ABSTRACT Objective: Based on hypothetical hypothyroidism and nonthyroidal illness syndrome (NTIS) gene expression similarities, we decided to compare the patterns of expression of both as models of NTIS. The concordant profile between them may enlighten new biomarkers for NTIS challenging scenarios. Materials and methods: We used Ion Proton System next-generation sequencing to build the hypothyroidism transcriptome. We selected two databanks in GEO2 platform datasets to find the differentially expressed genes (DEGs) in adults and children with sepsis. The ROC curve was constructed to calculate the area under the curve (AUC). The AUC, chi-square, sensitivity, specificity, accuracy, kappa and likelihood were calculated. We performed Cox regression and Kaplan-Meier analyses for the survival analysis. Results: Concerning hypothyroidism DEGs, 70.42% were shared with sepsis survivors and 61.94% with sepsis nonsurvivors. Some of them were mitochondrial gene types (mitGenes), and 95 and 88 were related to sepsis survivors and nonsurvivors, respectively. BLOC1S1, ROMO1, SLIRP and TIMM8B mitGenes showed the capability to distinguish sepsis survivors and nonsurvivors. Conclusion: We matched our hypothyroidism DEGs with those in adults and children with sepsis. Additionally, we observed different patterns of hypothyroid-related genes among sepsis survivors and nonsurvivors. Finally, we demonstrated that ROMO1, SLIRP and TIMM8B could be predictive biomarkers in children's sepsis.

ABSTRACT Objective: The risk of malignancy and diagnostic accuracy of fine-needle aspiration biopsy (FNAB) of thyroid nodules (TN) with diameters ≥ 3-4 cm remains controversial. However, some groups have indicated surgical treatment in these patients regardless of the FNAB results. We aimed to evaluate the diagnostic accuracy of the FNAB in systematically resected ≥4 cm TN and if the risk of malignancy is higher in these patients. Subjects and methods: We retrospectively evaluated 138 patients (142 nodules) with TN with diameters ≥4 cm who underwent thyroidectomy. Results: The FNAB results were nondiagnostic/unsatisfactory (ND/UNS) in 2.1% of the cases and benign in 51.4%. They indicated atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 23.9% of cases, follicular neoplasia/suspicious for a follicular neoplasm (FN/SFN) in 9.2%, suspicion of malignancy (SUS) in 8.5%, and malignant in 4.9%. The histopathological analysis after thyroidectomy revealed a thyroid cancer rate of 100% in the FNABs classified as malignant, 33.3% in SUS cases, 7.7% in FN/SFN, 17.6% in AUS/FLUS, and 4.1% in benign FNABs. None of the ND/UNS FNABs were malignant. The global malignancy diagnosis was 14.8% (n = 21). However, the rate of false negatives for FNAB was low (4.1%). Conclusion: We showed that the risk of malignancy in nodules with diameters ≥4 cm was higher compared to the risk of thyroid cancer in TN in general. However, we found a low rate of false-negative cytological results; therefore, our data do not justify the orientation of routine resection for these larger nodules.

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.

O objetivo desta pesquisa é analisar a associação de variações temporais dos agravos e das mortes por causas externas com períodos de maior fluxo de visitantes em municípios turísticos do litoral de São Paulo, Brasil, no período de 2004 a 2014. Trata-se de um estudo ecológico, de séries temporais diárias e mensais, baseado nos dados do Sistema de Informações sobre Mortalidade (SIM) e Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS) no período de 1º de janeiro de 2004 a 31 de dezembro de 2014, tendo como unidades de análise os quatro municípios do litoral norte do Estado de São Paulo. Modelos de regressão binomial negativa foram ajustados para o desfecho que representou o número de ocorrências de internações hospitalares e/ou óbitos por causas externas, tendo como preditores as variáveis de calendário (dias da semana, feriados, mês e ano de ocorrência). Os feriados de Ano Novo, Carnaval, Tiradentes e Proclamação da República destacaram-se com médias iguais ou superiores a 5 desfechos por dia. Dentre os dias da semana, a segunda-feira e o domingo apresentaram as maiores médias. Levando em consideração todos os preditores, verifica-se maior tendência de ocorrência dos desfechos na segunda-feira (OR = 1,11; IC95%: 1,05-1,18), nos feriados de Ano Novo (OR = 1,44; IC95%: 1,19-1,74) e Proclamação da República (OR = 1,49; IC95%: 1,13-1,94) e nos meses de janeiro (OR = 1,11; IC95%: 1,02-1,20) e fevereiro (OR = 1,13; IC95%: 1,04-1,23). A morbidade e a mortalidade por causas externas nos municípios estudados foram maiores no período de maior movimentação de turistas, subsidiando a estruturação do atendimento destas lesões e as ações de prevenção e de promoção de saúde direcionadas para este grupo de causas.

