[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.

The Association of Thyroid Hormones with Coronary Atherosclerotic Severity in Euthyroid Patients.

The aim of the work was to explore the correlation between thyroid hormones and coronary atherosclerotic severity. This cross-sectional study included 340 euthyroid patients who underwent diagnostic coronary artery angiography (CAG). Gensini Score (GS) was applied to assess the severity of coronary atherosclerosis. Thyroid hormones and routine biochemical parameters were measured. The associations between thyroid hormones and coronary atherosclerosis severity were analyzed. Thyroid hormones levels or parameters were taken as both continuous variables and tertiles into analysis, and the lowest tertile was usually used as the reference (OR=1) for medium and highest tertiles. Free triiodothyronine (FT3) level was associated with GS≥22 (Median GS) in Model I adjusted for age and sex [Continuous: OR=0.46, 95% CI (0.23, 0.92), p=0.029; Tertile 3: OR=0.54, 95% CI (0.30, 0.97), p=0.038], and Model II adjusted for all known risk factors of coronary artery disease (CAD) [Continuous: OR=0.44, 95% CI (0.20, 0.95), p=0.036; Tertile 3: OR=0.49, 95% CI (0.25, 0.96), p=0.039]. Subjects with highest tertile of FT3 to free thyroxine (FT4) ratio (FT3/FT4 ratio) appeared to have the remarkably decreased risk of CAD in both Non-adjusted Model [OR=0.49, 95% CI (0.24, 0.98), p=0.044] and Model I [OR=0.45, 95% CI (0.22, 0.93), p=0.031]. Higher FT3 level within normal range was independently and negatively associated with severity of coronary atherosclerosis. Besides, FT3/FT4 ratio was remarkably correlated with the prevalence of CAD in euthyroid population.

Euthyroid sick syndrome as an early surrogate marker of poor outcome in mild SARS-CoV-2 disease.

BACKGROUND: The new coronavirus 19 disease (COVID-19) represents the current worldwide emergency. According to past evidence, a simple biomarker, such as low free triiodothyronine (fT3) levels, within the framework of euthyroid sick syndrome (ESS), might help to identify patients with unfavourable outcomes. OBJECTIVE: Evaluation of ESS significance in hospitalized mild COVID-19 patients. DESIGN: Prospective study, from 1 April 2020 to 31 May 2021. PARTICIPANTS: COVID-19 patients with mild disease at hospital admission. MAIN MEASURES: At hospital admission, eligible patients underwent a complete thyroid function evaluation. Subjects with previous thyroid disease or with thyroid-interfering medications were excluded. Levels of fT3 were correlated to biochemical markers and to patient outcome, the latter considered as favourable in the event of infection recovery and unfavourable in the event of death or transfer to an intensive care unit (ICU). KEY RESULTS: Of 600 screened patients, 506 were eligible for this study. Of those, 94 (19%) died during hospitalization and 80 (18%) required a transfer to ICU. The most frequent thyroid disorder was ESS (57%). Admission levels of fT3 were significantly lower within the unfavourable outcome subgroup (p < 0.001) and were negatively associated with several poor prognostic markers, including IL-6 (p < 0.001). In Kaplan-Meier and Cox regression analyses, fT3 was independently associated with poor outcome and death (p = 0.005 and p = 0.037, respectively). A critical fT3 threshold for levels < 2.7 pmol/l (sensitivity 69%, specificity 61%) was associated with a 3.5-fold increased risk of negative outcome (95%CI 2.34-5.34). CONCLUSION: Low fT3 levels, in the framework of ESS, resulted as being a valid predictor of unfavourable outcomes in a very early stage population of COVID-19.

Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure.

BACKGROUND: In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF). METHODS: A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 < 2.3pg/mL, n = 168) and non-LT3S group (FT3 ≥ 2.3pg/mL, n = 426). RESULTS: In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP. Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality. CONCLUSIONS: In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.

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.

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.

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.

Low triiodothyronine syndrome and selenium deficiency - undervalued players in advanced heart failure? A single center pilot study.

BACKGROUND: The function of deiodinases - selenoproteins converting thyroid hormones may be disturbed by oxidative stress accompanying heart failure. Selenium (Se) may be used by glutathione peroxidase, leading to a lack of deiodinase and triiodothyronine (T3). The aim of the study was the evaluation of the prevalence and clinical significance of low T3 syndrome in heart failure and the assessment of the association of low fT3 and Se deficiency. METHODS: The study group consisted of 59 consecutive patients hospitalized due to decompensated HFrEF NYHA III or IV. Exclusion criteria were: thyroid dysfunction, severe systemic disease, treatment with amiodarone, steroids or propranolol. Group A included 9 patients with low free T3 (fT3) concentration below 3.1 pmol/L. Group B consisted of the remaining 50 patients with normal fT3 levels. RESULTS: The prevalence of low T3 syndrome was 15.3%. The prevalence of Se deficiency was 74.6%. We demonstrated correlations between fT3 and main clinical variables (i.e. NT-proBNP, LVEF, hsCRP), but we did not find correlation between fT3 and the Se level. Kaplan-Meier survival analysis showed lower survival probability in patients with low fT3 (p < 0.001). CONCLUSIONS: Low T3 syndrome is frequently found in patients with HFrEF and is associated with a poor outcome. We did not identify any significant correlation between Se and fT3 level.

Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL.

Free T3 to free T4 ratio less than 2.0 suggests low T3 syndrome rather than central hypothyroidism from the age of two to eighteen years.

No serological cut-off exists to separate low T3 syndrome (LT) and central hypothyroidism (CH). The objective of this retrospective study was to propose such a cut-off. The first participant group comprised 52 patients from the age of six to twenty years. This group consisted of patients of 36 anorexia nervosa with LT and 16 CH. The second participant groups comprised 229 patients of all the same range of ages at the same hospital and included LT (n = 58) and CH (n = 4) patients, respectively. The third group of participants comprised 125 LT and 27 CH patients at the same hospital at all ages less than eighteen years. The last group of participants comprised 10 CH patients from the other two hospitals. The main outcome measure was fT3/fT4 ratio (pg/mL, ng/dL respectively). This ratio in the first group was significantly different (p < 0.05) between LT and CH. When the cut off value of fT3/fT4 was set as 2.0, the sensitivity of the LT and CH patients in the second group was 62% and 100%, respectively. This cut-off value of 2.0 was useful for distinguishing LT from CH only above the age of two years, as shown in the third group. The fT3/fT4 in 10 subjects with CH in the last group, aged 2 to 7 years, ranged from 2.55 to 7.71. In conclusion, fT3/fT4 less than 2.0 suggests LT rather than CH for patients from the age of two to eighteen years.

Association of low baseline free thyroxin levels with progression of coronary artery calcification over 4 years in euthyroid subjects: the Kangbuk Samsung Health Study.

OBJECTIVE: Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). CONTEXT: This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. MEASUREMENTS: We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. RESULTS: The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472-0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537-1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. CONCLUSIONS: In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years.

Left ventricular function by speckle-tracking echocardiography in patients with low-T3 syndrome and acute myocardial infarction.

BACKGROUND AND OBJECTIVE: Low-T3 syndrome is common in patients with acute myocardial infarction (AMI). Recent experimental and clinical data have suggested a potential negative impact of low-T3 syndrome on myocardial function in patients with AMI. The aim of this study was to assess left ventricular (LV) myocardial function in patients with low-T3 syndrome and to investigate the association between hormonal profile and the severity of LV dysfunction using speckle-tracking echocardiography (STE). MATERIALS AND METHODS: In 130 patients with first-onset ST-segment elevation acute myocardial infarction (STEMI), conventional 2D and speckle-tracking echocardiography within 48-72h after the hospitalization was performed, and blood samples for TSH, fT4, fT3, and anti-TPO levels were obtained to investigate thyroid hormone production within 24h and on the fourth day after the onset of STEMI symptoms. RESULTS: The patients were divided into two groups according to their serum level of fT3: group 1 with fT3 concentration below 3.2pmol/L (n=34) and group 2 with normal fT3 (>3.2pmol/L) level (n=96). LV ejection fraction (EF) tended to be lower in the low fT3 group. The systolic longitudinal strain did not differ between the groups, but the late diastolic longitudinal strain rate was lower in group 1 (P=0.011). The systolic basal LV rotation positively correlated with the level of fT3 (r=0.4; P<0.001), while a negative correlation was detected between myocardial rotational parameters - systolic apical rotation (r=-0.2; P<0.05), torsion (r=-0.3; P<0.001), and diastolic apical rotation rate (r=-0.3; P<0.01) - and fT3 levels. CONCLUSIONS: The late diastolic longitudinal LV strain rate and LV rotation evaluated by speckle-tracking echocardiography were impaired in patients with low-T3 syndrome after AMI.

[THYROID STIMULATING HORMONE LEVELS IN EUTHYROID WOMEN WITH POLYCYSTIC OVARY SYNDROME].

UNLABELLED: The purpose of this study was to analyze the relationship of the main hormonal and metabolic abnormalities in PCOS with different levels of TSH in the limits of its reference values. MATERIAL AND METHODS: The study involved 70 women with PCOS aged 16 to 39 years and BMI between 18.3 and 39.5 kg/m2 and a control group of 22 clinically healthy women, corresponding to age and BMI. In all of the participating women fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, insulin, TSH, FT4, TPO-Ab and Tg-Ab, LH, FSH, estradiol, Androstenedione, testosterone, SHBG, DHEA-S, prolactin, 17-hydroxyprogesterone were assessed. BMI, LDL-cholesterol, LH/FSH ratio, FAI and HOMA-index were calculated. RESULTS: In patients with PCOS, TSH levels > 2.0 mlU/L are associated with significantly higher levels of total and LDL-cholesterol. However, we did not find a direct dependency of TSH indicators of insulin resistance neither across the group of women with PCOS, nor with the subgroups. Therefore, in euthyroid women with PCOS TSH has a more pronounced effect on lipid compared to carbohydrate metabolism and in particular on insulin sensitivity. CONCLUSION: TSH levels above 2.5 in patients with PCOS are a sign for further refinement of thyroid function, initiation or adjustment of the already commenced replacement therapy.

Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab.

A 68-year-old lady with metastatic malignant melanoma was treated with Ipilimumab. She presented to Eye Casualty unable to move her eyes. Physical examination confirmed ophthalmoplegia and identified proptosis bilaterally. Radiological imaging showed bilateral enlargement of all the extra-ocular muscles suggestive of thyroid eye disease. Laboratory investigations found this patient to be euthyroid. A diagnosis of thyroid-like orbitopathy secondary to Ipilimumab therapy was made. Thyroid function tests should be performed for all patients prior to their commencement of Ipilimumab. Thyroid-like eye disease may develop in patients treated with Ipilimumab even if they remain euthyroid.

Does an episode of diabetic ketoacidosis affect thyroid function tests in pediatric patients?

OBJECTIVES: The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA). METHODS: Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group. RESULTS: A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak. CONCLUSIONS: Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests.

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.

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine.

BACKGROUND: Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. METHODS: Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. RESULTS: In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using higher dose of T3 together with 5-Fu or during chemotherapy with 5-Fu were all available to achieve chemosensitization, but pretreatment with lower dose of T3 until the end of chemotherapy may be a safer and more efficient therapy. CONCLUSIONS: Taken together, thyroid hormones decreasing during chemotherapy was found in lots of breast cancer patients. On the other hand, thyroid hormones can enhance the chemotherapeutic efficacy through gatherring tumor cells in actively proliferating stage, which may provide a new adjuvant therapy for breast cancer in furture, especially for those have hypothyroidism during chemotherapy.

Nonthyroidal illness syndrome: is it far away from Crohn's disease?

