[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 prevalence, hospitalization outcomes and risk factors of euthyroid sick syndrome in patients with diabetic ketosis/ketoacidosis.

BACKGROUND: To investigate the prevalence of euthyroid sick syndrome (ESS) and to evaluate the outcomes and risk factors associated with ESS among hospitalized patients with diabetic ketosis (DK) or diabetic ketoacidosis (DKA). METHODS: Laboratory and clinical data of 396 adult hospitalized DK/DKA patients with or without ESS were collected and analyzed. Spearman linear analysis and multivariable logistic regression analyses were used to evaluate correlated factors of thyroid hormones and risk factors of ESS. RESULTS: Most of the individuals were diagnosed with type 2 diabetes (359/396, 90.7%). The prevalence of ESS was 57.8% (229/396). Patients in ESS group were older and had a longer course of diabetes. Levels of thyroid hormones, serum lipids, and parameters reflecting acidosis were significantly decreased in ESS group. The proportion of patients with infection, acute renal injury and DKA was significantly higher in ESS group than in control group, accompanied by longer hospitalization stay and higher hospitalization costs. Free triiodothyronine positively correlates with albumin, eGFR, parameters reflecting acidosis and lipid profiles (All P < 0.001), and negatively correlates with age, onset age, 24-h urine albumin, hsCRP and WBC count (All P < 0.001). Hypoalbuminemia, low level of carbon dioxide combining power, high level of HbA1c and WBC, and co-infection are shown to be risk factors for ESS (OR = 0.866, 0.933, 1.112, 1.146, 1.929, respectively; All P < 0.05). CONCLUSIONS: The prevalence of ESS was high in adult DK/DKA patients. Patients with ESS had inferior clinical and socioeconomic outcomes. Early recognition and management of patients with ESS may be necessary to improve outcome.

Thyroid hormones and platelet activation in COVID-19 patients.

PURPOSE: To retrospectively describe the association between thyroid hormones (TH) and platelet activation, as represented by mean platelet volume (MPV), in a cohort of patients hospitalized for COVID-19 with no known thyroid disease, and to correlate these data with the severity of COVID-19 and the occurrence of death/ARDS (Acute Respiratory Distress Syndrome). METHODS: 103 patients with real-time polymerase chain reaction (RT-PCR) testing-confirmed COVID-19 and hospitalized were enrolled. Serum samples were collected from patients upon admission before starting any treatment. Chi-squared test was used to determine the association between euthyroid sick syndrome (ESS) and COVID-19 severity. Multivariate logistic regression was performed to evaluate the best independent predictors of COVID-19 deaths/ARDS. RESULTS: 39/103 (37.9%) of patients were found to have ESS, and this condition was an independent predictor for the severity of COVID-19 (p = 0.003). Lower TSH and lower FT3/FT4 ratio correlated with higher MPV (p = 0,001 and p = 0.010), with an opposite trend with respect to what has been documented in non-COVID patients. Increasing MPV and lower FT3 significantly increased the risk, in COVID-19 patients, of an adverse outcome of death/ARDS. CONCLUSION: Increased platelet activation, as represented by increased MPV, has already been reported to correlate with COVID-19 severity, possibly as a consequence of cytokine release. We demonstrated, in a cohort of 103 patients with COVID-19, that MPV is inversely correlated to TH levels, in particular in the case of ESS, where downregulation of TH axis may occur in case of systemic cytokine inflammation and more severe outcomes (death/ARDS). That ESS itself may directly cause platelet activation, as demonstrated by higher MPV in these patients, is an interesting hypothesis which deserves further investigation.

Euthyroid Sick Syndrome as a Prognostic Indicator of COVID-19 Pulmonary Involvement, Associated With Poorer Disease Prognosis and Increased Mortality.

