[Abnormal thyroid markers in critically ill patients-harmless irritation or a real problem?] / Auffällige Schilddrüsenwerte bei kritisch Kranken ­ harmlose Irritation oder echtes Problem?

BACKGROUND: Abnormal thyroid markers are a frequent occurrence in emergency and intensive care medicine. Correct interpretation of their clinical relevance and distinction from a primary thyroid disease, particularly prior to potential administration of iodine-containing antiarrhythmic drugs such as amiodaron or radiocontrast agents, are both essential and challenging. OBJECTIVE: This article aims to present the pathophysiology of abnormal thyroid markers in acute or protracted critical disease. Their relevance for administration of amiodaron or iodine-containing radiocontrast agents is discussed, and concrete practical recommendations are presented. MATERIALS AND METHODS: The current work comprises a discussion of expert recommendations, guidelines, and basic research. RESULTS AND CONCLUSION: Approximately one third of intensive care patients develop non-thyroidal illness syndrome (NTIS) during the course of their critical disease. NTIS is characterized by a reduction in the serum concentration of fT3 and, during the course, also in those of thyroid-stimulating hormone (TSH) and fT4, despite an organically intact thyroid gland. A greater extent of the deviations correlates with a worse overall prognosis. The mechanisms involved are manifold and influence different levels of hormonal signaling axes. They are mediated by interaction with acute stress signals such as inflammatory factors and elevated cortisol levels and are influenced by medication. The components vary depending on disease severity and the protracted course. NTIS does not require any specific treatment; the focus is on treating the underlying disease. Latent hyperthyroidism in particular must be distinguished from NTIS. In unclear situations and high-risk constellations, perchlorate is indicated before (and after) iodine exposure.

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.

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.

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.

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 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.

Thyroid hormones modifications among COVID-19 patients undergoing pulmonary rehabilitation.

Introduction: Patients with severe COVID-19 often experience long-lasting disabilities that can improve after pulmonary rehabilitation. Moreover patients with severe COVID-19 display thyroid function alterations due to a non-thyroidal illness syndrome (NTIS). The aim of our study was to evaluate thyroid function parameters among patients hospitalized for COVID-19 who were eligible or not to respiratory rehabilitation and their modifications during follow-up. Materials and methods: Post-COVID-19 patients referred to a Respiratory Rehabilitation Unit were evaluated. Outpatients, not candidate for rehabilitation, were enrolled as Control group. Patients who had completed a 4-week-rehabilitation program were enrolled as Rehabilitation Group. All patients were evaluated at T0 (4 weeks after the discharge home in Control Group and after completion of rehabilitation in Rehabilitation Group) and at T1 (3 months after T0). Results: The final study group included 39 patients (20 in the Rehabilitation group and 19 in the Control group). Patients in the Rehabilitation Group had more frequently received invasive or non-invasive ventilation, had a longer length-of-stay in referring hospitals, had a higher number of comorbidities and displayed a worse performance at 6-minute-walking-test (6MWT) and Short-Physical-Performance-Battery-test (SPPB). FT3 values were lower at T0 in the Rehabilitation Group, while TSH and FT4 values were similar in the two groups. While no significant modifications in thyroid-function-parameters were observed in the Control Group, a significant increase in FT3 value was observed in the Rehabilitation Group at T1. Participants of both groups had improved the results of 6MWT at T1, while SPPB values improved only in the Rehabilitation Group. Conclusions: COVID-19 patients after pulmonary rehabilitation experience an increase in FT3 values during follow-up, paralleled with an amelioration of functional capabilities.

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.

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.

Study of Non-Thyroidal Illness Syndrome and Its Recovery in Critically Ill Patients at a Tertiary Care Centre in South India.

Background and Objectives: Transient thyroid hormone alterations are common during critical illness and are termed non-thyroidal illness syndrome (NTIS). We studied the prevalence of NTIS in the ICU setting and its impact on predicting mortality and other outcomes and compared it to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Materials and Methods: The study included 119 consecutive patients admitted with a critical illness. APACHE II score was calculated. Total T3, total T4, TSH, free T3, and free T4 were measured at admission and after six weeks of discharge. NTIS and euthyroid groups were studied for ICU, hospital stays, mortality, readmission, and recovery. Predictors of mortality were compared between survivors and non-survivors. Results: The mean age was 60.15 ± 14.50 years with M:F = 84 (71%):35 (29%). NTIS was observed in 84 (71%), low T3 being the most common abnormality in 53 (63%). The occurrence of NTIS was significantly higher among non-survivors (28/30, 93%) versus survivors (56/89, 63%) (P = 0.002). Non-survivors showed significantly lower T3, TSH, and FT3/FT4 ratios and higher readmissions. NTIS group showed significantly greater ICU stay (P = 0.02) and had higher readmission rates (P = 0.032). Baseline T3 had the greatest power to predict mortality. APACHE II score also correlated significantly with mortality (19.60 ± 10.58 vs 11.99 ± 6.80, P < 0.001). The area under the curve (0.677) for the T3 level was lower than the APACHE II score (0.760). After six weeks, 61% had recovered from NTIS. Conclusions: NTIS was common amongst critically ill patients (71.5%), which reversed in 61% at six weeks. Low T3 was the most common abnormality and independently predicted mortality. Free T3/free T4 also significantly predicted mortality. The correlation between thyroid dysfunction and the severity of primary illness makes it an additional attractive low-cost marker of mortality.

