Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients: A prospective observational cohort study.

BACKGROUND: Both phases of euthyroid sick syndrome (ESS) are associated with worse prognosis in septic shock patients. Although there are still no indications for supplementation therapy, there is no evidence that both phases (initial and prolonged) are adaptive or that only prolonged is maladaptive and requires supplementation. AIM: To analyze clinical, hemodynamic and laboratory differences in two groups of septic shock patients with ESS. METHODS: A total of 47 septic shock patients with ESS were divided according to values of their thyroid hormones into low T3 and low T3T4 groups. The analysis included demographic data, mortality scores, intensive care unit stay, mechanical ventilation length and 28-day survival and laboratory with hemodynamics. RESULTS: The Simplified Acute Physiology Score II score (P = 0.029), dobutamine (P = 0.003) and epinephrine requirement (P = 0.000) and the incidence of renal failure and multiple organ failure (MOF) (P = 0.000) were significantly higher for the low T3T4. Hypoalbuminemia (P = 0.047), neutrophilia (P = 0.038), lymphopenia (P = 0.013) and lactatemia (P = 0.013) were more pronounced on T2 for the low T3T4 group compared to the low T3 group. Diastolic blood pressure at T0 (P = 0.017) and T1 (P = 0.007), as well as mean arterial pressure at T0 (P = 0.037) and T2 (P = 0.033) was higher for the low T3 group. CONCLUSION: The low T3T4 population is associated with higher frequency of renal insufficiency and MOF, with worse laboratory and hemodynamic parameters. These findings suggest potentially maladaptive changes in the chronic phase of septic shock.

The Development of Myxedema Coma in the Setting of Euthyroid Sick Syndrome: A Diagnostic Dilemma and Review of Management Strategies.

Euthyroid sick syndrome (ESS), also referred to as nonthyroidal illness syndrome, is an intriguing condition characterized by dysregulation of thyroid hormones despite normal thyroid gland function. It is diagnosed by low serum triiodothyronine levels, and, in some cases, other thyroid hormones such as thyroxine and thyroid-stimulating hormone may be affected. This condition arises via various physiologic mechanisms and is associated with intensive care unit (ICU) admissions, caloric deprivation, and severe illness. Myxedema coma (MC) is a rare medical emergency with a high mortality rate. It is caused by severe hypothyroidism, resulting in multiorgan failure with features including adrenal insufficiency, thermal dysregulation, and altered mentation. Generally, it is observed in untreated and poorly managed cases of hypothyroidism. However, stress from infections, surgical procedures, and medical comorbidities may precipitate this condition. It is particularly uncommon to see MC arise in the setting of ESS, especially in a patient with no history of thyroid disease, which makes this diagnosis easy to miss. In our case, a 36-year-old female presented with septic shock and was admitted to the ICU, where she subsequently developed ESS and features of MC. This case report aims to explore the risk factors, features, and diagnostic and therapeutic management of these conditions, as well as the diagnostic challenges that arise when these diseases present simultaneously.

Thyroid dysfunction in the wake of Omicron: understanding its role in COVID-19 severity and mortality.

Purpose: SARS-CoV-2 can invade the thyroid gland. This study was to delineate the risk of thyroid dysfunction amidst the prevalence of the Omicron variant, and to investigate the correlation between thyroid function and Coronavirus disease 2019 (COVID-19) outcomes. The study also aimed to ascertain whether thyroid dysfunction persisted during COVID-19 recovery phase. Methods: This was a retrospective cohort study. COVID-19 patients from the Renmin Hospital of Wuhan University, China during the epidemic of Omicron variants were included, and their thyroid function were analyzed in groups. Results: A history of thyroid disease was not associated with COVID-19 outcomes. COVID-19 can lead to a bimodal distribution of thyroid dysfunction. The severity of COVID-19 was inversely proportional to the levels of thyroid- stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), leading to a higher prevalence of thyroid dysfunction. Severe COVID-19 was a risk factor for euthyroid sick syndrome (ESS) (OR=22.5, 95% CI, 12.1 - 45.6). Neutrophil to lymphocyte ratio mediated the association between severe COVID-19 and ESS (mediation effect ratio = 41.3%, p < 0.001). ESS and decreased indicators of thyroid function were associated with COVID-19 mortality, while high levels of FT3 and FT4 exhibited a protective effect against death. This effect was more significant in women (p < 0.05). During the recovery period, hyperthyroidism was quite uncommon, while a small percentage of individuals (7.7%) continued to exhibit hypothyroidism. Conclusion: COVID-19 severity was linked to thyroid dysfunction. Severe COVID-19 increased the risk of ESS, which was associated with COVID-19 mortality. Post-recovery, hyperthyroidism was rare, but some individuals continued to have hypothyroidism.

