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.

Diagnosis and treatment of low T3 syndrome in neurocritical patients.

WHAT IS KNOWN AND OBJECTIVE: Low levels of serum triiodothyronine (T3) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. The application of hormone replacement therapy (HRT) in the treatment of neurocritical patients with low T3 syndrome remains controversial. We studied the role of low T3 state as a predictor of outcomes in neurocritical patients and examined the effect of HRT on prognosis. METHODS: A retrospective analysis was performed on the data of 32 neurocritical patients with low T3 syndrome who were admitted to the neuro-intensive care unit of Peking Union Medical College Hospital between January 2012 and October 2018. While 18/32 (56.25%) patients received HRT (HRT group; n = 18), 14/32 (43.75%) patients did not receive HRT (non-HRT group; n = 14). Patients were followed up for periods ranging from 3 months to 72 months. Baseline clinical and laboratory data were compared between the two groups using Mann-Whitney U tests or the t tests. Overall survival was assessed by Kaplan-Meier curve and compared by log-rank tests. Univariate and multivariate regression analyses were performed to identify the factors associated with prognosis and estimate the effect of HRT. We also assessed the influence of HRT on final neurological function, using the Glasgow Coma Scale (GCS) and the Glasgow Outcome Scale (GOS) scores. RESULTS AND DISCUSSION: The neurocritical events in our cohort included post-operative complications (n = 18), traumatic brain injury (n = 8) and spontaneous intracerebral haemorrhage (n = 6). Mean GCS score in the cohort was 6.41 (6.44 ± 3.14 in HRT group vs 6.36 ± 2.06 in non-HRT group). A total of 15/32 (46.87%) deaths were recorded (7 in the HRT group, 8 in the non-HRT group). In the HRT group, 15 patients underwent repeat thyroid function tests after completion of HRT; the low T3 situation was corrected in only 5/15 (33.3%) patients. Overall survival was significantly shorter in the non-HRT group than in the HRT group (16.45 months vs 47.47 months; P = .034). In univariate regression analysis, the HRT group has the lower mortality risk than the non-HRT group (HR = 0.301, 95% Cl: 0.094-0.964; P = .043). However, multivariate regression analysis showed no significant difference in mortality risk between the two groups (HR = 0.340 95% CI: 0.099-1.172; P = .087). There was no significant difference in effects of HRT on the short- and long-term neurological function between the groups. WHAT IS NEW AND CONCLUSION: Low T3 syndrome may influence the prognosis of neurocritical patients, attention should be paid to the changes in serum T3 levels during treatment. Although it is unclear to what extent HRT can improve the short or long-term outcomes of neurological function, it can significantly improve the survival rates of neurocritical patients.

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.

The combination of nonthyroidal illness syndrome and renal dysfunction further increases mortality risk in patients with acute myocardial infarction: a prospective cohort study.

BACKGROUND: Both nonthyroidal illness syndrome and renal dysfunction are associated with increased mortality risk in acute myocardial infarction (AMI). However, it is unclear whether combined NTIS and renal dysfunction further increase mortality risk. Therefore, our aim is to investigate whether combined NTIS and renal dysfunction further increases mortality risk in patients with acute myocardial infarction (AMI). METHODS: A total of 1295 inpatients with AMI were divided into normal group (n = 692), NTIS group (n = 139), renal dysfunction group (n = 304), and combined NTIS and renal dysfunction group (n = 160). Heart function, in-hospital, all-cause and cardiovascular mortality were compared among the four groups. RESULTS: After adjustment for age and sex, left ventricular ejection fraction was significantly lower in the combined group (48 ± 11%) than in the NTIS group (52 ± 10%, P = 0.017), the renal dysfunction group (52 ± 10%, P = 0.001) and the normal group (56 ± 8%, P < 0.001). After controlling for confounding factors, compared with the normal group, the NTIS and the renal dysfunction group represented higher risks of in-hospital mortality (OR: 3.643, P = 0.028; OR:3.135, P = 0.042, respectively), all-cause mortality (HR: 2.138, P = 0.007; HR: 2.050, P = 0.003, respectively), and cardiovascular mortality (HR:2.134, P = 0.042; HR:2.237, P = 0.010, respectively). Compared to those in the NTIS and the renal dysfunction group, the patients in the combined group showed a further increased risk for in-hospital mortality (OR:2.916, P = 0.039; OR:2.487, P = 0.036, respectively), all-cause mortality (HR: 1.939, P = 0.015; HR: 2.020, P = 0.002, respectively) and cardiovascular mortality (HR:2.420, P = 0.010; HR:2.303, P = 0.002, respectively). CONCLUSIONS: Both NTIS and renal dysfunction increase short-term in-hospital mortality, and long-term all-cause and cardiovascular mortality risk in patients with AMI. Furthermore, the coexistence of NTIS and renal dysfunction presents further increased mortality risk in AMI patients.