Non-thyroidal illness syndrome and its relationship with mortality risk in critically ill children.

Introduction: Non-thyroidal illness syndrome (NTIS) is considered to be associated with adverse outcomes in critically ill children.The hypothesis that thyroid hormones and inflammatory markers are associated with increased prediction of mortality risk scores is tested in this paper. Methods: A prospective observational study was set up in a pediatric intensive care unit (PICU). One hundred and three patients were included. NTIS was defined as a low free triiodothyronine (FT3) value for the patient's age. Thyroid hormones levels and inflammatory markers were determined at admission: FT3, FT4 (free thyroxine), TSH (thyroid-stimulating hormone), rT3 (reverse triiodothyronine), CRP (C-reactive protein) and PCT (Procalcitonin). They were compared between children with a pediatric risk of mortality score PRISM-III >75th percentile (group A, n= 25) and the rest (group B, n = 78). Results: A FT4 value lower than 16.6 pmol/L showed an area under the curve (AUC) of 0.655 (0.56-0.78, p = 0.02), with 76% sensitivity and 61.5% specificity to detect a high risk of mortality. A multiple regression analysis revealed that a FT4 lower than 16.6 pmol/L [OR: 4.92 (1.60-18.19), p = 0.009] and having NTIS [OR: 6.04 (1.45-27.93), p = 0.016] could predict a high risk of mortality. Conclusions: In unselected critically ill children, FT4 and FT3 values at admission could be used as a good predictor of a high mortality risk. We have not achieved a predictive model that combines hormones with inflammatory markers.

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.

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.

Thyroid hormones and platelet activation in COVID-19 patients.

PURPOSE: To retrospectively describe the association between thyroid hormones (TH) and platelet activation, as represented by mean platelet volume (MPV), in a cohort of patients hospitalized for COVID-19 with no known thyroid disease, and to correlate these data with the severity of COVID-19 and the occurrence of death/ARDS (Acute Respiratory Distress Syndrome). METHODS: 103 patients with real-time polymerase chain reaction (RT-PCR) testing-confirmed COVID-19 and hospitalized were enrolled. Serum samples were collected from patients upon admission before starting any treatment. Chi-squared test was used to determine the association between euthyroid sick syndrome (ESS) and COVID-19 severity. Multivariate logistic regression was performed to evaluate the best independent predictors of COVID-19 deaths/ARDS. RESULTS: 39/103 (37.9%) of patients were found to have ESS, and this condition was an independent predictor for the severity of COVID-19 (p = 0.003). Lower TSH and lower FT3/FT4 ratio correlated with higher MPV (p = 0,001 and p = 0.010), with an opposite trend with respect to what has been documented in non-COVID patients. Increasing MPV and lower FT3 significantly increased the risk, in COVID-19 patients, of an adverse outcome of death/ARDS. CONCLUSION: Increased platelet activation, as represented by increased MPV, has already been reported to correlate with COVID-19 severity, possibly as a consequence of cytokine release. We demonstrated, in a cohort of 103 patients with COVID-19, that MPV is inversely correlated to TH levels, in particular in the case of ESS, where downregulation of TH axis may occur in case of systemic cytokine inflammation and more severe outcomes (death/ARDS). That ESS itself may directly cause platelet activation, as demonstrated by higher MPV in these patients, is an interesting hypothesis which deserves further investigation.

Different Hypothalamic Mechanisms Control Decreased Circulating Thyroid Hormone Levels in Infection and Fasting-Induced Non-Thyroidal Illness Syndrome in Male Thyroid Hormone Action Indicator Mice.

