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.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.

Decreased triiodothyronine (T3) as a predictor for prolonged mechanical ventilation in critically ill patients with cardiac surgery.

BACKGROUND: This study aimed to examine the correlation between thyroid hormone and prolonged mechanical ventilation (MV) in adult critically ill patients having undergone cardiac surgery. METHODS: The present study refers to a retrospective, cohort study conducted at Nanjing First Hospital from March 2019 to December 2020. Patients receiving cardiac surgery and admitting to the Cardiovascular Intensive Care Unit (CVICU) in the study period were screened for potential inclusion. Demographic information, thyroid hormone and other laboratory measurements and outcome variables were recorded for analysis. Prolonged MV was defined as the duration of MV after cardiac surgery longer than 5 days. Thyroid hormones were assessed for the prognostic significance for prolonged MV. RESULTS: One thousand eight hundred ninety-six patients who underwent cardiac surgery were screened for potential enrollment. Overall, 118 patients were included and analyzed in this study. Patients fell to the control (n = 64) and the prolonged MV group (n = 54) by complying with the duration of MV after cardiac surgery. The median value of total triiodothyronine (TT3) and free triiodothyronine (FT3) were 1.03 nmol/L and 3.52 pmol/L in the prolonged MV group before cardiac surgery, significantly lower than 1.23 nmol/L (P = 0.005) and 3.87 pmol/L, respectively in control (P = 0.038). Multivariate logistic regression analysis indicated that TT3 before surgery (pre-op TT3) had an excellent prognostic significance for prolonged MV (OR: 0.049, P = 0.012). CONCLUSIONS: This study concluded that decreased triiodothyronine (T3) could be common in cardiac patients with prolonged MV, and it would be further reduced after patients undergo cardiac surgery. Besides, decreased T3 before surgery could act as an effective predictor for prolonged MV after cardiac surgery.

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.

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

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

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.

The Intriguing Thyroid Hormones-Lung Cancer Association as Exemplification of the Thyroid Hormones-Cancer Association: Three Decades of Evolving Research.

Exemplifying the long-pursued thyroid hormones (TH)-cancer association, the TH-lung cancer association is a compelling, yet elusive, issue. The present narrative review provides background knowledge on the molecular aspects of TH actions, with focus on the contribution of TH to hallmarks of cancer. Then, it provides a comprehensive overview of data pertinent to the TH-lung cancer association garnered over the last three decades and identifies obstacles that need to be overcome to enable harnessing this association in the clinical setting. TH contribute to all hallmarks of cancer through integration of diverse actions, currently classified according to molecular background. Despite the increasingly recognized implication of TH in lung cancer, three pending queries need to be resolved to empower a tailored approach: (1) How to stratify patients with TH-sensitive lung tumors? (2) How is determined whether TH promote or inhibit lung cancer progression? (3) How to mimic the antitumor and/or abrogate the tumor-promoting TH actions in lung cancer? To address these queries, research should prioritize the elucidation of the crosstalk between TH signaling and oncogenic signaling implicated in lung cancer initiation and progression, and the development of efficient, safe, and feasible strategies leveraging this crosstalk in therapeutics.

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.

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

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

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

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

Low free T3 level may predict the severity of acute pancreatitis.

OBJECTIVES: To demonstrate that deterioration in thyroid function tests can serve as an indicator of severity and prognosis in acute pancreatitis despite a healthy thyroid gland. METHODS: This study is a retrospective, single-center study. Patients diagnosed with acute pancreatitis between May 2020 and June 2021 were evaluated. Acute pancreatitis was diagnosed and classified according to the 2012 revised Atlanta criteria. Patients were categorized into Non-Thyroidal Illness Syndrome and euthyroid groups and compared in terms of biochemical parameters and scoring systems such as Ranson, Glasgow, Balthazar and BISAP scores. RESULTS: A total of 152 patients were included in the study. Eighty-three patients (54%) were euthyroid, with free triiodothyronine (T3), free thyroxine (T4), and Thyroid-stimulating hormone (TSH) levels within normal limits. Sixty-nine patients (46%) had Non-Thyroidal Illness Syndrome with low serum free T3 levels and low/normal TSH levels. As expected, free T3 was significantly lower in the Non-Thyroidal Illness Syndrome group than in the euthyroid group (1.5 ± 0.04 vs 2.6 ± 0.04, respectively, p < 0.0001). In the Non-Thyroidal Illness Syndrome group, Ranson score (3.35 ± 0.2 vs 2.11 ± 0.18 p < 0.0001), Glasgow (2.4 ± 0.2 vs 1.3 ± 0.1, p < 0.0001), Atlanta (p = 0.007), and Balthazar (2.1 ± 0.1 vs 1.4 ± 0.1, p = 0.001) scores were significantly higher than euthyroid group. CONCLUSION: Non-Thyroidal Illness Syndrome provides insight into the prognosis of acute pancreatitis. Free T3 values are a significant parameter that may indicate the prognosis of acute pancreatitis. We believe that free T3 could be incorporated into an ideal scoring system in a disease such as acute pancreatitis, where early determination of prognosis is known to significantly reduce mortality.

Cardiovascular mechanisms of thyroid hormones and heart failure: Current knowledge and perspectives.

A multiple hormonal imbalance that accompanies heart failure (HF) may have a significant impact on the clinical course in such patients. The non-thyroidal illness syndrome (NTIS), also referred to as euthyroid sick syndrome or low triiodothyronine syndrome, can be found in about 30% of patients with HF. NTIS represents a systemic adaptation to chronic illness that is associated with increased cardiac and overall mortality in patients with HF. While conclusions on thyroid-stimulating hormone, free triiodothyronine, total and free thyroxine are currently unresolved, serum total triiodothyronine levels and the ratio of free triiodothyronine to free thyroxine seem to provide the best correlates to the echocardiographic, laboratory and clinical parameters of disease severity. HF patients with either hyper- or hypothyroidism should be treated according to the appropriate guidelines, but the therapeutic approach to NTIS, with or without HF, is still a matter of debate. Possible treatment options include better individual titration of levothyroxine therapy, combined triiodothyronine plus thyroxine therapy and natural measures to increase triiodothyronine. Future research should further examine the cellular and tissue mechanisms of NTIS as well as new therapeutic avenues in patients with HF.

Thyroid Density in CT Imaging as a Potential Marker of Lung Involvement in COVID-19: A Retrospective Analysis.

Background The SARS-CoV-2 pandemic has underscored the multifaceted impact of the virus on human health, extending beyond the respiratory system to involve other organ systems, including the endocrine system. Emerging evidence suggests a notable interaction between COVID-19 and thyroid function, characterized by alterations in thyroid hormone levels and structural changes within the gland. This study aims to explore the association between thyroid density on CT imaging and lung involvement in patients with COVID-19, potentially offering new insights into the systemic effects of the virus. Methodology A retrospective cross-sectional analysis was conducted on 1,066 patients with COVID-19 who underwent chest CT scans without contrast at Government Medical College, Omandurar Government Estate, Chennai, which was designated as the COVID-19 care center from April to June 2021. Thyroid density and lung involvement were quantitatively assessed, and their correlation was analyzed using descriptive and inferential statistics, including the Kruskal-Wallis H test and Shapiro-Wilk test for normality. Results The study population predominantly exhibited normal thyroid density (749, 70.3%), followed by altered (212, 19.9%), nodular (104, 9.8%), and a single instance (0.1%) of absent thyroid density. Despite variability in lung involvement across different thyroid density categories, statistical analysis revealed no significant association between thyroid density and the extent of lung involvement in patients with COVID-19. Conclusions This study found no significant correlation between thyroid density and lung involvement in patients with COVID-19, suggesting that thyroid density on CT imaging may not serve as a reliable marker for lung involvement in this population. Further research is warranted to explore the complex interactions between COVID-19 and thyroid function, as well as the potential implications for patient management and prognosis.

Non-thyroidal illness syndrome and the prognosis of heart failure: a systematic review and meta-analysis.

Background: Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis. Methods: Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to 1 July 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle-Ottawa Scale. The heterogeneity of the results was assessed with I2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted. Results: A total of 626 studies were retrieved, and 18 studies were finally included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE. Conclusions: This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation.

Non-thyroidal Illness Syndrome in an Infant With Acute Anorexia and Psychological Stress.

Non-thyroidal illness syndrome (NTIS), a remarkable ensemble of changes in serum thyroid hormone concentration during acute illness, was first reported in the 1970s. While NTIS is not a form of hypothyroidism, it is characterized by a decrease in serum triiodothyronine (T3) or thyroxine (T4) or both with normal or decreased thyroid-stimulating hormone (TSH). Notably, it typically resolves without thyroid hormone replacement therapy. We report a case of paralytic ileus caused by NTIS in an infant with psychological stress. This case illustrates the development of NTIS during psychological stress, which can lead to severe symptoms such as those seen in pathological hypothyroidism.

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.

The Effects of Obesity on Bone Turnover Markers in Diabetic Patients with Diabetic Ketosis or Ketoacidosis.