This study aims to analyze the association between temporal variations in injuries and deaths from external causes and periods of greater flow of visitors in tourist municipalities (counties) on the coastline of the state of São Paulo, Brazil, from 2004 to 2014. This is an ecological study of daily and monthly time series based on data from the Brazilian Mortality Information System (SIM) and Brazilian Hospital Information System of the Brazilian Unified National Health System (SIH/SUS) from January 1, 2004, to December 31, 2014, using as the analytical units the four municipalities on the northern coast of the State of São Paulo. Negative binomial regression models were adjusted for the outcome that represented the number of hospital admissions and/or deaths from external causes, with calendar variables as predictors (days of the week, holidays, month, and year of occurrence). The Brazilian holidays New Year’s Day, Carnival, Tiradentes, and Proclamation of the Republic stood out with mean numbers greater than or equal to 5 outcomes per day. Among the days of the week, Monday and Sunday had the highest mean numbers. Considering all the predictors, there was a higher tendency to the occurrence of outcomes on Monday (OR = 1.11; 95%CI: 1.05-1.18), New Year’s Day (OR = 1.44; 95%CI: 1.19-1.74), and Proclamation of the Republic Day (OR = 1.49; 95%CI: 1.13-1.94) and in the months of January (OR = 1.11; 95%CI: 1.02-1.20) and February (OR = 1.13; 95%CI: 1.04-1.23). Morbidity and mortality from external causes in these tourist towns were higher in the period with the greatest flow of tourists, emphasizing the need to organize care for these injuries, alongside measures for prevention and health promotion targeted to this group of causes.

El objetivo de esta investigación es analizar la asociación de variaciones temporales en enfermedades y muertes por causas externas, durante períodos de mayor flujo de visitantes en municipios turísticos del litoral de São Paulo, Brasil, durante el período de 2004 a 2014. Se trata de un estudio ecológico, de series temporales diarias y mensuales, basado en los datos del Sistema de Información sobre Mortalidad (SIM) y Sistema de Informaciones Hospitalarias del Sistema Único de Salud (SIH/SUS), durante el período del 1º de enero de 2004 al 31 de diciembre de 2014, teniendo como unidades de análisis los cuatro municipios del litoral norte del Estado de São Paulo. Modelos de regresión binomial negativa se ajustaron al resultado que representó el número de ocurrencias de internamientos hospitalarios y/u óbitos por causas externas, teniendo como predictores variables de calendario (días de la semana, festivos, mes y año de ocurrencia). Los festivos de Año Nuevo, Carnaval, Tiradentes y Proclamación de la República se destacaron con medias iguales o superiores a 5 resultados por día. Entre los días de la semana, el lunes y el domingo presentaron las mayores medias. Teniendo en consideración todos los predictores, se verifica una mayor tendencia de ocurrencia de los resultados: los lunes (OR = 1,11; IC95%: 1,05-1,18), festivo de Año Nuevo (OR = 1,44; IC95%: 1,19-1,74) y Proclamación de la República (OR = 1,49; IC95%: 1,13-1,94) y, en los meses de enero (OR = 1,11; IC95%: 1,02-1,20) y de febrero (OR = 1,13; IC95%: 1,04-1,23). La morbilidad y mortalidad por causas externas en los municipios estudiados fueron mayores en el período de mayor movimiento de turistas, apoyando la organización de la atención a esas lesiones, así como acciones de prevención y promoción de salud dirigidas hacia este grupo de causas.