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

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

Is Low-free Triiodothyronine (fT3) Associated with Increased Morbidity in Patients Admitted to Coronary Care Units?

BACKGROUND: The effects of thyroid hormone on patients hospitalized in coronary intensive care units are still controversial. Objective: We retrospectively examined thyroid hormone levels and their impact on cardiovascular morbidity in patients admitted to coronary intensive care units. METHODS: A total of 208 (Female/Male; 46.6%/53.4%) patients without any history of thyroid disease were enrolled and screened. Patients with specific heart disease and existing thyroid hormone parameters were included in the study. Low triiodothyronine syndrome is characterized by reduced serum total or free T3 (fT3) concentrations in normal free T4 (fT4) and TSH levels. RESULTS: The common diagnosis of the patients in the coronary care unit is acute coronary syndrome (n=59, 28.2 %) and heart failure (n=46, 23.3%). Patients were divided into two groups according to left ventricular ejection fraction percentages (LVEF ≤39% vs LVEF ≥40%). Plasma fT3 levels were significantly correlated with low LVEF (≤39%) (p =0.002). fT3 (r=-0.183, p =0.013) and hospitalization etiology (r=-0.161, p =0.023) were also the most critical parameters affecting the length of hospitalization. CONCLUSION: Low fT3 was associated with reduced ejection fraction and prolonged hospitalization, which may lead to potential morbidities in HF patients and may be useful in risk stratification and treatment strategies.

Total thyroxine, triiodothyronine, and thyrotropin concentrations during acute nonthyroidal illness and recovery in dogs.

BACKGROUND: Acute illness can result in changes in serum total thyroxine (tT4), total triiodothyronine (tT3), and thyrotropin (TSH) concentrations in euthyroid dogs defined as nonthyroidal illness syndrome, but longitudinal evaluation of these hormones during the recovery phase is lacking. OBJECTIVES: To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. ANIMALS: Nineteen euthyroid client-owned dogs hospitalized for acute illness at a veterinary teaching hospital. METHODS: Prospective longitudinal study. Serum tT4, tT3, and TSH concentrations were measured at the admission (T0), at last day of hospitalization (T1), and during the recovery phase at 3, 7, 14, and 21 days after the discharge (T2, T3, T4, and T5), respectively. RESULTS: tT4 and tT3 were below the reference interval (RI) at T0 in 3 (16%) and 18 (95%) dogs, respectively; tT4 normalized in all dogs early in the recovery phase, while low tT3 persisted at the end of the study in 16 (83%) dogs. Median TSH concentrations were increased at T5 compared with T1 (0.19 ng/mL [range 0.03-0.65] vs 0.11 ng/mL [range (0.05-0.26)], mean difference = 0.09 ng/mL; P = .03). Five (26%) dogs had TSH above the RI at least at 1 time point during the recovery phase. None of the dogs had concurrent low tT4 and high TSH during the study. CONCLUSIONS AND CLINICAL RELEVANCE: In euthyroid dogs acute illness can interfere with evaluation of thyroid function up to 21 days during the recovery phase. Thyroid testing should be avoided or postponed in these dogs.

A Cross-Sectional Study of Acute Coronary Syndrome and Thyroid Profile: Dissecting the Relationship to Improve Patient Care.

