[Related factors of euthyroid sick syndrome in patients with sepsis].

OBJECTIVE: To evaluate the prevalence of euthyroid sick syndrome (ESS) in sepsis patients and to explore its influencing factors. METHODS: In the study, 365 patients diagnosed with sepsis in the emergency critical care department of Shanghai First People's Hospital from January 2017 to January 2023 were retrospectively enrolled. The patients were divided into ESS and non-ESS groups based on whether the patients were complicated with ESS.Baseline variables and relevant clinical data of the enrolled patients were collected. The prevalence of ESS in sepsis patients and its influencing factors were evaluated by multivariate Logistic regression analysis, and the 30-day survival rates were compared between the two groups. The optimal cutoff value for free triiodothyronine (FT3) was explored to predict death in the patients with sepsis. RESULTS: There were 103 sepsis patients with ESS, accounting for 28.2% of the total cases. The severity of sepsis in ESS group was significantly higher than that in non-ESS group (P < 0.05). The acute physiology and chronic health evaluationⅡ(APACHEⅡ)score and sequential organ failure assessment (SOFA) score of ESS group were significantly higher than those of non-ESS group (P < 0.05). C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA) and interleukin-6 (IL-6) in ESS group were higher than those in non-ESS group. total cholesterol(TC)and high-density liptein cholesterol(HDL-C)in ESS group were lower than those in non-ESS group, and the differences were statistically significant (P < 0.05).Multivariate Logistic regression analysis showed that PCT, IL-6, CRP, SAA and activated partial thromboplatin time (APTT) were independent risk factors for ESS in the sepsis patients (OR values were 1.105, 1.006, 1.005, 1.009 and 1.033, respectively; 95% CI were 1.044-1.170, 1.001-1.012, 1.001-1.009, 1.005-1.014, 1.004-1.062, respectively, P < 0.05).The 30-day survival rate in ESS group was significantly lower than that in non-ESS group, the Long-rank chi-square test value was 16.611, and the difference was statistically significant (P < 0.05).The receiver operation characteristic area under the curve (AUCROC)of FT3 predicted death in the patients with sepsis was 0.924 (95% CI 0.894-0.954). The serum FT3 cutoff point was 3.705 pmol/L, the specificity was 0.868, and the sensitivity was 0.950. CONCLUSION: In this study, the incidence of ESS in sepsis patients was determined to be 28.2% with poor prognosis. The results showed that PCT, IL-6, CRP, SAA and APTT were independent risk factors for ESS in sepsis patients, while HDL-C was a protective factor (P < 0.05). FT3 is a novel potential biomarker for predicting death in patients with sepsis.

Does an episode of diabetic ketoacidosis affect thyroid function tests in pediatric patients?

OBJECTIVES: The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA). METHODS: Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group. RESULTS: A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak. CONCLUSIONS: Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests.

Non-thyroidal Illness in Children with Congestive Heart Failure

Objective: To estimate the proportion and risk factors of non-thyroidal illness (NTI) in children with congenital heart disease (CHD) with congestive heart failure (CHF). Methods: This study enrolled children (6 weeks to 60 months age) with CHD and CHF. The clinical profile and disease severity, derived from the Pediatric Early Warning Score (PEWS) was recorded. Baseline blood samples were taken within 24 hours of hospitalization and evaluated for free tri-iodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), N-terminal pro-brain natriuretic peptide (NT pro-BNP) and reverse T3. Results: A total of 80 (64 acyanotic CHD) children of median (interquartile range) age 5 (2.5, 8.0) months were enrolled. NTI was seen in 37 (46%) of whom 27 had low fT3 levels. The proportion of NTI was highest in children with severe disease (20/30), than moderate (4/9) or mild disease (13/41) (p=0.018). Ten (27%) patients with NTI died compared to 2 (4.7%) without NTI with unadjusted odds ratio (OR) [95% confidence interval (CI)] 7.593 (1.54, 37.38); p=0.006. After adjusting for NTI, shock and NT-pro-BNP levels, PEWS was the only significant predictor of mortality (OR: 1.41, 95% CI: 1.03, 1.92; p=0.032). Linear regression for fT3 identified a significant relationship with log NT-BNP [beta -3.541, (95% CI: -1.387, -0.388)] and with TSH [beta 2.652 (95% CI: 0.054, 0.383)]. The cutoff (area under the curve, 95% CI) that predicted mortality were fT4 <14.5 pmol/L (0.737, 0.60, 0.88), fT3/rT3 index <1.86 pg/ng (0.284, 0.129, 0.438) and NT pro-BNP >3725 pg/mL (0.702; 0.53, 0.88). Conclusion: NTI was present in a significant proportion of children with CHD and CHF. fT3 level was significantly associated with NTBNP levels and thus severity of CHF.

Elevated Thyroid Autoantibodies Aggravate Stroke Severity in Euthyroidism with Acute Ischemic Stroke.

Introduction: Studies have indicated that immune reactions contribute to endothelial dysfunction and atherosclerosis. It is unclear whether thyroid dysfunction or elevated thyroid autoantibodies are associated with atherosclerosis. Therefore, we investigated the influence of thyroid autoimmunity related to elevated thyroid autoantibodies on functional outcome in euthyroidism with acute ischemic stroke (AIS). Methods: All patients with AIS underwent tests for thyroid function and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin autoantibody). We divided the patients suffering from euthyroidism and AIS into positive thyroid autoantibody and negative thyroid autoantibody groups. Demographic profiles, risk factors, and functional outcomes were compared between the two groups. Results: Out of the total 422 patients, 50 (11.8%) were included in the positive thyroid autoantibody group. The National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge was higher in the positive thyroid autoantibody group than the negative thyroid autoantibody group (P < 0.05). In addition, there was significant difference in the mortality during hospitalizations between the two groups (P < 0.01). Conclusion: This study showed that thyroid autoantibodies aggravate stroke severity in euthyroidism with AIS. We speculate that vascular damage related to thyroid autoimmunity may aggravate the increased risk of unfavorable outcomes, independent of thyroid function.

The Association of Thyroid Hormones with Coronary Atherosclerotic Severity in Euthyroid Patients.

The aim of the work was to explore the correlation between thyroid hormones and coronary atherosclerotic severity. This cross-sectional study included 340 euthyroid patients who underwent diagnostic coronary artery angiography (CAG). Gensini Score (GS) was applied to assess the severity of coronary atherosclerosis. Thyroid hormones and routine biochemical parameters were measured. The associations between thyroid hormones and coronary atherosclerosis severity were analyzed. Thyroid hormones levels or parameters were taken as both continuous variables and tertiles into analysis, and the lowest tertile was usually used as the reference (OR=1) for medium and highest tertiles. Free triiodothyronine (FT3) level was associated with GS≥22 (Median GS) in Model I adjusted for age and sex [Continuous: OR=0.46, 95% CI (0.23, 0.92), p=0.029; Tertile 3: OR=0.54, 95% CI (0.30, 0.97), p=0.038], and Model II adjusted for all known risk factors of coronary artery disease (CAD) [Continuous: OR=0.44, 95% CI (0.20, 0.95), p=0.036; Tertile 3: OR=0.49, 95% CI (0.25, 0.96), p=0.039]. Subjects with highest tertile of FT3 to free thyroxine (FT4) ratio (FT3/FT4 ratio) appeared to have the remarkably decreased risk of CAD in both Non-adjusted Model [OR=0.49, 95% CI (0.24, 0.98), p=0.044] and Model I [OR=0.45, 95% CI (0.22, 0.93), p=0.031]. Higher FT3 level within normal range was independently and negatively associated with severity of coronary atherosclerosis. Besides, FT3/FT4 ratio was remarkably correlated with the prevalence of CAD in euthyroid population.

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.

An analysis of perinatal factors of low T3 syndrome in preterm neonates with a gestational age of 28-35 weeks.

OBJECTIVE: Low triiodothyronine syndrome (LT3S) is a common endocrine disease in preterm neonates. Various serious acute or chronic diseases result in LT3S. Few studies have investigated the causal relationship between perinatal factors and LT3S in preterm neonates with a gestational age (GA) of 28-35 weeks. The present study comprehensively analyzed the perinatal factors of LT3S in preterm neonates. METHODS: This was a retrospective study of neonates with and without LT3S from January 2018 to November 2019. Compared to 206 preterm neonates without LT3S, 158 neonates were diagnosed with LT3S, excluding neonates with congenital malformations, other endocrine diseases, genetic diseases and inherited metabolic diseases. RESULTS: Five perinatal risk factors for LT3S were confirmed using univariate and multivariate analyses: smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), neonatal sepsis, and dopamine use. CONCLUSIONS: LT3S in preterm neonates was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, RDS, sepsis, and dopamine use. Preterm neonates with a GA of 28-35 weeks who are exposed to a series of high-risk perinatal factors must be closely observed, diagnosed early and treated for primary diseases promptly to reduce the occurrence of LT3S and improve the outcomes.Key Message:Few studies have investigated the relationship between perinatal factors and Low triiodothyronine syndrome (LT3S) in preterm neonates with a gestational age (GA) of 28-35 weeks.LT3S was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), sepsis, and dopamine use.

Serial measurement of thyroid hormones in hospitalised dogs with canine parvoviral enteritis: Incidence of non-thyroidal illness syndrome and its association with outcome and systemic inflammatory response syndrome.