O objetivo desta pesquisa é analisar a associação de variações temporais dos agravos e das mortes por causas externas com períodos de maior fluxo de visitantes em municípios turísticos do litoral de São Paulo, Brasil, no período de 2004 a 2014. Trata-se de um estudo ecológico, de séries temporais diárias e mensais, baseado nos dados do Sistema de Informações sobre Mortalidade (SIM) e Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS) no período de 1º de janeiro de 2004 a 31 de dezembro de 2014, tendo como unidades de análise os quatro municípios do litoral norte do Estado de São Paulo. Modelos de regressão binomial negativa foram ajustados para o desfecho que representou o número de ocorrências de internações hospitalares e/ou óbitos por causas externas, tendo como preditores as variáveis de calendário (dias da semana, feriados, mês e ano de ocorrência). Os feriados de Ano Novo, Carnaval, Tiradentes e Proclamação da República destacaram-se com médias iguais ou superiores a 5 desfechos por dia. Dentre os dias da semana, a segunda-feira e o domingo apresentaram as maiores médias. Levando em consideração todos os preditores, verifica-se maior tendência de ocorrência dos desfechos na segunda-feira (OR = 1,11; IC95%: 1,05-1,18), nos feriados de Ano Novo (OR = 1,44; IC95%: 1,19-1,74) e Proclamação da República (OR = 1,49; IC95%: 1,13-1,94) e nos meses de janeiro (OR = 1,11; IC95%: 1,02-1,20) e fevereiro (OR = 1,13; IC95%: 1,04-1,23). A morbidade e a mortalidade por causas externas nos municípios estudados foram maiores no período de maior movimentação de turistas, subsidiando a estruturação do atendimento destas lesões e as ações de prevenção e de promoção de saúde direcionadas para este grupo de causas.

This study aims to analyze the association between temporal variations in injuries and deaths from external causes and periods of greater flow of visitors in tourist municipalities (counties) on the coastline of the state of São Paulo, Brazil, from 2004 to 2014. This is an ecological study of daily and monthly time series based on data from the Brazilian Mortality Information System (SIM) and Brazilian Hospital Information System of the Brazilian Unified National Health System (SIH/SUS) from January 1, 2004, to December 31, 2014, using as the analytical units the four municipalities on the northern coast of the State of São Paulo. Negative binomial regression models were adjusted for the outcome that represented the number of hospital admissions and/or deaths from external causes, with calendar variables as predictors (days of the week, holidays, month, and year of occurrence). The Brazilian holidays New Year’s Day, Carnival, Tiradentes, and Proclamation of the Republic stood out with mean numbers greater than or equal to 5 outcomes per day. Among the days of the week, Monday and Sunday had the highest mean numbers. Considering all the predictors, there was a higher tendency to the occurrence of outcomes on Monday (OR = 1.11; 95%CI: 1.05-1.18), New Year’s Day (OR = 1.44; 95%CI: 1.19-1.74), and Proclamation of the Republic Day (OR = 1.49; 95%CI: 1.13-1.94) and in the months of January (OR = 1.11; 95%CI: 1.02-1.20) and February (OR = 1.13; 95%CI: 1.04-1.23). Morbidity and mortality from external causes in these tourist towns were higher in the period with the greatest flow of tourists, emphasizing the need to organize care for these injuries, alongside measures for prevention and health promotion targeted to this group of causes.

El objetivo de esta investigación es analizar la asociación de variaciones temporales en enfermedades y muertes por causas externas, durante períodos de mayor flujo de visitantes en municipios turísticos del litoral de São Paulo, Brasil, durante el período de 2004 a 2014. Se trata de un estudio ecológico, de series temporales diarias y mensuales, basado en los datos del Sistema de Información sobre Mortalidad (SIM) y Sistema de Informaciones Hospitalarias del Sistema Único de Salud (SIH/SUS), durante el período del 1º de enero de 2004 al 31 de diciembre de 2014, teniendo como unidades de análisis los cuatro municipios del litoral norte del Estado de São Paulo. Modelos de regresión binomial negativa se ajustaron al resultado que representó el número de ocurrencias de internamientos hospitalarios y/u óbitos por causas externas, teniendo como predictores variables de calendario (días de la semana, festivos, mes y año de ocurrencia). Los festivos de Año Nuevo, Carnaval, Tiradentes y Proclamación de la República se destacaron con medias iguales o superiores a 5 resultados por día. Entre los días de la semana, el lunes y el domingo presentaron las mayores medias. Teniendo en consideración todos los predictores, se verifica una mayor tendencia de ocurrencia de los resultados: los lunes (OR = 1,11; IC95%: 1,05-1,18), festivo de Año Nuevo (OR = 1,44; IC95%: 1,19-1,74) y Proclamación de la República (OR = 1,49; IC95%: 1,13-1,94) y, en los meses de enero (OR = 1,11; IC95%: 1,02-1,20) y de febrero (OR = 1,13; IC95%: 1,04-1,23). La morbilidad y mortalidad por causas externas en los municipios estudiados fueron mayores en el período de mayor movimiento de turistas, apoyando la organización de la atención a esas lesiones, así como acciones de prevención y promoción de salud dirigidas hacia este grupo de causas.

Resumo Fundamento A prevalência da obesidade vem aumentando sistematicamente na população, inclusive nas crianças e adolescentes, ao redor do mundo. Objetivos Descrever curvas percentílicas de referência para a circunferência abdominal (CA) nas crianças brasileiras e fornecer pontos de corte da CA para identificar crianças com risco de obesidade. Métodos Um estudo multicêntrico, prospectivo, tranversal foi realizado em crianças com idades entre 6 e 10 anos, matriculadas no ensino fundamental de escolas públicas e particulares de 13 cidades do estado de São Paulo. A estatura, o peso e a CA foram medidos em duplicata em 22.000 crianças (11.199 meninos). Para estabelecer o melhor ponto de corte da CA para o diagnóstico da obesidade, foram calculadas curvas ROC com crianças classificadas como com peso normal e obesas, de acordo com as curvas do IMC, estratificadas por gênero e idade, e o índice Youden foi utilizado como a eficácia potencial máxima desse biomarcador. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Os valores da CA aumentaram com a idade, tanto nos meninos quanto nas meninas. A prevalência de obesidade em cada grupo variou de 17% (6 anos de idade) a 21,6 % (9 anos de idade), dentre os meninos, e de 14,1% (7 anos de idade) a 17,3 % (9 anos de idade), dentre as meninas. As análises ROC mostraram o percentil 75 como ponto de corte para o risco de obesidade, e o diagnóstico de obesidade está classificado no percentil 85 ou acima. Conclusão Curvas de referência da CA específicas para idade e sexo em crianças brasileiras e pontos de corte para o risco de obesidade podem ser usados em triagem nacional e estudos intervencionais para reduzir a carga da obesidade no Brasil. (Arq Bras Cardiol. 2020; 114(3):530-537)

Abstract Backgroud The prevalence of obesity has systematically been increased in the population, including children and adolescents, around the world. Objectives To describe reference percentile curves for waist circumference (WC) in Brazilian children and provide cut-off values of WC to identify children at risk for obesity. Methods A multicenter, prospective, cross-sectional study was performed with children aged from 6 to 10 years old, enrolled in public and private elementary schools from 13 cities of the São Paulo State. Height, weight, and WC were measured in duplicate in 22,000 children (11,199 boys). To establish the WC best cut-off value for obesity diagnosis, ROC curves with children classified as normal weight and obese were calculated, according to BMI curves, stratified by gender and age, and the Youden Index was utilized as the maximum potential effectiveness of this biomarker. A p < 0.05 was considered statistically significant. Results WC values increased with age in both boys and girls. The prevalence of obesity in each age group varied from 17% (6 years old) to 21.6% (9 years old) among boys, and from 14.1% (7 years old) to 17.3 % (9 years old) among girls. ROC analyses have shown the 75th percentile as a cut-off for obesity risk, and the diagnosis of obesity is classified on the 85th percentile or more. Conclusion Age and gender specific reference curves of WC for Brazilian children and cut-off values for obesity risk may be used for national screening and interventional studies to reduce the obesity burden in Brazil. (Arq Bras Cardiol. 2020; 114(3):530-537)

