Evaluation of non-thyroidal illness syndrome in shock patients admitted to pediatric intensive care unit in a developing country.

During critical illness, children my experience various changes in their thyroid hormone levels. Such changes are termed non-thyroidal illness syndrome (NTI). The extent of change correlates with the severity of the illness and its outcomes in critically ill patients. This study aimed to investigate the correlation between the severity of shock and thyroid hormone derangement. This prospective observational study included forty patients aged one month to five years who were admitted to the pediatric intensive care unit (PICU) with shock. Thyroid function tests were conducted on admission, after shock reversal, and five days later. NTI patterns were observed in 70% of patients. The PIM2 score showed a significant negative correlation with T3 (r = - 0.353, p = 0.026) and FT3 levels on admission (r = - 0.417, p = 0.007). Furthermore, after shock reversal, the PIM2 score continued to exhibit significant negative correlations with T4 (r = - 0.444, p = 0.004), T3 (r = - 0.329, p = 0.038), FT3 (r = - 0.355, p = 0.025), and FT4 levels (r = - 0.379, p = 0.016).    Conclusion: This study underscores the high prevalence of NTI in PICU shock patients and suggests monitoring thyroid hormone levels for outcome prediction and treatment guidance. Further research is needed to optimize NTI management in critically ill children. What is Known: • Non-thyroidal illness syndrome (NTIS) is a condition observed in critically ill patients. • There has been limited research on NTI in children, and existing studies have generated conflicting results regarding the relationship between thyroid hormones and clinical outcomes in cases of sepsis and septic shock. What is New: • The study has revealed dynamic changes in free triiodothyronine (FT3) levels during the process of shock reversal and recovery in children who experienced shock. • A significant negative correlation was found between the Pediatric Index of Mortality 2 (PIM2) score and several thyroid hormone levels, including FT3 on admission and T4, FT3, and FT4 on shock reversal.

Triiodothyronine hormone supplementation therapy in septic shock patients with euthyroid sick syndrome: two pilot, placebo-controlled, randomized trials.

BACKGROUND: To assess 28-day survival in two pilot groups of septic shock patients with euthyroid sick syndrome (ESS) supplemented with triiodothyronine (T3). METHODS: A total of 95 septic shock patients with ESS were divided according to values of the thyroid hormones into low T3 and low T3T4 groups. Among 48 patients with low T3, 24 (50%) were randomized to T3 for 4 days and 24 (50%) to placebo. Among 47 patients with low T3T4, 24 (51%) were randomized to T3 for 4 days and 23 (49%) to placebo. The analysis included 28-day survival as the primary outcome and laboratory with hemodynamics as the secondary outcomes. Laboratory data were analyzed on the day of admission (T0), on the first (T1), third (T2) and seventh day (T3) with hemodynamics analyzed for the first four days. RESULTS: In the low T3 population, 18 (75%) patients receiving T3 died at day 28 compared with 8 (33.3%) patients receiving placebo (p = 0.004). In the low T3T4 population, 6 (25%) patients receiving T3 died in ICU compared with 12 (52.1%) patients receiving placebo (p = 0.039). Oral T3 treatment increased mean arterial pressure values at day 1, day 3 and day 7 in the low T3T4 population, (p = 0.015, =0.005 and =0.042 respectively), and had no significant effect on these values in the low T3 population. CONCLUSION: T3 supplementation was associated with a low 28-day mortality rate in patients with low T3T4 but with increased mortality in patients with low T3 ESS. These results suggest caution before initiating thyroid supplementation in septic patients. REGISTRATION: ClinTrials.gov (NCT05270798).

Low T3 syndrome predicts more adverse events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM. METHODS: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis. RESULTS: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively). CONCLUSIONS: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population.

Low T3 syndrome as a predictor of poor outcomes in patients with follicular lymphoma.