INTRODUCTION: Thyroid-releasing hormones are pivotal in regulating cardiovascular (CVS) function and maintaining its hemodynamics and homeostasis. Even a minor alteration in thyroid function has an enormous implication on CVS morbidity and mortality. Moreover, hypothyroidism was found to be a potential menace for coronary artery disease (CAD). The objective of this study was to determine the role of thyroid-releasing hormones in patients suffering from acute coronary syndrome (ACS). METHODOLOGY: Among a cohort of 100 patients suffering with ACS, a complete history and clinical information followed by physical examination and electrocardiography were recorded. Blood samples were also collected to record the blood sugar levels i.e., fasting blood sugar (FBS), postprandial blood sugar (PPBS), and thyroid profile, including free thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and reverse triiodothyronine (rT3). The data was analyzed using SPSS version 26 software (IBM Corp., Armonk, NY, USA). RESULT: The study identified alterations in the thyroid hormone levels in 27% of patients suffering from ACS. The prevalence of euthyroid sick syndrome was found to be 59.3%, while subclinical hypothyroidism and subclinical hyperthyroidism were reported among 18.5% and 14.8% of patients respectively. There was no significant difference found between males and females. The study illustrated a greater occurrence of aberrant thyroid hormone profiles among those aged 40-60 years. The ST-elevated myocardial infarction (STEMI) group had a statistically significant higher prevalence of an aberrant thyroid hormone profile compared to the non-ST-elevated myocardial infarction (NSTEMI) and unstable angina (UA) groups (p=0.02). A total of nine patients died with ACS and all of those had statistically significant low fT3 and TSH values while higher rT3 values (p<0.05). CONCLUSION: An atypical thyroid status has been found to elevate the likelihood of developing CAD and experiencing CVS mortality. This condition can impact ventricular function and serum cholesterol levels as well as heart rate and rhythm. Therefore, understanding this relationship could potentially lead to improved treatment strategies for individuals with ACS which will further prevent major CVS complications.

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).

Contrast-enhanced ultrasonography of the thyroid gland in healthy dogs, hypothyroid dogs and dogs with non-thyroidal illness.

Diagnosis of canine hypothyroidism remains challenging, as non-thyroidal illness (NTI)-syndrome and medical treatment can influence thyroid hormone concentrations. Conventional ultrasound may give additional hints, however high interobserver variability has been described. Contrast-enhanced ultrasound (CEUS) allows detection of changes in tissue perfusion. The purpose of the present study was to assess the possible diagnostic value of CEUS regarding diagnosis of hypothyroidism. CEUS of the thyroid gland was performed in 52 healthy dogs, 16 hypothyroid dogs, and 20 NTI patients. The following perfusion parameters were calculated: Thyroid/carotid artery (TG/CA) ratios for peak enhancement (PE) and area under the curve (AUC), time to peak (TTP) and wash-in and wash-out rates (WiR, WoR) of the thyroid gland. Impact of sedation on perfusion parameters was investigated in 8 calm healthy dogs which were examined before and after sedation using midazolam and butorphanol. Significantly higher median TG/CA ratios for PE were detected for the left and right thyroid lobe in dogs with hypothyroidism (0.97/0.96) compared to healthy dogs (0.85/0.85) and dogs with NTI (0.84/0.84). AUCs were also significantly increased in hypothyroid dogs when compared to other groups. Dogs with NTI showed significantly lower WiR and WoR compared to other groups. Values for TTP were not significantly different between groups. Sedation had only impact on results of TTP which was significantly prolonged in sedated dogs. In conclusion, CEUS of the thyroid gland can provide an additional tool for diagnosis of hypothyroidism in dogs and support its differentiation from NTI. Sedation has limited impact on CEUS results.

A Review of Thyroid Dysfunction Due to COVID-19.

Coronavirus disease 2019 (COVID-19) affects thyroid function. These changes are due to the direct impact of the virus on thyroid cells via angiotensin-converting-enzyme 2 (ACE2) receptors, inflammatory reaction, apoptosis in thyroid follicular cells, suppression of hypothalamus-pituitarythyroid axis, an increase in activity of adrenocortical axis, and excess cortisol release due to cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Euthyroid sick syndrome (ESS), thyroiditis, clinical and subclinical hypothyroidism, central hypothyroidism, exacerbation of underlying autoimmune thyroid disease, and clinical and subclinical hyperthyroidism can be associated with coronavirus. Adjuvants in coronavirus vaccines induce autoimmune/inflammatory syndrome known as vaccine adjuvants (ASIA) syndrome. Thyroiditis and Graves' disease have been reported to be associated with ASIA syndrome after some coronavirus vaccinations. Some coronavirus medications, such as hydroxychloroquine, monoclonal antibodies, lopinavir/ritonavir, remdesivir, naproxen, anticoagulants, and glucocorticoids can also affect thyroid tests, and correct diagnosis of thyroid disorders will be more difficult. Changes in thyroid tests may be one of the most important manifestations of COVID-19. These changes can be confusing for clinicians and can lead to inappropriate diagnoses and decisions. Prospective studies should be conducted in the future to increase epidemiological and clinical data and optimize the management of thyroid dysfunctions in patients with COVID-19.