Nonthyroidal illness: a risk factor for coronary calcification and arterial stiffness in patients undergoing peritoneal dialysis?

OBJECTIVES: Low triiodothyronine levels, as part of the nonthyroidal illness syndrome, are common in dialysis patients and have repeatedly been shown to be associated with increased (cardiovascular) mortality rates. We hypothesized that increased vascular calcification may mediate this relationship. METHODS: A total of 84 patients from the Stockholm region receiving maintenance peritoneal dialysis were included in the study. Serum concentrations of free triiodothyronine (fT3), thyroxine and thyroid-stimulating hormone were measured. Coronary artery calcium (CAC) scores were assessed by cardiac computed tomography scans. Surrogates of arterial stiffness included aortic diastolic and systolic blood pressures, pulse pressure, augmentation pressure and Buckberg's subendocardial viability ratio measured by pulse waveform analyses. Patients were subsequently followed, and events of death and censoring were recorded. Thyroid hormone concentrations were associated with CAC scores, measures of arterial stiffness and all-cause mortality. The associations between CAC scores and arterial stiffness surrogates and mortality were also determined to evaluate a possible causal pathway. RESULTS: Both CAC scores and arterial stiffness surrogates were substantially higher in individuals with low fT3 levels. These associations persisted in multivariate logistic and linear regression analyses. During a median (interquartile range) follow-up of 32 (22-42) months, 24 patients died. Both fT3 levels below the median value [HR crude 4.1, 95% confidence interval (CI) 1.4-12.6] and CAC scores above the median value (HR crude 5.8, 95% CI 1.7-20.1) were strongly associated with mortality. CONCLUSIONS: In patients undergoing peritoneal dialysis, fT3 levels were strongly associated with arterial stiffness, coronary artery calcification and mortality. We speculate that the association between nonthyroidal illness and mortality may be partly mediated by acceleration of vascular calcification.

Evaluation and clinical application of changes in thyroid hormone and TSH levels in critically ill full-term newborns.

INTRODUCTION: The term "euthyroid sick syndrome" (ESS) has been used to describe a pattern of thyroid hormone changes during the course of critical illness in adult patients without thyroid disease, often associated with reduced thyroid hormone secretion. OBJECTIVE: To describe the thyroid hormone profile in full-term newborns critically ill compared with thyroid hormone profile of healthy infants, and determine if alterations could be related to the severity of the disease and outcome. METHODS: A cross-sectional, observational, and prospective study of full-term infants admitted to the neonatal intensive care unit (NICU) of the Hospital de Pediatría J.P. Garrahan between July 2007 and April 2008. Serum T3, T4, and thyroid stimulating hormone (TSH) levels were measured at admission and severity of the disease was evaluated through SNAP, lactic acid, respiratory assistance and number of organs affected. RESULTS: Sick newborns showed significantly lower T3 and T4 levels compared with healthy infants [T3: -0.97 µg/dL (95% CI -0.89, -1.13) and T4: -4.37 µg/dL (95% CI -2.95, -5.78)]. Only 29 out of 94 (31%) infants presented a normal profile; 37 (39%) infants showed isolated low T3 levels, 20 (21%) infants had low T3 and T4 levels and eight (9%) infants had low TSH, T3, and T4. Of this latter group, five of eight (62%) children died suggesting a significantly higher risk of death for patients with low T3 associated with low T4 and TSH [Risk ratio (RR) 10.75 95% CI 3.93, 29]. CONCLUSIONS: Full-term sick newborns frequently have lower thyroid hormone levels than healthy ones. These observed thyroid hormones changes might be related to the underlying disease and could be used as a prognostic marker of the severity and fatal outcome of the patient.