OBJECTIVE: The prevalence of euthyroid sick syndrome (ESS) and its association with the prognosis of COVID-19 and mortality in patients with lung involvement in COVID-19 have not yet been elucidated. METHODS: Clinical and laboratory data of patients with COVID-19 with or without ESS were collected retrospectively and analyzed on admission. All subjects were admitted to the Department of Internal Diseases and Clinical Pharmacology at Bieganski Hospital between December 2020 and April 2021. RESULTS: In total, 310 medical records of patients with COVID-19 were analyzed retrospectively. Among 215 enrolled patients, 82 cases of ESS were diagnosed. The patients with ESS had higher pro-inflammatory factor levels, longer hospitalizations, and a higher risk of requiring high-flow nasal oxygen therapy or intubation than the patients without ESS. The Kaplan-Meier curve indicated that the patients with ESS had a lower probability of survival when computed tomography showed ≤50% parenchymal involvement compared with that in patients without ESS. However, no differences in mortality were noted in those with more than 50% parenchymal involvement. The survival curve showed that ESS was associated with a higher risk of mortality during hospitalization. CONCLUSION: ESS is closely associated with a poor prognosis, including longer hospitalizations, more frequent intubation, transfer to the intensive care unit, and a higher mortality rate in patients with COVID-19. ESS is a potential prognostic predictor of survival, regardless of lung involvement in COVID-19.

Euthyroid sick syndrome as an early surrogate marker of poor outcome in mild SARS-CoV-2 disease.

BACKGROUND: The new coronavirus 19 disease (COVID-19) represents the current worldwide emergency. According to past evidence, a simple biomarker, such as low free triiodothyronine (fT3) levels, within the framework of euthyroid sick syndrome (ESS), might help to identify patients with unfavourable outcomes. OBJECTIVE: Evaluation of ESS significance in hospitalized mild COVID-19 patients. DESIGN: Prospective study, from 1 April 2020 to 31 May 2021. PARTICIPANTS: COVID-19 patients with mild disease at hospital admission. MAIN MEASURES: At hospital admission, eligible patients underwent a complete thyroid function evaluation. Subjects with previous thyroid disease or with thyroid-interfering medications were excluded. Levels of fT3 were correlated to biochemical markers and to patient outcome, the latter considered as favourable in the event of infection recovery and unfavourable in the event of death or transfer to an intensive care unit (ICU). KEY RESULTS: Of 600 screened patients, 506 were eligible for this study. Of those, 94 (19%) died during hospitalization and 80 (18%) required a transfer to ICU. The most frequent thyroid disorder was ESS (57%). Admission levels of fT3 were significantly lower within the unfavourable outcome subgroup (p < 0.001) and were negatively associated with several poor prognostic markers, including IL-6 (p < 0.001). In Kaplan-Meier and Cox regression analyses, fT3 was independently associated with poor outcome and death (p = 0.005 and p = 0.037, respectively). A critical fT3 threshold for levels < 2.7 pmol/l (sensitivity 69%, specificity 61%) was associated with a 3.5-fold increased risk of negative outcome (95%CI 2.34-5.34). CONCLUSION: Low fT3 levels, in the framework of ESS, resulted as being a valid predictor of unfavourable outcomes in a very early stage population of COVID-19.

Non-Thyroidal Illness Syndrome-Associated Multiorgan Dysfunction After Surgical Repair of Type A Aortic Dissection.

OBJECTIVE: The purpose of this cohort study was to investigate the relationship between non-thyroidal illness syndrome (NTIS) and severe multiorgan dysfunction, measured by Sequential Organ Failure Assessment score ≥11, after surgical repair of type A aortic dissection (TAAD). SETTING: An observational study. PARTICIPANTS: The present study included 310 patients with TAAD surgically repaired between January 2019 and December 2020 in Beijing Anzhen Hospital. INTERVENTIONS: Patients after surgical repair after TAAD. MEASUREMENTS AND MAIN RESULTS: Among a total of 310 patients with TAAD undergoing surgical repair included in this study, 132 (42.6%) experienced surgery-associated NTIS. Severe multiorgan dysfunction was experienced more often in patients with NTIS (27.3% v 11.2%, p < 0.0001). Multivariate analysis demonstrated NTIS was associated closely with an increased risk of severe multiorgan dysfunction (odds ratio [OR] = 2.54, 95% CI = 1.39-4.64 p = 0.002), which predicted an in-hospital death rate of 95%. Non-thyroidal illness syndrome also was related with in-hospital major adverse cardiovascular and cerebral events (OR = 2.12, 95% CI = 1.30-3.46 p = 0.003), acute kidney injury (OR = 3.17, 95% CI = 1.17-8.47 p = 0.023), and postoperative pulmonary complications (OR = 2.32, 95% CI = 1.34-4.03 p = 0.003). However, hepatic inadequacy was comparable in the NTIS and control groups. CONCLUSIONS: Non-thyroidal illness syndrome was associated closely with multiorgan dysfunction after surgical repair of TAAD, which may be correlated further with an increased incidence of in-hospital mortality and complications.

