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ABSTRACT Background: The aim of this study was to address the first cases of TOETVA done in Brazil, by TOETVA-Bra study group, regarding safety and complications. Materials and Methods: Series of the first 93 TOETVAs cases in Brazil. All authors except LPK, AJG JOR and RPT received TOETVA training including cadaveric hands-on in Thailand or United States (Johns Hopkins Medicine) during 2017. After they came back to Brazil and started doing their first TOETVA cases in the cities of Rio de Janeiro, Sao Paulo and Chapecó they agreed to collaborate and gather data using an online spreadsheet. All patients were submitted to the technique described by Anuwong. Results: A total of 93 patients underwent TOETVA. Most patients (58.1%) were submitted to total thyroidectomy and 59.1% had benign disease. Two patients (2.2%) needed conversion to open surgery. Five patients (9.3%) developed transient hypoparathyroidism and there were 3 (2.0%) temporary recurrent laryngeal nerve palsy. There was one (0.7%) permanent unilateral palsy. Twenty patients had some sort of complication, 16.1% were minor and 5.4% were major. A total of 73 patients (78.5%) had an uneventful recovery. Conclusion: The technique is reproducible with a low complication rate. While further studies are needed to confirm equivalency, early efforts suggest that TOETVA is not inferior to traditional open thyroidectomy in appropriately selected patients.

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ABSTRACT Background: This study was aimed at investigating the aesthetic impact of scars on the lives of patients who undergo conventional thyroidectomy. Materials and Methods: This cross-sectional study was based on a retrospective analysis of 98 electronic medical records of patients who underwent conventional thyroidectomy performed by the same surgeon. The impact was determined through a qualitative question and categorized into three levels of dissatisfaction. Results: Among the 98 patients, 96 (97.95%) reported experiencing no functional or visual discomfort with their scars. The two unsatisfied individuals were women, and both classified their discomfort as moderate. Although the diseases that indicated surgery varied, papillary thyroid carcinoma predominated. Conclusion: The sample’s satisfaction level indicates that, in line with the current literature, the decision to opt for cosmetically appealing methods is not justified by aesthetic complaints about scars. The benefits of lower cost and fewer complications make conventional thyroidectomy an old but reliable option for afflictions of the thyroid gland that require surgery.

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ABSTRACT Objective: To investigate the association between plasma Hydrogen Sulfide (H2S) levels and visceral fat area (VFA) among Chinese young men. Subjects and methods: This cross-sectional study involved 156 Chinese male subjects, aged 18–45 years, who visited the First Hospital of Qinhuangdao (Hebei, China) in 2014 for annual health check-up. Participants were categorized into: low (VFA < 75.57 cm2), medium (75.57 cm2 ≤ VFA<100.37 cm2), and high (VFA ≥ 100.37 cm2) (n = 52/group). We estimated VFA and plasma H2S levels by using bioelectrical impedance analysis and a fluorescence probe-based approach, respectively. The associations of H2S with VFA and obesity anthropometric measures were assessed. Results: In the high VFA group, the body mass index (BMI, 30.4 ± 2.45 kg/m2), total body fat (TBF, 27.9 ± 3.23 kg), plasma H2S (3.5 μmol/L), free fatty acid (FFA, 0.6 ± 0.24 mmol/L), triglyceride (TG, 2.0 mmol/L), and total cholesterol (TC, 5.5 ± 1.02 mmol/L) levels were significantly higher than that of those of the low and medium VFA groups, respectively (P < 0.05). Plasma H2S levels were found to be inversely correlated with VFA, TBF, waist circumference, BMI, FFA, LnFINS, LnHOMA-IR, LnTG, TC, and LDL-C (P < 0.05). Multiple backward stepwise regression analysis revealed an inverse correlation of plasma H2S levels with FFA (β = −0.214, P = 0.005) and VFA (β = −0.429, P < 0.001), independent of adiposity measures and other confounding factors. Conclusion: VFA was independently and inversely associated with plasma H2S levels among Chinese young men. Therefore, determining plasma H2S levels could aid in the assessment of abnormal VAT distribution.

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ABSTRACT Objectives: Thyroid nodules located in isthmus were found less prevalent, although papillary thyroid cancer in this location was reported to be more aggressive behaviour in some studies. Our aim was to evaluate hormonal,ultrasonographic, and cytopathologic features of nodules located in isthmus (isthmic nodules). Subjects and methods: Patients who underwent thyroidectomy between 2006-2014 reviewed retrospectively. Hormonal, ultrasonographic, and cytopathologic features compared between patients with isthmic (Group-1) and with lober (non-isthmic, Group-2) nodules. Results: Group-1 and Group-2 consisted of 251 and 2076 patients, respectively. 260 isthmic (5.5%) and 4433 non-isthmic (94.5%) nodules were compared.However,most ultrasonographical features such as presence of microcalcification and halo, diameters, echogenicity, texture, margin, and vascularity were similar between groups, macrocalcification rate was lower in isthmic nodules (18.8%, 25.9%; p = 0.012). Cytologic results were also similar.Although malignancy rate was lower in isthmic nodules (6.2%, 12.5%; p = 0.002), type of thyroid cancer was similar in isthmic and non-isthmic nodules.When malignant isthmic (n = 16,2.8%) and malignant non-isthmic nodules (n = 553, 97.2%) were compared, diameter and type of tumor, lymphovascular and capsular invasions, extrathyroidal extension and multifocality rates were not statistically significant.Malignant isthmic nodules (n = 16, 6.2%) had smaller size [10.1 (7.5-34.5) mm, 19.95 (8.4-74.1) mm; p = 0.002], and higher hypoechogenicity rate (31.3%, 5.7%, p = 0.003) compared to benign isthmic nodules (n = 244, 93.8%). Negative predictive value was higher and positive predictive value was lower in isthmic nodules compared to non-isthmic nodules (p = 0.033, p = 0.047, respectively). Conclusion: Isthmic nodules appear to be indolent because of having lower malignancy rate. FNAB might be required in isthmic nodules even if it has relatively small size.The surgery with limited extent or follow-up might seem to be reliable in the management of patients having isthmic nodules especially with indeterminate cytology.

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ABSTRACT Objectives: Alkaline phosphatase (ALP) is the main laboratory marker of hypophosphatasia (HPP), a rare disease unknown to most physicians. The prevalence of HPP has been widely discussed in the literature due to the diverse phenotypes of HPP. The purpose of this study was to search for patients with hypophosphatasemia based on previous biochemistry tests and reevaluate them to confirm the diagnosis of HPP. Subjects and methods: A total of 289,247 biochemical tests for ALP in adults were performed from 2015 to 2019 in two tertiary hospitals in Rio de Janeiro were reviewed (Clementino Fraga Filho University Hospital – HUCFF – and Bonsucesso Federal Hospital – BFH). Results: A total of 1,049 patients were identified with ALP levels below 40 U/L, and 410 patients had hypophosphatasemia confirmed by at least two exams. After the active search of medical reports and/or interviews based on structured questionnaires, 398 subjects were excluded due to secondary causes of reduced ALP. The remaining 12 patients were invited to attend the medical consultation at HUCFF, accompanied by at least one first-degree relative. None of the patients or their relatives had a history or clinical manifestations consistent with HPP. Serum ALP was within reference values in all relatives, but persistently low in further laboratory evaluation in all the 12 patients, in whom secondary causes were ruled out. Thus, we cannot exclude the possibility that they might carry the mutations associated with HPP. Conclusion: Further image evaluations and genetic testing would be appropriate to confirm this asymptomatic adult form of HPP.

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ABSTRACT Objective: To analyze the clinical, laboratory, and radiological findings and management of patients with clinical pituitary apoplexy and to screen for aryl hydrocarbon receptor-interacting protein (AIP) mutations. Subjects and methods: The clinical findings were collected from the medical records of consecutive sporadic pituitary adenoma patients with clinical apoplexy. Possible precipitating factors, laboratory data, magnetic resonance imaging (MRI) findings and treatment were also analyzed. Peripheral blood samples were obtained for DNA extraction from leukocytes, and the entire AIP coding region was sequenced. Results: Thirty-five patients with pituitary adenoma were included, and 23 (67%) had non-functioning pituitary adenomas. Headache was observed in 31 (89%) patients. No clear precipitating factor was identified. Hypopituitarism was observed in 14 (40%) patients. MRI from 20 patients was analyzed, and 10 (50%) maintained a hyperintense signal in MRI performed more than three weeks after pituitary apoplexy (PA). Surgery was performed in ten (28%) patients, and 25 (72%) were treated conservatively with good outcomes. No AIP mutation was found in this cohort. Conclusion: Patients with stable neuroophthalmological impairments can be treated conservatively if no significant visual loss is present. Our radiological findings suggest that hematoma absorption lasts more than that observed in other parts of the brain. Additionally, our study suggests no benefits of AIP mutation screening in sporadic patients with apoplexy.

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ABSTRACT Objective: To study the association of SLC16A11 gene variants with obesity and metabolic markers in nondiabetic Chilean adults. Materials and methods: This cross-sectional study included 263 non-diabetic adults. The genotype of the rs75493593 polymorphism of SLC16A11 gene was performed by real-time PCR. It's association with adiposity markers (body weight, BMI, waist circumference and fat mass percentage), metabolic markers (glucose, insulin, HOMAIR, leptin, total cholesterol, LDLc, HDLc, triglycerides, ALT, GGT and hsCRP) and blood pressure was analyzed by linear regression. Results: The minor allele (T) of the SLC16A11 gene (rs75493593) has a frequency of 29.7% among Chileans. Risk genotypes (GT and TT) were associated with a significant 1.49 mU/l increase in plasmatic insulin for each copy of the minor allele (95% CI: 0.12, 2.87, p < 0.05). This association remained significant after adjusting for socio-demographic variables, physical activity and smoking (1.36 mU/l, 95% CI: 0.16, 2.58 p < 0.05), but was lost when BMI was included as a confounding factor. Higher BMI was also significantly associated with polymorphic genotypes in SLC16A11, independent of socio-demographic variables. Conclusion: The minor allele of the SLC16A11 gene (T) is highly prevalent among Chileans and is associated with increased insulin and BMI in nondiabetic individuals. These findings suggest that the genetic variant in SLC16A11 is not only associated with type 2 diabetes as previously shown in Mexicans, but is also related to early metabolic alterations in healthy subjects that may lead to type 2 diabetes.

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ABSTRACT Objective: The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. Materials and methods: We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). Results: LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). Conclusions: This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.

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ABSTRACT Objective: Percutaneous ethanol injection (PEI) is an alternative to surgery for the treatment of thyroid nodules (TNs). However, size reductions of treated (TTNs) and untreated TN (UTNs) have not been compared. Volumetric reductions in TTNs with PEI were evaluated by comparing TTNs and UTNs in the same patient, and independent variables predicting good post-PEI outcomes were analyzed. Materials and methods: Overall, 282 patients with multinodular goiters were selected. Two nodules located in different lobes were compared for common disease behaviors. Overall, 150 nodules were selected from 75 patients (6 M: 69 F) with a mean age of 50.1 ± 17.4 years. This prospective nonrandomized intervention study prioritized treating TNs of greater volume or single hyperfunctioning TNs. A single observer experienced in PEI and an ultrasound specialist performed the interventions. Results and discussion: TTNs (mean volume: 14.8 ± 16.2 mL) were reduced by 72.6 ± 27.3% of their initial volume, while UTNs increased by a mean of 365.7 ± 1.403.8% (p < 0.00001). The patients underwent a mean of 4.0 ± 3.1 outpatient PEI sessions without relevant complications. Logistic regression analysis showed that the magnitude of the PEI induced reduction was associated with the number of treatment sessions (p = 0.03, CI [1.1-38.2]) and not with ultrasonographic characteristics of the nodules. Each PEI session increased the rate of TN reduction by a factor of 6.7. Conclusions: PEI is a well-tolerated outpatient procedure that effectively reduces the volume of TNs and is noticeably superior to conservative treatment for all ultrasonographic classifications.

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ABSTRACT Objective: To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. Materials and methods: Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. Results: A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). Conclusions: Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

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ABSTRACT Objective: To determine sonographic features of malignancy in partially cystic thyroid nodules and assess the diagnostic efficacy of these features for differentiating between benign and malignant lesions in the nodules with indeterminate cytology. Subjects and methods: From January 2016 to December 2017, a total of 91 patients with 94 partially cystic thyroid nodules who had undergone ultrasound-guided fine-needle aspiration biopsy and thyroid surgery in our hospital were included in this study. The sonographic features of the thyroid nodules were analyzed to identify the predictive features of malignancy and assess the diagnostic efficacy of these features. Results: The features of hypoechogenicity, microcalcification, composition, and an eccentric solid component with an acute angle had statistically significant associations with malignant nodule (p<005) by univariable analysis. Binary logistic regression analysis showed that microcalcification and hypoechogenicity were significantly associated with malignancy. Using the combination of microcalcification, hypoechogenicity, and a solid component comprising of greater than or equal to 50% of the total volume, the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 97.6%, 32.7%, 53.9%, and 94.4%, respectively. In these nodules with indeterminate cytology, this combination also exhibited a high sensitivity of 92.3% and an NPV of 83.3%. Conclusion: This study demonstrated that microcalcification and hypoechogenicity were independently associated with malignancy in partially cystic thyroid nodules. The combination of microcalcification, hypoechogenicity, and a solid portion that is greater than or equal to 50% of the total volume will help guide clinical decisions in mixed cystic solid nodules.

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ABSTRACT Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

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ABSTRACT Objective: To investigate the effect of iodine supplementation during gestation on the neurocognitive development of children in areas where iodine deficiency is common. Materials and methods: Based on the PRISMA methodology, we conducted the search for articles in the PubMed, LILACS and Scopus databases, between March and April 2020, without limitation of dates. We used descriptors in English, Portuguese, and Spanish, without filters. Four clinical trials and four cohort articles were included in the review. Results: The maximum supplementation was 300 μg of potassium iodide per day. The Bayley scale and Children’s Communication Checklist-Short were used to assess neurodevelopment in children. There was no significant improvement in the children’s mental development index and behavioural development index in the supplemented group; however, the psychomotor development index (PDI) showed improvement in the poorer gross motor skills. We found differences in the response time to sound in the supplemented group living in mild deficiency areas. Conclusion: Daily supplementation with iodine can improve poor psychomotor development of children living in mild to moderate iodine deficiency areas. Thus, it is necessary to perform further studies to assess the effect of supplementation on neurodevelopment before, during and after gestation in mild to moderate iodine deficiency areas.

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ABSTRACT This position statement was prepared to guide endocrinologists on the best approach to managing thyroid disorders during the coronavirus disease (COVID-19) pandemic. The most frequent thyroid hormonal findings in patients with COVID-19, particularly in individuals with severe disease, are similar to those present in the non-thyroidal illness syndrome and require no intervention. Subacute thyroiditis has also been reported during COVID-19 infection. Diagnosis and treatment of hypothyroidism during the COVID-19 pandemic may follow usual practice; however, should avoid frequent laboratory tests in patients with previous controlled disease. Well-controlled hypo and hyperthyroidism are not associated with an increased risk of COVID-19 infection or severity. Newly diagnosed hyperthyroidism during the pandemic should be preferably treated with antithyroid drugs (ATDs), bearing in mind the possibility of rare side effects with these medications, particularly agranulocytosis, which requires immediate intervention. Definitive treatment of hyperthyroidism (radioiodine therapy or surgery) may be considered in those cases that protective protocols can be followed to avoid COVID-19 contamination or once the pandemic is over. In patients with moderate Graves’ ophthalmopathy (GO) not at risk of visual loss, glucocorticoids at immunosuppressive doses should be avoided, while in those with severe GO without COVID-19 and at risk of vision loss, intravenous glucocorticoid is the therapeutic choice. Considering that most of the thyroid cancer cases are low risk and associated with an excellent prognosis, surgical procedures could and should be postponed safely during the pandemic period. Additionally, when indicated, radioiodine therapy could also be safely postponed as long as it is possible.

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SUMMARY Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

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ABSTRACT In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults “Detected” positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, “not Detected”, using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.

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ABSTRACT Objective: To evaluate the correlation between the prevalence of overweight condition and obesity with mortality rates due to COVID-19 in Brazil's state capitals. Materials and methods: This is an ecological study, whose units of analysis were the 26 state capitals and the Federal District of Brazil. Prevalence was estimated by the results of the Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico 2019 (VIGITEL). The general mortality rates due to COVID-19 were collected on the official website of the Brazilian Ministry of Health (MH) and stratified by the same Brazilian capitals evaluated in the VIGITEL survey. The rates included the period between the 1st and 29th Epidemiological Weeks of 2020. The Partial Correlation Test (r) was used, controlled for confounding factors, to evaluate the correlation between the prevalence of overweight/obesity and the overall mortality rates due to COVID-19. Results: The mean mortality rate for COVID-19 in the period was 65.1 deaths per 100,000 inhabitants. Regarding the prevalence of obesity and overweight, 20.2% and 54.7% were the mean values observed in the state capitals, respectively. The prevalence of obesity was positively correlated with the overall mortality rate due to COVID-19, with mean positive correlation (r=0.380) and statistically significant correlation (p=0.034). Conclusion: This study pointed out that, at the aggregate level, there is a concomitant and correlated increase in mortality rates due to COVID-19 and prevalence of obesity in Brazilian capitals. The data found may contribute to actions to cope with the pandemic aimed at this population.