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Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.”

OBJECTIVE: To evaluate the frequency of thyroid cancer and thyroid dysfunction in first-degree relatives of thyroid cancer patients, and to determine if there is a difference between familial and sporadic thyroid cancer. SUBJECTS AND METHODS: Fifteen first-degree relatives of seven families with at least two family members with thyroid cancer (TC) were compared with 128 first-degree relatives of 45 families with only one family member affected. Laboratory and ultrasound evaluation, fine-needle aspiration biopsy and thyroid surgery were used as normally done in clinical practice. RESULTS: Thyroid dysfunction was similar between the two groups. The frequency of TC and autoimmunity in the group that had two relatives with known thyroid cancer was higher, compared with the families that had sporadic thyroid cancer among their family members (40% vs. 2%, p = 0.0001). CONCLUSION: Frequency of TC increases when more than one member of the family is affected. These findings suggest that these relatives should be screened more frequently than individuals in families in which only one case of TC is observed. OBJETIVO: Avaliar a frequência de carcinoma de tireoide e disfunção tireoidiana em parentes de pacientes com câncer da tireoide e determinar se há diferença entre aqueles com mais de um familiar acometido e os casos esporádicos. SUJEITO E MÉTODOS: Quinze familiares de sete famílias com dois membros sabidamente acometidos foram submetidos à avaliação ultrassonográfica e laboratorial. Cento e vinte e oito familiares de pacientes com carcinoma de tireoide, porém sem outros casos na família, foram utilizados como grupo comparador. RESULTADOS: Em relação à disfunção tireoidiana, não houve diferença entre os grupos. A frequência de carcinoma da tireoide e autoimunidade foi maior nos parentes que tinham dois membros da família afetados (40% vs. 2%, p = 0.0001). A apresentação clínica foi semelhante nos dois grupos. CONCLUSÃO: Devido à maior frequência de carcinoma de tireoide em parentes que possuem mais de um familiar afetado, o rastreamento desses indivíduos talvez deva ser mais intenso do que nos casos em que há apenas um caso na família.

Thyroid cancer in children and adolescents is usually a major concern for physicians, patients, and parents. Controversies regarding the aggressiveness of the clinical presentation and the ideal therapeutic approach remain among the scientific community. The current recommendations and staging systems are based on data generated by studies in adults, and this might lead to overtreating in some cases as well as undertreating in others. Understanding the differences in the biology, clinical course, and outcomes in this population is crucial for therapeutic decisions. This paper evaluates the biology, clinical presentation, recurrences, and overall survival as well as the staging systems in children and adolescents with differentiated thyroid cancer.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:52:13Z No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Vicente_Lopes_da_Silva_Junior.pdf: 14856070 bytes, checksum: 4ef07d1d88440800c23f9c4394aaebfa (MD5) Made available in DSpace on 2021-01-06T20:52:13Z (GMT). No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Vicente_Lopes_da_Silva_Junior.pdf: 14856070 bytes, checksum: 4ef07d1d88440800c23f9c4394aaebfa (MD5) Previous issue date: 2018-06-27 For more than a decade, there are studies aiming gut microbiota, and many findings in literature are still conflicting. In this cross-sectional study, we investigated associations among gut microbiota, inflammatory biomarkers and microvascular reactivity in lean and obese individuals, diabetics or not. Forty-six individuals were included in the study and classified into three groups: controls (C), obese (OB) and obese diabetic or dysglycemic (OBD). We performed the study of microcirculation through LASER-Doppler flowmetry (LDF) and digital tonometry (EndoPat®). Moreover, evaluated the following inflammatory markers: tumor necrosis factor (TNF), interleukin-6 (IL6), bacterial lipopolysaccharide (LPS), LPS binding protein (LBP), leptin, adiponectin, ghrelin, glucagon-like peptide type-1 (GLP1) and retinol binding protein 4 (RBP4). Among the biochemical markers, we evaluated: glucose, insulin, insulin resistance index evaluated by homeostatic model assessment insulin resistance (HOMA-IR) and lipid profile. Some metabolites and markers (glucose, insulin, LPS, ghrelin, GLP1) were measured serially at baseline, 30 and 60 min; after food intake, while others (TNF, IL6, LBP, lipid profile, HOMA-IR, leptin, adiponectin and RBP4) only at the basal time (0 min). The diet of choice was Nutridrink®, a balanced liquid and standardized diet. Similarly, digital tonometry was performed at the initial and final times (60 min) while the LDF was performed continuously throughout the whole evaluation period. We tested the usual diet of each person by food frequency questionnaire, body composition by electric bioimpedance and gut microbiota, by characterization of bacterial 16s DNA. Comparisons were made aiming at the identification of differences between microbiota, metabolism, and inflammation among study groups, possibly caused, by differences in diet and body composition, besides other factors. Correlations were also made to evaluate the association among anthropometric markers of adiposity, metabolic and inflammatory features with gut microbiota. We did not find any statistically significant differences for most of the dietary macronutrients evaluated, possibly reflecting the little difference found in gut microbiota. In an original way, we observed a temporal decrease of the LPS curve in all groups, concurrently, although it only reached statistical significance in the OB group and showed a tendency to significance in the C group. We have established essential correlations among biochemical, inflammatory and microvascular markers that confirm outstanding concepts of metabolic diseases' physiology and their association with systemic inflammation; such as the negative relationship between the area under the glucose curve and the rate of reactive hyperemia, the positive correlation between triglycerides and LPS and IL6. Reinforcing with the complexity of the subject, we did not identify any distinctive pattern of gut microbiota in any of the evaluated groups. We hope this work may contribute to that new hypotheses will be tested in the study of the relationship between gut microbiota and metabolism in humans. A microbiota intestinal tem sido estudada há mais de uma década e muitos achados na literatura ainda são conflitantes. Neste estudo transversal foram avaliadas as associações entre microbiota intestinal, biomarcadores inflamatórios e reatividade microvascular em indivíduos magros e obesos, diabéticos ou não. Quarenta e seis indivíduos foram incluídos no estudo e classificados em três grupos: controles (C), obesos (OB) e obesos diabéticos ou disglicêmicos (OBD). O estudo da microcirculação foi realizado através da LASER-Doppler fluxometria cutânea (LDF) e pela tonometria digital (EndoPat®). Foram avaliados os seguintes marcadores inflamatórios: fator de necrose tumoral (TNF), interleucina-6 (IL6), lipopolissacarídeo bacteriano (LPS), proteína de ligação ao LPS (LBP), leptina, adiponectina, grelina, peptídeo glucagon-símile tipo-1 (GLP1) e proteína de ligação ao retinol 4 (RBP4). Entre os marcadores bioquímicos, avaliamos: glicose, insulina, índice de resistência insulínica avaliado pelo homeostatic model assessment insulin resistance (HOMA-IR) e perfil lipídico. Alguns metabólitos e marcadores (glicose, insulina, LPS, grelina, GLP1) foram dosados seriadamente nos tempos basal, 30 e 60 min; após uma ingesta alimentar, enquanto os demais (TNF, IL6, LBP, perfil lipídico, HOMA-IR, leptina, adiponectina e RBP4) somente no tempo basal (0 min). A alimentação usada correspondeu à ingestão de uma dieta balanceada, líquida e padronizada (Nutridrink®). De maneira análoga, a tonometria digital foi realizada nos tempos inicial e final (60 min) enquanto a LDF foi realizada de maneira contínua durante todo o período de avaliação. A dieta habitual de cada indivíduo foi avaliada pelo questionário de frequência alimentar, a composição corporal pela bioimpedância elétrica e a microbiota intestinal, caracterizada a partir do DNA 16s bacteriano. Foram realizadas comparações objetivando a identificação de diferenças entre microbiota, metabolismo e inflamação entre os grupos de estudo, possivelmente causadas, entre outros fatores, pelas