Thyroid Hormone Supplementation and All-Cause Mortality in Community-Dwelling Older Adults: Results from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Although elevated thyrotropin (TSH) is common in older adults, controversy exists over what degree of elevation should be treated with thyroid hormone supplements. Isolated, elevated TSH in this population can be consistent with aging-related adaptations rather than indicative of primary thyroid disease, raising the possibility that thyroid hormone replacement may be harmful. OBJECTIVES: Determine the association between all-cause mortality and levothyroxine use among older adults. DESIGN: Longitudinal observational study. SETTING: Baltimore Longitudinal Study of Aging. PARTICIPANTS: One thousand two hundred and fifty eight community dwelling adult participants aged 65+ with an average of 9 years of follow up. MEASUREMENTS: Thyroid and pituitary hormone levels and thyroid hormone supplementation were determined at each visit. Incident rate ratios (IRR) for all-cause mortality were calculated using time-dependent Poisson regression models to accommodate the varying start times. To isolate the effects of hormone replacement from its effects on TSH, the association between treatment and all-cause mortality was analyzed in participants with stable thyroid function status throughout follow-up (N = 638). RESULTS: Thyroid hormone supplementation was not associated with a significant increase all-cause mortality in the subsequent year in the fully adjusted model (IRR = 1.40, 95% confidence interval (CI) = 0.93-2.12). In a stratified analysis of euthyroid participants, thyroid hormone use was associated with significantly greater mortality, with an adjusted IRR = 1.81 (95% CI = 1.10-2.98). CONCLUSION: The increased mortality associated with thyroid hormone use among the subclass of euthyroid community dwelling older adults is consistent with a model in which TSH elevation can result from a variety of underlying pathophysiologic processes, not all of which should be treated with thyroid hormone supplementation. Clinicians should consider overall clinical status when interpreting an isolated elevated TSH in older adults.

Non-thyroidal illness syndrome and short-term survival in a hospitalised older population.

BACKGROUND: non-thyroidal illness syndrome (NTIS) has been associated with an adverse clinical outcome. OBJECTIVE: to evaluate the prevalence of NTIS, its impact on patients' survival and the possible pathogenic role of systemic inflammation. DESIGN: observational cross-sectional analysis. PARTICIPANTS AND SETTING: three hundred and one acutely ill older patients (156 women; median age 81 years, range 65-101) consecutively admitted to a primary care unit. METHODS: serum FT(3), FT(4) and thyrotropin levels as well as acute inflammation indexes were evaluated. RESULTS: the NTIS prevalence (specifically low T3 syndrome) was 31.9%. A significant association was found between NTIS and acute renal failure (P = 0.006), New York Heart Association classification (NYHA) IV heart failure (P = 0.003) and metastasised cancer disease (P = 0.0002). Serum FT(3) values correlated inversely with serum C-reactive protein (P < 0.0001), lactate dehydrogenase (P = 0.0004), fibrinogen (P = 0.03) and erythrocyte sedimentation rate (P < 0.0001) values, and progressively decreased with increasing tertiles of age (P = 0.0004). The mortality rate was significantly higher (P = 0.0002) among patients with low T3 syndrome, which emerged as the sole predictive factor of death (odds ratio 4.3; 95% confidence interval 1.7-10.5). CONCLUSIONS: low T3 syndrome is very common in the hospitalised older population, emerging as the most sensitive independent predictor of short-term survival. Serum FT(3) determination should be included in the assessment of short-term prognosis of acutely ill older patients.

Prognostic Value of Thyroid Hormone FT3 in General Patients Admitted to the Intensive Care Unit.

Low plasma triiodothyronine (T3) concentration indicates nonthyroidal illness syndrome (NTIS), which might be associated with a poor outcome in patients in the intensive care unit (ICU). This study evaluated the relationship between NTIS and prognostic indicators in patients admitted to the ICU and examined the fT3 cut-off points that could be associated with 28-day mortality. This prospective observational study included patients admitted to the ICU of The Third Hospital of Hebei Medical University from February to November 2018. The baseline variables and the occurrence of low free T3 (FT3) were collected. The patients were divided into the NTIS (FT3 < 3.28) and non-NTIS groups. Among 305 patients, 118 (38.7%) were in the NTIS group. FT3 (P < 0.001) and FT4 (P = 0.001) were lower, while the 28-day mortality rate (P < 0.001) and hospitalization expenses in ICU (P = 0.001) were higher in the NTIS group. The univariable analyses identified NTIS, FT3, free thyroxine/FT3, APACHEII, sequential organ failure score, duration of mechanical ventilation, creatinine, oxygenation index, white blood cells, albumin, age, and brain natriuretic peptide as being associated with 28-day mortality (all P < 0.05). The cut-off value of FT3 for 28-day mortality was 2.88 pmol/L. The 28-day mortality rate and hospitalization expenses in the ICU were higher in patients with NTIS. NTIS was independently associated with 28-day mortality.

Association between mild thyroid dysfunction and clinical outcome in acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Thyroid hormones profoundly influence the cardiovascular system, but the effects of mild thyroid dysfunction on the clinical outcome of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) are not well defined. This study aimed to determine the effect of mild thyroid dysfunction on 12-month prognosis in ACS patients undergoing PCI. METHODS: In this prospective cohort study with a 12-month follow-up, 1560 individuals were divided into four groups based on thyroid hormone levels upon admission: euthyroidism (used as a reference group), subclinical hypothyroidism, subclinical hyperthyroidism, and low triiodothyronine syndrome (low T3 syndrome). The outcomes measured were all-cause mortality, cardiac mortality, nonfatal rein-farction, and unplanned repeat revascularization. RESULTS: In this study, the prevalence of mild thyroid dysfunction was 10.8%. Multivariate analysis showed that low T3 syndrome, but not subclinical hypothyroidism or subclinical hyperthyroidism, was associated with a higher rate of all-cause (HR 2.553, 95% CI 1.093-5.964, p = 0.030) and cardiac mortality (HR 2.594, 95% CI 1.026-6.559, p = 0.034), compared with the euthyroidism group. CONCLUSIONS: Mild thyroid dysfunction was frequent in patients with ACS undergoing PCI. Low T3 syndrome was the predominant feature and was associated with 12-month adverse outcomes in these patients.

A prognostic role for non-thyroidal illness syndrome in chronic renal failure:a systematic review and meta-analysis.