PECULIARITIES OF THYROID STATUS OF PRESCHOOL CHILDREN WITH ACUTE BRONCHITIS.

OBJECTIVE: The aim: The aim of this study was to determine the characteristics of thyroid status (thyroid hormone, total and free fractions of triiodothyronine and thyroxine, reversible triiodothyronine, antibodies to thyroperoxidase) of preschool children with acute bronchitis. PATIENTS AND METHODS: Materials and methods: We examined 135 preschool children (from 3 to 6 years old) with acute bronchitis (main group) and 28 apparently healthy subjects who were in the control group. It used clinical-anamnestic, laboratory and instrumental research methods. Evaluation of the course of acute bronchitis was carried out in the acute period of the disease. All results were statistically processed using the SPSS 26 package. RESULTS: Results: In 33 % of patients with acute bronchitis there are subclinical abnormalities of thyroid hormones, which manifest themselves in the form of euthyroid sick syndrome. Namely, we found an increased concentration of reversible triiodothyronine in the serum, as well as a decrease in total triiodothyronine and its free fraction. CONCLUSION: Conclusions: In patients with acute bronchitis in almost every third case there are functional shifts in hormonal status, which are manifested in the form of the first variant of the euthyroid sick syndrome.

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.

Thyroid dysfunction in COVID-19 patients.

PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

Association between Thyroid Function and Prognosis of COVID-19: A Retrospective Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is a severe infectious illness. It has been reported that COVID-19 has an effect on thyroid function. However, the association between thyroid function and prognosis of COVID-19 is still unclear.Methods: This retrospective study included patients with COVID-19 admitted to Tongji Hospital in Wuhan from January 28 to April 4, 2020. Demographic, epidemiological, clinical, laboratory, treatment, and outcome data were collected from patients with laboratory-confirmed COVID-19. Patients without history of thyroid disease who had a thyroid function test at admission were enrolled in the final analysis. Risk factors of in-hospital death were explored using univariable and multivariable Cox regression analyses. Survival differences were assessed with Kaplan-Meier curves and log-rank test.Results: A total of 127 patients were included in this study, with 116 survivors and 11 non-survivors. The serum levels of thyroid stimulating hormone (TSH) [0.8 (0.5-1.7) vs. 1.9 (1.0-3.1) µIU/mL, P = .031] and free triiodothyronine (FT3) [2.9 (2.8-3.1) vs. 4.2 (3.5-4.7) pmol/L, P < .001] were lower in non-survivors than in survivors, and a low FT3 state (defined as FT3 < 3.1 pmol/L) at admission accounted for a higher proportion in non-survivors than in survivors (72.7% vs. 11.2%, P < .001). Univariate Cox regression analysis showed that FT3 level (HR 0.213, 95% CI: 0.101-0.451, P < .001) and the low FT3 state (HR 14.607, 95% CI: 3.873-55.081, P < .001) were negatively and positively associated with the risk of in-hospital death, respectively. Furthermore, multivariate Cox regression analysis revealed that a low FT3 state was associated with an increased risk of in-hospital death after adjusting for confounding factors (HR 13.288, 95% CI: 1.089-162.110, P = .043). Moreover, Kaplan-Meier curves indicated a lower survival probability in COVID-19 patients with a low FT3 status.Conclusion: Serum FT3 level is lower in non-survivors among moderate-to-critical patients with COVID-19, and the low FT3 state is associated with an increased risk of in-hospital mortality of COVID-19.