diferenças de dieta e composição corporal. Foram ainda realizadas correlações para avaliar a associação entre marcadores antropométricos de adiposidade, marcadores metabólicos e inflamatórios com a microbiota intestinal. Não foram encontradas diferenças estatisticamente significativas para a maioria dos macronutrientes dietéticos avaliados, o que possivelmente se refletiu na pouca diferença encontrada na microbiota intestinal. De maneira original, observamos um decréscimo temporal da curva de LPS em todos os grupos estudados, de maneira concordante entre si, embora somente tenha alcançado significância estatística no grupo OB e tenha demosntrado uma tendência à significância no grupo C. Conseguimos estabelecer importantes correlações entre marcadores bioquímicos, inflamatórios e microvasculares que corroboram importantes conceitos da fisiologia das doenças metabólicas e sua associação com inflamação sistêmica, como a relação negativa entre a área sob a curva da glicose e o índice de hiperemia reativa, a correlação positiva entre triglicerídeos e LPS e IL6. Corroborando com a complexidade do tema, não identificamos nenhum padrão característico de microbiota intestinal em nenhum dos grupos avaliados. Esperamos que este trabalho possa contribuir para que novas hipóteses sejam testadas no estudo das relações entre a microbiota intestinal com o metabolismo em humanos.

Orientador : Prof. Dr. Hans Graf Coorientadora : Profª. Drª. Fernanda Vaisman Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa : Curitiba, 15/09/2017 Inclui referências : f. 36-39 Resumo: Objetivo: Avaliar retrospectivamente os desfechos clínicos de pacientes com carcinoma diferenciado de tireoide de risco baixo e intermediário tratados com tiroidectomia total (TT) e não submetidos à ablação de remanescente tireoidianos (ART) e compará-los com pacientes que receberam baixa atividade de radioiodo (RAI) (30 mCi). Avaliar o comportamento da tireoglobulina (Tg) em ambos os grupos de pacientes. Material e métodos: Foram analisados 189 pacientes com câncer diferenciado de tireóide (CDT) tratados com TT seguida ou não de 30mCi de RAI para ART em dois centros de referência no Brasil. Resultados: Dos 189 pacientes, 68,8% eram de baixo risco pela classificação da American Thyroid Association (ATA), 30,6% de risco intermediário e 0,6% de alto risco. Oitenta e sete pacientes foram submetidos a ART e 102 não. Os pacientes do grupo submetido à ART tenderam a ser mais jovens e tiveram uma maior frequência de extensão extra-tireoidiana (EET). A ART não teve impacto na resposta à terapia inicial nem em pacientes de baixo (p=0,24) nem em pacientes de risco intermediário (p=0,46). Também não teve impacto no resultado final, a maioria dos pacientes apresentou-se sem evidência de doença (SED) no final do seguimento. A recorrência/persistência da doença foi encontrada em 1,2% do grupo ART e 2% em pacientes tratados apenas com TT (p=0,59). Conclusões: O estudo mostra que, em pacientes de baixo e intermediário risco, ART com 30 mCi não ofereceu benefício em relação aos pacientes não submetidos à ART, em relação à resposta à terapia inicial em cada grupo de risco analisado e também em relação à resultados a longo prazo. Uma resposta excelente ao tratamento pôde ser confirmada pelos valores iniciais e pela tendência da Tg, analisados como preditores de seguimento livre de doença. Palavras-chave: Carcinoma de tireoide - Ablação com radioiodo - Baixa atividade - Tendência tireoglobulina Abstract: Objective: To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). To evaluate the thyroglobulin (Tg) behavior in both groups of patients. Materials and methods: A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30 mCi for RRA or not followed in two references centers in Brazil were analyzed. Results: From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p=0.24) nor in intermediate risk patients (p=0.46) It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up .Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p=0.59). Conclusions: Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes. An excellent response to treatment could be confirmed by the initial values and trend of Tg, analyzed as predictors of disease-free follow-up. Keywords: Thyroid carcinoma - Radioiodine ablation - Low activity - Trend of Thyroglobulin