The prevalence, hospitalization outcomes and risk factors of euthyroid sick syndrome in patients with diabetic ketosis/ketoacidosis.

BACKGROUND: To investigate the prevalence of euthyroid sick syndrome (ESS) and to evaluate the outcomes and risk factors associated with ESS among hospitalized patients with diabetic ketosis (DK) or diabetic ketoacidosis (DKA). METHODS: Laboratory and clinical data of 396 adult hospitalized DK/DKA patients with or without ESS were collected and analyzed. Spearman linear analysis and multivariable logistic regression analyses were used to evaluate correlated factors of thyroid hormones and risk factors of ESS. RESULTS: Most of the individuals were diagnosed with type 2 diabetes (359/396, 90.7%). The prevalence of ESS was 57.8% (229/396). Patients in ESS group were older and had a longer course of diabetes. Levels of thyroid hormones, serum lipids, and parameters reflecting acidosis were significantly decreased in ESS group. The proportion of patients with infection, acute renal injury and DKA was significantly higher in ESS group than in control group, accompanied by longer hospitalization stay and higher hospitalization costs. Free triiodothyronine positively correlates with albumin, eGFR, parameters reflecting acidosis and lipid profiles (All P < 0.001), and negatively correlates with age, onset age, 24-h urine albumin, hsCRP and WBC count (All P < 0.001). Hypoalbuminemia, low level of carbon dioxide combining power, high level of HbA1c and WBC, and co-infection are shown to be risk factors for ESS (OR = 0.866, 0.933, 1.112, 1.146, 1.929, respectively; All P < 0.05). CONCLUSIONS: The prevalence of ESS was high in adult DK/DKA patients. Patients with ESS had inferior clinical and socioeconomic outcomes. Early recognition and management of patients with ESS may be necessary to improve outcome.

Prognostic role of euthyroid sick syndrome in MIS-C: results from a single-center observational study.

Background: Euthyroid sick syndrome (ESS) is characterized by low serum levels of free triiodothyronine (fT3) with normal or low levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) and is reported in different acute clinical situations, such as sepsis, diabetic ketoacidosis and after cardiac surgery. Our aim was to evaluate the predicting role of ESS for disease severity in patients with Multisystem Inflammatory Syndrome in children (MIS-C). Methods: A single-centre observational study on consecutive patients with MIS-C. Before treatment clinical, and laboratory data were collected and, in a subset of patients, thyroid function tests were repeated 4 weeks later. Variables distribution was analyzed by Mann-Whitney U-test and correlations between different parameters were calculated by Spearman's Rho coefficient. Results: Forty-two patients were included and 36 (85.7%) presented ESS. fT3 values were significantly lower in patients requiring intensive care, a strong direct correlation was shown between fT3 and Hb, platelet count and ejection fraction values. A significant inverse correlation was retrieved between fT3 levels and C-reactive protein, brain natriuretic peptide, IL-2 soluble receptor and S-100 protein. Subjects with severe myocardial depression (EF < 45%) had lower fT3 values than subjects with higher EF. The thyroid function tests spontaneously normalized in all subjects who repeated measurement 4 weeks after admission. Conclusion: ESS is a frequent and transient condition in acute phase of MIS-C. A severe reduction of fT3 must be considered as important prognostic factor for severe disease course, with subsequent relevant clinical impact in the management of these patients.

The severity of valvular heart disease in euthyroid individuals is associated with thyroid hormone levels but not with TSH levels.

Background: Abnormal thyroid function is a metabolic disorder and can lead to several complications, including cardiovascular diseases. In this study, we aimed to examine the relationship between clinical traits and outcomes and the thyroid hormone level of euthyroid individuals with valvular heart disease (VHD). Method: The thyroid function was evaluated in 526 euthyroid VHD patients and 155 healthy control people. As well as clinical indicators were collected and analyzed. Results: No difference in TSH levels (p>0.05) was recorded; however, fT3, TT3, and TT4 levels were lower in the euthyroid VHD patients than in healthy control(4.3 vs 4.63; 1.37 vs 1.48; 97.7 vs 102.09, respectively, all p<0.05), while the fT4 level was higher (12.91 vs 12.35, p<0.05). Moreover, all showed a continuous trend with the change of NYHA grade which does not consist of the incidence of euthyroid sick syndrome(ESS). Further analysis showed that for every 10-fold increase in BNP, fT4 increases by 83%, fT3 decreases by 30%, and TT3 decreases by 12% after being adjusted for other influencing factors. Meanwhile, adjusted fT4 was correlated with multiple worse clinical indicators, which were influenced by age. Conclusion: Thyroid hormones are widely regulated in VHD patients even with acceptable cardiac function, except for TSH level. And the adjusted fT4 is related to worse clinical indicators and outcomes which are only recorded in patients under 53 years old.

Critically ill patients: Histopathological evidence of thyroid dysfunction.

PURPOSE: Critical illness is characterized by severe biphasic physical and metabolic stress as result of systemic inflammatory response syndrome and/or multiple organ dysfunction syndrome, and is frequently associated with non-thyroidal illness. Purpose of this study is to better understand the cytomorphological basis of NTI by performing histopathological examinations of thyroid gland on autopsies of patients who died from critical illness. METHODS: Histopathological examination of thyroid gland of 58 critically ill patients was performed in our hospital. The cases included 24 cases of burn injury, 24 cases of traumatic brain injury, and 10 cases of cerebral stroke. Thyroid samples obtained during autopsy were preserved in formol saline and stained with hematoxylin and eosin. The sections were visualized under light microscopy. RESULTS: Out of 58 cases examined, 21 patients showed normal thyroid findings, and rest of the cases had unusual thyroid findings in the histopathological study. The principal finding was distortion of thyroid follicular architecture. Other findings include mononuclear cell infiltration, clumping of thyroglobulin, and exhaustion of thyroid follicles. CONCLUSION: Critical illness produces metabolically damaging effects on thyroid gland, which functionally corresponds to a state of low T3 syndrome. These changes are more pronounced in BI and cerebral stroke than in TBI.

The diurnal change of thyroid-stimulating hormone and the effect of this change on thyroid functions in patients with chronic kidney disease.

PURPOSE: Thyroid-stimulating hormone (TSH) has a pulsatile and circadian rhythm in healthy individuals. We aimed to evaluate the diurnal changes of free thyroid hormones and serum TSH levels in patients with end-stage renal failure (ESRF) whose thyroidal functions are at normal ranges. METHODS: Thirty hemodialysis patients with chronic renal failure and without a known thyroidal disease who are over 18 and 35 healthy individuals were included. The serum TSH, free T3, and free T4 levels were examined among the patient and control group which were taken at 8:00 a.m., 4:00 p.m., and 0:00 a.m. RESULTS: Twenty-two (73.3%) patients were male, and the mean age of the patient group was 64 (sd = 14.45 years). Seventeen (48.6%) of the control group were female, and the mean age was 31.9 (sd = 6.4 years). Serum free T3 levels, measured at three different time points (8:00 a.m., 4:00 p.m., and 0:00 a.m.), were significantly lower in the patient group than in the control group and serum free T4 levels were measured at three different time points (8:00 am, 4:00 p.m., and 0:00 a.m.) were significantly higher in the patient group than in the control group. Serum TSH levels were higher in the patient group than in the control group at 08:00, and were lower at 24:00 (p < 0.001). The nocturnal increase of serum TSH level under 0.525 suggested diurnal rhythm disruption with 83% sensitivity and 87% specificity. CONCLUSION: The nocturnal serum TSH increase is not seen in ESRF patients who did not have a thyroid disease. We think that not observing a nocturnal TSH increase could be an early indication of the sick euthyroid syndrome.

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.

Low T3 Syndrome on Admission and Response to Nutritional Support in Malnourished Medical Inpatients.

CONTEXT: During illness, deiodination of thyroxine (T4) to triiodothyronine (T3) is downregulated. This is called "low T3 syndrome", an adaptive metabolic mechanism to reduce energy expenditure and prevent catabolism. OBJECTIVE: We aimed to investigate the prognostic role of low T3 syndrome in patients at nutritional risk regarding mortality, clinical outcomes, and response to nutritional support. METHODS: This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled, Swiss, multicenter trial comparing effects of individualized nutritional support with usual care in adult medical inpatients at nutritional risk. The primary endpoint was all-cause mortality over 30, 180 days, and 5 years. RESULTS: We had complete data including fT3 concentration of 801/2028 (39.5%) patients from the initial trial. Of these 492 (61.4%) had low T3 syndrome (fT3 < 3.2 pmol/L). Low T3 syndrome was associated with higher mortality over 30 days (adjusted hazard ratio 1.97, 95% CI 1.17-3.31, P = .011) and other adverse clinical outcomes. Nutritional support only lowered mortality in the group of patients with low T3 syndrome but not in those without low T3 syndrome (adjusted odds ratio of nutritional support of 0.82 [95% CI 0.47-1.41] vs 1.47 [95% CI 0.55-3.94]). This finding, however, was not significant in interaction analysis (P for interaction = .401). CONCLUSION: Our secondary analysis of a randomized trial suggests that medical inpatients at nutritional risk with low T3 syndrome have a substantial increase in mortality and may show a more pronounced beneficial response to nutritional support interventions.

Effects of covid-19 infection on thyroid functions.

Background: COVID-19 may affect many endocrine tissues as well as thyroid gland and hypothalamus-pituitary-thyroid axis. It has been shown that COV D-19 infection suppresses thyroid hormones in some studies and causes subacute thyroiditis in the others so that its effects are still not fully known. The aim of our study is to retrospectively evaluate thyroid functions, clinical findings, biochemical and inflammatory markers in PCR positive patients infected with COVID-19; and to evaluate the relationship between abnormal thyroid function tests (TFT) and clinical and laboratory findings and whether it has potential prognostic significance. Methods: The data of patients aged 18 years and older, 201 patients who applied to Mersin City Training and Research Hospital due to COVID-19 infection between 1st of March and 1st of April in 2021 and received inpatient treatment were evaluated retrospectively. Results: Large TFT (TSH, T3, T4, anti-TPO) and laboratory data of 201 patients with mild, moderate or severe pneumonia on CT were scanned retrospectively. 121 (60.2%) of the patients were male, mean age was 51.9 ± 14.6 years, and the most common comorbid disease was hypertension in 65 (32.3%) patients. Conclusions: It has been determined that the deterioration in TFTs is associated with LDH and D-dimer which are indicators of cell and endothelial damage, duration of hospitalization, clinical severity, and having mutant strains and it has been concluded that low TSH can be used as a prognostic indicator in COVID-19 patients. Further studies with healthy control groups, quantitative RT-PCR tests, histological and pathological correlations, and long-term follow-up are needed.

Thyroid Function During and After COVID-19 Infection: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to multiorgan dysfunction through pulmonary and systemic inflammation. Infection also affects the thyroid gland directly via cytopathological effects of the virus or indirectly through cytokines, complement systems and coagulation mechanisms. The thyroid gland regulates innate and adaptive immune systems by genomic and nongenomic pathways. During or after SARS-CoV-2 infection, Graves' disease and subacute thyroiditis might be triggered resulting in hyperthyroidism; alternatively, the effect of the virus on the hypophyseal.hypothalamic axis might cause central hypothyroidism. Severe cases of coronavirus disease 2019 (COVID-19) can present with hypoxia, which requires the use of dexamethasone. This can depress basal serum concentrations of 3,5,3'-triiodothyronine. Thyroid function should be monitored when using dexamethasone in patients with COVID-19. This article briefly reviews the direct and indirect effects of SARS-CoV-2 on the thyroid gland and function.

Hypothyroxinemia in sick term neonates and its risk factors in an extramural neonatal intensive care unit: a prospective cohort study

ABSTRACT Objective: Thyroid functions in the sick newborns may be altered in the first week of life. Transient hypothyroxinemia has been reported in these babies, which could be due to the immaturity of the hypothalamic-pituitary-thyroid axis or to acute illness. We conducted this study to estimate the incidence of hypothyroxinemia and determine its risk factors in sick term newborns. Materials and methods: We analyzed free T4 (FT4) and thyroid-stimulating hormone (TSH) levels in sick term neonates (≤7 days of life) admitted to the neonatal intensive care unit. FT4 and TSH levels were estimated in the first week of life in all the enrolled neonates (N = 98) and then repeated at 14-21 days of life in 46 babies. Risk analysis was conducted using univariate and multivariate logistic regression, and numerical data was compared using the Mann-Whitney U test and t-test. Results: Hypothyroxinemia was seen in 10 (10.2%) of the admitted term babies. Male gender, vaginal delivery, presence of hypoxic ischemic encephalopathy, and need for mechanical ventilation (>24 hours) were identified as risk factors. There was a significant negative linear correlation between FT4 level in the first week of life and duration of hospital stay. Conclusion: Hypothyroxinemia is common in sick term neonates.