The effect of oral triiodothyronine supplementation on lactate and pyruvate after paediatric cardiac surgery.

OBJECTIVE: To determine if triiodothyronine alters lactate, glucose, and pyruvate metabolism, and if serum pyruvate concentration could serve as a predictor of low cardiac output syndrome in children after cardiopulmonary bypass procedures. METHODS: This study was ancillary to the Oral Triiodothyronine for Infants and Children undergoing Cardiopulmonary bypass (OTICC) trial. Serum pyruvate was measured in the first 48 patients and lactate and glucose were measured in all 208 patients enrolled in the OTICC study on the induction of anaesthesia, 1 and 24 hours post-aortic cross-clamp removal. Patients were also defined as having low cardiac output syndrome according to the OTICC trial protocol. RESULT: Amongst the designated patient population for pyruvate analysis, 22 received placebo, and 26 received triiodothyronine (T3). Lactate concentrations were nearly 20 times greater than pyruvate. Lactate and pyruvate levels were not significantly different between T3 and placebo group. Glucose levels were significantly higher in the placebo group mainly at 24-hour post-cross-clamp removal. Additionally, lactate and glucose levels peaked at 1-hour post-cross-clamp removal in low cardiac output syndrome and non-low cardiac output syndrome patients, but subsequently decreased at a slower rate in low cardiac output syndrome. Lactate and pyruvate concentrations correlated with glucose only prior to surgery. CONCLUSION: Thyroid supplementation does not alter systemic lactate/pyruvate metabolism after cardiopulmonary bypass and reperfusion. Pyruvate levels are not useful for predicting low cardiac output syndrome. Increased blood glucose may be regarded as a response to hypermetabolic stress, seen mostly in patients with low cardiac output syndrome.

Euthyroid sick syndrome in paediatric and adult patients requiring extracorporeal circulatory support and the role of thyroid hormone supplementation: a review.

Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.

Persistent anemia and hypoalbuminemia in rheumatoid arthritis patients with low serum triiodothyronine level.

Objectives: To determine the clinical characteristics of rheumatoid arthritis (RA) patients with low serum triiodothyronine (T3) levels.Methods: We evaluated serum free T3 (fT3), free T4, and thyroid-stimulating hormone (TSH) levels in 338 RA patients. After excluding patients taking anti-thyroid drugs or having anti-thyroid antibodies, we compared the clinical characteristics of the RA patients with low fT3 to those with normal/high fT3, before and after RA treatment.Results: Six percent of RA patients had low fT3 levels. Patients with low fT3 were older and had higher disease activity scores (DAS28), higher Steinbrocker stage, higher health assessment questionnaire scores, lower body mass index, and lower hemoglobin and albumin levels compared with normal/high-fT3 patients. After RA treatment, fT3 levels normalized in half of the low-fT3 patients and remained low in the other half. Although DAS28 scores were similarly improved in both subgroups of the low-fT3 patients, anemia and hypoalbuminemia did not normalize in the persistently low-fT3 subgroup.Conclusion: Low serum fT3 levels represent the profound wasting seen in RA patients that is characterized by anemia and hypoalbuminemia and that cannot be evaluated by DAS28 scores alone.

Low T3 Syndrome Is Associated With High Mortality in Hospitalized Patients With Heart Failure.