BACKGROUND: Chronic renal failure (CRF) is a serious disease that has become a burden on global and local economics and public health. In addition, non-thyroidal illness syndrome (NTIS) has become increasingly more prevalent in CRF patients. MATERIALS AND METHODS: A data search was conducted on the PubMed/Medline, Cochrane Library, Web of Science, Embase, and CBM databases to identify studies up to November 1st, 2018, that compared low T3 and normal T3 levels in patients with CRF. Data analysis was done by calculating the relative risks (RR) and 95% confidence intervals (95% CI) and continuous variables were described by weighted mean difference (WMD) and 95% CI. The efficacy outcomes included renal function and mortality. The Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality scale were used to assess the quality of the cohort and cross-sectional studies, respectively. A funnel plot was used to identify publication bias. RESULTS: Seventeen studies with a total of 4593 patients were finally included in the analysis. Among the 17 studies, 11 reported the mortality of CRF patients with low T3 and normal T3 levels. Subgroups were assigned according to different follow-up times and different methods of treatment. The mortality rate in the low T3 group was much higher than in the normal T3 group. 11 studies reported creatinine (Cr) results in patients with low T3 and normal T3 levels and our analysis found no significant differences between the two groups (95%CI: 0.46-0.25; P-heterogeneity = 0.000; P = 0.559). Five studies reported uric acid results and we found no significant differences between the two groups (95%CI: 0.08-0.22; P-heterogeneity = 0.438; P = 0.377). Five studies reported the urea levels in the two groups and our analysis found no significant differences (95%CI: 1.60-1.23; I2 = 0.0%; P-heterogeneity = 0.498;P = 0.798). CONCLUSION: Low T3 had a greater impact on the short-term prognosis of patients with CRF than on the long-term prognosis. NTIS did not cause substantial kidney damage.

[Prevalence and prognostic value of non-thyroidal illness syndrome among critically ill children]. / Prevalencia y valor pronóstico del síndrome del enfermo eutiroideo en niños críticos.

INTRODUCTION: Alterations in thyroid hormones during critical illness, known as non-thyroidal illness syndrome (NTIS), were suggested to have a prognostic value. However, pediatric data is limited. The aim of this study was to assess prevalence and prognostic value of NTIS among critically ill children. MATERIALS AND METHODS: A prospective observational study conducted on 70 critically ill children admitted into pediatric intensive care unit (PICU). Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were measured within 24hours of PICU admission. Primary outcome was 30-day mortality. RESULTS: NTIS occurred in 62.9% of patients but it took several forms. The most common pattern was low FT3 with normal FT4 and TSH (25.7% of patients). Combined decrease in FT3, FT4, and TSH levels occurred in 7.1% of patients. An unusual finding of elevated TSH was noted in three patients, which might be related to disease severity. Low FT4 was significantly more prevalent among non-survivors compared with survivors (50% versus 19.2%, P=.028). NTIS independently predicted mortality (OR=3.91; 95% CI=1.006-15.19; P=.0491). Concomitant decrease in FT3, FT4, and TSH was the best independent predictor of mortality (OR=16.9; 95% CI=1.40-203.04; P=.026). TSH was negatively correlated with length of PICU stay (rs=-0.35, P=.011). FT3 level was significantly lower among patients who received dopamine infusion compared with those who did not receive it (2.1±0.66 versus 2.76±0.91pg/mL, P=.011). CONCLUSION: NTIS is common among critically ill children and appears to be associated with mortality and illness severity.

Low triiodothyronine serum levels as a predictor of poor prognosis in burn patients.

OBJECTIVE: Euthyroid sick syndrome is a common finding in critically ill patients with nonthyroidal illness, characterized by low serum levels of free triiodothyronine (fT3) with a peculiar increase in reverse T3 (rT3) and normal-to-low free thyroxine (fT4) as well as thyroid-stimulating hormone (TSH) levels. This condition has been proposed as a prognostic factor of worse outcome in critically ill patients, while no conclusive data are available in burns. METHODS: Since thyroid function testing is contained in our baseline laboratory tests at admission, we retrospectively evaluated fT3, fT4 and TSH in 295 consecutive burn patients admitted to the Burn Center of Turin from January 2002 to December 2006, comparing hormone levels in survivors and non-survivors. RESULTS: fT3 and TSH levels were significantly lower (p

Prognostic significance of high free T4 and low free T3 levels in non-thyroidal illness syndrome.