PURPOSE: Despite the fact that diabetes individuals are often associated with a higher risk of bone fracture, our previous research demonstrated that Diabetic ketosis (DK) or ketoacidosis (DKA) induced significant alterations in bone biomarkers. It is unknown whether there is a difference in bone metabolism between obese and non-obese diabetic populations while they are in DK or DKA; hence the current study will investigate this further to aid in the prognosis and prediction of bone fracture risk in patients with different BMIs. METHODS: We categorized patients into four groups based on their BMI utilizing data from our hospital's medical record system from 2018 to 2020 in the Department of Endocrinology: obese DK or DKA patients (OB+DK/DKA, n = 41), non-obese DK or DKA patients (DK/DKA, n = 201), obese type 2 diabetes patients without DK or DKA (OB+T2D, n = 93), and patients with type 2 diabetes only (T2D only, n = 304). The comparisons were made on glycosylated hemoglobin (HbA1c), body mass index (BMI), fasting plasma C-peptide (FPCP), and plasma lipids, in addition to bone metabolism indicators such as total 25-OH-VitD3 (25-OH-VitD3), N-terminal middle molecular fragment of osteocalcin (NMID), -C terminal cross-linking telopeptide of type 1 collagen (-CTX), parathyroid hormone (PTH), and blood calcium (Ca2+). RESULTS: The OB+DK/DKA group had a lower average age (p < 0.05) than the DK/DKA group, while the DK/DKA group had a significantly lower FPCP (p < 0.05). The 25-OH-VitD3 levels of DK/DKA patients were considerably lower than those of the T2D-only group (p < 0.05). In contrast, NMID and Ca2+ levels were significantly lower than those of non-ketosis or acidosis patients (p < 0.05), and PTH levels in the DK/DKA group were significantly lower than those of OB+ T2D patients (p < 0.05). In contrast, the ß-CTX of the DK or DKA group (OB+DK/DKA and DK+DKA) was significantly greater than that of the non-DK or DKA group (p < 0.05), although there was no significant difference in blood phosphorus between OB+DK/DKA and DK/ DKA (p > 0.05). The levels of thyroid-stimulating hormone (TSH) and free T4 (FT4) did not differ significantly among the four groups (p > 0.05); however, the levels of total T3 (TT3), T4 (TT4), and free T3 (FT3) were significantly lower in the DK/DKA group (p < 0.05); the ratio of TT3 to TT4 (TT3/TT4) was significantly decreased in the DK/DKA group, whereas the ratio of FT3/FT4 was significantly lower (p < 0.05). CONCLUSION: Obese patients with DK or DKA have a younger onset age, superior pancreatic function, and better blood glucose management than non-obese patients with DK/DKA. Despite having higher bone absorption signals than non-DK/DKA patients, OB+DK/DKA patients have stronger bone formation markers than non-obese DK/DKA patients, according to a recent study. Changes in markers of bone metabolism may be linked to non-thyroidal illness syndrome in cases of DK or DKA.

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.

The prognostic utility of serum thyrotropin in hospitalized Covid-19 patients: statistical and machine learning approaches.

PURPOSE: To assess the prognostic value of serum TSH in Greek patients with COVID-19 and compare it with that of commonly used prognostic biomarkers. METHODS: Retrospective study of 128 COVID-19 in patients with no history of thyroid disease. Serum TSH, albumin, CRP, ferritin, and D-dimers were measured at admission. Outcomes were classified as "favorable" (discharge from hospital) and "adverse" (intubation or in-hospital death of any cause). The prognostic performance of TSH and other indices was assessed using binary logistic regression, machine learning classifiers, and ROC curve analysis. RESULTS: Patients with adverse outcomes had significantly lower TSH compared to those with favorable outcomes (0.61 versus 1.09 mIU/L, p < 0.001). Binary logistic regression with sex, age, TSH, albumin, CRP, ferritin, and D-dimers as covariates showed that only albumin (p < 0.001) and TSH (p = 0.006) were significantly predictive of the outcome. Serum TSH below the optimal cut-off value of 0.5 mIU/L was associated with an odds ratio of 4.13 (95% C.I.: 1.41-12.05) for adverse outcome. Artificial neural network analysis showed that the prognostic importance of TSH was second only to that of albumin. However, the prognostic accuracy of low TSH was limited, with an AUC of 69.5%, compared to albumin's 86.9%. A Naïve Bayes classifier based on the combination of serum albumin and TSH levels achieved high prognostic accuracy (AUC 99.2%). CONCLUSION: Low serum TSH is independently associated with adverse outcome in hospitalized Greek patients with COVID-19 but its prognostic utility is limited. The integration of serum TSH into machine learning classifiers in combination with other biomarkers enables outcome prediction with high accuracy.