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Evidence for a relationship between T4 and T3 and glucose metabolism appeared over 100 years ago when the influence of thyroid hormone excess in the deterioration of glucose metabolism was first noticed. Since then, it has been known that hyperthyroidism is associated with insulin resistance. More recently, hypothyroidism has also been linked to decreased insulin sensitivity. The explanation to this apparent paradox may lie in the differential effects of thyroid hormones at the liver and peripheral tissues level. The purpose of this paper is to explore the effects of thyroid hormones in glucose metabolism and analyze the mechanisms whereby alterations of thyroid hormones lead to insulin resistance

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

Thyroid dysfunction, manifesting as either overt or subclinical hypothyroidism, negatively affects lipid metabolism: this leads to hypercholesterolemia which progressively increases the risk for cardiovascular disease and, potentially, mortality. Hypercholesterolemia in hypothyroidism is mainly due to a reduction in low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant diminishing control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate-limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity. Recently, 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, was found to repress the transcription factor carbohydrate-response element-binding protein (ChREBP) and also to be involved in lipid catabolism and lipogenesis, though via a different pathway than that of T3. While thyroid hormone could therapeutically reverse the dyslipidemic profile commonly occurring in hypothyroidism, it should be borne in mind that the potency of the effects may be age-and sex-dependent. Thyroid hormone administration possibly also sustains and enhances the efficacy of hypolipidemic drugs, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9), in patients with dyslipidemia and hypothyroidism

Editorial: New insights in thyroid and Covid-19

The Coronaviruses Disease 2019 (Covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is perhaps the most dramatic threat to human health since the Spanish flu in 1918. Almost 700 million cases and more than 6 million deaths have been reported worldwide by November 20, 2022 (1). The lung is the main affected organ, and the most critical clinical presentation has been characterized by interstitial pneumonia, acute respiratory distress syndrome, multiple organ failure, and death (2). Multiple endocrine organs, such as the pituitary, pancreas, adrenal, gonads, and thyroid gland, have also been affected (3). Detrimental effects on thyroid function have been reported in patients with and without pre-existing thyroid disease. Nonthyroidal illness syndrome (NTIS), subacute thyroiditis (SAT), Hashimoto’s thyroiditis, and Graves’ disease have been the most frequent thyroid dysfunctions associated with Covid-19 (4). Two major pathophysiological models have been implicated, a direct effect by virus attack causing follicular cells damage and an indirect effect caused by an immune-inflammatory abnormal response to the virus (5). Most recently, thyroid autoimmune diseases have also been reported following Covid-19 vaccination (6).info:eu-repo/semantics/publishedVersio

Atherogenic lipoproteins in subclinical hypothyroidism and their relationship with hepatic lipase activity: Response to replacement treatment with levothyroxine

Background: Qualitative lipoprotein changes, such as an increase in fasting remnants, are reported in subclinical hypothyroidism (SCH). It was hypothesized that such changes are due to reduced hepatic lipase (HL) activity in SCH: HL is an enzyme regulated by thyroid hormones, and is involved in the degradation of triglyceride (TG)-rich remnants. This study aimed to quantify remnant-like lipoproteins (RLP), small dense LDL (sdLDL), and HL activity in women with SCH, and to assess these parameters after levothyroxine replacement therapy. Methods: This was an observational cross-sectional study with a subsequent longitudinal follow-up. Findings in women with thyrotropin levels >4.5 mIU/L (SH group) were compared with age- and body mass index (BMI)-matched euthyroid women (control group). In addition, a subgroup analysis was undertaken in SCH women who chose to receive levothyroxine treatment (0.9 μg/kg/day) for 6 months. RLP was quantified by measuring cholesterol (RLP-C) and triglycerides (RLP-TG) after immunoaffinity chromatography, and sdLDL by automated standardized methods; HL activity was measured in post-heparin plasma. Results: The SCH group included 37 women; 29 women were included in the control group. In addition, 22 women with SCH were included in the subgroup analysis (levothyroxine treatment). Significantly higher RLP values were observed in the SCH group than in the control group: RLP-C (median [range], mg/dL): 20.3 (5.8-66.8) versus 10.2 (2.7-36.3), p = 0.005; RLP-TG (mg/dL): 26.3 (3.2-123.3) versus 12.1 (2.5-61.6), p = 0.033. HL activity (mean ± standard deviation [SD], μmol free fatty acid/mL post-heparin plasma.h) - 9.83 ± 4.25 versus 9.92 ± 5.20, p = 0.707 - and sdLDL levels (mg/dL) - 23.1 ± 10.7 versus 22.6 ± 8.4, p = 0.83 - were similar. After levothyroxine, RLP-C decreased - 21.5 (5.8-66.8) versus 17.2 (4.1-45.6), p = 0.023 - and HL increased - 9.75 ± 4.04 versus 11.86 ± 4.58, p = 0.012 - in the subgroup of SCH women. No changes in sdLDL were observed. Conclusions: Women with SCH have higher RLP levels than matched controls do, but their RLP-C levels decrease significantly following levothyroxine therapy. Furthermore, HL activity also increases after levothyroxine therapy and can be interpreted as a possible explanation for the decrease in RLP-C.Fil: Brenta, Gabriela. Unidad Asistencial Doctor César Milstein; ArgentinaFil: Berg, Gabriela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miksztowicz, Verónica Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lopez, Graciela Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lucero, Diego Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Faingold, María Cristina. Unidad Asistencial Doctor César Milstein; ArgentinaFil: Murakami, Masami. Gunma University Graduate School Of Medicine; JapónFil: Machima, Tetsudo. Gunma University Graduate School Of Medicine; JapónFil: Nakajima, Katsuyuki. Graduate School Of Health Sciences, Gunma University; JapónFil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

High TSH and low T4 as prognostic markers in older patients

OBJECTIVE: To examine the association between thyroid profile and morbidity/mortality (MM) in hospitalized older patients. DESIGN: This is a retrospective study of patients over the age of 60yr admitted to the Dr. Cesar Milstein Hospital between 2009 and 2010 and who had thyroid function tests (TFT). The patients were grouped as per their thyroid tests and their clinical characteristics and MM was associated with their TFT. High MM was defined as mortality, intensive care unit (ICU) requirement or prolonged hospital stay (>18 days, 75thpercentile), and mortality assessed during an 18-month follow-up period after their hospital discharge. RESULTS: Out of 2599 older patients admitted to our hospital, 7% had TFT performed for various reasons. The patients who had TFT were mostly women and presented in a more serious clinical condition compared to the rest of the patients. The patients were grouped as per their thyroid values as follows: 61% of them had a non-thyroidal illness, 25% were euthyroid, 7% had overt hyperthyroidism, 5% overt hypothyroidism and 1% had subclinical hyper- or hypothyroidism. The hypothyroid patients had a worse clinical outcome compared to the others. Patients with increased MM exhibited higher TSH and lower TT4 (p<0.005). Short-term MM (OR=2.0,95%CI=1.1-3.6, p<0.01) was associated with the decrease of TT4 adjusted by age, sex, T3 and TSH, while for long-term MM the increase in TSH (OR=1.6,95%CI 1.1-2.3, p<0.05) was also significant. CONCLUSION: Among hospitalized older patients who had TFT tests, low TT4 and high TSH were associated with a worse prognosis. We propose that TFT be used as an additional tool in assessing MM in elderly hospitalized patients.Fil: Mingote, Evelin. Hospital "Dr. César Milstein"; ArgentinaFil: Meroño, Tomás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rujelman, Rocío. Hospital "Dr. César Milstein"; ArgentinaFil: Marquez, Alejandra. Hospital "Dr. César Milstein"; ArgentinaFil: Fossati, Pia. Hospital "Dr. César Milstein"; ArgentinaFil: Gurfinkiel, Mirta. Hospital "Dr. César Milstein"; ArgentinaFil: Schnitman, Marta. Hospital "Dr. César Milstein"; ArgentinaFil: Brites, Fernando Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Faingold, Cristina. Hospital "Dr. César Milstein"; ArgentinaFil: Brenta, Gabriela. Hospital "Dr. César Milstein"; Argentin

Low plasma triiodothyronine levels in heart failure are associated with a reduced anabolic state and membrane damage

BACKGROUND: Low plasma triiodothyronine (T(3)) levels are considered a prognostic predictor of death in heart failure (HF) patients. AIM: To study an association between plasma T(3) levels and several cardiac, neurohormonal, and metabolic markers of HF. METHODS: A total of 133 ambulatory HF patients (114 males; mean age 63.2 years) with left ventricular ejection fraction <40% were enrolled. TSH, total tetraiodothyronine (T(4)) and T(3), N-terminal pro-brain natriuretic peptide (NT-proBNP), and other cardiac and metabolic parameters were measured. The lowest tertile of T(3) (group 1) was compared against the two upper ones (group 2). RESULTS: In simple logistic regression, the lowest T(3) tertile was associated with more advanced HF disease status: older (age: odds ratio (OR)=1.05; confidence interval (CI) 95% 1.01-1.09, P=0.004), lower functional capacity (walking test: OR=0.996; CI 95% 0.993-0.999, P=0.008), higher NT-proBNP (OR=1.64; CI 95% 1.19-2.27, P=0.003) and adiponectin levels (OR=1.07; CI 95% 1.02-1.11, P=0.004), lower DHEAS log-transformed (OR=0.50; CI 95% 0.31-0.80, P=0.004), and the presence of lower phase angle values as measured by body bioelectrical impedance analysis (OR=3.18; CI 95% 1.50-6.71, P=0.04) and worse renal function (OR=0.96; CI 95% 0.94-0.98, P=0.003). T(3) levels in the lowest tertile were independently associated with low phase angle values (OR=2.95, CI 95% 1.16-7.50, P=0.02) and the log transformation of DHEAS (OR=0.56; CI 95% 0.32-0.97, P=0.04). CONCLUSION: We have demonstrated an association between plasma T(3) levels in the lower range and other deranged hormonal and metabolic parameters in HF patients.Fil: Brenta, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital César Milstein; ArgentinaFil: Thierer, Jorge. Instituto Cardiovascular de Buenos Aires; ArgentinaFil: Sutton, Marcela. Instituto Cardiovascular de Buenos Aires; ArgentinaFil: Acosta, Adriana. Instituto Cardiovascular de Buenos Aires; ArgentinaFil: Vainstein, Nora. Instituto Cardiovascular de Buenos Aires; ArgentinaFil: Brites, Fernando Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Boero, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Gomez Rosso, Leonardo Adrián. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Anker, Stefan. Istituto di Ricovero e Cura a Carattere Scientifico; Italia. Charité Universitätsmedizin Berlin; Alemani

Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity

Background and aims Glomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown. Methods and results Cross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m2. Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (−12%), NEFA (−26%) and uric acid (−22%) than those without GH (all p 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = −0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05). Conclusion GH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings. Keywords ObesityChildrenChemokinesHyperfiltrationRenal diseas

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk

BackgroundHypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk.MethodsOlder adults (age&gt;65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH&gt; 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests,ResultsFinally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p&lt;0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p&lt;0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p&lt;0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR.ConclusionIn older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies

Differential profile of ultrasound findings associated with malignancy in mixed and solid thyroid nodules in an elderly female population

Objective. Ultrasonographic characteristics are associated with thyroid malignancy. Our aim was to compare the diagnostic value of ultrasound features in the detection of thyroid malignancy in both solid and mixed nodules. Methods. We prospectively studied female patients (≥50 years) referred to ultrasound-guided fine needle aspiration biopsy. Ultrasound features considered suspicious were hypoechogenicity, microcalcifications, irregular margins, high anteroposterior (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed and solid nodules. Results. In a group of 504 elderly female patients (age =  years), the frequency of malignant cytology was 6%. Thirty-one percent of nodules were mixed and 60% were solid. The rate of malignant cytology was similar for mixed and solid nodules (7.4 versus 5.8%, : 0.56). While in mixed nodules none of the ultrasound characteristics were associated with malignant cytology, in solid nodules irregular margins and microcalcifications were significant (all ). The combination of irregular margins and/or microcalcifications significantly increased the association with malignant cytology only in solid nodules (OR: 2.76 (95% CI: 1.25–6.10), : 0.012). Conclusions. Ultrasound features were of poor diagnostic value in mixed nodules, which harbored malignant lesions as often as solid nodules. Our findings challenge the recommended minimal size for ultrasound-guided fine needle aspiration biopsy in mixed nodules.Fil: Vera, María Inés. Dr. Cesar Milstein Hospital; ArgentinaFil: Meroño, Tomás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Urrutia, María Agustina. Dr. Cesar Milstein Hospital; ArgentinaFil: Parisi, Carina. Dr. Cesar Milstein Hospital; ArgentinaFil: Morosan, Yanina. Dr. Cesar Milstein Hospital; ArgentinaFil: Rosmarin, Melanie. Dr. Cesar Milstein Hospital; ArgentinaFil: Schnitman, Marta. Dr. Cesar Milstein Hospital; ArgentinaFil: Brites, Fernando Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Grisendi, Silvio. Dr. Cesar Milstein Hospital; ArgentinaFil: Serrano, María Sol. Dr. Cesar Milstein Hospital; ArgentinaFil: Luciani, Wilfredo. Dr. Cesar Milstein Hospital; ArgentinaFil: Serrano, Leonardo. Dr. Cesar Milstein Hospital; ArgentinaFil: Zuk, Carlos. Dr. Cesar Milstein Hospital; ArgentinaFil: de Barrio, Guillermo. Dr. Cesar Milstein Hospital; ArgentinaFil: Cejas, Claudia. Dr. Cesar Milstein Hospital; ArgentinaFil: Faingold, María Cristina. Dr. Cesar Milstein Hospital; ArgentinaFil: Brenta, Gabriela. Dr. Cesar Milstein Hospital; Argentin

Risk factors for thyroid dysfunction in pregnancy: an individual participant data meta-analysis

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction