Microcarcinoma papilar de tiroides: vigilancia activa. Revisión de la bibliografía / Papillary thyroid microcarcinoma: active surveillance. Literature review

El cáncer de tiroides ha aumentado en incidencia, sin embargo, la mortalidad se mantiene estable. Muchas de estas lesiones son a expensas de un microcarcinoma papilar de tiroides definido por la OMS como aquel carcinoma papilar de tiroides que en su diámetro máximo no sobrepasa los 10 mm. El avance de la imagenología sobre todo la ecografía de alta resolución y el hallazgo en pieza de anatomía patológica por lesiones benignas son las principales causas del aumento en el diagnóstico de esta entidad. La vigilancia activa surge entonces como alternativa de manejo para pacientes portadores de microcarcinoma papilar con bajo riesgo de progresión, obteniendo resultados oncológicos comparables. Independiente de su tratamiento el pronóstico de estos pacientes es excelente con sobrevida cercana al 100% en 10 años. A pesar de lo dicho la morbilidad de las distintas opciones terapéuticas es muy distinta. Será fundamental buscar elementos clínicos y paraclínicos que permitan tomar una decisión práctica, con el fin de determinar qué pacientes con microcarcinomas papilares que podrán entrar en un protocolo de vigilancia activa. Esta revisión pretende examinar la bibliografía publicada al respecto como alternativa de manejo, y su eventual aplicación en Uruguay.

Thyroid cancer has increased in incidence; however, mortality remains stable. Many of these lesions are at the expense of papillary thyroid microcarcinoma defined by the WHO as papillary thyroid carcinoma that in its maximum diameter does not exceed 10 mm. The advance of imaging, especially high-resolution ultrasound and the finding of benign lesions in pathological anatomy specimens are the main causes of the increase in the diagnosis of this entity. Active surveillance arises then as a management alternative for patients with papillary microcarcinoma with low risk of progression, obtaining comparable oncologic results. Regardless of their treatment, the prognosis of these patients is excellent with a survival rate close to 100% in 10 years. In spite of what has been said, the morbidity of the different therapeutic options is very different. It will be essential to look for clinical and paraclinical elements that will allow making a practical decision, in order to determine which patients with papillary microcarcinomas will be able to enter an active surveillance protocol. This review aims to examine the literature published on this subject as a management alternative, and its eventual application in Uruguay.

Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer

Summary Total thyroidectomy, radioiodine (RAI) therapy, and TSH suppression are the mainstay treatment for differentiated thyroid carcinomas (DTCs). Treatments for metastatic disease include surgery, external-beam radiotherapy, RAI, and kinase inhibitors for progressive iodine-refractory disease. Unresectable locoregional disease remains a challenge, as standard therapy with RAI becomes unfeasible. We report a case of a young patient who presented with unresectable papillary thyroid carcinoma (PTC), and treatment with sorafenib allowed total thyroidectomy and RAI therapy. A 20-year-old male presented with severe respiratory distress due to an enlarging cervical mass. Imaging studies revealed an enlarged multinodular thyroid gland, extensive cervical adenopathy, severe tracheal stenosis, and pulmonary micronodules. He required an urgent surgical intervention and underwent tracheostomy and partial left neck dissection, as the disease was deemed unresectable; pathology revealed PTC. Treatment with sorafenib was initiated, resulting in significant tumor reduction allowing near total thyroidectomy and bilateral neck dissection. Postoperatively, the patient underwent radiotherapy for residual tracheal lesion, followed by RAI therapy for avid cervical and pulmonary disease. The patient's disease remains stable 4 years after diagnosis. Sorafenib has been approved for progressive RAI-refractory metastatic DTCs. In this case report, we describe a patient with locally advanced PTC in whom treatment with sorafenib provided sufficient tumor reduction to allow thyroidectomy and RAI therapy, suggesting a potential role of sorafenib as an induction therapy of unresectable DTC.