BACKGROUND: We aimed to clarify the prognosis and pathophysiological parameters of low T3 syndrome in patients with heart failure (HF). METHODS AND RESULTS: Hospitalized patients with HF and euthyroidism (n = 911) were divided into 2 groups on the basis of free triiodothyronine (FT3) serum levels: the normal FT3 group (FT3 ≥2.3 pg/mL; n = 590; 64.8%) and the low FT3 group (FT3 <2.3 pg/mL; n = 321; 35.2%). We compared post-discharge cardiac and all-cause mortality by means of Kaplan-Meier analysis and Cox proportional hazard analysis, and the parameters of echocardiography and cardiopulmonary exercise testing by means of Student t test. In the follow-up period of median 991 (interquartile range 534-1659) days, there were 193 all-cause deaths, including 88 cardiac deaths. Cardiac and all-cause mortality were higher in the low FT3 group (log-rank P < .01). Low FT3 was a predictor of cardiac death (hazard ratio 1.926, 95% confidence interval [CI] 1.268-2.927; P = .002) and all-cause death (hazard ratio 2.304, 95% CI 1.736-3.058; P < .001). Although left ventricular ejection fraction was similar between the groups, the low FT3 group showed lower peak VO2 (13.6 ± 4.6 vs 16.6 ± 4.4 mL·kg-1·min,-oneP < .001) and higher VE/VCO2 slope (36.5 ± 8.2 vs 33.0 ± 7.5; P = .001). CONCLUSION: Low T3 syndrome in patients with HF is associated with higher cardiac and all cause-mortality.

The Role of Thyroid Hormones in Heart Failure.

Cardiovascular diseases are the leading cause of death worldwide. Heart failure is the terminal manifestation of cardiovascular diseases, and its morbidity and mortality remain high. The prevalence of heart failure with preserved ejection fraction (HFpEF) among heart failure patients remains uncertain. However, recent studies have found that it ranged from 40 to 71%. There is still no effective treatment for HFpEF. Thyroid hormones (TH) have central regulatory actions in the cardiovascular system, particularly in the heart. Changes in plasmatic or tissue thyroid hormone levels are associated with significant alterations in cardiovascular function. A significant proportion of patients with heart failure presents some form of thyroid dysfunction including hypothyroidism, hyperthyroidism, and low T3 syndrome. Furthermore, thyroid hormones can vary at a local level independently of the serum TH levels. This may lead to local cardiac hypothyroidism in heart failure. Based on these findings and the role that TH play in cardiovascular regulation, they were proposed as a potential target for heart failure therapy. Several clinical and experimental studies have shown beneficial effects of TH supplementation. Data from epidemiological studies supports a higher risk of heart failure and a worse prognosis in heart failure patients with low levels of TH. In addition, animal studies and small clinical studies suggest that TH supplementation may improve cardiac function in heart failure. Although further studies are needed to evaluate the safety and efficacy of TH in this context, the available evidence suggests that TH modulation is a promising therapeutic approach to heart failure.

Relationships of Chronic Kidney Disease and Thyroid Dysfunction in Non-Dialysis Patients: A Pilot Study.

CONTEXT: Patients with chronic kidney disease (CKD) usually manifest with disorder of thyroid hormone; however, the correlation is unknown. OBJECTIVE: The study was designed to explore the relationships between CKD and thyroid dysfunction. DESIGN, SETTING, AND PARTICIPANTS: A total number of 905 non-dialysis participants were collected at Nanjing First Hospital from August 2009 to October 2012 according to the case records system. Patients were grouped via the estimated glomerular filtration rate (eGFR) according to the KDIGO guideline. Levels of thyroid hormone and biomarkers in different CKD groups were compared by ANOVA. Prevalence of different thyroid diseases was calculated by χ2 test. RESULTS: We found that FT3 or T3 became more prevalent with increasing eGFR with the lowest level in CKD5 (p < 0.01). No significant differences were found between groups in FT4, T4, or TSH (p > 0.05). Frequency of euthyroid sick syndrome (ESS) in CKD groups was high, especially in CKD stage 5 (69.1%, p < 0.01). eGFR had positive correlation with T3 and FT3 (r = 0.239, p = 0.0001; r = 0.292, p = 0.0001). ESS had correlations with prealbumin, ß2-microglobin, eGFR, and C-reactive protein (r = 0.095, p = 0.004; r = -0.12, p = 0.001; r = 0.091, p = 0.007; r = -0.096, p = 0.008; r = 0.154, p = 0.001). After adjustment for prealbumin, uric acid, HbA1c, age, gender, eGFR, and ß2-microglobin, binary regression revealed that hemoglobin, C-reactive protein, and albumin were independent influence factors of ESS (p = 0.016, r = 1.014; p = 0.023, r = 1.007; p = 0.029, r = 0.996). CONCLUSION: CKD patients have a high morbidity of ESS, mainly low T3 syndrome. Anemia, inflammation, and malnutrition may contribute to ESS in CKD.