The aim of this study was to investigate the prognostic value of low T3 syndrome in follicular lymphoma (FL). A total of 221 FL patients with detailed serum thyroid hormone levels and other complete clinical data were enrolled. Baseline features associated with low T3 syndrome were analyzed and balanced by propensity score matching. Univariate and multivariate regression analyses were performed to determine independent risk factors for progression-free survival (PFS) and overall survival (OS). A receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) was calculated to assess the predictive accuracy of FL international prognostic index FLIPI-1/FLIPI-2 and low T3 syndrome. A total of 22 patients (10.0%) had low T3 syndrome at diagnosis, which was associated with poor PFS and OS in the rituximab era. It is an independent prognostic factor for PFS and OS. Low T3 syndrome and FLIPI-1/FLIPI-2 significantly increased the AUC of PFS and OS compared to FLIPI-1/FLIPI-2 alone. Low T3 is a risk factor for POD24. In conclusion, low T3 syndrome may be a good candidate for predicting the prognosis of CLL in future clinical practice. Our study demonstrates that low T3 syndrome is associated with poorer survival outcomes in FL patients.

Evolution of non-thyroidal illness syndrome in acute decompensation of liver cirrhosis and acute-on-chronic liver failure.

Background and aims: Non-thyroidal illness syndrome (NTIS) is frequent in critically ill patients and associated with adverse outcomes. We aimed to characterize the evolution of NTIS in patients with acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF), since NTIS is not well described in these newly defined syndromes. Methods: Thyroid hormones (TH) were quantified at baseline in consecutive patients with cirrhosis. In addition, 76 inflammatory mediators were quantified by proximity extension analysis assay in a subgroup of patients. Associations between TH, cirrhosis stage, mortality and inflammation were assessed. Results: Overall, 437 patients were included, of whom 165 (37.8%), 211 (48.3%), and 61 (14%) had compensated cirrhosis (CC), AD, and ACLF. FT3 concentrations were lower in AD versus CC, and further decreased in ACLF. Importantly, NTIS was present in 83 (39.3%) patients with AD and in 44 (72.1%) patients with ACLF (P<0.001). Yet, TSH and TSH-based indexes (TSH/FT3-ratio, thyroid index) showed an U-shaped evolution during progression of cirrhosis, suggesting a partially preserved responsiveness of the hypothalamus and pituitary in AD. Infections were associated with lower FT3 concentrations in AD, but not in ACLF. Low FT3 concentrations correlated significantly with 90-day mortality. Both, AD/ACLF and NTIS, were associated with signatures of inflammatory mediators, which were partially non-overlapping. Conclusion: NTIS is frequent already in AD and therefore precedes critically illness in a subgroup of patients with decompensated cirrhosis. This might constitute a new paradigm of TH signaling in cirrhosis, offering opportunities to explore preventive effects of TH in AD.

Euthyroid sick syndrome and its association with complications of type 1 diabetes mellitus onset.

OBJECTIVE: To evaluate (i) the prevalence and association of euthyroid sick syndrome (ESS) [decreased FT3 and/or FT4 and normal/decreased TSH] with severity indexes of type 1 diabetes mellitus (T1DM) onset such as diabetic ketoacidosis (DKA) and kidney damage [acute kidney injury (AKI) based on KDIGO criteria, acute tubular necrosis (ATN), renal tubular damage (RTD)], (ii) relationship between clinical/metabolic parameters at T1DM onset and thyroid hormones, and (iii) ESS as a prognostic indicator of delayed recovery from kidney damage. METHODS: A total of 161 children with T1DM onset were included. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin (NGAL) and/or tubular reabsorption of phosphate <85% and/or fractional excretion of Na>2%. ATN was defined by RTD+AKI. RESULTS: Of 161 participants, 60 (37.3%) presented ESS. It was more prevalent in case of more severe T1DM presentation both in terms of metabolic derangement (DKA) and kidney function impairment (AKI, RTD and ATN). Only ATN, however, was associated with ESS at adjusted analysis. FT3 inversely correlated with serum triglycerides and creatinine, and urinary calcium/creatinine ratio and NGAL. Participants with euthyroidism showed earlier recovery from AKI than those with ESS. ESS spontaneously disappeared. CONCLUSIONS: ESS is associated with T1DM onset severity and spontaneously disappears. ESS delayed the recovery from AKI. IMPACT: This is the first longitudinal study describing in detail the relationship between clinical/metabolic factors at type 1 diabetes mellitus (T1DM) onset and thyroid hormones, with particular attention to the relationship between diabetic ketoacidosis (DKA)-related kidney function impairment and euthyroid sick syndrome (ESS). Participants with more severe T1DM onset presentation both in terms of metabolic derangement and kidney function impairment had an increased prevalence of ESS. Children with ESS had a slower recovery from acute kidney injury compared with those without ESS. ESS spontaneously disappeared in all participants.

Early detection of thiamine deficiency by non-thyroidal illness syndrome in a hemodialysis patient.

An 88-year-old male patient on maintenance hemodialysis (HD) therapy experienced gradual losses in appetite and liveliness during the course of 1 month. Physical examinations revealed no abnormalities. However, blood testing indicated non-thyroidal illness syndrome (NTIS) typically observed in patients with severe illness, with serum levels of thyroid stimulating hormone, free triiodothyronine, and free thyroxine of 0.17 µIU/mL, < 1.0 pg/mL, and 0.23 ng/dL, respectively. Brain magnetic resonance imaging to exclude the possibility of central hypothyroidism unexpectedly displayed slight abnormalities inside of the thalami that were characteristic of Wernicke's encephalopathy. Additional examination disclosed low serum thiamine of 20 ng/mL. Thiamine injections of 100 mg at every HD treatment rapidly restored his appetite, liveliness, and NTIS findings. HD patients are at a particularly high risk of thiamine deficiency (TD) and associated severe symptoms due to losses of thiamine during HD sessions. However, its non-specific initial symptoms, including decreases in appetite and liveliness, as well as undetectability in routine blood tests complicate early detection, resulting in underdiagnosis and more severe outcomes. In the present case, TD manifested only as non-specific symptoms and was ultimately revealed by the presence of NTIS, which was resolved with thiamine supplementation. Thus, NTIS might assist in the early detection of TD as an initial sign in HD patients.

Low T3 syndrome is associated with peripheral neuropathy in patients with type 2 diabetes mellitus.

INTRODUCTION/AIMS: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. Diabetic patients often have thyroid dysfunction. The aim of this study was to investigate the association between low triiodothyronine (T3) syndrome and DPN in patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective review was performed of 928 patients with T2DM for whom data was available for clinical manifestations and nerve conduction studies (NCS), and of 134 non-diabetic controls. The composite Z scores of conduction velocity and amplitude were calculated. Low T3 syndrome was defined as T3 levels below the lower limit of the reference interval. RESULTS: Among the patients with T2DM, 632 (68.1%) had DPN, and a larger proportion of these patients presented with low T3 syndrome than patients without DPN. After adjusting for potential confounders, low T3 syndrome was independently associated with the occurrence of DPN (odds ratio [OR] = 2.049, 95% confidence interval [CI] 1.319-3.181, p = .001) and the severity of DPN (OR = 1.597, 95% CI 1.030-2.476, p = .036). Adding the criterion of low T3 syndrome improved the prognostic performance of the traditional model (age + gender + diabetic duration + glycated hemoglobin [HbA1c]) for predicting DPN. DISCUSSION: Low T3 syndrome is associated with a higher risk and increased severity of DPN in patients with T2DM. These findings suggest that low T3 syndrome could be a predictor for risk stratification in patients with T2DM.

Thyroid diseases are associated with coronavirus disease 2019 infection.

Background: In 2019, there was a global outbreak of new coronary pneumonia. Studies have found that the severity of patients with new coronary pneumonia may be related to their comorbidities. This article discusses the impact of thyroid disease on the severity of new coronary pneumonia through a meta-analysis and provides new treatment ideas for the later treatment and recovery of new coronary pneumonia. Methods: Databases including PubMed, Embase, Cochrane Library, SINOMED, China national knowledge infrastructure (CNKI), and Wanfang for coronavirus disease 2019 (COVID-19) infection and thyroid diseases were searched. Reference lists of all eligible articles and related previous review articles were handsearched. Fifty-three articles were included to conduct the meta-analysis. Results: Fifty-three articles with 12,022 COVID-19 infection patients were included in this meta-analysis. The proportion of patients with thyroid diseases in all COVID-19 infection patients fluctuates between 0% and 88.46%. Of the 53 included studies, 22 studies reported the severity of COVID-19 infection and grouped. The fixed-effects model was used to merge odds ratio (OR) values, and the pooled effect size in favor of non-severe patients is 2.62 (95% CI = 1.96-3.49, P < 0.0001), which means that patients with severe COVID-19 infection are more likely to have thyroid diseases. The analysis subgrouped into Asia and Europe shows that patients with COVID-19 severe infection in Asia are 3.77 times more likely to have thyroid diseases than non-severe patients (fixed-effects model: OR = 3.77, 95% CI = 2.66-5.35, P < 0.00001). No significant statistical heterogeneity was found by the heterogeneity analysis (chi-square = 19.85, P = 0.34, I 2 = 9%). Severe COVID-19 infection patients are more likely to be complicated by hypothyroidism and low T3 syndrome. The pooled ORs with fixed-effects model are 3.72 (95% CI = 1.62-8.58, P = 0.002) and 5.86 (95% CI = 2.79-12.33, P < 0.00001), respectively. Conclusion: COVID-19 infection patients with thyroid diseases are very common, and severe patients are more likely to have thyroid diseases. Asian COVID-19 infection, hypothyroidism patients, and patients with low T3 syndrome are more likely to progress to severe condition. Systematic Review Registration: https://inplasy.com, identifier INPLASY202190079.

