The severity of valvular heart disease in euthyroid individuals is associated with thyroid hormone levels but not with TSH levels.

Background: Abnormal thyroid function is a metabolic disorder and can lead to several complications, including cardiovascular diseases. In this study, we aimed to examine the relationship between clinical traits and outcomes and the thyroid hormone level of euthyroid individuals with valvular heart disease (VHD). Method: The thyroid function was evaluated in 526 euthyroid VHD patients and 155 healthy control people. As well as clinical indicators were collected and analyzed. Results: No difference in TSH levels (p>0.05) was recorded; however, fT3, TT3, and TT4 levels were lower in the euthyroid VHD patients than in healthy control(4.3 vs 4.63; 1.37 vs 1.48; 97.7 vs 102.09, respectively, all p<0.05), while the fT4 level was higher (12.91 vs 12.35, p<0.05). Moreover, all showed a continuous trend with the change of NYHA grade which does not consist of the incidence of euthyroid sick syndrome(ESS). Further analysis showed that for every 10-fold increase in BNP, fT4 increases by 83%, fT3 decreases by 30%, and TT3 decreases by 12% after being adjusted for other influencing factors. Meanwhile, adjusted fT4 was correlated with multiple worse clinical indicators, which were influenced by age. Conclusion: Thyroid hormones are widely regulated in VHD patients even with acceptable cardiac function, except for TSH level. And the adjusted fT4 is related to worse clinical indicators and outcomes which are only recorded in patients under 53 years old.

Analysis of clinical features and 7-year all-cause mortality in older male patients with non-thyroidal illness syndrome on general wards.

PURPOSE: Older patients with non-thyroidal illness syndrome (NTIS) have a poor prognosis. However, there are few studies on the association of NTIS and mortality among older inpatients on general wards. In a 7-year retrospective observational study, we aimed to investigate the clinical features of NTIS and the association of NTIS and all-cause mortality in older inpatients. METHODS: A total of 959 older male inpatients whose average age was 86.3 ± 8.1 years were enrolled and divided into the NTIS group and non-NTIS group. Cox models were performed to explore the association of thyroid hormone level and mortality. RESULTS: Patients had more respiratory disease and chronic kidney disease in the NTIS than in the non-NTIS group, especially in primary nursing care, respiratory failure and haemodialysis patients; serum total protein, albumin, prealbumin, haemoglobin, uric acid and high-density lipoprotein cholesterol levels were lower, and urea nitrogen and fasting blood glucose levels were higher, in the NTIS than in the non-NTIS group. Patients in the NTIS group had a lower survival rate over 7 years follow-up (P < 0.01). A lower free T3 level was associated with all-cause mortality with a HR of 1.50 (1.36, 1.66). Lower free T4 level was associated with reduced all-cause mortality with a HR of 0.91 (0.88, 0.94) even after adjusting for confounding factors (P < 0.01). CONCLUSIONS: Among older male inpatients, the survival rate was lower in the NTIS group. A reduced free T3 level with low albumin and Hb levels was associated with all-cause mortality; moreover, a higher free T4 in the normal range may be a strong predictor for long-term mortality risk in hospitalised older male patients.

To Study the Association between Sick Euthyroid State and the Incidence of ACS.

The low T3 syndrome, the most common type of Sick Euthyroid syndrome, once believed to be a beneficial adaptive mechanism under conditions of stress, has emerged as a strong prognostic determinant in chronic systolic heart failure. Sick Euthyroid Syndrome is frequently observed in Chronic Heart Failure, Acute Myocardial Infarction. Acute myocardial infarction (AMI) may be associated with a number of endocrine alterations, including those of the SES which reflect the acute hormone response to stress and trauma. It is known from several studies that several cytokines can be found elevated in patients with cardiac ischemia or AMI. From in vitro studies it is of particular interest that ischemic myocytes produce cytokines such as interleukin-6 (IL-6) and its synthesis is accelerated by reperfusion. Interleukin-6 seemed to be an important cytokine produced by the injured myocytes in patients with AMI, and strong negative correlation between serum IL-6 concentration and left ventricular ejection fraction (LVEF) has been demonstrated. Similar observations have been made by studying tumor necrosis factor-a (TNF-a), IL-1a and soluble IL-2 receptor (sIL-2-R) which were found to be significantly elevated in AMI, with the highest levels noted in the most severe and complicated cases of myocardial infarction. MATERIAL: Study design : hospital based analytical cross-sectional study. MATERIALS: serial ECGs, Thyroid profile (FT3, FT4, TSH, rT3) and echocardiography. The study group included 100 patients who were admitted in ward/ICU with the diagnosis of myocardial infarction. INCLUSION CRITERIA: All patient with age 18yrs or above. History of chest pain with ECG changes and cardiac biomarkers of myocardial infarction. EXCLUSION CRITERIA: Patient below 18 yrs. Known case of hypothyroidism/hyperthyroidism Known case of malignancy Patients who have reached iodinated contrast in past one week. OBSERVATION: Out of 100 patients included with myocardial infarction, 27 patients had sick euthyroid state. Seven patients died, five with SES and two with normal thyroid profile. Mean value of fT3 was 2.37pg/ml for the patients who improved and 1.61pg/ml for the patient who expired, indicating statistical significance. Mean fT4 and TSH was not significant across those who improved or expired. However high rT3 value was associated with the worst outcome. CONCLUSION: Prevalence of SES is commom in patient with ACS. SES is a strong prognostic indicationin ACS. It is frequently observed in chronic heart failure, acte MI and is related to increased mortality.

Covid-19, the thyroid and the pituitary - The real state of play.

Thyroid and pituitary disorders linked to the coronavirus SARS-CoV-2, responsible for the COVID-19 epidemic, are mainly due to direct infection of the endocrine glands by the virus and to cell damage induced by the immune response. The two most frequent thyroid complications of COVID-19 are low T3 syndrome, or "non-thyroidal illness syndrome" (NTIS), and thyroiditis. Studies among in-patients with COVID-19 have shown that between one out of six and half of them have a low TSH level, related to NTIS and thyroiditis, respectively, sometimes found in the same patient. In NTIS, the decrease in free T3 concentration correlates with the severity of the infection and with a poor prognosis. Assessment of thyroid function in patients after a COVID-19 infection, shows normalization of thyroid function tests. Thyroiditis linked to COVID-19 can be divided into two groups, which probably differ in their pathophysiology. One is "destructive" thyroiditis occurring early in infection with SARS-CoV-2, with a severe form of COVID-19, usually observed in men. It is often asymptomatic and associated with lymphopenia. The other is subacute thyroiditis occurring, on average, one month after the COVID-19 episode, usually in clinically symptomatic women and associated with moderate hyperleukocytosis. Post-infection, one quarter to one third of patients remain hypothyroid. An Italian study demonstrated that low TSH in patients hospitalized for COVID-19 was associated with prolonged hospitalization and a higher mortality risk. Pituitary diseases associated with SARS-CoV-2 infection are much rarer and the causal relationship more difficult to ascertain. Several cases of pituitary apoplexy and diabetes insipidus during COVID-19 infection have been reported. Hyponatremia occurs in 20-50% of patients admitted to hospital for COVID-19. The prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) amongst these hyponatremic cases is difficult to determine. These endocrine complications may influence the prognosis of infection with SARS-CoV-2. Although they rarely require specific treatment, it is important that endocrinologists recognize them to ensure appropriate management, particularly in the acute phase.

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.

Suppression of the hypothalamic-pituitary-thyroid axis is associated with the severity of prognosis in hospitalized patients with COVID-19.