Resumo Fundamento: A associação de disfunção tireoidiana subclínica (DST) com arritmias cardíacas permanece controversa, particularmente na população não idosa. Objetivo: Investigar se a DST está associada a arritmias cardíacas em uma coorte de adultos de meia-idade e idosos. Métodos: Dados da linha de base do Estudo Longitudinal de Saúde do Adulto, ELSA-Brasil (35-74 anos) foram coletados de 2008 a 2010. Após exclusão de hipo e hipertireoidismo clínicos, os participantes foram categorizados como eutireoidismo (TSH = 0,4 a 4,0 µU/mL), hipotireoidismo subclínico (TSH > 4,0 µU/mL; T4L = 0,8-1,9 ng/dL) e hipertireoidismo subclínico (TSH <0,4 µU/mL; T4L = 0,8 a 1,9 ng/dL). As prevalências de taquicardia (Frequência cardíaca [FC] > 100) e bradicardia (FC < 60), fibrilação atrial/flutter, distúrbios de condução, extrassístoles, baixa voltagem do QRS, intervalos QT prolongados e ritmo supraventricular persistente foram comparadas entre os grupos após ajuste por idade, sexo, comorbidades, estilo de vida, índice de massa corporal e uso de medicamentos. Resultados: Foram analisados os dados da FC de 13.341 participantes (52% do sexo feminino; idade média de 51 anos) e das leituras de 11.795 ECG; 698 participantes (5,23%) foram classificados como hipotireoidismo subclínico, 193 (1,45%) como hipertireoidismo subclínico e 12.450 (93,32%) como eutireoidismo. A prevalência de distúrbios de ritmo e condução foi semelhante, assim como as médias de FC, mesmo nos subgrupos com TSH < 0,01 UI/mL ou > 10,0 UI/mL ou em idosos. Distúrbios de condução foram menos prevalentes em idosos com hipotireoidismo subclínico (OR ajustado = 0,44; IC95% 0,24-0,80). Conclusão: Neste grande estudo multicêntrico e transversal, a DST não foi associada a arritmias cardíacas, mas uma avaliação longitudinal é necessária.

Abstract Background: The association of subclinical thyroid dysfunction (STD) with cardiac arrhythmias remains controversial, particularly in the non-elderly population. Objective: To investigate whether STD was associated with cardiac arrhythmias in a cohort of middle-aged and older adults. Methods: Baseline data of the Longitudinal Study of Adult Health, ELSA-Brasil (35-74 years) were collected from 2008 to 2010. After exclusion of clinical hypothyroidism and hyperthyroidism, participants were categorized as euthyroidism (TSH = 0.4-4.0 µU/mL), subclinical hypothyroidism (TSH > 4.0 µU/mL; FT4 = 0.8-1.9 ng/dL), and subclinical hyperthyroidism (TSH < 0.4 µU/mL; FT4 = 0.8-1.9 ng/dL). The prevalence rates of tachycardia (HR > 100) and bradycardia (HR < 60), atrial fibrillation/flutter, conduction disorders, extrasystoles, low QRS voltage, prolonged QT intervals, and persistent supraventricular rhythms were compared between groups after adjusting for age, sex, comorbidities, lifestyle, body mass index and medications. Results: The HR data of 13,341 participants (52% female; median age, 51 years) and the electrocardiogram readings of 11,795 were analyzed; 698 participants (5.23%) were classified as subclinical hypothyroidism, 193 (1.45%) as subclinical hyperthyroidism, and 12,450 (93.32%) as euthyroidism. The prevalence of rhythm and conduction disorders was similar, as were HR medians, even in the subgroups with TSH < 0.01 UI/mL or > 10.0 UI/mL or in older adults. Conduction disorders were less prevalent in older adults with subclinical hypothyroidism (adjusted OR = 0.44; 95% CI 0.24 to 0.80). Conclusion: In this large, multicenter and cross-sectional study, STD was not associated with cardiac arrhythmias, but a longitudinal assessment is necessary.