Low triiodothyronine syndrome is associated with stroke-associated pneumonia.

OBJECTIVE: Stroke-associated pneumonia (SAP) is the most common early consequence in patients suffering from an acute ischaemic stroke (AIS). The purpose of this study was to explore the possible relationship between low triiodothyronine (T3) syndrome and SAP in stroke patients. METHODS: This study recruited 2460 consecutive AIS patients. SAP was defined according to the modified Centers for Disease Control and Prevention criteria for hospital-acquired pneumonia. The thyroid hormones levels were measured within 24 h after admission. Low T3 syndrome was characterized as T3 below the lower limit of the reference interval accompanied by normal TSH levels. RESULTS: Among the total patients, 336 (13.7%) patients were diagnosed with SAP. SAP in individuals with low T3 syndrome was substantially greater (p < .001) as compared to those without low T3 syndrome. After adjusting for possible confounders, low T3 syndrome (adjusted odds ratio [aOR] = 1.59; 95% confidence interval [CI], 1.20-2.09; p = .001) remained significant in our logistic model. Patients with low T3 syndrome had a higher risk of severe SAP (aOR = 2.17, 95% confidence interval [CI] 1.38-3.44; p = .001). CONCLUSION: Low T3 syndrome, independent of recognized risk factors, is a possible risk factor for in-hospital SAP, which can help clinicians in the early detection and treatment of high-risk patients.

Low T3 syndrome is associated with poor prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a critical disease with high mortality risk. Low triiodothyronine syndrome (LT3S) is associated with various severe acute and chronic diseases. We investigated the relationship between LT3S and poor prognosis in patients with HBV-ACLF. RESEARCH DESIGN AND METHODS: A total of 198 patients with HBV-ACLF were enrolled between January 2018 and March 2019. We screened for independent risk factors for 28-day mortality using univariate and multivariate logistic regression analyses. Spearman's correlation analysis was used to evaluate the correlation between LT3S and the poor prognostic parameters of HBV-ACLF. RESULTS: LT3S was an independent risk factor for 28-day mortality in HBV-ACLF patients (odds ratio: 4.035, 95% confidence interval 1.117-14.579; p = 0.033). The death group had a lower serum FT3 level (Z-value = 2639.000, p < 0.001). Serum FT3 levels were negatively correlated with age, C-reactive protein, international normalized ratio, and neutrophil count but positively correlated with lymphocyte count. A negative correlation between FT3 and various prognostic scores was observed, indicating that a low FT3 level was closely related to a poor prognosis. CONCLUSIONS: LT3S was an independent risk factor for 28-day mortality and was correlated with poor prognosis in patients with HBV-ACLF.

The Association Between Low T3 Syndrome and Survival in Patients With Newly Diagnosed Multiple Myeloma: A Retrospective Study.

Objective: The correlation between low triiodothyronine (T3) syndrome and shorter survival in malignant tumor patients has been increasingly reported. The objective of the present study was to investigate the association between low T3 syndrome and survival in multiple myeloma (MM) patients. Methods: A total of 201 newly diagnosed MM patients were included in this retrospective study. All participants were divided into 2 groups based on serum free T3 (FT3) level: low T3 syndrome group (FT3 < 2.3 pg/mL) and non-low T3 syndrome group (FT3 ≥ 2.3 pg/mL). Baseline clinical characteristics, overall survival (OS) and progression free survival (PFS) were analyzed. Results: 80 (39.8%) patients had low T3 syndrome. Patients with low T3 syndrome had significantly lower blood hemoglobin and albumin, higher creatinine and ß2-microglobulin (ß2-MG), higher neutrophil/lymphocyte and (neutrophil + monocyte)/lymphocyte ratio, and more advanced ISS and R-ISS stages (all P < .05). Serum FT3 level was positively associated with blood hemoglobin and albumin, and negatively correlated with ß2-MG, creatinine, neutrophil/lymphocyte ratio, and (neutrophil + monocyte)/lymphocyte ratio (all P < .05). Patients with low T3 syndrome had significantly inferior OS time and PFS time (both P < .001). In multivariate Cox analysis, low T3 syndrome was found to be an independent factor associated with OS (P < .001) and PFS (P = .002). Receiver operator characteristic curve analyses showed that FT3 was a predictive marker for death during the entire follow-up period (the area under the curve [AUC] = 0.720, P < .001) and during 1 year (AUC = 0.747, P < .001). Conclusion: Low T3 syndrome might be useful for predicting survival in patients with newly diagnosed MM.

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.

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

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

Nonthyroidal illness syndrome in acute pancreatitis patients: an 8-year cohort study.

BACKGROUND: Nonthyroidal illness syndrome (NTIS) is common in critical illness and is associated with poor prognosis. The aim of this study was to find the prevalence, charateristics, and prognosis of NTIS and its correlation with outcomes in AP patients. METHODS: A retrospective review of AP patients with a diagnosis of NTIS from Jan 2012 to September 2020 was performed. The serum thyroidal hormone (TH) disturbances, as well as the demographic characteristics and clinical outcomes of the study patients, were collected and analyzed. RESULTS: Over the eight years, 183 included AP patients were diagnosed as NTIS, constituting an incidence of 64.7%. Patients with NTIS were admitted with worse condition based on the higher APACHE II score, SOFA score, Balthazar's CT score, CRP and lower albumin than euthyroid patients. Also, these patients had a longer ICU duration (3, 2-10 vs 2, 0-3, days, P = 0.039) and tended to be more likely to develop infected pancreatic necrosis (IPN) (15.3% vs 6.3%, P = 0.087) and gastrointestinal fistula (6% vs 0%, P = 0.082) than euthyroid patients. Free triiodothyronine (FT3) was found the best performance in predicting death compared by other well-recognized biomarkers. CONCLUSION: NTIS is common in AP patients within 7 days after the onset of the disease. NTIS is associated with the worse characteristics at admission and poor outcome during the course. FT3 should be investigate as a potential biomarker in the prediction of death in AP patients.

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

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

Frequency of Euthyroid Sick Syndrome before and after renal transplantation in patients with end stage renal disease and its association with oxidative stress.

OBJECTIVE: In this study, we aimed to evaluate the frequency of euthyroid sick syndrome (ESS) before and after renal transplantation in patients with end-stage renal disease (ESRD), and its association with oxidative stress (OS) by evaluating thiol-disulfide levels. METHODS: Free triiodothyronine (fT3), free thyroxine (fT4) thyroid stimulating hormone (TSH), and thiol and disulfide levels were recorded before and after renal transplantation in patients with ESRD. ESS was diagnosed in patients with unresponsive TSH to low fT3 and/or fT4 levels. RESULTS: A total of 121 patients were included in the study. Of these, 69 (57%) were males and 52 (43%) were females. The mean age was 45 ± 12.61 years. ESS was detected in 39 (32%) of 121 patients. Of 39 patients, 24 (61%) had ESS before transplantation and 15 (39%) after transplantation. Sixteen of 24 (66.7%) patients with ESS before transplantation reached normal thyroid functions after transplantation. In post transplantation period, patients with ESS had significantly higher urea and creatinine (p = 0.025 and p = 0.009, respectively) compared to patients without ESS. Furthermore, thiol-disulfide levels of 20 patients with ESS at any time compared with 68 patients without ESS. It was found that native thiol and total thiol were significantly lower in patients with ESS (p = 0.025 and p = 0.044, respectively). CONCLUSION: The present study is an initial evaluation of the OS and antioxidant status in the etiology of ESS in patients with renal transplantation. These patients have markedly low levels of antioxidant products, which support the possible role of OS in ESS.

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.

Gene signature and immune cell profiling by high-dimensional, single-cell analysis in COVID-19 patients, presenting Low T3 syndrome and coexistent hematological malignancies.

BACKGROUND: Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies. METHODS: Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant'Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC). RESULTS: Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3. CONCLUSIONS: Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified.