Introducción: Pocos son los estudios que analizan la relación entre el síndrome metabólico y la enfermedad nodular tiroidea, tema en el que existe un vacío de conocimiento. El objetivo de este estudio es determinar la asociación entre síndrome metabólico y enfermedad nodular tiroidea en un hospital de Lima, Perú. Materiales y métodos: Estudio longitudinal, prospectivo, analítico, observacional de casos y controles, realizado en el Hospital Nacional Edgardo Rebagliati Martins en Lima - Perú. Un total de 182 pacientes se separaron como casos a los pacientes en los que se encontrara por lo menos un nódulo tiroideo detectado por ultrasonografía mayor a 3 mm (n=91) y como controles a los pacientes en los cuales se excluyera la presencia del nódulo de las características descritas por la misma técnica diagnostica (n=91). Se evaluaron el nivel y la fuerza de asociación entre la presencia de síndrome metabólico y cada uno de sus componentes por separado con la presencia de enfermedad nodular tiroidea. Resultados: El análisis bivariado muestra asociación significativa entre la presencia de nódulo tiroideo y síndrome metabólico con un OR de 2.56 (IC: 95% 1.41 a 4.66, p < 0.05). Se evidenció que los niveles de HDL bajo y la glicemia basal alterada se encuentran asociadas significativamente con la presencia de nódulo tiroideo, independientemente de la presencia de síndrome metabólico con OR de 2.81 ( IC: 95% 1.54 a 5.12, p<0.05) y 2.05 (IC:95% 1.10 a 3.78, p<0.05) respectivamente. El análisis multivariado mantuvo la asociación entre nódulo tiroideo y el síndrome metabólico con un OR de 2.96 (IC: 95% 1,47 a 5,95 , p<0.05), así mismo con niveles de HDL bajo con un OR de 2.77 (IC:95 % 1,44 a 5,3, p<0.05) y con la glicemia basal alterada con un OR de 2,23 (IC:95% 1,14 a 4,34, p<0,05). Conclusiones: El Síndrome metabólico incrementa el riesgo de padecer enfermedad nodular tiroidea, específicamente la disminución de valores de HDL y la glicemia basal alterada fueron los factores en los que halló mayor asociación. / Introduction: Few studies analyses the relation between metabolic syndrome and thyroid nodular disease, subject in which there is a knowledge gap. The object of this study is to determinate the association between metabolic syndrome and thyroid nodular disease in a hospital in Lima, Peru. Materials and methods: A longitudinal, prospective, analytic, observational, case - control study, was performed “Hospital Nacional Edgardo Rebagliati Martins” in Lima- Peru. A total of 182 patients were separated as cases in which at least find a thyroid nodule detected by ultrasonography greater than 3 mm ( n = 91) and controls as patients in whom the presence of the node with the characteristics described was excluded by the same technique (n=91). The level and strength of association was evaluated between the presence of metabolic syndrome and each of its components by itself with the presence of thyroid nodular was evaluated. Results: Bivariate analysis shows significant association between the presence of thyroid nodule and metabolic syndrome with an OR of 2.56 (IC:95% 1.41 to 4.66, p < 0.05). Low levels of HDL and impaired fasting glucose are significant associated with the presence of thyroid nodule, independent of the presence of metabolic syndrome, with an OR of 2.81 (IC:95% 1.54 to 5.12, p<0.05) and 2.05 (IC: 95% 1.10 to 3.78, p<0.05) respectively. The multivariate analysis maintained the association between thyroid nodule and metabolic syndrome with an OR of 2.96 (IC: 95% 1,47 to 5,95 , p<0.05); like was the low levels of HDL with an OR of 2.77 ( IC: 95% 1,44 to 5,3, p<0.05) and with impaired fasting glucose with an OR of 2,23 ( IC 95% 1,14 to 4,34, p<0,05).Conclusions: Metabolic syndrome increases de risk of having thyroid nodule disease. Low HDL levels and impaired fasting glucose were the factors with more association.

Orientadores: Denise Engelbrecht Zantut-Wittmann, José Vassallo, Patrícia Sabino Matos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T16:27:46Z (GMT). No. of bitstreams: 1 Maia_FredericoFernandesRibeiro_M.pdf: 3526510 bytes, checksum: 65aa0cfcc1c703f9021864119260a326 (MD5) Previous issue date: 2011 / Resumo: Introdução: A punção aspirativa por agulha fina (PAAF) permanece como o procedimento de referência na avaliação dos nódulos de tireóide. No entanto, em cerca de 10 a 30% dos casos, o diagnóstico citológico é indeterminado. Alguns estudos recentes buscam estabelecer modelos de predição de risco para malignidade no nódulo de tireóide, correlacionando fatores de risco, como idade, sexo, nódulo solitário, níveis de hormônio estimulador da tireóide (TSH), auto-imunidade tireoidiana, nódulos frios e aspectos ultrassonográficos, entre outros. No entanto, os resultados são discordantes, carecendo de novos estudos sobre o tema. Objetivos: Avaliar os parâmetros clínicos, laboratoriais, de ultra-sonografia (US), cintilografia e cito-patologia em nódulos de tireóide, incluindo nódulos de citologia indeterminada, e investigar o papel destes fatores como preditores de malignidade em nódulos de tireóide com resultados citológicos inicialmente benignos submetidos à repetição criteriosa da PAAF. Métodos: Cento e quarenta e três pacientes tratados cirurgicamente em um único centro hospitalar, sendo confirmadas pela histologia que 65% (93) apresentavam nódulos de tireóide benignos e 35%, lesões malignas (50). Todas as citologias foram revisadas por patologista experiente na área e pelo autor, sendo reclassificadas prospectivamente pelo sistema de Bethesda. As variáveis clínicas, laboratoriais, cintilográficas, ultrassonográficas e cito-patológicas foram definidas com base na literatura consensual e comparadas retrospectivamente, definindo-se os marcadores de risco de malignidade após análise de regressão multivariada. Dentre os 143 casos, em 80 estabeleceu-se o diagnóstico de citologia indeterminada, sendo pesquisados os preditores clínicos, ultrassonográficos e variáveis citológicas apontadas pela classificação de Bethesda. Dentre o total dos 143 nódulos, avaliamos a evolução de 35 deles que apresentaram resultados citológicos inicialmente benignos e foram submetidos à PAAF de repetição guiada por US (PAAF-US). Resultados: Entre os grupos de pacientes com diagnóstico histológico de nódulos benignos e malignos, não houve diferença significativa quanto ao sexo, função tireoidiana avaliada por níveis séricos de TSH e T4L, doença auto-imune da tireóide, e padrão cintilográfico, incluindo os nódulos com citologia indeterminada e o grupo de nódulos com citologia inicial benigna. O modelo obtido após análise de regressão multivariada evidenciou como fatores preditivos de malignidade em nódulo de tireóide a idade do paciente acima de 38,5 anos (determinado pela análise da curva ROC), o diâmetro do nódulo (> 2 cm), presença de microcalcificações e irregularidade da borda ao ultra-som, exibindo acurácia de 81,7%. A comparação entre os achados de US mostrou diferenças em relação às características suspeitas de malignidade (microcalcificações, fluxo central, irregularidade da borda e hipoecogenicidade). A prevalência de malignidade nos nódulos com citologia indeterminada (n=80) foi de 25% (20/80). A análise de regressão multivariada mostrou irregularidade da borda ao ultra-som e citologia categoria IV de Bethesda como variáveis significativas para prever a malignidade em nódulos de tireóide com citologia indeterminada, proporcionando 76,9% de acurácia. Quanto aos pacientes com nódulos apresentando citologia inicial benigna e submetidos à repetição da PAAF, obtivemos 10 casos malignos (28,5%) (G1) e 25 nódulos que mantiveram diagnóstico de benignidade (G2) à histologia final. Dentre o total de 35 pacientes, a PAAF de repetição resultou em 28 citologias indeterminadas durante o seguimento, sendo que 23 (82,1%) foram identificadas até a 3ª PAAF-US. O intervalo entre a 1ª e 3ª PAAF-US foi de 13 meses (mediana). A análise dos dados obtidos pelos laudos do estudo ultrassonográfico mostrou diferença significativa entre as características suspeitas no G1: microcalcificações, irregularidade da borda, fluxo central, hipoecogenicidade, em relação ao G2. Conclusões: Verificamos maior risco de carcinoma em nódulos de tireóide de pacientes com idade acima de 39 anos e US com características suspeitas de malignidade. O estudo de ultra-som e resultado categoria IV de Bethesda à citologia mostraram alta acurácia para predição de malignidade em nódulos com citologia indeterminada. Em nódulos com citologia inicial benigna, seguidos ambulatorialmente, observou-se maior taxa de malignidade na presença de US suspeito inicial, indicando que a repetição da PAAF-US por até duas vezes, em um período médio de 13 meses após a 1ª punção pode elevar a taxa de diagnóstico. Estes resultados podem ser usados para orientar a tomada de decisões cirúrgicas com maior propriedade / Abstract: Background: Althout fine-needle aspiration cytology (FNAC) is considering the gold standard for evaluating thyroid nodules, in about 10-30% of the cases, cytology is indeterminate. Some studies in literature showed different models of prediction for thyroid nodule malignancy, including age, gender, solitary nodule, thyrotropin (TSH) levels, thyroid auto-immunity, cold nodules and suspect ultrasound aspects. However, the adequate predictor model for clinical application and surgical guidance for thyroid nodule management is not well established in medical literature. Objectives: This study aimed to evaluate clinical, laboratory, ultrasound (US) and scintigraphyc parameters in thyroid nodule. This study still aimed to investigate the role of these predictors to determine malignancy in thyroid nodules with indeterminate cytology and nodules with initially benign cytological result at 1st presentation. Methods: This study enrolled 143 patients surgically treated in a single center, 65% (93) of benign thyroid nodule vs. 35% (50) malignant lesions at final histology (1998 to 2008). The clinical, laboratory, scintigraphyc and US features were retrospectively compared and a predictor model was designed after multivariate analysis to predict malignancy in this group. 80/143 selected cases of indeterminate cytology were prospective studied and re-classified by Bethesda System. The clinical, scintigraphyc, sonographic and cytological classification (Bethesda) variables were analyzed in this specific group. At finally, we studied 35/143 nodules with initially benign cytological result who underwent serious ultrasound guided re-biopsy [fine-needle aspiration cytology (FNAC-US)]. Results: Between the benign and malignant nodules groups, there were no differences in gender, serum TSH and FT4 levels, thyroid auto-antibodies, thyroid dysfunction and scintigraphyc result, including indeterminate cytology group and the specific group of thyroid nodules with initially benign cytology result. Sonographic study showed differences between the presences of suspected characteristics of nodule in the group of malignant lesions: microcalcifications, central flow, border irregularity and hypoechogenicity. The model obtained after multivariate analysis, showed age (>39yrs), border irregularity, microcalcifications and nodule size as factors predictive of malignancy, featuring 81.7% of accuracy. In the specific group of indeterminate cytology, there was a 25% prevalence of malignancy (20/80). The model obtained after multivariate analysis demonstrated border irregularity by US and category IV of Bethesda as significant variables to predict malignancy in indeterminate thyroid nodules (76.9% of accuracy). By means of surgery, malignancy histology results were confirmed in 10 (28.5%) cases (G1) vs. 25 (71.5%) benign nodules (G2) in the group of nodules with initially cytological result. Of the 28/35 indeterminate FNAC result during the follow up, 23 (82.1%) was identified until the 3rd FNAC-US. The interval between 1st and 3rd re-biopsy was 13 months (median). Sonographic studies showed malignant suspected US features in G1: microcalcifications, central flow, hypoechogenicity and border irregularity. Conclusions: This study confirmed significantly increased risk for malignancy in patients over 39 years and suspects US features. The ultrasound study and category IV of Bethesda were correlated to malignancy in thyroid nodules with indeterminate cytology. This study demonstrated malignancy rate in thyroid nodules with first benign cytologic result and suspicious US features of malignancy and suggests repeating FNAC-US in this group of nodules for at least two times (until the 3rd FNAC) in about 13 months horizon. These findings can be used to guide surgical decision making / Mestrado / Clinica Medica / Mestre em Clinica Medica

Thyroid nodules represent a very common pathology. Using modern high-resolution ultrasound, nodules could be found in up to 68 % of patients. The most important task is the diagnosis of thyroid cancer which represents only about 5-15 % of nodules, however the incidence is still growing. Even with the use of a fine needle aspiration biopsy, it is not always possible to decide on the biological nature of the nodule. A significant proportion of such patients have to undergo thyroid surgery for diagnostic reason. Thyroid surgery is associated with risks to the patient and financial costs to the health-care system. In recent decades, the efforts to improve non-invasive diagnostics of thyroid nodules have been made. The thyroid elastography and thyroid autoimmunity are among the examined risk parameters. Using real-time strain elastography, thyroid carcinomas elasticity has been significantly reduced compared to benign thyroid nodules in our group of patients. The elastography of thyroid nodules can be used as a suitable complement to conventional sonographic examination. In our work, the combination of both methods (conventional ultrasound and elastography) increased the negative predictive value compared to both methods individually. The results of our work further indicate that, in case of absence of...

Nódulos de tireoide são achados clínicos comuns e, atualmente, o método diagnóstico de escolha para diferenciar lesões benignas de lesões malignas é a análise citopatológica dos nódulos através de punção aspirativa por agulha fina (PAAF). Estudos prévios já indicaram que os níveis séricos de TSH podem estar associados ao risco de malignidade nodular. O objetivo deste estudo foi avaliar se o TSH sérico é um preditor de malignidade em nódulos de tireoide em pacientes submetidos à PAAF. A amostra contemplou 100 indivíduos puncionados consecutivamente no Centro de Pronto Diagnóstico Ambulatorial, CPDA, HCPA e que apresentavam níveis de TSH dentro da normalidade. Todos os pacientes foram submetidos à PAAF da tireoide com controle ultrassonográfico e tiveram, posteriormente, a análise citopatológica da PAAF e a avaliação histopatológica do bloco celular. A análise estatística baseou-se em dados de frequências e testes não-paramétricos foram utilizados para correlacionar as variáveis. A população de estudo foi composta por 100 pacientes, sendo 89 mulheres e 11 homens. A média de idade foi de 54,1 ± 14,2 anos e o tamanho médio dos nódulos foi de 2.53 ± 1.36 centímetros. Vinte e seis % destes pacientes apresentavam algum tipo de doença tireoidiana prévia. A média do nível de TSH sérico entre os 100 indivíduos foi de 1.81 ± 1.08 uUI/mL. De acordo com o diagnóstico citopatológico da PAAF complementado pelos achados do bloco celular foram classificados como malignos 8% dos nódulos, 70% benignos, 11% suspeitos/ indeterminados, 8% insuficientes e 3% lesões foliculares. A média de TSH para os grupos maligno, benigno, suspeito/indeterminado, insuficiente e lesão folicular foi de, respectivamente, 2.48, 1.59, 2.21, 2.35 e 2.20 uUI/ml (p>0.05). Não houve diferença estatística significante entre os grupos diagnósticos avaliados, apesar de haver uma variação entre os níveis de TSH entre os grupos refletindo, provavelmente, o pequeno tamanho da amostra. / Thyroid nodules are common and currently the first choice of investigation in distinguishing benign from malignant disease is the cytological analysis of fine needle aspiration biopsy (FNAB). Previous studies have indicated that serum TSH levels might be associated with the likelihood of malignancy. The aim of this study was to evaluate whether serum TSH is a predictor of malignancy of thyroid nodules in patients undergoing FNAB. One hundred consecutive patients, who underwent FNAB as part of clinical investigation of thyroid nodule in a multidisciplinary setting tertiary hospital, underwent ultrasonography followed by FNAB, cytology and cell block analysis. Independent-Samples Kruskal-Wallis test was used to compare the groups. The study population comprised of 89 female and 11 male patients. The mean age was 54.1 ± 14.2 years. 26% had previous thyroid disease. Mean TSH levels was 1.81 ± 1.08 uUI/mL and the mean nodule size was 2.53 ± 1.36cm. Final cytology/cell block diagnosis classified 8% as malignant, 70% as benign, 11% suspicious/indeterminate, 8% insufficient and 3% follicular lesion. The mean TSH values for malignant, benign, suspect, insufficient and follicular lesion group were as follows: 2.48, 1.59, 2.21, 2.35 and 2.20 uUI/ml, respectively. No statistical significance was detected between TSH levels and final cytology/cell block diagnosis, possibly reflecting the small sample size (P>0.05). We observed a variation between TSH levels among the groups covered in this study, but there was no statistically significant difference among them.

Somatostatinrezeptoren (SSTRs) hemmen die Hormonsekretion und Proliferation in einer Vielzahl von neuroendokrinen Geweben. Eine erhöhte Dichte dieser Rezeptoren konnte im Zusammenhang mit verschiedenen Schilddrüsenpathologien nachgewiesen werden. Mittels Gallium-68 (Ga-68) DOTA-Phe(1)-Tyr(3)-Octreotid (DOTATOC) Positronen-Emissions-Tomographie (PET), einem nuklearmedizinischen Untersuchungsverfahren, ist die funktionelle Darstellung der SSTR-Expression in vivo möglich. Unser Studienziel war es, den Ga-68-DOTATOC Uptake als Korrelat für die SSTR-Dichte in gesundem und pathologisch verändertem Schilddrüsengewebe zu quantifizieren. Die Ga-68-DOTATOC PET Bilder von insgesamt 165 Patienten wurden mittels (ROI)- Technik ausgewertet und die Studienteilnehmer verschiedenen Schilddrüsenpathologiegruppen zugeordnet. Ergänzend erfolgte eine schilddrüsenspezifische Anamnese, eine Ultraschalluntersuchung der Schilddrüse, sowie die Bestimmung der Laborparameter TSH and Anti-TPO-Antikörper für jeden Studienteilnehmer. Normale Schilddrüsen, ohne eine erkennbare Pathologie, zeigten eine klar nachweisbare SSTR-Expression mit einer großen Spannweite innerhalb der ermittelten TBR-Werte. In acht Fällen war es möglich, Folgeuntersuchungen von Patienten mit normaler Schilddrüse, aber erhöhten Uptake-Werten in der Gallium-68-DOTATOC PET Untersuchung, auszuwerten (TBR>4). Der Abstand der durchgeführten Kontrollen lag im Mittel bei 11,4 Monaten mit einer Spannweite von sechs bis vierzehn Monaten. In keiner der durchgeführten Kontrolluntersuchungen konnte eine neu aufgetretene Schilddrüsenpathologie nachgewiesen werden. Eine erhöhte SSTR-Dichte (TBR>3.4) zeigte sich zudem im Fall von autonomen Adenomen, disseminierten Schilddrüsenautonomien, sowie bei den meisten Patienten (fünf von acht) mit aktiven Hashimoto-Thyreoiditiden. Vor allem die gesunden Schilddrüsen von männlichen Studienteilnehmern fielen mit erhöhten Radiotraceruptake-Werten in der durchgeführten Untersuchung auf. Diese unterschieden sich signifikant von der Gruppe weiblicher Studienteilnehmer mit normaler Schilddrüse. Patienten ohne eine nachweisbare Schilddrüsenpathologie, aber mit erhöhten Uptake-Werten (TBR>4.0), zeigten in den späteren Kontrolluntersuchungen keinen Hinweis auf eine sich entwickelnde Pathologie, speziell keine Hinweise auf eine sich entwickelnde Hashimoto-Thyreoidititis. Alle Patienten mit verschiedenen Formen der Schilddrüsenautonomie zeigen einen erhöhten DOTATOC Uptake in unserer Studie.

Nódulos de tireoide são achados clínicos comuns e, atualmente, o método diagnóstico de escolha para diferenciar lesões benignas de lesões malignas é a análise citopatológica dos nódulos através de punção aspirativa por agulha fina (PAAF). Estudos prévios já indicaram que os níveis séricos de TSH podem estar associados ao risco de malignidade nodular. O objetivo deste estudo foi avaliar se o TSH sérico é um preditor de malignidade em nódulos de tireoide em pacientes submetidos à PAAF. A amostra contemplou 100 indivíduos puncionados consecutivamente no Centro de Pronto Diagnóstico Ambulatorial, CPDA, HCPA e que apresentavam níveis de TSH dentro da normalidade. Todos os pacientes foram submetidos à PAAF da tireoide com controle ultrassonográfico e tiveram, posteriormente, a análise citopatológica da PAAF e a avaliação histopatológica do bloco celular. A análise estatística baseou-se em dados de frequências e testes não-paramétricos foram utilizados para correlacionar as variáveis. A população de estudo foi composta por 100 pacientes, sendo 89 mulheres e 11 homens. A média de idade foi de 54,1 ± 14,2 anos e o tamanho médio dos nódulos foi de 2.53 ± 1.36 centímetros. Vinte e seis % destes pacientes apresentavam algum tipo de doença tireoidiana prévia. A média do nível de TSH sérico entre os 100 indivíduos foi de 1.81 ± 1.08 uUI/mL. De acordo com o diagnóstico citopatológico da PAAF complementado pelos achados do bloco celular foram classificados como malignos 8% dos nódulos, 70% benignos, 11% suspeitos/ indeterminados, 8% insuficientes e 3% lesões foliculares. A média de TSH para os grupos maligno, benigno, suspeito/indeterminado, insuficiente e lesão folicular foi de, respectivamente, 2.48, 1.59, 2.21, 2.35 e 2.20 uUI/ml (p>0.05). Não houve diferença estatística significante entre os grupos diagnósticos avaliados, apesar de haver uma variação entre os níveis de TSH entre os grupos refletindo, provavelmente, o pequeno tamanho da amostra. / Thyroid nodules are common and currently the first choice of investigation in distinguishing benign from malignant disease is the cytological analysis of fine needle aspiration biopsy (FNAB). Previous studies have indicated that serum TSH levels might be associated with the likelihood of malignancy. The aim of this study was to evaluate whether serum TSH is a predictor of malignancy of thyroid nodules in patients undergoing FNAB. One hundred consecutive patients, who underwent FNAB as part of clinical investigation of thyroid nodule in a multidisciplinary setting tertiary hospital, underwent ultrasonography followed by FNAB, cytology and cell block analysis. Independent-Samples Kruskal-Wallis test was used to compare the groups. The study population comprised of 89 female and 11 male patients. The mean age was 54.1 ± 14.2 years. 26% had previous thyroid disease. Mean TSH levels was 1.81 ± 1.08 uUI/mL and the mean nodule size was 2.53 ± 1.36cm. Final cytology/cell block diagnosis classified 8% as malignant, 70% as benign, 11% suspicious/indeterminate, 8% insufficient and 3% follicular lesion. The mean TSH values for malignant, benign, suspect, insufficient and follicular lesion group were as follows: 2.48, 1.59, 2.21, 2.35 and 2.20 uUI/ml, respectively. No statistical significance was detected between TSH levels and final cytology/cell block diagnosis, possibly reflecting the small sample size (P>0.05). We observed a variation between TSH levels among the groups covered in this study, but there was no statistically significant difference among them.

La grande fréquence des nodules thyroïdiens et la relative agressivité des traitements conventionnels ont motivé l'étude d'une méthode non invasive utilisant des Ultrasons Focalisés (HIFU). Matériel et méthodes : Les HIFU ont été testés initialement sur un modèle de brebis afin de réaliser une lésion thyroïdienne. Ces études animales ont été suivies de trois études cliniques sur des patients porteurs de nodules thyroïdiens. L'appareil utilisé associe un système d'imagerie échographique et un système de tir. Résultats : Le réglage des paramètres de tir et la mise au point de plusieurs prototypes chez l'animal a permis d'obtenir l'autorisation du comité d'éthique pour les expérimentations humaines. Ces essais ont démontré la capacité des HIFU à détruire des nodules thyroïdiens. Le dernier appareil mis au point a obtenu le marquage CE. Conclusion : Cette technique permet de réaliser une nécrose localisée dans un lobe thyroïdien et de détruire des nodules. Ces résultats doivent être confirmés par des études plus larges, mais ont été assez encourageants pour justifier la création d'une entreprise dédiée à la mise au point d'un appareil spécifique en collaboration avec l'INSERM / -

Nódulos de tireoide são achados clínicos comuns e, atualmente, o método diagnóstico de escolha para diferenciar lesões benignas de lesões malignas é a análise citopatológica dos nódulos através de punção aspirativa por agulha fina (PAAF). Estudos prévios já indicaram que os níveis séricos de TSH podem estar associados ao risco de malignidade nodular. O objetivo deste estudo foi avaliar se o TSH sérico é um preditor de malignidade em nódulos de tireoide em pacientes submetidos à PAAF. A amostra contemplou 100 indivíduos puncionados consecutivamente no Centro de Pronto Diagnóstico Ambulatorial, CPDA, HCPA e que apresentavam níveis de TSH dentro da normalidade. Todos os pacientes foram submetidos à PAAF da tireoide com controle ultrassonográfico e tiveram, posteriormente, a análise citopatológica da PAAF e a avaliação histopatológica do bloco celular. A análise estatística baseou-se em dados de frequências e testes não-paramétricos foram utilizados para correlacionar as variáveis. A população de estudo foi composta por 100 pacientes, sendo 89 mulheres e 11 homens. A média de idade foi de 54,1 ± 14,2 anos e o tamanho médio dos nódulos foi de 2.53 ± 1.36 centímetros. Vinte e seis % destes pacientes apresentavam algum tipo de doença tireoidiana prévia. A média do nível de TSH sérico entre os 100 indivíduos foi de 1.81 ± 1.08 uUI/mL. De acordo com o diagnóstico citopatológico da PAAF complementado pelos achados do bloco celular foram classificados como malignos 8% dos nódulos, 70% benignos, 11% suspeitos/ indeterminados, 8% insuficientes e 3% lesões foliculares. A média de TSH para os grupos maligno, benigno, suspeito/indeterminado, insuficiente e lesão folicular foi de, respectivamente, 2.48, 1.59, 2.21, 2.35 e 2.20 uUI/ml (p>0.05). Não houve diferença estatística significante entre os grupos diagnósticos avaliados, apesar de haver uma variação entre os níveis de TSH entre os grupos refletindo, provavelmente, o pequeno tamanho da amostra. / Thyroid nodules are common and currently the first choice of investigation in distinguishing benign from malignant disease is the cytological analysis of fine needle aspiration biopsy (FNAB). Previous studies have indicated that serum TSH levels might be associated with the likelihood of malignancy. The aim of this study was to evaluate whether serum TSH is a predictor of malignancy of thyroid nodules in patients undergoing FNAB. One hundred consecutive patients, who underwent FNAB as part of clinical investigation of thyroid nodule in a multidisciplinary setting tertiary hospital, underwent ultrasonography followed by FNAB, cytology and cell block analysis. Independent-Samples Kruskal-Wallis test was used to compare the groups. The study population comprised of 89 female and 11 male patients. The mean age was 54.1 ± 14.2 years. 26% had previous thyroid disease. Mean TSH levels was 1.81 ± 1.08 uUI/mL and the mean nodule size was 2.53 ± 1.36cm. Final cytology/cell block diagnosis classified 8% as malignant, 70% as benign, 11% suspicious/indeterminate, 8% insufficient and 3% follicular lesion. The mean TSH values for malignant, benign, suspect, insufficient and follicular lesion group were as follows: 2.48, 1.59, 2.21, 2.35 and 2.20 uUI/ml, respectively. No statistical significance was detected between TSH levels and final cytology/cell block diagnosis, possibly reflecting the small sample size (P>0.05). We observed a variation between TSH levels among the groups covered in this study, but there was no statistically significant difference among them.

Background: Reported results for thyroid nodule fine-needle aspiration (FNA) cytology mainly originate from tertiary centers. However, thyroid nodule FNA cytology is mainly performed in primary care settings for which the distribution of FNA Bethesda categories and their respective malignancy rates are largely unknown. Therefore, this study investigated FNA cytology malignancy rates of a large primary care setting to determine to what extent current evidence-based strategies for the malignancy risk stratification of thyroid nodules are applied and applicable in such primary care settings. Methods: In a primary care setting, 9460 FNAs of thyroid nodules were retrospectively analyzed from 8380 patients evaluated by one cytologist (I.R.) during a period of two years. The 8380 FNA cytologies were performed by 64 physicians in different private practices throughout Germany in primary care settings. Results: The cytopathologic results were classified according to theBethesda Systemas non-diagnostic in 19%, cyst/ cystic nodule in 21%, benign (including thyroiditis) in 48%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 6%, follicular neoplasms/suspicious for follicular neoplasm (FN/SFN) in 4%, suspicious for malignancy (SFM) in 1%, and malignant in 1%. The proportion of patients proceeding to surgery or with a follow-up of at least one year and the observed risks of malignancy were 22%/8% for AUS/FLUS, 69%/ 17% for FN/SFN, 78%/86% for SFM, and 71%/98% for malignant. For 112 cytologically suspicious and malignant FNAs, there were 102 true positives and 10 false positives, considering histology as gold standard. Conclusion: At variance with other data mostly originating from tertiary centers, these data demonstrate low percentages for malignant, SFM, FN/SFN, and AUS/FLUS, and high percentages for cysts/cystic nodules in this primary care setting in Germany. The risks of malignancy for malignant, SFM, AUS/FLUS, and FN/SFN FNA cytologies are according to Bethesda recommendations.:1 ABKÜRZUNGSVERZEICHNIS ............................................................................................................... 1 2 EINFÜHRUNG .......................................................................................................................................... 2 2.1 DAS ORGAN SCHILDDRÜSE ................................................................................................................................ 3 2.1.1 Anatomie der Schilddrüse ......................................................................................................................... 3 2.1.2 Funktion der Schilddrüse .......................................................................................................................... 3 2.2 SCHILDDRÜSENKNOTEN ..................................................................................................................................... 4 2.2.1 Epidemiologie der Schilddrüsenknoten .............................................................................................. 4 2.2.2 Ätiologie der Schilddrüsenknoten ......................................................................................................... 4 2.2.3 Jodversorgung in Deutschland ................................................................................................................ 5 2.2.4 Symptomatik der Schilddrüsenknoten ................................................................................................ 5 2.2.5 Diagnostik von Schilddrüsenknoten ..................................................................................................... 6 2.2.6 Die Feinnadelaspirationszytologie (FNA) ......................................................................................... 9 2.2.7 Therapeutisches Management ............................................................................................................ 11 2.3 DIE ABLEITUNG DER RATIONALE .................................................................................................................. 13 3 PUBLIKATIONSMANUSKRIPT ........................................................................................................ 14 4 ZUSAMMENFASSUNG ......................................................................................................................... 22 4.1 SCHLUSSFOLGERUNG ....................................................................................................................................... 26 5 LITERATURVERZEICHNIS ................................................................................................................ 28 6 ANLAGEN ............................................................................................................................................... 33 6.1 TABELLE 1: MALIGNITÄTSRISIKO NACH SONOGRAPHISCHEM ERSCHEINUNGSBILD UND FNA INDIKATION FÜR SCHILDDRÜSENKNOTEN (36) ........................................................................................................... 33 6.2 TABELLE 2: DAS BETHESDA SYSTEM FOR REPORTING THYROID CYTHOPATHOLOGY. DIAGNOSTISCHE KATEGORIEN UND MALIGNITÄTSRISIKEN (36) ........................................................................................................... 34 6.3 ABBILDUNG 1: ALGORITHMUS FÜR PATIENTEN MIT SCHILDDRÜSENKNOTEN NACH DER AMERICAN THYROID ASSOCIATION (36) .......................................................................................................................................... 35 6.4 DARSTELLUNG DES EIGENEN BEITRAGS AN DER PUBLIKATION ............................................................... 36 6.5 ERKLÄRUNG ÜBER DIE EIGENSTÄNDIGE ABFASSUNG DER ARBEIT .......................................................... 54 6.6 LEBENSLAUF ..................................................................................................................................................... 55 6.7 VERZEICHNIS WISSENSCHAFTLICHER VERÖFFENTLICHUNGEN ................................................................ 56 6.8 DANKSAGUNG ................................................................................................................................................... 57

<p>Uvod: Hirur&scaron;ko lečenje nodozne bolesti &scaron;titaste žlezde predstavlja jednu od najče&scaron;će izvođenih operacija u endokrinoj hirurgiji. Pored klasičnih hirur&scaron;kih metoda, poslednjih godina su se pojavile različite tehnike minimalno invazivne tireoidektomije kao rezultat sveukupnog trenda razvoja minimalno invazivnih hirur&scaron;kih tehnika. Kliničke indikacije i prednosti izvođenja minimalno invazivne video-asistirane tiroidektomije (MIVAT) u odnosu na klasičnu hirur&scaron;ku tehniku u lečenju nodozne bolesti &scaron;titaste žlezde su i dalje nedovoljno definisane i u fokusu su savremenih istraživanja. Cilj istraživanja je procena učestalosti komplikacija (intraoperativno i postoperativno krvarenje, pareza i paraliza laringealnog živca, hipoparatireoidizam) tokom i nakon minimalno invazivne tireoidektomije u nodoznim benignim oboljenjima &scaron;titaste žlezde uz poređenje sa klasičnom tireoidektomijom, da se ispita intenzitet postoperativnog bola, merenjem pomoću vizuelno analogne skale tokom sedam postoperativnih dana, nakon minimalno invazivne tireoidektomije u nodoznim benignim oboljenjima &scaron;titaste žlezde uz poređenje sa klasičnom tireoidektomijom, kao i da se ispita dužina bolničkog boravka nakon minimalno invazivne tireoidektomije u nodoznim benignim oboljenjima &scaron;titaste žlezde uz poređenje sa klasičnom tireoidektomijom. Metodologija: Ispitivanje je sprovedeno kao prospektivna, kontrolisana randomizirana studija, u trajanju od novembra 2014. do aprila 2016. godine i obuhvatila je analizu 100 pacijenata operisanih na Klinici za grudnu hirurgiju Instituta za plućne bolesti Vojvodine zbog nodozne bolesti &scaron;titaste žlezde. Svi ispitanici su podeljeni u dve osnovne grupe u odnosu na operativnu tehniku: klasična metoda (KM) i minimalno invazivna videoasistirana metoda (MIVAM). Faze u toku ispitivanja su obuhvatile: analizu podataka o preoperativnim morfo-funkcionalnim dijagnostičkim testovima za nodoznu bolest &scaron;titaste žlezde (karakteristike ultrazvučnog nalaza nodozne promene i vrednosti volumena izmenjenog režnja &scaron;titaste žlezde), nalaz citolo&scaron;kog pregleda punktata tiroidnog nodusa dobijenog tankom iglom, laboratorijski pokazatelji poremećaja &scaron;titaste žlezde u cilju definisanja funkcionog stanja, odnosno postojanja autoimunog oboljenja &scaron;titaste žlezde; analizu perioperativnih karakteristika hirur&scaron;kih metoda [dužina incizije (cm), operativno vreme (min), težina odstranjenog patoanatomskog supstrata (gr), intraoperativni gubitak krvi (ml)], analiza ranih postoperativnih komplikacija (krvarenje i hematom, povreda donjeg rekurentnog laringealnog živca (nalaz direktne laringoskopije na kraju operacije), hipokalcemija, kolaps traheje, edem larinksa, serom, infekcija, dehiscencija], analiza nehirur&scaron;kih komplikacija, dužina hospitalizacije u danima, intenzitet i dužina trajanja postoperativnih bolova [(upotreba vizuelno analogne skale (VAS) bola 1, 2 i 7 postoperativnog dana)], kasne postoperativne komplikacije (6 meseci nakon operacije), stepen zadovoljstva esteskim rezultatom (anketa sprovedena na kontrolnom pregledu 6 meseci nakon operacije-kozmetski skor). Rezultati: U periodu izvođenja studije od novembra 2014. do aprila 2016. godine, nakon primene kriterijuma za uključivanje/isključivanje iz studije od 175 preostalo je 102 ispitanika, zbog patohistolo&scaron;kog nalaza maligniteta ex tempore biopsije kod jednog pacijenta, a kao i zbog intraoperativno uočenih izraženih adhezivnih promena kod jednog pacijenta urađena je konverzija, odnosno promena operativne tehnike minimalno invazivne u klasičnu metodu. U statističku obradu je uključeno ukupno 100 ispitanika podeljenih u dve grupe: grupu I bolesnika - KM (n = 50) i grupu II bolesnika - MIVAM (n = 50). U ispitivanje je ukupno uključeno 78 žena i 22 mu&scaron;karca. U odnosu na polnu strukturu u ispitivanim grupama nije uočena postojanje statistički značajne zastupljenosti u zastupljenosti mu&scaron;kog (p = 0,18), odnosno ženskog pola (p = 0,59). Takođe, uočeno je da među grupama ispitanika ne postoji statistički značajna razlika po godinama života (p = 0,16). Nije bilo statistički značajne razlike između ispitivanih grupa u odnosu na vrstu oboljenja &scaron;titaste žlezde i funkcioni status, kao ni u odnosu na ultrazvučne karakteristike solitarnog (dominantnog) nodusa kod ispitanika (veličine nodusa, ehogenost nodusa, ivica nodusa, kalcifikacija, vaskularizacije), u odnosu na citolo&scaron;ku dijagnozu aspirata uboda tankom iglom (benigni, neodgovarajući, sumnjivi), te u odnosu na volemn izmenjenog režnja. Analizom perioperativnih pokazatelja hirur&scaron;kih metoda u grupi MIVAM je utvrđena statički značajno manja dužina incije u odnosu na KM grupu (2,0 &plusmn; 0,5 cm vs. 7 &plusmn; 1,9 cm, p = 0,00), dok se težina patoanatomskog supstata (18,3 &plusmn; 6,4 vs. 19,6 &plusmn; 5,2 gr, p = 0,21), operativno vreme za izvođenje lobektomije (54 &plusmn; 14 vs. 61 &plusmn; 16 min, p = 0,25), odnosno operativno vreme za izvođenje tireoidektomije (72 &plusmn; 27 vs. 85 &plusmn; 24 min, p = 0,36) nisu statitički značajno razlikovali između ispitivanih grupa. U grupi MIVAM, rane postoperativne komplikacije (krvarenje, povreda donjeg rekurentnog laringealnog živca I hipokalcemija) su se javile kod 8% (4/50), a u KM grupi kod je 10% (5/50), &scaron;to nije bilo statistički značajno (p = 0,72). U odnosu na kasne postoperativne komplikacije, samo je kod jednog pacijenta iz MIVAM grupe registrovano postojanje keloida, dok se (trajni hipoparatiroidizam, recidivantni hipertiroidizam, reakcija na strano telo) nije zabeleženo. Nije uočena statistički značajna razlika (p &gt; 0,005 za sve) u zastupljenosti vrste nalaza patohistolo&scaron;kog pregleda odstranjenog supstrata (koloidna struma, folikularni adenoma, cista, papilarni karcinom i Hashimoto tiroiditis). Pacijenti iz MIVAM grupe statistički značajno imaju manji prosečan intenzitet bola po VAS skali u vremenskim intervalima nakon operacije 6h, 24h i 48 h (p &lt; 0,05, za sve). Ukupni kozmetski skor je bio statistički značajno vi&scaron;i u MIVAM grupi u odnosu na KM grupu (18,9 &plusmn; 1,4 vs. 15,8 &plusmn; 1,3, p = 0,00). Zaključci:Učestalost ranih postoperativnih komplikacija (intraoperativno i postoperativno krvarenje, pareza i paraliza laringealnog živca, hipokalcemija) je bez signifikantne razlike, praktično podjedanaka kod pacijenata operisanih minimalno invazivnom metodom u komparaciji sa klasičnom metodom. Prosečna dužina trajanja minimalno invazivne tireoidektomije i klasične tireoidektomije je bez signifikatne razlike, &scaron;to može govoriti o odgovarajućem nivou hirur&scaron;ke tehnike koji omogućava prednosti minimalne invazivnosti kao hirur&scaron;kog principa. Dužina hospitalizacije nakon minimalno invazivne tireoidektomije je značajno kraća u odnosu na klasičnu tireoidektomiju, &scaron;to značajno doprinosi sveukupnom oporavku pacijenta, a na taj način i tro&scaron;kovi lečenja se umanjuju.Primena minimalno invazivne tireoidektomije u odnosu na klasičnu tireoidektomiju, dovodi do smanjenja subjektivnog osećaja postoperativnog bola, u toku hospitalizacije (6 i 24 h), kao i sedam dana nakon intervencije. Kozmetski skor, kao pokazatelj zadovoljstva pacijenta sa izgledom ožiljka je statistički značano vi&scaron;i kod pacijenata koji su operisani minimalno invazivnom hirur&scaron;kom tehnikom u odnosu na pacijente koji su operisani klasičnom metodom, &scaron;to je u odnosu na predominantnu zastupljenost ženskog pola u ispitivanim grupama od posebnog značaja pri odabiru terapijskog tretmana. Prema rezultatima studije, nameće se opravdanost i potreba uvođenja minimalno invazivne tiroidektomije u standardnu kliničku praksu kao metode hirur&scaron;kog lečenja nodozne bolesti &scaron;titaste žlezde kod pacijenata sa urednim funkcionim statusom &scaron;titaste žlezde, kod kojih je veličina solitarnog/dominantnog nodusa do 35 mm.</p> / <p>INTRODUCTION: Surgical treatment of nodular thyroid disease is one of the most commonly performed procedures in endocrine surgery. In addition to traditional surgical methods, different techniques of minimally invasive thyreoid surgery have been developed. Clinical indications for the surgical treatment of nodular thyroid disease with minimally invasive video-assisted surgical technique are still insufficiently defined. The aim of the study was to estimate the incidence of complications (intraoperative and postoperative bleeding, paresis and paralysis of the laryngeal nerve, hypoparathyroidism) during and after minimally invasive thyroidectomy in benign nodular thyroid disease with a comparison with conventional thyroidectomy, to examine the intensity of postoperative pain, measured by a visual analog scale for seven postoperative days after surgery, as well as to examine the length of hospitalisation after minimally invasive thyroidectomy with a comparison with conventional thyroidectomy. METHODOLOGY: The study was conducted as a prospective, randomized controlled studies, from November 2014 to April 2016 and included the analysis of 100 patients operated at the Clinic for Thoracic Surgery, Institute for Pulmonary Diseases due to nodular thyroid disease. All subjects were divided into two basic groups according to the surgical technique: classical method (KM) and minimally invasive video-assisted method (MIVAM). Stages during the study included: analysis of data on preoperative morpho-functional diagnostic tests for thyroid disease (characteristic ultrasound findings, nodule caracteristics, volume of exchanged thyroid gland lobe), cytologic examination of aspirates of thyroid nodules obtained by fine needle, laboratory indicators of thyroid disorders gland in order to define the functional status and the presence of autoimmune thyroid disease; analysis of perioperative characteristics of surgical methods [incision length (cm), operative time (min), weight of removed pathoanatomic substrate (gr), intraoperative blood loss (ml)], the analysis of early postoperative complications (bleeding and hematoma, injury to lower recurrent laryngeal nerve (finding direct laryngoscopy at the end of the operation), hypocalcemia, the collapse of the trachea, laryngeal edema, seroma, infection, dehiscence] analysis nonsurgical complications, length of hospitalisation in hours, the intensity and duration of postoperative pain [(use of the visual analog scale (VAS) pain 1, 2 and 7 postoperative days)], late postoperative complications (6 months after surgery), the level of aesthetic satisfaction score (on control examination 6 months after surgery-cosmetic score). RESULTS: In the period of the study from November 2014 to April 2016, from 175 patients with nodular thyreoid disease 102 was observed after application of the inclusion/exclusion criteria. Since in the further analysis two patients was exluded (due to histological findings of malignancy ex tempore biopsy in one patient, and because of a perceived intraoperatively expressed adhesive changes in one patient underwent conversion) in statistical analysis patients were devided into two groups: group I patients - KM (n = 50) and group II patients - MIVAM (n = 50). The study included a total of 78 women and 22 men, it was observed that between the groups there was no statistically significant difference according to age (p = 0,16). There were no statistically significant differences between the groups in terms of the type of thyroid gland function and functional status, as well as in relation to the ultrasonographic characteristics of solitary (dominant) nodule in the subjects (the size of nodules, echogenicity nodes, the edge nodes, calcification, vascularization), the cytological diagnosis of fine needle aspiration puncture (benign, inappropriate, suspicious) and with respect to the lobe volume. The analysis of indicators of perioperative surgical methods in the group MIVAM was significantly smaller length compared to KM group (2,0 &plusmn; 0,5 cm vs. 7 &plusmn; 1,9 cm, p = 0,00), until the weight of pathoanatomic supstrate (18,3 6 &plusmn; 4 vs. 19 &plusmn; 6 5 2 g, p = 0,21), the operating time for performing a lobectomy (54 &plusmn; 14 vs. 61 &plusmn; 16 min, p = 0,25) or operative time to perform the surgery (72 &plusmn; 27 vs. 85 &plusmn; 24 min, p = 0,36) were not significantly different between the groups. The group MIVAM, early postoperative complications (bleeding, injury to the lower recurrent laryngeal nerve and hypocalcemia) occurred in 8% (4/50), and KM group in 10% (5/50), which was not statistically significant (p = 0,72). Compared to late postoperative complications, only one patient from group MIVAM registered the existence of keloids, while (permanent hypoparathyroidism, recurrent hyperthyroidism, a reaction to a foreign body) was not recorded. There was no statistically significant difference (p &gt; 0,005 for all) in the presence of histological types of findings review the removed substrate (colloid goiter, follicular adenoma, cysts, papillary carcinoma and Hashimoto&#39;s thyroiditis). Patients in MIVAM groups have significantly lower average pain intensity by VAS scale at intervals after surgery 6h, 24h and 48 h (p &lt; 0,05, for all). Total cosmetic score was significantly higher in MIVAM group compared to the KM group (18,9 &plusmn; 1,4 vs. 15,8 &plusmn; 1,3, p = 0,00). CONCLUSIONS: The incidence of early postoperative complications (intraoperative and postoperative bleeding, paresis and paralysis of the laryngeal nerve, hypocalcemia) were without significant differences between patients operated with minimally invasive method in comparison to the classical method. The average duration of minimally invasive thyroidectomy and classical thyroidectomy were without statistical significance difference, suggesting the appropriate level of surgical technique that enables the advantages of minimal invasiveness as surgical principles. Length of hospitalization after minimally invasive thyroidectomy was significantly shorter compared to conventional thyroidectomy, which significantly contributes to the overall recovery of the patient, lowering the cost of treatment. Minimally invasive thyroidectomy compared to conventional thyroidectomy, decreases the subjective feeling of postoperative pain, during hospitalization (6 and 24 h), as well as seven days after the intervention. In one-fifth of patients who underwent minimally invasive surgery method in the postoperative course of the subjective sensation of pain was not recorded. Cosmetic score as an indicator of patient satisfaction with the appearance of the scar was statistically higher in patients who underwent surgery less invasive surgical technique compared to patients who were operated by the classical method. According to the study, minimally invasive thyroidectomy has been demonstrated to be safe and superior to conventional open techniques for surgical treatment of nodular thyroid disease in patients with normal thyroid function with solitary/dominant nodule size &lt; 35 mm.</p>