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.

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.

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.

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.

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.

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.

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.

Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC).

Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3'-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5'-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1. NF-κB activation by inflammatory cytokines inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits RXR-dependent transcription and activates NF-κB. Here, we interrogated the role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3-mediated gene regulation was analyzed in human HCC cells, with overexpression or knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1 mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1 knockdown induced DIO1 expression. An inverse correlation was observed between AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator recruitment to RXR and activation of NF-κB were identified to play a role in AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS associated with HCC and other cancers.

Antioxidant therapy improves non-thyroidal illness syndrome in uremic rats.

BACKGROUND: The roles of antioxidant therapy on non-thyroidal illness syndrome (NTIS) in uremic rats is still unclear. MATERIALS AND METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into blank, 5/6 nephrectomy (Nx), pyrrolidine dithiocarbamate (PDTC, 10 mg/100 g), sodium bicarbonate (SB, 0.1 g/100 g), N-acetylcysteine (NAC, 80 mg/100 g) and thyroid hormones (TH, levothyroxine 2 µg/100 g) groups. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), advanced oxidation protein products (AOPP), interleukin (IL)-1ß, free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were detected in the sixth week. The expressions of IL-1ß and deiodinase type 1 (DIO1) were assessed by western blotting. The nuclear factor kappa B (NF-κB) inflammatory signal pathway was confirmed by electrophoretic mobility shift assay (EMSA). RESULTS: Compared with 5/6 Nx group, PDTC and NAC significantly reduced the levels (p < 0.01, respectively) of serum MDA, AOPP, TSH, and elevated levels of serum SOD (p < 0.01, respectively) and FT3 (p = 0.016 and p < 0.01). Neither had significant effects on serum IL-1ß content (p = 0.612 and p = 0.582). PDTC and NAC markedly decreased the protein expression of IL-1ß (p < 0.01) and increased the protein expression of DIO1 (p < 0.01), respectively. Both had been considerably blunted NF-κB activity (p < 0.01). CONCLUSIONS: In uremic rat model, PDTC and NAC can effectively improve oxidative stress level and NTIS. In terms of improving oxidative stress level, NAC is probably superior to PDTC.

Emerging pharmacotherapy for treatment of traumatic brain injury: targeting hypopituitarism and inflammation.

INTRODUCTION: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the developed world. In particular, TBI is an important cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. AREAS COVERED: There is a large body of evidence that suggest that TBI conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90%. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in TBI conditions. EXPERT OPINION: The aim of this paper is to review the history and pathophysiology of TBI and to summarize the best evidence of TBI as a cause of pituitary deficiency. Moreover, in this article we will describe the multiple changes which occur within the hypothalamic-pituitary-thyroid axis in critical illness, giving rise to 'sick euthyroid syndrome', focus our attention on thyroid hormones circulating levels from the initial insult to critical illness.

Dynamic neuroendocrine changes in critically ill patients with polytrauma.

OBJECTIVE: Acute multiple-trauma induces activation of neuroendocrine system. Nonthyroidal illness syndrome (NTIS) is considered to be associated with adverse outcome in intensive care unit (ICU) patients. This study was aimed to assess dynamic changes of neuroendocrine hormones in patients with polytrauma and their association with the polytrauma score (PTS). METHODS: Blood samples from 24 critically ill patients with polytrauma were obtained on 1st, 2nd, 3rd and 7th day after admission to ICU for analysis of thyroid-stimulating hormone (TSH), total triiodothyronine (T3); free triiodothyronine (fT3), total thyroxine (T4), free thyroxine (fT4), growth hormone (GH), prolactin (PRL) and procalcitonin levels. RESULTS: Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16±5 points on average at the admission to ICU. All patients had normal baseline TSH, T4, fT4, but low T3, and fT3 levels were found in 20% and 33% ICU patients, respectively. On the 7th day after admission to ICU TSH had tendency to increase (p=0.07) and fT4 significantly decreased (p=0.03). The PRL level significantly increased on the 3rd day after admission as compared to 1st day (p=0.04). PTS positively correlated with fT3 (r=0.582, p=0.004) and negatively with fT4 (r=-0.422, p=0.04) at the 1st day in ICU. CONCLUSION: Critical illness in patients with polytrauma leaded to trauma severity-dependent alterations of the thyroid axis response early after injury. Our findings suggest that detection of dynamic hormonal response is more appropriate than single measurement. However supplemental therapy for NTIS should be used after more detailed studies are completed.

Isolated vitamin D deficiency is not associated with nonthyroidal illness syndrome, but with thyroid autoimmunity.

AIM: This study aimed to compare thyroid functions, thyroid autoantibodies, and the existence of nonthyroidal illness syndrome (NTIS) according to vitamin D level. MATERIALS AND METHODS: The study included age- and BMI-matched healthy volunteers with and without vitamin D deficiency. In addition, the nonthyroidal illness syndrome status was evaluated. RESULTS: Anti-TPO positivity was significantly more common in those with severe and moderate vitamin D deficiency, as compared to those with a normal 25(OH)D level. Furthermore, TSH levels were significantly lower in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. In addition, there was a significant weak inverse correlation between anti-TPO positivity and the 25(OH)D level and a positive correlation between the TSH level and 25(OH)D level. Only 1 thyroid function test result was compatible with NTIS among the participants with moderate vitamin D deficiency; therefore the difference was not significant. CONCLUSIONS: The prevalence of thyroid autoantibody positivity was higher in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. Additional large-scale studies must be conducted to determine if vitamin D deficiency plays a causal role in the pathogenesis of Hashimoto's thyroiditis and NTIS.

[Thyroid dysfunction in adults infected by human immunodeficiency virus]. / Disfuncion tiroidea en adultos infectados por el virus de inmunodeficiencia humana.

Patients infected with human immunodeficiency virus (HIV) have a higher prevalence of thyroid dysfunction when compared with the general population. The most frequently observed manifestations are euthyroid sick syndrome, Graves' disease and subclinical hypothyroidism. The relationship between the use of highly active antiretroviral therapy and the increased prevalence of thyroid dysfunction has been demonstrated in several series of patients. Grave's disease is recognized as a consequence of immune restitution syndrome. Besides, several studies have suggested an association between hypothyroidism and the use of nucleoside reverse transcriptase inhibitors, particularly stavudine and non-nucleoside reverse transcriptase inhibitors such as efavirenz. Further studies could provide additional evidence of the need for routine assessment of thyroid function in HIV-infected patients.

Nonthyroidal illness syndrome: is it far away from Crohn's disease?

GOALS: This study was designed to investigate the clinical features of nonthyroidal illness syndrome (NTIS) compared with euthyroid patients in Crohn's disease (CD), to explore the etiology of NTIS in CD, to evaluate the clinical outcomes of NTIS patients, and to inspect the correlation of clinical variables and NTIS, and their ability of differentiating NTIS from euthyroid patients. BACKGROUND: NTIS has been described for more than 30 years. However, only few studies focused on the relationship between NTIS and CD. The incidence, underlying pathogenesis, clinical outcomes, and correlation with other inflammatory disease severity and nutritional variables of NTIS in CD have not been completely established. METHODS: Prospectively, 44 CD patients were enrolled. Medical records and various laboratory values (including thyroidal, nutritional, and inflammatory variables) were collected in all participants. RESULTS: The incidence of NTIS in CD was 36.4%. Albumin, Acute Physiology and Chronic Health Evaluation II score, and Crohn's Disease Activity Index score in NTIS group were statistically different from those in euthyroid group. A decreased sum activity of deiodinases and a reduced ratio of TT4/FT4 were observed in NTIS group. Duration of hospitalization was significantly longer for NTIS patients than euthyroid patients. Albumin was confirmed as a protective factor of NTIS in CD. Receiver operating characteristic curve analysis demonstrated the differentiating capacity of albumin, suggesting 37.6 g/L as optimal cut-off value with sensitivity and specificity of 81.3% and 79.2%, respectively. CONCLUSIONS: NTIS was a common complication in CD. NTIS patients showed worse nutrition status and clinical outcome, and more critical disease activity and severity compared with euthyroid patients. A hypodeiodination condition and a potential thyroid-hormone-binding dysfunction may play a role in the etiology of NTIS in CD. Albumin was a meaningful protective and distinguishing marker of NTIS in CD.

[Nonthyroidal illness syndrome in acute bacterial endotoxicosis: pathogenesis and methods of correction].

Nonthyroidal illness syndrome is characterized by alterations of thyroid status inpatients with severe nonthyroidal illness who are clinically euthyroid. Mechanisms of nonthyroidal illness syndrome are poorly understood and controversial. Our investigations on nonthyroidal illness syndrome in acute endotoxicosis revealed two principal mechanisms of its development. The peripheral mechanism is the first to develop and referred to disturbance of thyrocytes secretory cycle due to increase of thyroglobulin synthesis, endocytosis and decrease of its proteolytic cleavage. It manifests with drop of serum thyroxine, not triiodthyronine, and increase of serum thyroid stimulating hormone. The central mechanism is associated with hypothalamic-pituitary hypofunction developed simultaneously with systemic inflammatory response. Rate of supplementation of the peripheral mechanism with the central one accounts for different types of nonthyroidal illness syndrome with high, normal and low serum levels of thyroid stimulating hormone. Our research showed that thyroid hormone replacement in nonthyroidal illness syndrome could only suppress thyroid function. Unlike thyroid hormones administration of thyroid stimulating hormone restores thyroid hormone secretion in nonthyroidal illness syndrome, decreases endotoxinemia and secretion of proinflammatory cytokines and improves liver function.

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.