The aim of this study was to serially evaluate the serum concentrations of total thyroxine (tT4), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) in dogs with canine parvoviral enteritis (CPVE) during a 5-day hospitalisation period and assess the association of these hormone concentrations with the outcome and the development of systemic inflammatory response syndrome (SIRS). Dogs with confirmed CPVE that were hospitalised for at least 5 days were included. The thyroid hormones concentrations were measured on days 1, 3 and 5 of hospitalisation. Twenty-eight dogs were included. All (28/28, 100%), 19/28 (69.7%) and 23/28 (82.1%) dogs had a low serum tT4, fT4 and TSH concentration, respectively, on at least 1 day during the hospitalisation period. Overall, 11/28 (39.3%) dogs were diagnosed with SIRS on at least 1 day. In survivors, serum tT4 concentration was significantly higher on day 5 (median, range: 11.8 nmol/L, <6.4-32.2 nmol/L) compared to those on days 1 (<6.4 nmol/L, <6.4-20.1 nmol/L; P = 0.010) or 3 (7.6 nmol/L, <6.4-25.2 nmol/L; P = 0.019). Survivors had a significantly higher tT4 concentration (median, range: 11.8 nmol/L, <6.4-32.2 nmol/L) on day 5 compared to non-survivors (<6.4 nmol/L, <6.4-7.2 nmol/L; P = 0.002). Regardless of the day of hospitalisation, dogs with SIRS had significantly lower tT4 (<6.4 nmol/L, <6.4-16.3 nmol/L) compared to dogs without SIRS (8.6 nmol/L, <6.4-32.2 nmol/L; P = 0.006). A significant difference was also found in fT4 between dogs with SIRS (<3.9 pmol/L, <3.9-16.2 pmol/L) and dogs without SIRS (15.1 pmol/L, <3.9-59.2; pmol/L; P < 0.001). Non-thyroidal illness syndrome was frequently observed in dogs with CPVE, and a negative association between tT4 and fT4 concentrations and SIRS was noted. Serial measurements of tT4 concentrations appeared to have prognostic value.

Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure.

BACKGROUND: In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF). METHODS: A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 < 2.3pg/mL, n = 168) and non-LT3S group (FT3 ≥ 2.3pg/mL, n = 426). RESULTS: In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP. Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality. CONCLUSIONS: In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.

Thyroid dysfunction in COVID-19 patients.

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

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.

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome.

BACKGROUND: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. METHODS: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. RESULTS: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003). CONCLUSIONS: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

Association Between Low T3 Syndrome and Poor Prognosis in Adult Patients With Acute Myocarditis.

Background: This study aims to investigate the role of free triiodothyronine (fT3) in predicting poor prognosis of adult patients with acute myocarditis. Methods: A total of 173 consecutive adult patients with acute myocarditis completed thyroid function evaluations. They were divided into two groups according to fT3 levels: low fT3 group (n = 54, fT3 < 3.54 pmol/liter) and normal fT3 group (n = 119, fT3 ≥ 3.54 pmol/liter). The primary endpoint was major adverse cardiac events (MACE). Results: During the 3.5 ± 2.8 years follow-up, the rate of MACE was 29.6% versus 3.5% in low fT3 group versus normal fT3 group, respectively (P < 0.0001). Long-term at 8 years MACE-free survival were lower in low fT3 group versus normal fT3 group (52.9% versus 92.3%, log-rank P < 0.0001), respectively. Univariate Cox analysis showed that left ventricular ejection fraction (LVEF) < 50% [hazard ratio (HR) 10.231, 95% confidence interval (CI): 3.418-30.624, P < 0.0001) and low fT3 level (HR 0.360, 95% CI: 0.223-0.582, P < 0.0001) were strongest two predictors of MACE. After adjustment for traditional risk predictors, the prognostic value of fT3 status was still significant (HR 0.540, 95% CI: 0.316-0.922, P = 0.024). Compared with normal fT3 group, those in low fT3 group were at a much higher risk of MACE (HR 5.074, 95% CI: 1.518-16.964, P = 0.008). Conclusions: Low T3 syndrome was a strong predictor of poor prognosis in adult patients with acute myocarditis. These findings suggest that fT3 level could serve as a biomarker for risk stratification in acute myocarditis patients.

The Association of TSH and Thyroid Hormones With Lymphopenia in Bacterial Sepsis and COVID-19.

CONTEXT: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. OBJECTIVE: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. METHODS: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n = 224) and COVID-19 patients (n = 161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. RESULTS: Only T3 significantly correlated (ρ = 0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n = 56 per group). Severe lymphopenic COVID-19 patients (n = 17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n = 18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. CONCLUSION: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved.

Clinical and laboratory aspects of 3,3',5'-triiodothyronine (reverse T3).

Reverse T3 (3,3',5'-triiodothyronine or rT3) is the third most abundant iodothyronine circulating in human blood and is produced by the inner ring deiodination of the pro-hormone thyroxine (T4). Unlike the more abundant and active metabolite T3, the measurement of serum rT3 is yet to find a routine clinical application. As rT3 binds weakly to the T3 thyroid nuclear hormone receptors, it is thought to represent an inactive end-product of thyroid hormone metabolism, diverting T4 away from T3 production. The analysis of serum rT3 has, up until recently, been measured by competitive radioimmunoassay, but these methods have been superseded by mass-spectrometric methods which are less susceptible to interference from other more abundant iodothyronines. Serum rT3 concentration is increased as part of the non-thyroidal illness syndrome, and by administration of common medications such as amiodarone which inhibit the metabolism of rT3. Serum rT3 concentration is also affected by genetic conditions that affect the iodothyronine deiodinases, as well as thyroid transporters and transport proteins. Analysis of rT3 can provide a useful diagnostic fingerprint for these conditions. rT3 has been shown to bind extra-nuclear iodothyronine receptors with a potential role in cell proliferation; however, the clinical relevance of these findings awaits further study.

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.

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.

Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE.

OBJECTIVES: Nonthyroidal illness syndrome (NTIS), also known as low triiodothyronine (T3) syndrome, frequently affects patients with systemic lupus erythematosus (SLE) and may affect lipid metabolism. Dyslipidemia is highly prevalent and associated with the long-term prognosis of SLE. The aim of the present study was to explore the clinical significance of NTIS on disease activity and dyslipidemia in patients with SLE. METHODS: Clinical and laboratory data were collected retrospectively from 223 patients with SLE. The correlation between free triiodothyronine (FT3), SLE disease activity, and lipid profiles were estimated. The correlation coefficient (r) was calculated using a Pearson's regression model. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for dyslipidemia in SLE. RESULTS: Serum FT3 levels were negatively correlated with the levels of 24 h urine protein (UP), blood urea nitrogen (BUN), creatinine (Cr) and SLE disease activity index (SLEDAI) (all p < 0.001) in NTIS patients but not in euthyroid patients. ApoB/ApoA1 was significantly correlated with SLEDAI (p < 0.01) in NTIS patients and CRP (p < 0.001) and ESR (p < 0.01) in euthyroid patients. A multivariate analysis revealed that only FT3 exhibited an independent negative association with dyslipidemia (P = 0.01; OR = 0.48; 95% CI 0.27-0.85). CONCLUSION: NTIS frequently occurs in patients with SLE. Low FT3 is associated with disease activity in SLE patients complicated with NTIS. Low FT3 is an independent risk factor for dyslipidemia in patients with SLE.

Higher Caloric Exposure in Critically Ill Patients Transiently Accelerates Thyroid Hormone Activation.

INTRODUCTION: The inflammatory response of critical illness is accompanied by nonthyroidal illness syndrome (NTIS). Feeding has been shown to attenuate this process, but this has not been explored prospectively over time in critically ill patients. OBJECTIVE: To explore the impact of calorie exposure on NTIS over time in critically ill patients. METHODS: Mechanically ventilated patients with systemic inflammatory response syndrome (SIRS) were randomized to receive either 100% or 40% of their estimated caloric needs (ECN). Thyroid hormones were measured daily for 7 days or until intensive care unit discharge or death. Mixed level regression modeling was used to explore the effect of randomization group on plasma triiodothyronine (T3), reverse triiodothyronine (rT3), thyroxine (T4), and thyroid stimulating hormone (TSH), as well as the T3/rT3 ratio. RESULTS: Thirty-five participants (n=19 in 100% ECN; n=16 in 40% ECN) were recruited. Adjusting for group differences in baseline T3/rT3 ratio, the parameters defining the fitted curves (intercept, linear effect of study day, and quadratic effect of study day) differed by randomization group (P = 0.001, P = 0.01, and P = 0.02 respectively). Plots of the fitted curves revealed that participants in the 100% ECN group had a 54% higher T3/rT3 ratio on postintervention day 1 compared with the 40% ECN group, a difference which attenuated over time. This was driven by a 23% higher plasma T3 and 10% lower plasma rT3 levels on postintervention 1. CONCLUSIONS: Higher caloric exposure in NTIS patients transiently attenuates the drop of the plasma T3/rT3 ratio, an effect that is minimized and finally lost over the following 3 days of continued higher caloric exposure.

Low triiodothyronine syndrome is associated with platelet function in patients with nephrotic syndrome.

OBJECTIVE: The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS: Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS: The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION: NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.