Oral Triiodothyronine Supplementation Decreases Low Cardiac Output Syndrome After Pediatric Cardiac Surgery.

The oral triiodothyronine for infants and children undergoing cardiopulmonary bypass (OTICC) trial showed that Triiodothyronine (T3) supplementation improved hemodynamic and clinical outcome parameters. We tested the validity of low cardiac output syndrome (LCOS), derived using clinical parameters and laboratory data, by comparing the LCOS diagnosis with objective parameters commonly measured in a cardiac intensive care unit (CCU) setting. OTICC, a randomized, placebo-controlled trial included children younger than 3 years with an Aristotle score between 6 and 9. We used the existing trial data set to compare the LCOS diagnosis with echocardiographic hemodynamic parameters. Additionally, we determined if LCOS, prospectively assigned during a clinical trial, served as an early predictor of clinical outcomes. All LCOS subjects at 6 and 12 h after cross-clamp release later showed significantly lower pulse pressure, stroke volume and cardiac output, and higher systemic vascular resistance. These LCOS patients also had significantly longer time to extubation (TTE) and higher mortality rate. LCOS incidence was significantly lower in the T3 treatment group [n = 86 vs. 66, respectively, p < 0.001; OR (95% CI) 0.43 (0.36-0.52)] particularly at 6 h. Also, LCOS patients in the placebo group had significantly lower FT3 serum levels over time. These analyses confirm that early clinically defined LCOS successfully predicts cardiac dysfunction determined later by objective hemodynamic echocardiographic parameters. Furthermore, early LCOS significantly impacts TTE and mortality. Finally, the data support prior clinical trial data, showing that oral T3 supplementation decreases early LCOS in concordance with reducing TTE.

Predictors for euthyroid sick syndrome and its impact on in-hospital clinical outcomes in high-risk patients undergoing coronary artery bypass grafting.

OBJECTIVE: The purpose of this cohort study was to investigate the independent relationship between euthyroid sick syndrome and in-hospital outcomes in high-risk patients undergoing isolated coronary artery bypass grafting, and we also examined the direct correlation between pre- or intra-operative variables and the incidence of coronary artery bypass grafting-associated euthyroid sick syndrome. METHODS: The present study enrolled high-risk patients undergoing coronary artery bypass grafting from 1 January 2017 to 31 December 2017 in Beijing Anzhen hospital, including 387 (58.7%) patients with coronary artery bypass grafting-associated euthyroid sick syndrome and 272 (41.3%) patients without coronary artery bypass grafting-associated euthyroid sick syndrome. RESULTS: The mean age of euthyroid sick syndrome group was significantly older than that of no euthyroid sick syndrome group (65.9 ± 7.5 vs 60.9 ± 9.6, p < 0.0001). Compared with the control group, significantly higher proportions of patients with euthyroid sick syndrome had presented with the following clinical characteristics at hospital admission: moderate and poor left ventricular ejection fraction (42.9% vs 28.7%, p < 0.0001), higher euroscore II (9.2 ± 4.1 vs 8.0 ± 3.9, p < 0.0001). Multivariate logistic regression analysis on the total patients revealed that the independent risk factors for coronary artery bypass grafting-associated euthyroid sick syndrome were advanced age (odds ratio = 1.07, 95% confidence interval = 1.05-1.09, p < 0.0001), higher euroscore II (odds ratio = 1.06, 95% confidence interval = 1.01-1.11, p = 0.013), and moderate and poor left ventricular ejection fraction (odds ratio = 2.26, 95% confidence interval = 1.61-3.18, p < 0.0001). Furthermore, euthyroid sick syndrome was independently correlated with an increased risk of in-hospital major adverse cardiovascular and cerebral events (odds ratio = 3.40, 95% confidence interval = 1.64-7.02, p = 0.001) and post-infection (odds ratio = 8.11, 95% confidence interval = 3.97-16.57, p < 0.0001) Besides, we also confirmed coronary artery bypass grafting-associated euthyroid sick syndrome was associated with Sequential Organ Failure Assessment maximum greater than 11 (odds ratio = 2.98, 95% confidence interval = 1.90-4.65, p < 0.0001), which predicted an in-hospital death rate of 95%, independently. CONCLUSION: Coronary artery bypass grafting-associated euthyroid sick syndrome exerted detrimental effects on short-term clinical outcomes in high-risk patients undergoing isolated coronary artery bypass grafting. Advanced age, higher euroscore II, and moderate and poor left ventricular ejection fraction were independent risk factors for coronary artery bypass grafting-associated euthyroid sick syndrome.

