José Augusto Sgarbi

Background: Recently, a new biomarker index that reflects inflammation and protein energy malnutrition has emerged as a predictor of mortality in cardiovascular diseases. The metabolic vulnerability index (MVX) derives from blood-based inflammation (IVX) and malnutrition (MMX) markers measured by nuclear magnetic resonance (NMR) spectroscopy. We aimed to explore the association of subclinical hypothyroidism and thyroid-related parameters with IVX, MMX, and MVX scores. Methods: This cross-sectional study used the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Individuals with normal thyroid function and subclinical hypothyroidism were included. Thyroid-related parameters—thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), the FT3–FT4 ratio, and antithyroperoxidase antibodies (TPOAb)—were the explanatory variables. The primary outcomes, MVX, MMX, and IVX scores, were analyzed as continuous variables. Linear regression analyses were performed for both univariate and multivariable models, with sensitivity and subgroup analyses applied to assess robustness. Findings: There were 3979 participants (51.4% female) with a mean age of 51.26 (SD: 9.02) years. After full adjustment for potential confounder variables, FT3 levels [B: −1.37 (−2.43;−0.31) p = 0.011] and the FT3–FT4 ratio [B: −0.90 (−1.79;−0.01) p = 0.047] were inversely associated with MVX scores. FT3 levels were also inversely associated with IVX [B: −1.32 (−2.39;−0.24) p = 0.017]. These results were consistent in euthyroid individuals and those with cardiometabolic diseases. In the sex-stratified analysis, FT3 levels were inversely associated with MVX, MMX, and IVX scores for men. Conclusion: Lower FT3 levels and the FT3–FT4 ratio were associated with a higher metabolic vulnerability in our cohort. Our study sheds light on the importance of metabolic surveillance in these patients, especially for men with cardiometabolic diseases.

Context: Subclinical thyroid dysfunction (ScTD), comprising subclinical hypothyroidism (SHypo) and subclinical hyperthyroidism (SHyper), has been associated with increased risk for cardiovascular events. Objective: To assess associations between ScTD and cardiovascular risk factors (cvRFs) according to age and sex. Methods: This analysis of pooled participant data from large prospective cohort studies from the Thyroid Studies Collaboration assessed cvRFs (blood pressure [BP], lipid levels, high-sensitivity C-reactive protein [hs-CRP]) among participants aged 18 to 103 years with SHypo (thyroid-stimulating hormone [TSH] > 4.50 mU/L, normal fT4) and SHyper (TSH < 0.45 mU/L, normal fT4) vs euthyroid (TSH 0.45-4.50 mU/L). Results: Of 69 006 participants (mean age 62 years, 55% women, 25% current smokers) from 16 international cohorts, 3748 (5.4%) had SHypo and 3428 (5.0%) had SHyper. In both women and men, systolic and diastolic BP were similar regardless of thyroid status. Exceptions were lower diastolic BP in women with SHyper compared to euthyroid participants (adjusted mean difference [aMD] −1.3 mmHg, 95% CI −2.0 to −0.5), and lower systolic BP in men with SHyper compared to euthyroid participants (aMD −3.1 mmHg, 95% CI −4.8 to −1.4). In both women and men, lipid levels (total, HDL, LDL-cholesterol, triglycerides) and hs-CRP were similar regardless of thyroid status. The only exception were women with SHyper who had lower LDL-cholesterol vs euthyroid (aMD −0.17 mmol/L, 95% CI −0.29 to −0.05). Conclusion: Participants with ScTD and euthyroid participants have similar cvRFs and differences are arguably too small to explain the increased cardiovascular risk in ScTD observed in previous studies.

Purpose Understanding the relationship between antithyroperoxidase antibodies (TPOAb) and carotid intima-media thickness (cIMT) could provide insights into the mechanisms linking thyroid autoimmunity and cardiovascular disease. We aimed to explore the association of multiple categories of TPOAb with the increased cIMT at baseline and at follow-up in participants from the ELSA-Brasil Study. Methods This prospective cohort study analyzed data from 9,264 participants (51.5 ± 8.9 years old, 55.9% women) without a history of cardiovascular disease. Fasting serum TPOAb levels were determined. Values of cIMT equal to or above one deviation standard of the sample’s mean were classified as increased cIMT at baseline. The increased cIMT after the 8-year follow-up was calculated after excluding participants with increased cIMT at baseline. Multivariate analyses were done using binary logistic and Poisson regression models. Results The increased cIMT was prevalent in 14.3% of the participants at baseline and its development occurred in 16.8% participants during the cohort. After adjustment for all confounder variables, TPOAb detectability (OR = 1.84, 95%CI = 1.21–2.79), and low detectable (OR = 1.81, 95%CI = 1.18–2.75), high detectable (OR = 2.01, 95%CI = 1.29–3.11) and positive (OR = 1.70, 95%CI = 1.07–2.70) TPOAb were positively associated with increased cIMT at baseline. The associations of low and high detectable TPOAb and increased cIMT at baseline were consistent when excluding those with thyroid dysfunction. There was no statistically significant association between TPOAb levels and increased cIMT at follow-up (p > 0.05), neither for all sample nor for euthyroid individuals. Conclusion Different levels of TPOAb, including its detectability, were associated with increased cIMT at baseline in the studied sample. We highlight that may be relevant to consider the levels of TPOAb detectability as possible marker of increased cardiovascular risk.

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs—leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson’s coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism.

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated [...] ABSTRACT Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated

Type 1 diabetes mellitus (T1DM) is one of the major chronic diseases in children worldwide. This study aimed to investigate interleukin-10 (IL-10) gene expression and tumor necrosis factor-alpha (TNF-α) in T1DM. A total of 107 patients were included, 15 were T1DM in ketoacidosis, 30 patients had T1DM and HbA1c ≥ 8%; 32 patients had T1DM and presented HbA1c < 8%; and 30 were controls. The expression of peripheral blood mononuclear cells was performed using the reverse transcriptase–polymerase chain reaction in real time. The cytokines gene expression was higher in patients with T1DM. The IL-10 gene expression increased substantially in patients with ketoacidosis, and there was a positive correlation with HbA1c. A negative correlation was found for IL-10 expression and the age of patients with diabetes, and the time of diagnosis of the disease. There was a positive correlation between TNF-α expression with age. The expression of IL-10 and TNF-α genes showed a significant increase in DM1 patients. Once current T1DM treatment is based on exogenous insulin, there is a need for other therapies, and inflammatory biomarkers could bring new possibilities to the therapeutic approach of the patients.

Editorial: New insights in thyroid and Covid-19

Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a [...] ABSTRACT Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a

Background and Objective: Thyroid function reference ranges are statistically defined by the 2.5^th and 97.5^th percentiles, which do not account for potential risk of clinical outcomes. We aimed to define the optimal ranges of thyroid-stimulating hormone (TSH) and free thyroxine (FT4), based on the risk of cardiovascular disease (CVD) and mortality. Methods: We performed an individual-participant data analysis and identified prospective cohorts with baseline TSH and FT4 concentrations as well as CVD outcomes and mortality through the Thyroid Studies Collaboration, supplemented with a systematic literature search. The primary outcome was a composite of incident CVD (coronary heart disease, stroke, heart failure), CVD mortality and all-cause mortality, while secondary analysis assessed these outcomes separately. In a one-step approach, we analyzed TSH and FT4 in percentiles, using cohort-stratified Cox proportional hazard models or cause-specific hazard models with nonlinear associations assessed by restricted cubic splines. For the two-step analysis, we used thyroid function quintiles and pooled estimates from each cohort using a random-effects model. All analyses were adjusted for age and sex, and further adjusted for cardiovascular risk factors (e.g. diabetes), and stratified by age (P=0.18) and only marginally associated with the composite outcome (P=0.02) with individuals in the lowest quintile had a hazard ratio (HR) of 1.04 (0.99-1.08) compared to those in the third quintile. In contrast, FT4 was nonlinearly associated with the composite outcome as well as secondary outcomes in a J-shape pattern (all P85^th percentile while 5% and 10% for men with FT4 concentrations >75^th and >90^th percentiles respectively. Conclusion: Overall TSH was not associated with CVD events. FT4 between the 20^th and 40^th percentiles represented the optimal health ranges based on the risk of cardiovascular disease and mortality, which has potential implications for treatment targets when managing clinical and subclinical thyroid disease.