Association of Reduced Free T3 to Free T4 Ratio with Lower Serum Creatinine in Japanese Hemodialysis Patients

Purpose: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients. Methods: This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study. Results: The serum FT4 and TSH of HD patients (n = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9IU/mL, which were within the respective normal range, while serum FT3 was 2.2 ± 0.3 pg/mL. As many as 101 out of 332 (30.4%) HD patients exhibited a serum FT3 less than the normal lower limit of 2.2 pg/mL. The serum FT3/FT4 ratio correlated significantly positively with serum creatinine, and inversely with serum log CRP and total cholesterol, while it exhibited a tendency towards positive correlation with serum albumin. Multiple regression analysis, which included serum creatinine, albumin, and log CRP, simultaneously, in addition to sex, age, diabetic kidney disease or not, log HD duration, body mass index, systolic blood pressure, and Kt/V, as independent variables, revealed an independent and significant positive association of serum creatinine, but not serum albumin or CRP, with the serum FT3/FT4 ratio. Conclusions: The present study demonstrated an independent and positive correlation of serum creatinine with the serum FT3/FT4 ratio in HD patients. The lack of association of the serum FT3/FT4 ratio with serum albumin and CRP suggested the presence of a creatinine-specific mechanism to associate with serum FT3/FT4 ratio. Because of the local activation of T4 to T3 at muscle tissue, a lower muscle mass may be causatively associated with low T3 syndrome.

Hypovitaminosis D and Low T3 Syndrome: A Link for Therapeutic Challenges in Patients with Acute Myocardial Infarction

Background and Aims: Vitamin D counteracts the reduction in the peripheral conversion of tiroxine (T4) into triiodothyronine (T3), which is the mechanism of low T3 syndrome (LT3) in acute myocardial infarction (AMI). The aim of this study was to assess the relationship between LT3 and hypovitaminosis D in AMI patients. Methods and Results: One hundred and twenty-four AMI patients were enrolled. Blood samples were taken at admission, and at 3, 12, 24, 48, and 72 h after admission. LT3 was defined as a value of fT3 ≤ 2.2 pg/mL, occurring within 3 days of hospital admission. Levels were defined as follows: sufficiency as a value of ±30 ng/mL, vitamin D insufficiency as 25-hydroxyvitamin D (25(OH)D) between 21 and 29 ng/mL, deficiency in 25(OH)D as below 20 ng/mL, and severe deficiency as values under 10 ng/mL. The percentage of subjects with severe 25(OH)D deficiency was significantly higher in the LT3 group (33% vs. 13%, p < 0.01). When LT3S was evaluated as a dependent variable, severe 25(OH)D deficiency (OR 2.6: 95%CI 1–6.7, p < 0.05) remained as an independent determinant after logistic multivariate adjustment together with age (>69 yrs, 50th percentile; OR 3.4, 95% CI 1.3–8.3, p < 0.01), but not female gender (OR 1.7, 95% CI 0.7–4.2, p = ns). Conclusions: This pilot study shows a relationship between hypovitaminosis D and LT3 in AMI patients. This association opens potential therapeutic challenges concerning the restoration of euthyroidism through vitamin D administration, together with the normalization of hypovitaminosis.

THYROID HORMONE ABNORMALITY IN PATIENTS WITH ACUTE STROKE- A HOSPITAL BASED CASE CONTROL STUDY

Introduction: Stroke or Cerebrovascular accident (CVA) is a major cause of disability worldwide. The estimation of serum Total T3, Total T4 and TSH are very much essential in patients with stroke. Any disturbances in thyroid hormones may have negative influence on the outcome of acute phase of strokes. Aims And Objectives: Aims and objective was to estimate the Total T3, Total T4 and TSH of patients with acute Stroke and to compare it with age/sex matched healthy controls. Materials & Methods: This Hospital Based Case Control Study, consist of total 100 subjects out of which 50 were control ,was carried out in Jorhat Medical College & Hospital, Assam for a period of one year, from July 2017 to June 2018. Age more than 40 years of both sexes was included. Estimation for total T3, total T4, and TSH was carried out in Access 2 ImmunoAssay Systems (Beckman Coulter). Cases were selected randomly . Results And Observations: Out of 50 Stroke patients ,the age group of 50 - <60 years constituted the majority of cases(32%) . Greater preponderance of stroke was seen in males (62%) with male to female ratio of 1.63:1. Hemorrhagic stroke was found to be more common than ischemic stroke (54% V/s 46%). Hemorrhagic strokes occurred more in early age than ischemic strokes. The mean ± SD of serum Total T3 levels in stroke patients and controls were 0.960 ± 0.327 and 1.248 ± 0.269 respectively, with statistically significant mean value difference (p<0.05) when cases were compared to the controls. A greater number of low T3 was present in ischemic strokes (43.5%) when compared to hemorrhagic strokes (18.5%). Conclusion: Nonthyroidal illness syndrome (Low T3 syndrome) is observed in the present study with decreased T3 values without alteration of T4 and TSH levels. Further studies with a large sample size should attempt to investigate whether treatment of low T3 syndrome can improve the final outcome.

Endocrine Dysfunction in Covid-19

Introduction: Evidence pertaining to new-onset endocrine dysfunction in patients with COVID-19 is currently limited and extrapolated from prior SARS epidemics. Further, identifying whether the quantum of this dysfunction is associated with the severity of disease in patients with COVID-19 is unknown. We aimed to to comprehensively explore the prevalence, nature and degree of endocrine dysfunction stratified based on disease severity at a dedicated COVID care centre. Patients and Methods: Consecutive patients enrolled at PGIMER Chandigarh, were stratified on the basis of disease severity as: group I (moderate to severe disease including oxygen saturation &lt;94% on room air or those with comorbidities) and group II (mild disease, with oxygen saturation &gt;94% and without comorbidities). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed. Results: Patients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% patients, without significant difference between both groups. Conclusion: COVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease. Involvement of multiple axes, particularly at hypothalamo-pituitary level suggests the possibility of hypophysitis as an underlying etiology. We also observed less characterised findings like atypical thyroiditis and normal DHEAS despite secondary hypocortisolism. Follow-up surveillance of these patients at periodic intervals and estimation of anti-pituitary antibodies could be considered to elucidate viral cytopathic effect or inflammation as the major underlying mechanism of endocrine dysfunction.

The Prevalence of low T3 syndrome in chronic heart failure: A Hospital-based study

Background: Effect of thyroid hormone on cardiac functions is mediated by biologically active T3 which binds to nuclear TR. There is increasing evidence that patients with mild thyroid dysfunctions are presenting with adverse cardiovascular manifestations which includes heart failure. Aim: The present study aimed to determine the existence of low T3 syndrome in patients with chronic heart failure. Material and Methods: This prospective study was conducted in the Department of General Medicine and Cardiology, KMC, and MGM Hospital, Warangal. patients with heart failure were included in the study. A total of n=100 patients were included in the study detailed physical examination was conducted to assess the patient's volume status (rales, edema, jugular venous distension), weight, height, body mass index, and orthostatic blood pressure changes. Complete blood count, blood glucose (fasting and 2 hours postprandial), Fasting serum lipid profile, blood urea, serum creatinine, and serum electrolytes were measured in all patients. Two-dimensional echocardiography was done in patients. Results:Analysis of Echocardiography parametersCompared to patients who were alive (n=90),left ventricular end-diastolic diameter was higher in those whodied (n=10). The mean ejection fraction in died and alive groups were27.19% and 35.12% respectively. Persons who died had asignificantly lower ejection fraction than those alive.When the mean ejection fraction was compared betweenpatients with low total T3 (T3<80 ng/dl) and normal T3 , patients with low T3 had a mean ejection fraction of 29.2% and those with normal T3 levels had a mean ejection fraction of 34.78%. This indicates the mean ejection fraction is lower in patients with low total T3 levels. Conclusion:Within the limitations of the present study it can be concluded that the prevalence of low T3 syndrome in patients with chronic heart failure is common. It was found that patients with lower T3 levels were having a lower ejection fraction.The LVEDD diameterwas negatively correlated with total T3. Therefore, Total T3 levels can be used as an adjunct to other parameters for risk stratification and survival estimation in chronic heart failure.

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

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

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

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