Investigation of the Oxidative Stress and DIO1 Expression in CRF Patients Accompanied With and Without Euthyroid Sick Syndrome.

BACKGROUND/AIMS: Chronic renal failure (CRF) is often accompanied by increased oxidative stress and euthyroid sick syndrome (ESS). The cause of ESS is unknown, and it is unknown whether there exists a link between oxidant stress and ESS in CRF patients. Therefore, we aim to investigate oxidative stress and type 1 deiodinase (DIO1) expression, which plays the key role in the ESS in CRF patients. METHODS: In-patients with CRF were divided into the two group: Group 1 is ESS patients consisting of 60 patients with low free triiodothyronine (FT3) and Group 2 consisting of 60 patients with normal FT3. Group 3 consisted of 60 healthy volunteers recruited as controls. The baseline clinical parameters of patients were evaluated with standard routine methods in a clinical laboratory. Serum levels of 8-isoprostane and DIO1 were measured by enzyme-linked immunosorbent assay (ELISA). Multiple regression analysis was used to analyze the relationship between oxidative stress, DIO1 and FT3. RESULTS: The concentrations of serum 8-Isoprostane in Group 1 and Group 2 were substantially higher than that of Group 3 (p< 0.05), however there was no significant difference between Group 1 and Group 2 (p=0.516). The serum DIO1 level was higher in Group 2 than in Group 1 and Group 3 (p< 0.001). Multivariate linear regression analysis revealed that the DIO1 concentration and FT3 level were not associated with the concentration of serum 8-Isoprostane. CONCLUSIONS: CRF patients showed elevated oxidative stress. The CRF patients without ESS showed higher expression of DIO1 than patients with ESS and the control group. The concentration of serum 8-Isoprostane was not correlated with FT3 and DIO1 levels.

THE ASSOCIATION OF LOW TRIIODOTHYRONINE SYNDROME, PROTEIN-ENERGY WASTING AND CHRONIC INFLAMMATION WITH MORTALITY IN PREVALENT DIALYSIS PATIENTS.

- This prospective study in prevalent dialysis patients investigated prognostic properties of low triiodothyronine syndrome, protein-energy wasting and chronic inflammation. Ninety-four prevalent dialysis patients were followed-up for a median of 39 months. Demographic, anthropometric and biochemical parameters were collected at baseline. Univariate and multivariate analysis was done using Cox regression analysis. ROC curve analysis using survival status as a classification variable was performed with the goal of determining optimal cut-off values for numerical variables. In our population, low total triiodothyronine (hazard ratio (HR) 2.19, p=0.038), catheter as vascular access (HR 2.76, p=0.023), higher vintage (HR 1.01, p=0.014) and higher Charlson comorbidity index (HR 1.28, p=0.017) were statistically significantly associated with inferior survival. In our group of steady-state dialysis patients, total triiodothyronine seemed to be the strongest predictor of inferior survival among thyroid hormones. Taking this parameter into account, it was possible to identify patients at an increased risk of death even after adjustment for other prognostically relevant variables. However, after further adjustment for significant risk factors, the impact of C-reactive protein and albumin on survival disappeared due to the overlapping prognostic properties. We concluded that triiodothyronine was an independent prognostic factor in our study group.