan, China, in 2019. Data on clinical and inflammatory parameters were collected from all participants. Circulating FT3(Free Triiodothyronine) levels were measured by Electrochemiluminescence immunoassay. Finally, we investigated the correlation between FT3 and related variables with linear regression analysis. RESULTS: Serum FT3 was lower in the sepsis group than in control group(2.59 + 1.17 vs 2.83 + 1.01 pg/mL, p < 0.05). Significant moderately negative correlations(|r| > 0.3) of FT3 levels with ferritin, PCT, duration of symptoms, SOFA score, and mortality were revealed. Moreover, we observed that FT3 had the positive correlation with albumin, as well as white blood cell count. CONCLUSIONS: Concentrations of serum FT3 are dramatically declined in sepsis children than in control children. Our results demonstrate that recognizing the potential abnormality of thyroid hormones in sepsis patients and examine timely through abnormal common clinical data and inflammatory biomarkers is a fine option.

Investigating Investigation (Ab)Use: Thyroid Function Test Audit in a Tertiary Care Teaching Institute in Eastern India.

An essential component of contemporary health care is laboratory testing. As the utilization of diagnostic tests grow, there is also an increase in the scrutiny of such tests for its effectiveness, balance of cost and over- utilization. Thyroid dysfunction is common across all age groups and is associated with a number of comorbid states. The thyroid function tests (TFTs) are very important for the diagnosis and monitoring of such patients. The guidelines recommend serum thyroid stimulating hormone (TSH) as the single most reliable test to diagnose all common forms of hypothyroidism and hyperthyroidism, except in few cases. This study was conducted to study the investigation requesting pattern of TFTs. Our results showed that TFT panel was ordered in almost equal numbers (35.58%) as single test of TSH (41.27%). Subclinical thyroid disease was diagnosed in 22.1% of cases and the rest were excluded as having any thyroid dysfunction. Over 2/3rd of all requests were for women. An important conclusion from our study was that, the essentiality of lab tests is a decision entirely in the hands of the treating physician keeping in mind the cost and best outcome for patients. Hospitals can develop strategic protocols for ordering laboratory tests keeping resources, need and patient satisfaction and outcomes optimal.

Independent associations of thyroid-related hormones with hepatic steatosis and insulin resistance in euthyroid overweight/obese Chinese adults.

PURPOSE: The aim of the study is to explore the independent association of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) with hepatic steatosis and insulin resistance. METHODS: A cross-sectional study of 88 overweight/obese adults who underwent anthropometric measurements [BMI, waist circumference (WC) and waist-to-height ratio (WHtR)], hepatic steatosis assessment (FibroScan) and thyroid-related hormones tests was conducted from 2018 to 2020 in Xiamen, China. RESULTS: Subjects with increasing tertiles of FT3 showed significantly higher levels of controlled attenuation parameter (CAP) ((295.4 ± 44.1, 290.1 ± 68.2 and 331.7 ± 43.6 (dB/m) for tertile 1-3, respectively, p = 0.007) and fatty liver index (FLI) score (47.7 (33.9-60.8), 61.5 (45.1-88.9) and 90.5 (84.5-94.8), respectively, p < 0.001). FT3 significantly and positively correlated with obesity index (BMI, WC, and WHtR), homeostatic model assessment of insulin resistance (HOMA-IR) and hepatic steatosis (CAP and FLI). Multivariable linear regression analyses with adjustment for potential confounding factors showed FT3 was independently associated with BMI (regression coefficient (ß (95%CI): 0.024 (0.004-0.043), p = 0.020), HOMA-IR (ß (95%CI): 0.091 (0.007-0.174), p = 0.034), CAP (ß (95%CI): 25.45 (2.59-48.31), p = 0.030) and FLI (ß (95%CI): 0.121 (0.049-0.194), p = 0.001). Neither FT4 nor TSH was significantly associated with any indicators of obesity, insulin resistance or hepatic steatosis. CONCLUSIONS: Increased FT3, but not FT4 or TSH, was independently associated with higher risks of hepatic steatosis and insulin resistance in euthyroid overweight/obese Chinese adults. Trial registration Registration is not applicable for our study.

Low free-T3 serum levels and prognosis of COVID-19: systematic review and meta-analysis.

OBJECTIVES: There is increasing interest regarding the relationship between serum levels of free triiodothyronine (fT3) and outcomes of COronaVIrus Disease-19 (COVID-19) patients. As several recent reports have described a worse prognosis in patients with low fT3 levels, we performed a meta-analysis to assess the prognostic role of fT3 serum levels in patients with COVID-19 as this information could be clinically relevant for the management of these patients. METHODS: The methodology was registered in the International prospective register of systematic reviews (PROSPERO) database under the protocol number CRD42021260952. A systematic search was carried out on PubMed, Embase, Web of Science, and Scopus from May to June 2021 without time and language restrictions. The literature search strategy was based on the following keywords: (T3 OR fT3 OR triiodothyronine) AND (COVID-19) AND (prognosis OR survival). RESULTS: The literature search identified 163 studies. Seven retrospective studies met the inclusion and exclusion criteria and were included in the meta-analysis. The included studies had a total of 1,183 patients. From the analysis of the included studies, lower fT3 serum levels were consistently observed in intensive care unit (ICU) than in non-ICU patients and in non-survivors than survivors, respectively. CONCLUSIONS: Serum fT3 concentrations are significantly lower in patients with severe COVID-19 than in non-severely ill patients and predict all-cause mortality of patients with severe COVID-19. Accordingly, fT3 may become a simple tool for stratified management of patients with severe COVID-19.

The ratio of HDL-C to apoA-I interacts with free triiodothyronine to modulate coronary artery disease risk.

OBJECTIVE: In the present work, research was carried out to explore the correlation between the high-density lipoprotein cholesterol (HDL-C)/apolipoprotein A-I (apoA-I) ratio and serum free triiodothyronine (FT3) and their interaction on the risk of coronary artery disease (CAD). METHODS: A total of 1686 patients who underwent selective coronary angiography were enrolled in the present study, including 1279 patients with CAD and 407 controls. The subjects were divided into three groups according to tertiles of the HDL-C/apoA-I ratio. Binary logistic regression analysis was used to evaluate the interaction of the HDL-C/apoA-I ratio and FT3 level with the risk of CAD. RESULTS: The group with the highest HDL-C/apoA-I ratio had the lowest levels of FT3. Multiple linear regression analysis showed that the HDL-C/apoA-I ratio was negatively associated with FT3 after adjusting for age, sex, body mass index (BMI), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), FT4 and TSH. A logistic regression model showed that a high HDL-C/apoA-I ratio (> 0.89 mmol/g) and high FT3 levels (> 4.5 pmol/l) were protective factors for CAD. Patients with a lower HDL-C/apoA-I ratio (≤ 0.89 mmol/g) and lower FT3 level (≤ 4.5 pmol/l) had an increased risk of CAD (OR = 2.441, P = 0.000, S = 1.13, AP = 0.068, AP* = 0.116, RERI = 0.168). CONCLUSIONS: The HDL-C/apoA-I ratio was negatively associated with FT3, and there was a significant interaction between the HDL-C/apoA-I ratio and FT3 with the risk of CAD.

Investigation of thyroid blood tests and thyroid ultrasound findings of patients with rosacea.

We aimed to investigate the relationship between rosacea and thyroid diseases by analyzing thyroid blood tests and ultrasound findings of our patients recently diagnosed with rosacea. This study was designed as a prospective, single-center study. Dermatological examination findings, lesion locations were recorded, and rosacea clinical scores were calculated for all study group patients. The control group consisted of completely healthy women presented to our hospital during the study period for check-up purposes. Serum-free thyroxine, free triiodothyronine, thyroid-stimulating hormone, antithyroglobulin antibody, antithyroid peroxidase antibody levels were measured, and thyroid ultrasound examinations were performed for all study participants. The entire study cohort consisted of 123 patients (63 cases and 60 controls). There was no significant difference between the groups in terms of mean patient age (P < .05). Cheek was the most common lesion location (96.8%). There was no difference between the groups in terms of thyroid-related laboratory parameters. However, anti-TPO levels differed significantly with increasing disease severity (ie, RCSs). There were significant relationships between cheek lesions and fT4 (P = .021), while nose and chin lesions were associated with fT3 (P = .01, P = .001). Thyroid ultrasound findings revealed that rosacea patients tended to have larger thyroid nodules and more heterogeneous thyroid parenchymas than controls. Our findings indicate that thyroid blood tests, including thyroid autoantibodies, should be tested and thyroid ultrasounds should be performed in patients diagnosed with rosacea. However, these findings need to be validated by prospective studies conducted in larger patient series with more extended follow-up periods.

Analysis of basal serum TSH, FT3, and FT4 levels based on age, sampling time in women with infertility.

BACKGROUND: To analyze the characteristics of basal thyroid hormone levels in infertile women consulting for assisted reproductive technology (ART) treatment. METHODS: This was a retrospective study. Serum TSH, FT3 and FT4 levels of women seeking ART consultation were tested routinely. Analyses were performed based on age and sampling time. One-way ANOVA or Kruskal-Wallis rank sum test was used to compare the continuous data among the groups, and the chi-square test or Fisher's exact test was used to compare categorical data where appropriate. RESULTS: A total of 6426 women were initially included in the study. After exclusion criteria were applied, the remaining 4126 women were categorized into different groups. The prevalence of subclinical hypothyroidism significantly decreased with age and sampling time, from 21.09 to 11.91% and from 28.57 to 10.67%, respectively (P < 0.001, respectively). Mean serum TSH, FT3, and FT4 levels decreased significantly with age (P = 0.017, < 0.001, < 0.001, respectively). In the context of sampling time, TSH levels from early in the morning were significantly higher (P < 0.001), while FT4 and FT3 levels were similar in different groups (P = 0.258, 0.300, respectively). CONCLUSIONS: The prevalence of subclinical hypothyroidism significantly decreased with increasing age and sampling time, as did the serum TSH levels. Even though, the establishment of reference interval of TSH level based on age or sampling time was not recommended. Full consideration of age and sampling time should be carefully taken before initiation of treatment.

Free triiodothyronine /free thyroxine ratio as an index of deiodinase type 1 and 2 activities negatively correlates with casual serum insulin levels in patients with type 2 diabetes mellitus.

Free triiodothyronine/free thyroxine (FT3/FT4) ratio is considered as an index of the activities of iodothyronine deiodinase types 1 and 2 (DIO1 and DIO2, respectively) and is reportedly associated with insulin resistance in euthyroid adults. Euthyroid women with polycystic ovary syndrome accompanied with insulin resistance have lesser deiodinase activities. Correspondingly, the serum insulin level in a fasted condition positively correlates with the FT3/FT4 ratio, and insulin depletion decreases the DIO2 activity in mice. Selected genetic variants in DIO1 are also associated with insulin resistance measures. Therefore, if insulin positively regulates DIO1 and DIO2, the FT3/FT4 ratio should decrease under impaired insulin action, and the casual insulin level and FT3/FT4 ratio should be negatively correlated. To evaluate this hypothesis, we conducted a single-center retrospective study between 2018 and 2021. All participants visited the selected hospitals monthly for type 2 diabetes mellitus treatment and casual plasma glucose and HbA1c level measurements. Furthermore, their casual serum insulin levels were measured annually. Meanwhile, we excluded patients treated with insulin injection. Ultimately, we evaluated 71 patients, which all exhibited euthyroid conditions. The FT3/FT4 ratio was independently associated with thyroid-stimulating hormone, casual plasma glucose, and casual insulin levels. In terms of the regression coefficients of the univariate linear regression analysis, the FT3/FT4 ratio negatively correlated with the casual serum insulin levels. Therefore, the risk of FT3/FT4 ratio underestimation should be considered when diagnosing Graves' disease, which is often accompanied with insulin resistance.