Potential Determinants of Thyroid Peroxidase Antibodies and Mortality Risk: Results From the ELSA-Brasil Study.

CONTEXT: The presence of thyroid peroxidase antibodies (TPOAbs) may be considered as an indicator of adverse health outcomes. OBJECTIVE: We aimed to investigate the potential determinants of TPOAb levels and to analyze the association between TPOAb titers and the risk of all- and specific-cause mortality. METHODS: Baseline and longitudinal data of 13 187 participants from the ELSA-Brasil Study were analyzed. We investigated the association of TPOAb, detectability, positivity, and persistent positivity with sociodemographic and lifestyle factors using logistic regressions. Cox proportional hazards and Fine-Gray subdistribution hazard regression analyses were used to verify the association of TPOAbs with mortality. RESULTS: The determinants of TPOAb detectability and positivity were younger age, higher body mass index, female sex, and former and current smoking status. Black, mixed, and other self-reported races, intermediate and higher education, and heavy drinking were determinants of detectable and positive TPOAb levels. Female sex, White race, and former smoking were determinants of persistent TPOAb positivity at 2 visits, although only the female sex maintained its association at 3 visits. Moreover, after multivariate adjustment, there were associations between higher levels of TPOAbs and higher risk of cancer-related mortality among men, and TPOAb detectability and mortality by other causes among women. CONCLUSION: Sociodemographic and lifestyle-related factors were determinants of multiple TPOAb categories. TPOAb levels were associated with mortality risk; however, the low mortality rate in this sample might have compromised this finding. We suggest further studies to explore the clinical importance of detectable TPOAb levels, not only its positivity, as a potential marker of inflammation.

The association of diabetes, subclinical hypothyroidism and carotid intima-media thickness: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil).

INTRODUCTION: The association of diabetes with subclinical thyroid diseases may increase the risk of cardiovascular diseases. We analyzed the association of subclinical hypothyroidism, diabetes, and both diseases with carotid Intima-Media Thickness (cIMT) as a surrogate maker for early cardiovascular disease in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Cross-sectional analysis with data from the 3rd visit (2017‒2019). Linear regression models were used to evaluate the association of subclinical hypothyroidism, diabetes and of both diseases with a cIMT presented as Beta (95% Confidence Interval ‒ 95% CI) without adjustment, with adjustment for sociodemographic variables (Model 1) and multivariable adjustment (Model 1 more cardiovascular risk factors). We also used logistic regression models to analyze the Odds Ratio (OR) and 95% CI for the association of both diseases using cIMT > P75%. RESULTS: After the exclusion of patients with previous cardiovascular disease, 5,077 participants with no diseases, 1578 with diabetes, 662 with subclinical hypothyroidism, and 234 with both diseases were included in the analysis. Linear regression models showed an association of cIMT with only diabetes (ß = 0.019; 95% CI 0.012 to 0.027; p < 0.0001) and subclinical hypothyroidism more diabetes (ß = 0.03; 95% CI 0.010‒0.047, p < 0.0001). The logistic regression model reported an association between diabetes and CIMT higher than P75% (OR = 1.49, 95% CI 1.30‒1.71). No interaction between diabetes and subclinical hypothyroidism was detected using cIMT respectively as a continuous (p = 0.29) or as a categorical variable (p = 0.92). DISCUSSION: Diabetes was associated with higher cIMT values. However, no additive effect of subclinical hypothyroidism associated with diabetes over cIMT was detected.

The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis.

Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

Substantially elevated TSH, not traditional clinical subclinical thyroid disorder groupings, are associated with smaller LDL-P mean size: ELSA-Brasil.

BACKGROUND: LDL appears to drive atherogenesis in overt hypothyroidism, but in subclinical dysfunction, its role is not completely elucidated. OBJECTIVE: The aim of this study was to evaluate subfractions of LDL in subclinical (SC) thyroid disorders. METHODS: Individuals were divided into three groups by baseline thyroid function (SC hypothyroidism, euthyroidism, and SC hyperthyroidism). LDL particle (LDL-P) subfractions were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy. The association between LDL-P subfractions and thyroid groups and quintiles was evaluated by linear regression models. RESULTS: We evaluated 3304 participants (54.1% women, 51.2% white, mean age 50.6 ± 8.7 years). In the univariate analysis, small LDL particle concentrations (SLDL-P) were not different between SC hypo- and hyperthyroidism compared to euthyroid individuals (p = 0.485 and p = 0.314, respectively). Large LDL-P (LDL-P) levels also did not differ in SC hyperthyroidism and SC hypothyroidism compared to euthyroidism (p = 0.698 and 0.788 respectively). Intermediate LDL-P levels were not different across the groups. These numbers did not materially change in multivariate analysis. However, we also analyzed LDL subfractions according to quintiles of TSH. We showed that in the higher TSH quintile LDL subfractions presented a significantly smaller mean size of LDL subfractions compared to the first quintile. CONCLUSIONS: SC thyroid disorders are not associated with significant changes in LDL-P subfractions measured by NMR spectroscopy. However, it seems that the LDL mean size decreases as TSH levels increase, which may represent a more atherogenic lipid profile.

Subtle Thyroid Dysfunction Is Not Associated with Cognitive Decline: Results from the ELSA-Brasil.

BACKGROUND: Subtle thyroid alterations have a controversial role in cognition. OBJECTIVE: We investigated the longitudinal association of baseline thyroid function, thyrotropin (TSH), and thyroxine (FT4) levels with cognitive performance after 4 years of follow-up in middle-aged and older adults without overt thyroid dysfunction. METHODS: We included 4,473 individuals, age≥55 years at the second study wave, without overt thyroid dysfunction at baseline. Individuals were divided according to thyroid function and TSH and FT4 tertiles. Cognition was assessed at baseline and after 4 years of follow-up by the word recall (DWR), semantic verbal fluency (SVF), and trail making (TMT) tests. The longitudinal association of thyroid function and TSH and FT4 tertiles with cognitive performance was investigated using generalized estimating equations adjusted for sociodemographic characteristics, lifestyle, cardiovascular risk factors and depression. RESULTS: There was no longitudinal association of thyroid function and TSH and FT4 baseline levels with performance on the cognitive tests. However, there was a baseline cross-sectional U-shaped association of FT4 tertiles with poorer performance in the SVF (first FT4 tertile: ß= -0.11, 95% CI = -0.17; -0.04; third FT4 tertile: ß= -0.10, 95% CI = -0.17; -0.04) and of the third FT4 tertile with poorer performance in the DWR (ß= -0.09, 95% CI = -0.16; -0.02). CONCLUSION: Thyroid function and hormone levels were not associated with cognitive decline during 4 years of follow-up in middle-aged and older adults without overt thyroid dysfunction. Future studies with longer follow-up could clarify the implications of subtle thyroid alterations in cognition.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVE: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. METHODS: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. RESULTS: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. CONCLUSION: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Unfavorable Triglyceride-rich Particle Profile in Subclinical Thyroid Disease: A Cross-sectional Analysis of ELSA-Brasil.

Subclinical thyroid disorders have been associated with atherosclerosis and increased cardiovascular risk. As triglyceride-rich lipoprotein particles (TRLPs) have recently emerged as a casual factor for atherogenesis, the aim of this study was to evaluate the relationship between subclinical hypo- and hyperthyroidism and TRLP subfractions. We selected 5066 participants from the ELSA-Brasil cohort with available data of thyroid function and lipid profile measured by nuclear magnetic resonance (NMR) spectroscopy. Individuals were divided into 3 groups by baseline thyroid function (subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism). Triglyceride-rich lipoprotein particle subfractions were analyzed through NMR spectroscopy. To examine the association between TRLP subfractions and thyroid function, we conducted univariate and multivariate linear regression models adjusted for demographic characteristics, body mass index, diabetes, smoking status, and alcohol use. Of 3304 individuals, 54% were women, with a mean age of 50.6 ± 8.7 years, 51% white, and 53% with at least a college education. Of these individuals, 92% were euthyroid, whereas 6.8% had subclinical hypothyroidism and 1.2% had subclinical hyperthyroidism. The univariate linear regression showed that very small TRLPs (P = 0.026) and very large TRLPs (P = 0.008) were statistically increased in subclinical hypothyroidism when compared with euthyroidism. In subclinical hyperthyroidism, there was a reduction in total TRLPs (P = 0.003), seemingly driven by reduced very small TRLPs (P = 0.067). The findings were confirmed when adjusted for demographic characteristics, as well as comorbidities. This study suggests that subclinical hypothyroidism is associated with very small and very large TRLPs, which are related to an unfavorable atherogenic profile. Subclinical hyperthyroidism is associated to lower very small TRLPs.

Urinary iodine and sodium concentration and thyroid status in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVES: To evaluate urinary iodine concentration (UIC) in civil servants aged 35-74 years of the Brazilian Study of Adults Health (ELSA-Brasil) to analyze its relationship with sociodemographic, clinical risk factors, lifestyle, urinary Na and thyroid status. DESIGN: Cross-sectional study in six Brazilian cities. METHODS: This analysis included 792 participants with information about urinary iodine concentration (UIC). Thyroid status was defined by serum levels of TSH/FT4 and the current use of antithyroid drugs for treatment of overt hyperthyroidism or levothyroxine to treat overt hypothyroidism. The determination of UIC was carried out with an inductively coupled plasma mass spectrometer (ICP-MS) and was expressed as median with Interquartile Range (IQR). RESULTS: In 792 participants, thereof 52% women, mean age was 51.9 (9.0) years. The median UIC was 219 (IQR, 166-291) for all persons studied, thereof 211 (IQR, 157-276) for women and 231 (IQR, 178-304) for men. According to the WHO classification, for all persons studied, 60% had more than adequate iodine-supply (UIC ≥200 µg/L), 37% were adequately supplied (UIC 100-199 µg/L) and <3% had a deficient iodine status (<100 µg/L). In the 35-44-year age strata, which includes women of childbearing age, 23.2% of women presented less than 150 µg/L of UIC. No differences in UIC were detected according to thyroid status. (P = 0.39) The correlation between Ur-Na and UIC showed a Spearman coefficient of 0.52 (P < 0.0001) and it was also found an association of Ur-Na with UIC: Beta of 1.76 (95% Confidence Interval (95% CI): 1.01 to 2.51. The urinary Na concentration showed a synergy with the UIC, that means medians of 57, 72, 107 and 141 mmol Na/L urine (P < 0.001) in the groups with the four UIC classes according to the WHO grading mentioned above. The very low Na content in the persons exhibiting <100 µg/L UIC seems to reflect also a higher urine volume due to the frequent use of diuretics. The strong relationship between the urinary Na concentration and the UIC points to a dependence of the UIC on the individual consumption of iodized salt, which should be more considered in future studies. The strong relationship between the urinary Na concentration and the UIC points to a dependence of the UIC on the individual consumption of iodized salt, which should be more considered in future studies. CONCLUSIONS: Euthyroid persons were dominating by more than four fifths and no significant association was found between UIC and thyroid status. Although most of the persons studied present more than adequate iodine intake it was observed that nearly a quarter of women in childbearing age are iodine deficient.

Incidence of thyroid diseases: Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVE: To evaluate incidence of subclinical and overt hyperthyroidism and hypothyroidism. METHODS: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective cohort study of 15,105 civil servants, examined at baseline and over a 4-year follow-up. This analysis included 9,705 participants with normal thyroid function at baseline, follow-up information about thyroid function and with no report of using drugs that may interfere in the thyroid function. Thyroid function was defined by TSH/FT4 levels or routine use of thyroid hormones/anti-thyroid medications. Annual and cumulative (over 4-year) incidence rates were presented as percentages (95% Confidence Intervals). RESULTS: The incidence of all overt and subclinical thyroid disease was 6.7% (1.73%/year): 0.19% for overt hyperthyroidism (0.048%/year), 0.54% for subclinical hyperthyroidism (0.14%/year), 1.98% for overt hypothyroidism (0.51%/year), and 3.99% for subclinical hypothyroidism (1.03%/year). The incidence of all thyroid diseases was higher in women, when compared to men, with a low women:men ratio (1.36). For Blacks the highest incidence was for overt hyperthyroidism, while for Whites, the highest incidence was for overt hypothyroidism. However, the highest incidence of overt hyperthyroidism was detected in Asian descendants. The presence of antithyroperoxidase antibodies at baseline was associated with higher incidence of overt thyroid diseases. CONCLUSION: These results showed a high incidence of hypothyroidism, which is compatible with a country with a more-than-adequate iodine intake. The low women:men ratio of the incidence of thyroid dysfunction highlights the importance of the diagnosis of thyroid diseases among men in Brazil.

Differences in HDL particle size in the presence of subclinical thyroid dysfunctions: The ELSA-Brasil study.

BACKGROUND AND AIMS: Thyroid dysfunction is related to several lipid abnormalities. There is no consensus about concentration of high-density lipoprotein (HDL) in different studies. The aim of this report is to evaluate HDL particle (HDL-P) subfractions across a spectrum of thyroid functions in a Brazilian population. METHODS: Individuals were divided into three groups by baseline thyroid function (subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism). HDL-P subfractions were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy. To examine the association between HDL-P subfractions and thyroid function, we used univariate and multivariate linear regression models adjusted for demographic characteristics, comorbidities, lifestyle factors, and traditional lipid measurement (HDL-C, LDL-C and triglycerides). RESULTS: Of 3304 participants, 54.1% were women, 51.2% white, with mean age 50.6 ± 8.7 years. HDL-C and triglycerides levels (p = 0.032 and p = 0.016, respectively) were higher in the SC hypothyroid group. There were no statistically significant differences in total cholesterol levels and LDL-C levels. In univariate analysis, small HDL-P subfractions were significantly lower in subclinical hypothyroidism (p = 0.026) whereas intermediate HDL-P were higher in subclinical hyperthyroidism (p = 0.049), compared to euthyroidism. After adjustment for demographic data, SC hypothyroidism was still statistically associated with lower levels of small HDL-P. After adjusting for comorbidities, lifestyle factors, and traditional lipid measurements, SC hypothyroidism had an established association with lower levels of small HDL-P while SC hyperthyroidism was associated with lower levels of large HDL-P. CONCLUSIONS: In this large cohort from a Brazilian population, subclinical hypothyroidism was associated with lower small HDL-P subfractions, and subclinical hyperthyroidism with lower large HDL-P subfractions and higher intermediate HDL-P subfractions.

Prevalence of antithyroperoxidase antibodies in a multiethnic Brazilian population: The ELSA-Brasil Study.

OBJECTIVE: In this study, we aimed to describe the prevalence and distribution of positive antithyroperoxidase antibodies (TPOAb) according to sex, age strata, and presence of thyroid dysfunction using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). MATERIALS AND METHODS: Thyroid hormone tests were obtained from each study participant at baseline. Levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured using a third-generation immunoenzymatic assay. Antithyroperoxidase antibodies were measured by electrochemiluminescence and were considered to be positive when ≥ 34 IU/mL. RESULTS: The prevalence of TPOAb among 13,503 study participants was 12%. Of participants with positive TPOAb, 69% were women. Almost 60% of the individuals with positive TPOAb were white. The presence of positive TPOAb was associated with the entire spectrum of thyroid diseases among women, but only with overt hyperthyroidism and overt hypothyroidism in men. CONCLUSION: The distribution of positive TPOAb across sex, race, age, and thyroid function in the ELSA-Brasil study is aligned with the worldwide prevalence of positive TPOAb reported in iodine-sufficient areas. In women, the presence of TPOAb was related to the entire spectrum of thyroid dysfunction, while in men, it was only related to the occurrence of overt thyroid disease.

Association between Thyroid-Stimulating Hormone Levels and Non-Alcoholic Fatty Liver Disease Is Not Independent from Metabolic Syndrome Criteria.

INTRODUCTION: Thyroid hormones are involved in the regulation of body composition, lipid metabolism, and insulin resistance. Thus, it is possible that they might play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of thyroid function on NAFLD is not well defined. In this study, we evaluated the relationship between thyroid-stimulating hormone (TSH) levels, within the reference range, and presence of NAFLD in asymptomatic individuals. STUDY DESIGN: We included all individuals evaluated at a preventive clinic of the Hospital Israelita Albert Einstein, between 2014 and 2015. The prevalence of NAFLD (analyzed by abdominal ultrasound), according to TSH quartiles, within the reference range, was determined. The association between TSH quartiles and NAFLD was analyzed by logistic regression adjusted for possible confounders. RESULTS: We evaluated 10,539 individuals (73% male, age 43.4 ± 9.4 years). The prevalence of NAFLD was 34, 38, 38, and 39% in the first to the fourth TSH quartiles (0.46-1.44, 1.45-1.97, 1.98-2.68, and 2.69-4.68 mUI/L, respectively, p for trend < 0.001). At univariate analysis, higher TSH levels were associated with the diagnosis of NAFLD. When data were adjusted for the metabolic syndrome characteristics (waist circumference, HDL-cholesterol and triglycerides levels, presence of diabetes, and systemic arterial hypertension), the association was no longer significant. CONCLUSIONS: Although the TSH variability within the reference range is associated with NAFLD in univariable models, once adjusted for metabolic syndrome factors no significant association is noted.

Thyroid cancer burden and economic impact on the Brazilian public health system.

OBJECTIVE: Recent data indicates an increasing incidence of thyroid cancer not accompanied by a proportional increase in mortality, suggesting overdiagnosis, which may represent a big public health problem, particularly where resources are scarce. This article aims to describe and evaluate the procedures related to investigation of thyroid nodules and treatment and follow-up of thyroid cancer and the costs for the Brazilian public health system between 2008 and 2015. MATERIALS AND METHODS: Data on procedures related to investigation of thyroid nodules and treatment/follow-up of thyroid cancer between 2008 and 2015 in Brazil were collected from the Department of Informatics of the Brazilian Unified Health System (Datasus) website. RESULTS: A statistically significant increase in the use of procedures related to thyroid nodules investigation and thyroid cancer treatment and follow-up was observed in Brazil, though a reduction was noted for procedures related to the treatment of more aggressive thyroid cancer, such as total thyroidectomy with neck dissection and higher radioiodine activities such as 200 and 250 milicuries (mCi). The procedures related to thyroid nodules investigation costs increased by 91% for thyroid ultrasound (p = 0.0003) and 128% in thyroid nodule biopsy (p < 0.001). Costs related to treatment and follow-up related-procedures increased by 120%. CONCLUSION: The increase in the incidence of thyroid cancer in Brazil is directly associated with an increased use of diagnostic tools for thyroid nodules, which leads to an upsurge in thyroid cancer treatment and followup-related procedures. These data suggest that substantial resources are being used for diagnosis, treatment and follow-up of a potentially indolent condition.

Impact of self-reported fasting duration on lipid profile variability, cardiovascular risk stratification and metabolic syndrome diagnosis.

OBJECTIVE: We sought to investigate the impact of self-reported fasting duration times on the lipid profile results and its impact on the cardiovascular risk stratification and metabolic syndrome diagnosis. SUBJECTS AND METHODS: We analyzed data from all consecutive individuals evaluated in a comprehensive health examination at the Hospital Israelita Albert Einstein from January to December 2015. We divided these patients in three groups, according to the fasting duration recalled (< 8h, 8-12h and > 12h). We calculated the global cardiovascular risk and diagnosed metabolic syndrome according to the current criteria and estimated their change according to fasting duration. RESULTS: A total of 12,196 (42.3 ± 9.2 years-old, 30.2% females) patients were evaluated. The distribution of cardiovascular risk was not different among groups defined by fasting duration in both men and women (p = 0.547 for women and p = 0.329 for men). Similarly, the prevalence of metabolic syndrome was not influenced by the fasting duration (p = 0.431 for women and p = 0.166 for men). CONCLUSION: Self-reported fasting duration had no significant impact on the lipid profile results, including triglyceride levels. Consequently, no changes on the cardiovascular risk stratification using the Framingham risk score nor changes on the prevalence of metabolic syndrome were noted.

Association between psoriasis and thyroid function: results from the Brazilian Longitudinal Study of Adults Health (ELSA-Brasil)

ABSTRACT Objective: To determine the relationship between psoriasis, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3), thyroid peroxidase antibodies (TPOAb), and subclinical thyroid dysfunctions in middle-aged and older adults. Materials and methods: Cross-sectional analyses included a self-reported medical diagnosis of psoriasis and thyroid function from the 3rd visit (2017-2019) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TSH, FT4, and FT3 levels were analyzed as continuous variables and quintiles, and TPOAb positivity and subclinical hypothyroidism as a yes/no variable. Logistic regression models were built as crude and adjusted by main confounders (age, sex, education level, race/ethnicity, and smoking). Results: From 9,649 participants (52.3% women; 59.2 ± 8.7 years old), the prevalence of psoriasis was 2.8% (n = 270). TSH, FT4, TPOAb positivity, and subclinical hypothyroidism were not associated with psoriasis in the main analyses. In the stratified analysis, our findings showed positive associations of the lowest (OR = 2.01; 95% CI 1.05-3.84; p = 0.036) and the highest (OR = 2.13; 95% CI 1.12-4.05; p = 0.022) quintiles of FT4 and a protective association of TPOAb positivity (OR = 0.43; 95% CI 0.19-0.98; p = 0.046) with prevalent psoriasis in women. In the logistic regression for FT3, participants in the 1st quintile showed a statistically significant association with psoriasis for the whole sample (OR = 1.66; 95% CI 1.11-2.46; p = 0.013) and for men (OR = 2.25; 95% CI 1.25-4.04; p = 0.007) in the sex-stratified analysis. Conclusions: The present study showed that the association of FT4 levels with psoriasis are different according to sex, with a possible U-shaped curve in women but not in men. Although there were some associations of FT3 with psoriasis, they may be a consequence of non-thyroidal illness syndrome. Further prospective data may clarify the association of thyroid function and psoriasis.

The association of diabetes, subclinical hypothyroidism and carotid intima-media thickness: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil)

Abstract Introduction: The association of diabetes with subclinical thyroid diseases may increase the risk of cardiovascular diseases. We analyzed the association of subclinical hypothyroidism, diabetes, and both diseases with carotid Intima-Media Thickness (cIMT) as a surrogate maker for early cardiovascular disease in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: Cross-sectional analysis with data from the 3rd visit (2017‒2019). Linear regression models were used to evaluate the association of subclinical hypothyroidism, diabetes and of both diseases with a cIMT presented as Beta (95% Confidence Interval - 95% CI) without adjustment, with adjustment for sociodemographic variables (Model 1) and multivariable adjustment (Model 1 more cardiovascular risk factors). We also used logistic regression models to analyze the Odds Ratio (OR) and 95% CI for the association of both diseases using cIMT > P75%. Results: After the exclusion of patients with previous cardiovascular disease, 5,077 participants with no diseases, 1578 with diabetes, 662 with subclinical hypothyroidism, and 234 with both diseases were included in the analysis. Linear regression models showed an association of cIMT with only diabetes (β = 0.019; 95% CI 0.012 to 0.027; p < 0.0001) and subclinical hypothyroidism more diabetes (β = 0.03; 95% CI 0.010‒0.047, p < 0.0001). The logistic regression model reported an association between diabetes and CIMT higher than P75% (OR = 1.49, 95% CI 1.30‒1.71). No interaction between diabetes and subclinical hypothyroidism was detected using cIMT respectively as a continuous (p = 0.29) or as a categorical variable (p = 0.92). Discussion: Diabetes was associated with higher cIMT values. However, no additive effect of subclinical hypothyroidism associated with diabetes over cIMT was detected.

Association of subclinical inflammation, glycated hemoglobin and risk for obstructive sleep apnea syndrome.

OBJECTIVE: To investigate the inter-relation between high sensitivity C-reactive protein and glycated hemoglobin in prediction of risk of obstructive sleep apnea. METHODS: We included all individuals participating in a check-up program at the Preventive Medicine Center of Hospital Israelita Albert Einstein in 2014. The Berlin questionnaire for risk of obstructive sleep apnea was used, and the high sensitivity C-reactive protein and glycated hemoglobin levels were evaluated. RESULTS: The sample included 7,115 participants (age 43.4±9.6 years, 24.4% women). The Berlin questionnaire showed changes in 434 (6.1%) individuals. This finding was associated with high sensitivity C-reactive protein and glycated hemoglobin levels (p<0.001). However, only the association between the Berlin questionnaire result and glycated hemoglobin remained significant in the adjusted multivariate analysis, for the traditional risk factors and for an additional model, including high-density lipoprotein cholesterol and triglycerides. CONCLUSION: The glycated hemoglobin, even below the threshold for diagnosis of diabetes, is independently associated with obstructive sleep apnea syndrome, even after adjustment for obesity and C-reactive protein. These findings suggest a possible pathophysiological link between changes in insulin resistance and obstructive sleep apnea syndrome, independently from obesity or low-grade inflammation. OBJETIVO: Investigar a inter-relação entre proteína C-reativa de alta sensibilidade e hemoglobina glicada na predição do risco de apneia obstrutiva do sono. MÉTODOS: Foram incluídos todos os indivíduos participantes do programa de check-up do Centro de Medicina Preventiva Hospital Israelita Albert Einstein em 2014. Foi aplicado o questionário de Berlin sobre risco de apneia do sono, e avaliadas as dosagens de hemoglobina glicada e proteína C-reativa de alta sensibilidade. RESULTADOS: Foram incluídos 7.115 participantes (idade 43,4±9,6 anos, 24,4% mulheres). A prevalência de alteração no questionário de Berlin foi de 434 (6,1%). A alteração do questionário de Berlin associou-se positivamente aos resultados da proteína C-reativa de alta sensibilidade e da hemoglobina glicada (p<0,001). No entanto, apenas a associação entre o resultado do questionário de Berlin e a hemoglobina glicada permaneceu significativa na análise multivariada ajustada tanto para fatores de risco tradicionais quanto para um modelo adicional, que incluiu também lipoproteína de alta densidade-colesterol (HDL-c) e triglicérides. CONCLUSÃO: A hemoglobina glicada, mesmo em valores abaixo do critério diagnóstico para diabetes mellitus, está associada de forma independente ao risco para síndrome da apneia obstrutiva do sono, mesmo após ajuste para obesidade e proteína C-reativa. Estes achados sugerem possível ligação fisiopatológica entre alterações na resistência insulínica e a síndrome da apneia obstrutiva do sono, que independe da obesidade ou inflamação de baixo grau.

The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis

SUMMARY Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. Materials and methods: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. Results: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. Conclusion: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Sleep characteristics in type 1 diabetes and associations with glycemic control: systematic review and meta-analysis.

OBJECTIVES: The association between inadequate sleep and type 2 diabetes has garnered much attention, but little is known about sleep and type 1 diabetes (T1D). Our objectives were to conduct a systematic review and meta-analysis comparing sleep in persons with and without T1D, and to explore relationships between sleep and glycemic control in T1D. METHODS: Studies were identified from Medline and Scopus. Studies reporting measures of sleep in T1D patients and controls, and/or associations between sleep and glycemic control, were selected. RESULTS: A total of 22 studies were eligible for the meta-analysis. Children with T1D had shorter sleep duration (mean difference [MD] = -26.4 minutes; 95% confidence interval [CI] = -35.4, -17.7) than controls. Adults with T1D reported poorer sleep quality (MD in standardized sleep quality score = 0.51; 95% CI = 0.33, 0.70), with higher scores reflecting worse sleep quality) than controls, but there was no difference in self-reported sleep duration. Adults with TID who reported sleeping >6 hours had lower hemoglobin A1c (HbA1c) levels than those sleeping ≤6 hours (MD = -0.24%; 95% CI = -0.47, -0.02), and participants reporting good sleep quality had lower HbA1c than those with poor sleep quality (MD = -0.19%; 95% CI = -0.30, -0.08). The estimated prevalence of obstructive sleep apnea (OSA) in adults with TID was 51.9% (95% CI = 31.2, 72.6). Patients with moderate-to-severe OSA had a trend toward higher HbA1c (MD = 0.39%, 95% CI = -0.08, 0.87). CONCLUSION: T1D was associated with poorer sleep and high prevalence of OSA. Poor sleep quality, shorter sleep duration, and OSA were associated with suboptimal glycemic control in T1D patients.