GOALS: This study was designed to investigate the clinical features of nonthyroidal illness syndrome (NTIS) compared with euthyroid patients in Crohn's disease (CD), to explore the etiology of NTIS in CD, to evaluate the clinical outcomes of NTIS patients, and to inspect the correlation of clinical variables and NTIS, and their ability of differentiating NTIS from euthyroid patients. BACKGROUND: NTIS has been described for more than 30 years. However, only few studies focused on the relationship between NTIS and CD. The incidence, underlying pathogenesis, clinical outcomes, and correlation with other inflammatory disease severity and nutritional variables of NTIS in CD have not been completely established. METHODS: Prospectively, 44 CD patients were enrolled. Medical records and various laboratory values (including thyroidal, nutritional, and inflammatory variables) were collected in all participants. RESULTS: The incidence of NTIS in CD was 36.4%. Albumin, Acute Physiology and Chronic Health Evaluation II score, and Crohn's Disease Activity Index score in NTIS group were statistically different from those in euthyroid group. A decreased sum activity of deiodinases and a reduced ratio of TT4/FT4 were observed in NTIS group. Duration of hospitalization was significantly longer for NTIS patients than euthyroid patients. Albumin was confirmed as a protective factor of NTIS in CD. Receiver operating characteristic curve analysis demonstrated the differentiating capacity of albumin, suggesting 37.6 g/L as optimal cut-off value with sensitivity and specificity of 81.3% and 79.2%, respectively. CONCLUSIONS: NTIS was a common complication in CD. NTIS patients showed worse nutrition status and clinical outcome, and more critical disease activity and severity compared with euthyroid patients. A hypodeiodination condition and a potential thyroid-hormone-binding dysfunction may play a role in the etiology of NTIS in CD. Albumin was a meaningful protective and distinguishing marker of NTIS in CD.

Evaluation of positive inotropic drug effects on thyroid hormone levels after open heart surgery.

OBJECTIVE: The aim of this study was to examine the effects of positive inotropic drugs, including adrenaline, dopamine, and dobutamine on thyroid hormone levels following open heart surgery. METHODS: We analyzed free thyroid hormones (FT3 and FT4) and thyroid-stimulating hormones (TSH) in 200 consecutive patients undergoing open heart surgery. Patients were divided into 5 groups according to the inotropic drug administration as follows: Group A (n = 46) received dopamine alone; Group B (n = 40), dopamine and dobutamine; Group C (n = 36), dopamine, dobutamine, and adrenaline; Group D (n = 32), adrenaline alone; and Group E (n = 46), placebo. Procedural factors affecting thyroid hormones were recorded and included cardiopulmonary bypass (CPB) time, cross-clamping time, degree of hypothermia, and the duration and doses of positive inotropic drugs. Blood samples for hormone assays were collected before initiation of inotropic drug therapy (baseline) and postoperatively at 24, 72, and 120 hours after drug therapy. RESULTS: FT3, FT4, and TSH levels at baseline were similar in all groups. Although there was a trend showing very slight increases in thyroid hormone levels from baseline to the 24th, 72nd, and 120th postoperative hours after drug therapy, these changes were not significant, and there were also no significant differences between the groups. There was also no significant statistical difference in CPB time, cross-clamping time, degree of hypothermia, and duration and doses of positive inotropic drugs between groups. CONCLUSION: Although thyroid hormone levels were affected by positive inotropic drug usage after open heart surgery, this effect was not significant and thyroid hormone levels remained within normal ranges.

Significant association between thyroid hormones and erythrocyte indices in euthyroid subjects.

OBJECTIVE: Hypothyroidism and hyperthyroidism are each associated with anaemia, but relationships between thyroid function and erythrocyte indices in euthyroid subjects have not been examined. The aim of this study was to examine these relationships in a community-based cohort. DESIGN, SUBJECTS AND MEASUREMENTS: Linear regression models with free T4, free T3 and TSH as predictors of erythrocyte indices and serum iron parameters were fitted to data from a cohort of 1179 participants in the 1994 Busselton health study and a subset of 1011 euthyroid participants. All models were adjusted for age, age(2), sex and an age-sex interaction. RESULTS: In the full cohort and euthyroid subset, there were significant, positive linear relationships between free T4 and each of haemoglobin, haematocrit and erythrocyte count (P < 0·01 for each), such that in euthyroid participants, each 1·0 pM increase in free T4 was associated with an increase in haemoglobin of 0·39 g/l. There were significant relationships between free T3 and each of haemoglobin, haematocrit and erythrocyte count (P < 0·001 for each), with the best model fits obtained using free T3(2), indicating curved relationships. TSH had a significant (P < 0·05) inverse relationship with serum iron and transferrin saturation in the full cohort and the euthyroid subset. Serum iron concentrations were lower in participants with subclinical hypothyroidism (n = 87) than euthyroid subjects [mean (SD) 15·9 (4·7) vs 18·4 (6·0) µM, P = 0·001]. CONCLUSION: In euthyroid subjects, small differences in thyroid function are associated with significant differences in erythrocyte indices.