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

ABSTRACT Several complications can arise, either directly or indirectly, from implementation of measures to correct soil acidity in established fruit orchards, such as impaired roots, lower root volume, risk of plant infection, propagation of diseases, promotion of pest development (especially nematodes), and soil disaggregation and compaction. These factors can have a negative effect on crop yield. Therefore, it becomes critical to implement an effective method of neutralizing soil acidity, especially at the level of the tree roots. To assess the effect that the rates and forms of limestone applied on the soil surface have on soil fertility and on nutrition and yield of guava, an experiment was conducted in a commercial orchard. A randomized block experimental design was implemented with three replicates consisting of two forms of limestone [common limestone with relative neutralizing value (RNV) = 80 % and calcined limestone with RNV = 131 %], which were applied at five different rates (0, 0.5, 1, 1.5, and 2 times the recommended rate to raise the V value to 70 %), without incorporation. Liming with common or calcined limestone caused a drop in soil acidity in the 0.00-0.10 m layer at 6, 12, and 24 months after application. Soil acidity decreased in the 0.10-0.20 m layer at 6 and 12 months after use of calcined limestone, and at 24 months after liming with the common form of limestone. The chemical composition (N, P, K, Ca, Mg, S, B, Cu, Fe, Mn, Zn) of leaves was not affected at 14 months after surface liming treatments, nor the chemical composition of fruit at 20 months after the treatments. Guava yield was not affected by surface liming.

ABSTRACT Objective To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC. Subjects and methods Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in 4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31). Results 18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease. Conclusion 18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.

ABSTRACT Objectives The presence of thyroglobulin (Tg) in needle washouts of fine needle aspiration biopsy (Tg-FNAB) in neck lymph nodes (LNs) suspected of metastasis has become a cornerstone in the follow-up of patients with papillary thyroid carcinoma (PTC). However, there are limited data regarding the measurement of anti-Tg antibodies in these washouts (TgAb-FNAB), and it is not clear whether these antibodies interfere with the assessment of Tg-FNAB or whether there are other factors that would more consistently justify the finding of low Tg-FNAB in metastatic LNs. Materials and methods We investigated 232 FNAB samples obtained from suspicious neck LNs of 144 PTC patients. These samples were divided according to the patient’s serum TgAb status: sTgAb- (n = 203 samples) and sTgAb+ (n = 29). The TgAb-FNAB levels were measured using two different assays. Tg-FNAB was also measured using two assays when low levels (< 10 ng/mL) were identified in the first assay of the metastatic LNs from the sTgAb+ samples. Results The TgAb-FNAB results were negative in both assays in all samples. Low levels of Tg-FNAB were identified in 11/16 of the metastatic LNs of the sTgAb+ patients and 16/63 of the sTgAb- patients (p < 0.05) using assay 1. The measurement of the Tg-FNAB levels using assay 2 indicated additional metastases in 5 LNs of the sTgAb+ patients. Conclusions Factors other than the presence of TgAb-FNAB may contribute to the higher number of metastatic LNs with undetectable Tg-FNAB in the sTgAb+ group. In addition, the measurement of Tg-FNAB using different assays was useful to enhance the diagnosis of metastatic LNs, particularly when cytological and Tg-FNAB results are discordant.