BACKGROUND: Non-thyroidal illness syndrome is characterized by decreased serum free T3 (FT3) level and associates with long term mortality. Serum free T4 (FT4) may affect on mortality with FT3 in course of chronic illness. This study performed to evaluate the association between both decreased FT3 with elevated FT4 levels and mortality risk. METHODS: This study is a retrospective cohort analysis and consisted up 1164 (571 male, 593 female) patients with a 36 months follow up period. Patients divided into four groups according to thyroid functions. Patients with euthyroidism were in Group A, elevated FT3 in group B, decreased FT3 in group C and both decreased FT3 and elevated FT4 levels in group D. The levels of thyroid hormones and all cause mortality were compared between four groups. RESULTS: Mortality rate was elevated between Groups A and B, A and C, A and D, B and C, B and D, C and D, (p < .001, p < .001, p < .001, p < .001, p < .001, p:0.019, respectively). A multivariate Cox proportional hazards model was performed to evaluate the mortality risk between groups. A close relationship was observed in Group C and D patients for the mortality risk (OR:1.561, 95% CI:1.165-2.090, p:0.003 and OR:2.224, 95% CI:1.645-3.006, p:0.0001, respectively). CONCLUSION: Both decreased FT3 and elevated FT4 levels are independent predictor for long term mortality risk in hospitalized chronic patients with non-thyroidal illness syndrome.

Low T3 syndrome improves risk prediction of in-hospital cardiovascular death in patients with acute myocardial infarction.

BACKGROUND: Low triiodothyronine (T3) syndrome (LT3S) is frequently seen in patients with acute myocardial infarction (AMI). We examined the association between LT3S and severity of myocardial injury and determined whether LT3S adds predictive value over thrombolysis in myocardial infarction (TIMI) risk score for in-hospital cardiovascular (CV) death. METHODS: Of 2459 AMI patients, 529 pairs of euthyroid and LT3S individuals with similar baseline characteristics were identified using 1:1 propensity score matching. LT3S was defined as free T3 (fT3) <2.36pg/mL, normal values of thyroid-stimulating hormone and free thyroxin. Primary outcome was in-hospital CV death. Receiver operating characteristic curves were generated to assess the predictive effects of fT3, TIMI risk score, and TIMI-LT3S risk score on in-hospital CV death. RESULTS: LT3S was found in 23.3% of patients with AMI. The peak values of cardiac troponin I in ng/mL and N-terminal pro-brain natriuretic peptide in ng/mL were significantly higher in LT3S: 6.6 (1.3-19.6) vs. 3.5 (0.8-12.1), p<0.001 and 3625 (1046-12,776) vs. 2158 (774-6759), p<0.001. Patients with LT3S had significantly higher rate of in-hospital CV death than those without (4.7% vs. 1.7%, p=0.005). Lower levels of fT3 yielded an area under the curve (AUC) of 0.741 for predicting CV death. LT3S, when added to the TIMI risk score, significantly increased AUC for in-hospital CV death than TIMI risk score alone (0.775 vs. 0.738, p=0.005). CONCLUSIONS: LT3S was associated with more severe myocardial injury and increased in-hospital CV mortality in patients with AMI. Furthermore, it improved risk prediction of in-hospital CV death post-AMI when it was added to the TIMI risk score.

[The euthyroid sick syndrome in severe acute illness]. / Syndrome de dyshormonémie euthyroïdienne au cours de la maladie aiguë grave.

OBJECTIVE: To describe euthyroid sick syndrome (ESS) and its different clinical variants in severe acute illness. DESIGN: This prospective cohort study examined hormone results and outcome for patients admitted to our intensive care unit (ICU). METHODS: In this heterogeneous group of 108 patients from our ICU we analyzed the prevalence of ESS and its influence on mortality and sought to determine if any thyroid indicators had a prognostic value. RESULTS: The prevalence of ESS was similar to that described by other authors (68.5% for ESS type I, 15.7% for type II and 1.9% for type III). Patients developed thyroid alterations on their third day of hospitalization and those with ESS type II had a higher mortality rate. The only thyroid indicator with prognostic value was a reverse triiodothyronine (rT3) value exceeding 0.61 ng/mL. CONCLUSION: Severe acute illness induced the thyroid alterations known as ESS. Type I had the highest prevalence, but type II was correlated with a higher mortality rate. The only thyroid indicator with a prognostic value was rT3.

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.

Relationship Between Circulating Thyroid-Stimulating Hormone, Free Thyroxine, and Free Triiodothyronine Concentrations and 9-Year Mortality in Euthyroid Elderly Adults.

OBJECTIVES: To determine the association between plasma thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and all-cause mortality in older adults who had levels of all three hormones in the normal range. DESIGN: Longitudinal. SETTING: Community-based. PARTICIPANTS: Euthyroid Invecchiare in Chianti study participants aged 65 and older (N = 815). MEASUREMENTS: Plasma TSH, FT3, and FT4 levels were predictors, and 9-year all-cause mortality was the outcome. Cox proportional hazards models adjusted for confounders were used to examine the relationship between TSH, FT3, and FT4 quartiles and all-cause mortality over 9 years of follow-up. RESULTS: During follow-up (mean person-years 8,643.7, range 35.4-16,985.0), 181 deaths occurred (22.2%). Participants with TSH in the lowest quartile had higher mortality than the rest of the population. After adjusting for multiple confounders, participants with TSH in the lowest quartile (hazard ratio = 2.22, 95% confidence interval = 1.19-4.22) had significantly higher all-cause mortality than those with TSH in the highest quartile. Neither FT3 nor FT4 was associated with mortality. CONCLUSION: In elderly euthyroid subjects, normal-low TSH is an independent risk factor for all-cause mortality.

Low T3 syndrome is a strong predictor of poor outcomes in patients with community-acquired pneumonia.

Low T3 syndrome was previously reported to be linked to poor clinical outcomes in critically ill patients. The aim of this study was to evaluate the predictive power of low T3 syndrome for clinical outcomes in patients with community-acquired pneumonia (CAP). Data for 503 patients were analyzed retrospectively, and the primary end point was 30-day mortality. The intensive care unit (ICU) admission rate and 30-day mortality were 8.3% and 6.4% respectively. The prevalence of low T3 syndrome differed significantly between survivors and nonsurvivors (29.1% vs 71.9%, P < 0.001), and low T3 syndrome was associated with a remarkable increased risk of 30-day mortality and ICU admission in patients with severe CAP. Multivariate logistic regression analysis produced an odds ratio of 2.96 (95% CI 1.14-7.76, P = 0.025) for 30-day mortality in CAP patients with low T3 syndrome. Survival analysis revealed that the survival rate among CAP patients with low T3 syndrome was lower than that in the control group (P < 0.01). Adding low T3 syndrome to the PSI and CURB-65 significantly increased the areas under the ROC curves for predicting ICU admission and 30-day mortality. In conclusion, low T3 syndrome is an independent risk factor for 30-day mortality in CAP patients.

Delivery dependent oxygen consumption in patients with septic shock: daily variations, relationship with outcome and the sick-euthyroid syndrome.

Delivery dependent oxygen consumption (DDOC) is observed in patients with sepsis and vital organ dysfunction, and has been related to outcome. Similarly the sick-euthyroid syndrome is associated with a high mortality. We examined the daily variations of DDOC and its relation to hormonal changes, particularly those of the thyroid. In 22 patients, 14 with septic shock and 8 post-operative controls, oxygen delivery was increased by increasing cardiac output with vasodilation by phentolamine, during a total of 207 days. DDOC varied markedly between consecutive days in individual patients with sepsis, in both survivors and non-survivors. DDOC was related to severity of illness, assessed by APACHE II score (r = 0.50, p = 0.017), and plasma levels of triiodothyronine (T3), r = -0.49, p = 0.011, and thyroxine (T4), r = -0.53, p = 0.012. No correlation was observed between DDOC and outcome, nor blood levels of lactate, epinephrine, norepinephrine, dopamine or cortisol. In conclusion, we observed a marked disturbance of systemic oxygen uptake autoregulation in patients with septic shock which varied during the clinical course and was related to the sick-euthyroid syndrome.