Background: Non-Thyroidal Illness Syndrome (NTIS) caused by infection or fasting is hallmarked by reduced circulating thyroid hormone (TH) levels. To better understand the role of local TH-action in the development of NTIS, we assessed tissue-specific changes of TH signaling in Thyroid Hormone Action Indicator (THAI) mice. Methods: NTIS was induced in young adult THAI mice by bacterial lipopolysaccharide (LPS)-administration or by 24 or 48 hours' fasting. Tissue-specific TH-action was assessed by the detection of changes of the Luciferase reporter of THAI mice with quantitative polymerase chain reaction along with tissue-specific examination of regulators of TH metabolism and signaling. Age dependence of revealed alterations of hypothalamic TH-action was also studied in 1-year-old male THAI mice. Results: LPS-treatment increased TH-action in the hypothalamic arcuate nucleus-median eminence (ARC-ME) region preceded by an increase of type 2 deiodinase (D2) expression in the same region and followed by the suppression of proTrh expression in the hypothalamic paraventricular nucleus (PVN). In contrast, LPS decreased both TH-action and D2 activity in the pituitary at both ages. Tshß expression and serum free thyroxine (fT4) and free triiodothyronine (fT3) levels decreased in LPS-treated young adults. Tshß expression and serum fT4 levels were not significantly affected by LPS treatment in aged animals. In contrast to LPS treatment, TH-action remained unchanged in the ARC-ME of 24 and 48 hours fasted animals accompanied with a modest decrease of proTrh expression in the PVN in the 24-hour group. Tshß expression and fT3 level were decreased in both fasted groups, but the fT4 decreased only in the 48 hours fasted animals. Conclusions: Although the hypothalamo-pituitary-thyroid (HPT) axis is inhibited both in LPS and fasting-induced NTIS, LPS achieves this by centrally inducing local hyperthyroidism in the ARC-ME region, while fasting acts without affecting hypothalamic TH signaling. Lack of downregulation of Tshß and fT4 in LPS-treated aged THAI mice suggests age-dependent alterations in the responsiveness of the HPT axis. The LPS-induced tissue-specific hypo-, eu-, and hyperthyroidism in different tissues of the same animal indicate that under certain conditions TH levels alone could be a poor marker of tissue TH signaling. In conclusion, decreased circulating TH levels in these two forms of NTIS are associated with different patterns of hypothalamic TH signaling.

Management of thyroiditis in the context of Covid-19: cause-effect and beyond.

Background: The COVID-19 pandemic hit the world in late 2019, and by 2020, everyone was affected. Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) belongs to the beta-coronavirus genre and uses the angiotensin-converting enzyme 2 (ACE2) receptor to penetrate cells. Thyroid cells are rich in such receptors. Therefore, this gland is frequently involved alongside other organs in the COVID-19 disease. Aim: To describe COVID-19 inflammation and, eventually, dysregulations of normal thyroid function in a case series of patients diagnosed in a tertiary endocrinology care centre. Patients and Methods: We described subacute thyroiditis cases related to COVID-19 infection or vaccination against SARS-CoV2 infection (clinical manifestations and evolution). We also reviewed the literature data regarding COVID-19 infection or vaccination implications in thyroid pathology. Results: The literature describes two types of thyroid involvement in SARS-CoV2 infection or vaccination: subacute thyroiditis (SAT) and non-thyroidal illness syndrome (NTIS). In our case series, 5 patients (3 males), aged 41-54 years, developed the classical clinical manifestation of SAT related to COVID-19 infection (3 patients, concomitantly to upper respiratory infection or a few weeks apart) or anti-SARS-CoV2 ARNm vaccination (1-2 weeks after the vaccine administration). Clinical, laboratory and imaging findings and the evolution (steroid anti-inflammatory treatment used in 4/5 cases) were unremarkable compared to other SAT etiologies. Conclusion: We found no differences between the "typical" viral and post-COVID-19 SAT regarding clinical presentation, severity, response to treatment, and thyroid function alteration. The only remarkable difference is the association of SAT with anti-SARS-CoV2 ARNm vaccination.

Thyrotropin Levels in Patients with Coronavirus Disease 2019: Assessment during Hospitalization and in the Medium Term after Discharge.

BACKGROUND: The objectives of this study were (1) to compare TSH levels between inpatients with critical versus non-critical coronavirus disease 19 (COVID-19), and (2) to describe the status of TSH levels three months after hospitalization. METHODS: We collected data on adult patients hospitalized with COVID-19 at Amiens University Hospital. We compared TSH levels between inpatients with critical (intensive care unit admission and/or death) versus non-critical COVID-19. Thereafter, survivors were invited to return for a three-month post-discharge visit where thyroid function tests were performed, regardless of the availability of TSH measurement during hospitalization. RESULTS: Among 448 inpatients with COVID-19, TSH assay data during hospitalization were available for 139 patients without prior thyroid disease. Patients with critical and non-critical forms of COVID-19 did not differ significantly with regard to the median (interquartile range) TSH level (0.96 (0.68-1.71) vs. 1.27 mIU/L (0.75-1.79), p = 0.40). Abnormal TSH level was encountered in 17 patients (12.2%); most of them had subclinical thyroid disease. TSH assay data at the three-month post-discharge visit were available for 151 patients without prior thyroid disease. Only seven of them (4.6%) had abnormal TSH levels. Median TSH level at the post-discharge visit was significantly higher than median TSH level during hospitalization. CONCLUSIONS: Our findings suggest that COVID-19 is associated with a transient suppression of TSH in a minority of patients regardless of the clinical form. The higher TSH levels three months after COVID-19 might suggest recovery from non-thyroidal illness syndrome.