BACKGROUND: The outbreak of severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. SARS-CoV-2 has been found to cause multiple organ damage; however, little attention has been paid to the damage to the endocrine system caused by this virus, and the subsequent impact on prognosis. This may be the first research on the hypothalamic-pituitary-thyroid (HPT) axis and prognosis in coronavirus disease 2019 (COVID-19). METHODS: In this retrospective observational study, 235 patients were admitted to the hospital with laboratory-confirmed SARS-CoV-2 infection from 22 January to 17 March 2020. Clinical characteristics, laboratory findings, and treatments were obtained from electronic medical records with standard data collection forms and compared among patients with different thyroid function status. RESULTS: Among 235 patients, 17 (7.23%) had subclinical hypothyroidism, 11 (4.68%) severe non-thyroidal illness syndrome (NTIS), and 23 (9.79%) mild to moderate NTIS. Composite endpoint events of each group, including mortality, admission to the ICU, and using IMV were observed. Compared with normal thyroid function, the hazard ratios (HRs) of composite endpoint events for mild to moderate NTIS, severe NTIS, subclinical hypothyroidism were 27.3 (95% confidence interval [CI] 7.07-105.7), 23.1 (95% CI 5.75-92.8), and 4.04 (95% CI 0.69-23.8) respectively. The multivariate-adjusted HRs for acute cardiac injury among patients with NTF, subclinical hypothyroidism, severe NTIS, and mild to moderate NTIS were 1.00, 1.68 (95% CI 0.56-5.05), 4.68 (95% CI 1.76-12.4), and 2.63 (95% CI 1.09-6.36) respectively. CONCLUSIONS: Our study shows that the suppression of the HPT axis could be a common complication in COVID-19 patients and an indicator of the severity of prognosis. Among the three different types of thyroid dysfunction with COVID-19, mild to moderate NTIS and severe NTIS have a higher risk of severe outcomes compared with subclinical hypothyroidism.

Analysis of the Incidence of Euthyroid Sick Syndrome in Comprehensive Intensive Care Units and Related Risk Factors.

Objective: A low concentration of plasma triiodothyronine (T3) indicates euthyroid sick syndrome (ESS), which could be associated with a poor outcome in patients in intensive care units (ICUs). This study evaluated the relationship between ESS and prognostic indicators in patients admitted to an ICU and examined the free T3 (FT3) cut-off points that could be associated with 28-day mortality. Methods: This prospective observational study included patients admitted to the ICU of The Third Hospital of Hebei Medical University between February and November 2018. Baseline variables and data on the occurrence of low FT3 were collected. The patients were divided into ESS (FT3 < 3.28 pmol/L) and non-ESS groups. The relationship between ESS and prognostic indicators in patients admitted to the ICU was evaluated, and the FT3 cut-off points that could be associated with 28-day mortality were examined. Results: Out of a total of 305 patients, 118 (38.7%) were in the ESS group. Levels of FT3 (P < 0.001) and FT4 (P = 0.001) were lower, while the 28-day mortality rate (P < 0.001) and hospitalization expenses in the ICU (P = 0.001) were higher in the ESS group. A univariable analysis identified ESS, FT3, free thyroxine (FT4)/FT3, the APACHE II score, the sequential organ failure (SOFA) score, the duration of mechanical ventilation, creatinine (CREA) levels, the oxygenation index (HGB), white blood cells, albumin (ALB) levels, age, and brain natriuretic peptide (BNP) levels as factors associated with 28-day mortality (all P < 0.05). The cut-off value of FT3 for 28-day mortality was 2.88 pmol/L, and the 28-day mortality rate and hospitalization expenses in the ICU were higher in patients with ESS. The syndrome was confirmed to be independently associated with 28-day mortality. Conclusion: This study determined the incidence of ESS in the comprehensive ICU to be 38.7%. APACHE II, SOFA, BNP, APTT, HGB, PLT, CREA, ALB, FT4, SBP, and DBP are closely related to ESS, while BNP, PLT, and ALB are independent risk factors for the syndrome.

An update on non-thyroidal illness syndrome.

The non-thyroidal illness syndrome (NTIS) was first reported in the 1970s as a remarkable ensemble of changes in serum TH (TH) concentrations occurring in probably any severe illness. Ever since, NTIS has remained an intriguing phenomenon not only because of the robustness of the decrease in serum triiodothyronine (T3), but also by its clear correlation with morbidity and mortality. In recent years, it has become clear that (parenteral) feeding in patients with critical illness should be taken into account as a major determinant not only of NTIS but also of clinical outcome. Moreover, both experimental animal and clinical studies have shown that tissue TH concentrations during NTIS do not necessarily reflect serum low TH concentrations and may decrease, remain unaltered, or even increase according to the organ and type of illness studied. These differential changes now have a solid basis in molecular studies on organ-specific TH transporters, receptors and deiodinases. Finally, the role of inflammatory pathways in these non-systemic changes has begun to be clarified. A fascinating role for TH metabolism in innate immune cells, including neutrophils and monocytes/macrophages, was reported in recent years, but there is no evidence at this early stage that this may be a determinant of susceptibility to infections. Although endocrinologists have been tempted to correct NTIS by TH supplementation, there is at present insufficient evidence that this is beneficial. Thus, there is a clear need for adequately powered randomized clinical trials (RCT) with clinically relevant endpoints to fill this knowledge gap.

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.

Severe hyperthyroidism without symptoms due to nonthyroidal illness in a child with acute hepatitis: case report and literature review.

While liver enzyme changes are frequently reported in hyperthyroidism, liver dysfunction itself can lead to alterations in thyroid hormone metabolism. However, the exact relationship between hyperthyroidism and liver dysfunction is unclear. We report an 11-year-old boy presenting with acute hepatitis of unknown etiology, who was incidentally found to have asymptomatic biochemical hyperthyroidism. Despite significant total and free T4 elevation, clinical evidence of thyrotoxicosis was absent. Thyroid I-123 uptake was also reduced. Additional testing revealed slight T3 elevation and significant rT3 elevation. Graves' and Hashimoto's thyroiditis testing was negative. We hypothesize that the biochemical hyperthyroidism was due to transient thyroiditis. Although an etiology for the boy's hepatitis was never determined, and an undiagnosed infectious etiology causing subacute thyroiditis was considered, subsequent testing showing positive thyroid peroxidase antibodies, suggesting autoimmune Hashimoto's thyroiditis as the likely cause of the hyperthyroidism. We believe, furthermore, that the absence of symptoms was the result of concurrent nonthyroidal illness resulting in the biochemical findings of slight T3 elevation and significant rT3 increase despite significant T4 elevation.

Changes in thyroid function in patients with liver failure and their clinical significance: A clinical study of non-thyroidal illness syndrome in patients with liver failure.

BACKGROUND: Non-thyroidal illness syndrome (NTIS) develops in a large proportion of critically ill patients and is associated with high risk for death. We aimed to investigate the correlation between NTIS and liver failure, and the short-term mortality of patients with these conditions. METHODS: The clinical data of 87 patients with liver failure were collected retrospectively, 73 of them were randomly selected for an observational study and to establish prognostic models, and 14 for model validation. Another 73 sex- and age-matched patients with mild chronic hepatitis were randomly selected as a control group. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured. The clinical characteristics of patients with liver failure and NTIS were analyzed. The follow-up of patients lasted for 3 months. Additionally, the values for predicting short-term mortality of model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP), chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores, FT3-MELD model, and FT3 were evaluated. RESULTS: The observation group had significantly lower FT3 (2.79 ± 0.71 vs. 4.43 ± 0.75 pmol/L, P < 0.001) and TSH [0.618 (0.186-1.185) vs. 1.800 (1.570-2.590) mIU/L, P < 0.001], and higher FT4 (19.51 ± 6.26 vs. 14.47 ± 2.19 pmol/L, P <0.001) than the control group. NTIS was diagnosed in 49 of the patients with liver failure (67.12%). In the observation group, patients with NTIS had a higher mortality rate than those without (63.27% vs. 25.00%, P = 0.002). Across the whole cohort, the 3-month mortality was 50.68%. The international normalized ratios (INR) were 2.40 ± 1.41 in survivors and 3.53 ± 1.81 in deaths (P = 0.004), the creatinine (Cr) concentrations were 73.27 ± 36.94 µmol/L and 117.08 ± 87.98 µmol/L (P = 0.008), the FT3 concentrations were 3.13 ± 0.59 pmol/L and 2.47 ± 0.68 pmol/L (P < 0.001), the MELD scores were 22.19 ± 6.64 and 29.57 ± 7.99 (P < 0.001), the CTP scores were 10.67 ± 1.53 and 11.78 ± 1.25 (P = 0.001), and the CLIF-SOFA scores were 8.42 ± 1.68 and 10.16 ± 2.03 (P < 0.001), respectively. FT3 was negatively correlated with MELD score (r = -0.430, P < 0.001). An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula: Logit(P) = -1.337 × FT3+0.114 × MELD+0.880. The area under the receiver operating characteristic (ROC) curve was 0.827 and the optimal cut-off value was 0.4523. The corresponding sensitivity and specificity were 67.6% and 91.7%. The areas under the ROC curve for FT3 concentration, MELD score, CTP score, and CLIF-SOFA score were 0.809, 0.779, 0.699, and 0.737, respectively. CONCLUSIONS: Patients with liver failure often develop NTIS. FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure. Thus, the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.

Nonthyroidal illness in critically ill children.

PURPOSE OF REVIEW: This review summarizes recent literature on nonthyroidal illness syndrome (NTI) and outcome of pediatric critical illness, to provide insight in pathophysiology and therapeutic implications. RECENT FINDINGS: NTI is typically characterized by lowered triiodothyronine levels without compensatory TSH rise. Although NTI severity is associated with poor outcome of pediatric critical illness, it remains unclear whether this association reflects an adaptive protective response or contributes to poor outcome. Recently, two metabolic interventions that improved outcome also altered NTI in critically ill children. These studies shed new light on the topic, as the results suggested that the peripheral NTI component, with inactivation of thyroid hormone, may represent a beneficial adaptation, whereas the central component, with suppressed TSH-driven thyroid hormone secretion, may be maladaptive. There is currently insufficient evidence for treatment of NTI in children. However, the recent findings raised the hypothesis that reactivation of the central NTI component could offer benefit, which should be tested in RCTs. SUMMARY: NTI in critically ill children can be modified by metabolic interventions. The peripheral, but not the central, component of NTI may be a beneficial adaptive response. These findings open perspectives for the development of novel strategies to improve outcome of critical illness in children.

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.

Nonthyroidal Illness Syndrome and Thyroid Hormone Actions at Integrin αvß3.

Context: The nonthyroidal illness syndrome (NTIS) is a constellation of changes in circulating thyroid hormone levels that occur in euthyroid patients with acute or chronic systemic diseases. The changes that occur include a reduction in serum T3, an increase in serum rT3, and variable changes in circulating T4 levels. No consensus exists regarding therapeutic intervention for NTIS. Methods: We briefly review the published literature on the physiological actions of T4 and of rT3-hormones that until recently have been seen to have little or no bioactivity-and analyze the apparent significance of changes in circulating T4 and T3 encountered in the setting of NTIS in patients with cancer. In the case of T4, these actions may be initiated at a cancer or endothelial cell plasma membrane receptor on integrin αvß3 or at the cytoskeleton. Results: This review examines possible therapeutic intervention in NTIS in patients with cancer in terms of T4 reduction and T3 support. Evidence also exists that rT3 may support cancer. Conclusions: Prospective study is proposed of pharmacological reduction of normal or elevated T4 in cancer-associated NTIS. We also support investigation of normally circulating levels of T3 in such patients.

Effects of Anorexia Nervosa on the Endocrine System.

Anorexia nervosa (AN) is characterized by severe undernutrition associated with alterations in multiple endocrine axes, which are primarily adaptive to the state of caloric deprivation. Hormonal changes include growth hormone (GH) resistance with low insulin like growth factor-1 (IGF-1) levels, hypothalamic hypogonadism, relative hypercortisolemia and changes in appetite regulating hormones, including leptin, ghrelin, and peptide YY. These alterations contribute to abnormalities in bone metabolism leading to low bone mass, impaired bone microarchitecture, and increased risk for fracture, and may also negatively impact cognition, emotions and mood. The best strategy to improve all biologic outcomes is weight and menstrual recovery. Physiological estrogen replacement improves bone accrual rates and measures of trait anxiety in adolescents with AN. Other therapies including testosterone and IGF-1 replacement, and use of DHEA with oral estrogen-progesterone combination pills, bisphosphonates and teriparatide have also been studied to improve bone outcomes.

Association of triiodothyronine levels with left ventricular function, cardiovascular events, and mortality in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients have altered free triiodothyronine (fT3) levels. A low fT3 level is a strong and inverse mortality predictor in HD patients. However, little is known about the relationship between fT3 and left ventricular function in HD patients. METHODS: A total of 128 maintenance HD patients were enrolled in this study. A thyroid function test with blood sampling and echocardiography was conducted. Low-T3 syndrome was defined as fT3 level <3.62 pmol/L and normal thyroid stimulating hormone (TSH). Overall mortality and rate of cardiovascular (CV) events were assessed during 48 months of follow-up. RESULTS: Low-T3 syndrome was detected in 57 (44.5%) of the 128 patients. Patients with low-T3 syndrome had a shorter duration of HD (49.1 vs. 73.3, p = 0.01), and lower serum albumin (35.1 vs. 40.4 g/L, p<0.001), left ventricular ejection fraction (LVEF; 54.7% vs. 63.9%, p<0.001), and fractional shortening at endocardial levels (endoFS; 29.3% vs. 34.8%, p = 0.001) compared to those with normal fT3 levels. In multivariate linear regression, LVEF, albumin, and duration of HD were independently correlated with fT3 levels. In addition, fT3 was also correlated with LVEF. During the study period, 13 (10.1%) patients died, CV events occurred in 15 (11.7%) patients. In Cox regression analysis, low fT3 level and elevated high-sensitivity C-reactive protein (hs-CRP) were associated with mortality and CV events. CONCLUSIONS: In HD patients, fT3 level is positively correlated with LVEF. Low fT3 level and elevated hs-CRP predicted all-cause mortality and CV events.

Treatment for non-thyroidal illness syndrome in advanced chronic kidney disease: a single-blind controlled study.

AIM: Non-thyroidal illness syndrome (NTIS) is common among patients with advanced chronic kidney disease (CKD) and is strongly associated with poor prognosis. However, it remains unclear in how to correct this disorder and this study aimed to evaluate the effectiveness of sodium bicarbonate (SB) and N-acetyl-cysteine (NAC) for correcting NTIS status. METHODS: Patients with CKD stage 3-4 were single-blind, placebo-controlled treated with placebo, SB, or NAC for 18 weeks. The primary end points were the correction of NTIS and the occurrence of end-stage renal disease (ESRD). The secondary point was the change in estimated glomerular filtration rate (eGFR) after the follow-up. RESULTS: The Kaplan-Meier survival analysis showed significant lower correcting ratio of NTIS in control group compared with SB group [Hazard ratio (HR) 0.19, 95 % confidence interval (CI) 0.04-0.89, p = 0.035] and NAC group (HR 0.09, 95 % CI 0.02-0.38, p = 0.001), and increased ESRD risk in control group than in SB group (HR 1.97, 95 % CI 1.02-3.84, p = 0.045) and NAC group (HR 5.50, 95 % CI 2.23-13.57, p < 0.001). The Cox regression analysis demonstrated significantly different effectiveness of placebo, SB and NAC on NTIS correction and ESRD risk, p < 0.05, respectively. Variance analysis displayed a greater reduction in eGFR in controls than in SB (p = 0.044) and NAC group (p < 0.001). CONCLUSION: SB and NAC are effective in promoting the recovery from NTIS status and delaying the deterioration of renal function in advanced CKD patients.