OBJETIVO: Avaliar risco de malignidade de nódulos tiroidianos por meio de aspectos clínicos, laboratoriais, ultrassonográficos e citológicos. PACIENTES E MÉTODOS: 741 nódulos de 407 pacientes. RESULTADOS: A citologia foi benigna (60,5%), indeterminada (23,3%), maligna (8,6%) ou não diagnóstica (7,6%). A prevalência de câncer nas citologias indeterminadas foi 18,5% (16% nas lesões foliculares, 44% nas suspeitas). O diagnóstico de malignidade foi 17,2% (n = 70). A frequência de câncer em mulheres (15,2%) foi menor do que em homens (27,9%). Houve uma relação inversa entre idade e risco de câncer. Não houve significância estatística na prevalência de câncer de acordo com número, tamanho dos nódulos ou níveis de TSH. Hipoecogenicidade e microcalcificações ao ultrassom foram fatores de risco. CONCLUSÃO: O risco de malignidade foi maior em homens, nódulos hipoecogênicos, com microcalcificações e inversamente relacionado à idade. O nível de TSH não foi um preditor independente de malignidade.

OBJECTIVE: To evaluate the risk of malignancy in thyroid nodules through clinical, laboratory, ultrasonographic and cytological aspects. PATIENTS AND METHODS: 741 nodules of 407 patients. RESULTS: The cytology was benign (60,5%), indeterminate (23,3%), malignant (8,3%) or nondiagnostic (7,6%). The prevalence of cancer in indeterminate citology was 18,5% (16% in follicular lesions, 44% in suspicious). The diagnosis of malignancy was 17,2% (n = 70). The frequency of cancer in women (15,2%) was lower than in men (27,9%). There was an inverse relation between age and cancer risk. There was no statistical significance in the prevalence of cancer according to number, size of nodules or TSH levels. Hypoechogenicity and microcalcifications on ultrasound were risk factors. CONCLUSION: The risk of malignancy was higher in men, hypoechoic nodules, with microcalcifications and was inversely related to age. The TSH level was not an independent factor predictive of malignancy.

A forma hereditária do carcinoma medular da tiróide pode ocorrer de modo isolado, o carcinoma medular da tiróide familiar (FMTC), ou como parte das neoplasias endócrinas múltiplas tipo 2A (MEN2A) e 2B (MEN2B). MEN2B é uma síndrome rara e seu fenótipo é usualmente, mas nem sempre, notado pelo médico. Na infância, nenhuma das características de MEN2B estão presentes, exceto pela disfunção gastrintestinal precoce, causada pelos neuromas intestinais. Quando disponível, a análise genética confirma o diagnóstico e orienta a avaliação pré-operatória e extensão da cirurgia. Neste artigo, apresentamos quatro casos de MEN2B, nos quais o diagnóstico tardio teve impacto significativo na evolução clínica e, potencialmente, na mortalidade em geral. APRESENTAÇÃO DOS CASOS: Apresentamos quatro casos, dois homens e duas mulheres, com diferenças em seus fenotipos e com diagnóstico tardio. O primeiro caso tem história de obstrução gastrintestinal importante em que foi necessária cirurgia dois dias após o nascimento. O segundo paciente apresentava nódulos na mucosa oral e constipação desde a infância. O terceiro referia história de constipação desde o nascimento até 5 meses de idade. O quarto tinha história de constipação intestinal desde a infância. DISCUSSÃO: Novos conceitos emergiram desde que o oncogene RET foi identificado, em 1993, como o gene responsável pelo carcinoma medular da tiróide hereditário. A maioria dos indivíduos apresenta a mutação M918T no éxon 16 do RET, enquanto poucos casos apresentam a mutação A883F ou a associação de V804M com E805K, Y806C ou S904C. O consenso recomenda a tiroidectomia total com dissecção dos linfonodos no compartimento central até os 6 meses após o nascimento. O diagnóstico rápido e preciso é essencial para o atingir os objetivos. CONCLUSÃO: O diagnóstico precoce de MEN2B é muito importante para propiciar a investigação apropriada de doenças associadas e para permitir aconselhamento e rastreamento dos parentes para uma mutação do RET. Pacientes com MEN2B, que apresentam frequentemente achados típicos ao exame físico, podem não ser reconhecidos e seguidos como casos esporádicos. Por causa disso, todos os casos de neoplasia endócrina múltipla devem ser avaliados pelo teste genético para mutações do RET.

BACKGROUND: The hereditary form of medullary thyroid carcinoma may occur isolated as a familial medullary thyroid carcinoma (FMTC) or as part of Multiple Endocrine Neoplasia 2A (MEN2A) and 2B (MEN2B). MEN2B is a rare syndrome, its phenotype may usually, but not always, be noted by the physician. In the infant none of the MEN2B characteristics are present, except by early gastrointestinal dysfunction caused by intestinal neuromas. When available, genetic analysis confirms the diagnosis and guides pre-operative evaluation and extent of surgery. Here we report four cases of MEN2B in which the late diagnosis had a significant impact in clinical evolution and, potentially, in overall survival. CASE REPORT: We report four cases, 2 men and 2 women, with differences in their phenotypes and with a late diagnosis. The first case has a history of severe gastrointestinal obstruction requiring a surgery intervention two days after his birth. The second told had nodules in the oral mucosa and constipation since childhood. The third case referred a history of constipation from birth until 5 months of life. The fourth has had a history of chronic constipation since childhood. DISCUSSION: New concepts have emerged since the RET oncogene was identified in 1993 as the responsible gene for hereditary medullary thyroid carcinoma. The majority of MEN2B individuals have M918T mutation in the exon 16 of RET, with a few cases having a mutation A883F or the association of V804M with E805K, Y806C or S904C mutations. The consensus classifies the RET mutation in codon 918 as of highest risk and recommends total thyroidectomy and central lymph node dissection until 6 months after birth. A fast and precise diagnosis is essential to reach these goals. The identification of early manifestations such as intestinal ganglioneuromatosis and oral mucosal neuromas should prompt the physician to initiate an investigation for multiple endocrine neoplasia type 2B. CONCLUSION: The diagnosis of MEN2B is very important to allow appropriate investigation of associated diseases and to allow counseling and appropriate screening of relatives for a RET mutation. Even patients with MEN2B, which often have typical physical features, may not be properly recognized and be followed as a sporadic case. Based on this, all suspicious cases of multiple endocrine neoplasia should undergo a molecular genetic test.

Com a introdução da ultra-sonografia cervical (USC) no seguimento dos pacientes com carcinoma papilífero de tiróide (CPT), tornou-se freqüente o encontro de pequenos linfonodos (LNs) cervicais. Porém, apesar de a USC apresentar alta sensibilidade, o estudo citológico obtido por punção aspirativa (PAAF) e, nos últimos anos, a dosagem da tiroglobulina (Tg) no lavado da agulha da PAAF (Tg-PAAF) vêm assumindo papel importante no diagnóstico de LNs cervicais. O objetivo deste estudo é verificar a acurácia da combinação da USC, citologia e Tg-PAAF em LNs suspeitos. Estudamos 32 pacientes que apresentavam 44 LNs à USC, classificados como "inflamatórios" (19) ou "suspeitos" (25). Dos 25 LNs suspeitos, 15 apresentavam Tg-PAAF elevada (13 com citologia compatível com metástases e 2 com citologia não-diagnóstica). Esses 15 LNs (11 pacientes) foram confirmados como metástase de CP pelo exame histopatológico. Os 19 LNs "inflamatórios" e os 10/25 LNs "suspeitos" apresentaram citologia negativa e Tg-PAAF indetectável. Concluímos que a USC apresenta alta sensibilidade na detecção de linfonodos cervicais, porém citologia e dosagem de Tg-PAAF são fundamentais para o diagnóstico. A associação USC, citologia e Tg-PAAF pode ser considerada a abordagem mais sensível e específica na detecção de LNs metastáticos em pacientes com CPT.

The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA-Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those 25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2 indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine needle aspiration biopsy and FNA-Tg combined with neck US are essential for detecting positive cervical lymph nodes due to its high sensitivity and specificity and it should be considered the standard for investigating locally recurrent disease in patients with PTC.