Possíveis novos determinantes da qualidade de vida de pacientes com câncer de tireoide tratado: um estudo qualitativo / New possible determinants of the quality of life of patients with treated thyroid cancer: a qualitative study

Resumo Objetivou-se uma abordagem qualitativa de fatores que determinariam a qualidade de vida de pacientes com carcinoma papilífero de tireoide tratados. Foram feitas 16 entrevistas em profundidade com indivíduos de 18 a 45 anos sobre suas representações e experiências com esta enfermidade, seguidas por análise de conteúdo de enunciados. Os resultados contêm aspectos já previstos em questionários estruturados sobre qualidade de vida, mas outros estão parcialmente presumidos nesses questionários (manejo do conceito de etiologia da doença, a inserção “forçada” dos pacientes no universo conceitual médico, o medo do prognóstico e as mudanças “positivas” no estilo de vida). A interpretação desses resultados beneficiou-se de elaborações teóricas de desenvolvimento recente: as angústias sobre a experiência da doença parecem configurar-se, para os participantes, como um “risco moderno”, no contexto de uma “sociedade de riscos”. O desenvolvimento de questionários estruturados de qualidade de vida requer constantes estudos qualitativos que captem mudanças nos aspectos subjetivos do construto, dada a dinamicidade dos significados histórico-culturais e psicológicos do processo saúde-doença, constantemente influenciados por inovações tecnológicas e sucessivas interpretações epidemiológicas.

Abstract The aim of this study was to develop a qualitative approach of determinant factors of the quality of life of treated patients with papillary thyroid carcinoma. Sixteen in-depth interviews were conducted with individuals 18 to 45 years old regarding their disease representations and experiences, followed by statements content analysis. The results show issues already provided in structured questionnaires about quality of life, although others were only partially assumed in these surveys (management of the concept of disease etiology; the “forced” patient introduction into the medical conceptual universe; the fear of the prognosis and positive changes in lifestyle). The results interpretation were benefited from recently developed theoretical elaborations: the anxieties related to illness experience seem to be configured as a “modern risk”, in the context of a “risk society”. The development of structured questionnaires on quality of life requires frequent qualitative studies to capture changes in subjective aspects of the construct, given the dynamic changes of historical, cultural and psychological meanings of the health disease process, constantly influenced by technological innovations and continuing epidemiological interpretations.

Carcinoma papilar en quiste tirogloso. Propuesta de algoritmo diagnóstico y terapéutico / Papillary carcinoma in a thyroglossal duct cyst. Proposal of an algorithm for diagnosis and treatment / Carcinoma papilar em cisto tirogloso: proposta de algoritmo diagnóstico e terapêutico

Antecedentes: el carcinoma diferenciado de tiroides en quiste tirogloso (CaQT) es una entidad rara. La incidencia de CaQT es de 1 a 2%. Usualmente su forma de presentación clínica es indistinguible de una lesión benigna y el diagnóstico definitivo es postquirúrgico. No hay en la actualidad un consenso sobre la indicación de tiroidectomía total, radioablación con iodo y/o terapia supresiva con levotiroxina luego de ser extirpado quirúrgicamente...

Introduction: the development of well -differentiated thyroid carcinoma in thyroglossal duct cysts (TGDCa) is uncommon. The incidence of TGDCa lies within 1 to 2%. Usually the clinical appearance is indistinguishable from a benign thyroglossal duct cyst. The definitive diagnosis is post-operative. After the surgery of choice, the other alternative treatments such as thyroidectomy, radioiodine and L-T4 therapy are controversial...

Antecedentes: o carcinoma diferenciado de tireoide em cisto tirogloso (CaQT) é uma entidade rara. A incidência de CaQT é de 1 a 2 por cento. Em geral, a sua forma de apresentação clínica é indistinguível de uma lesão benigna e o diagnóstico definitivo é pós-cirúrgico. Não existe atualmente um consenso sobre a indicação de tiroidectomia total, radioablação com iodo e/ou terapia supressiva com levotiroxina após ser extirpado cirurgicamente...

Should a family history of papillary thyroid carcinoma indicate more aggressive therapy in patients with this tumor? / História familiar de carcinoma papilífero de tireoide deve indicar terapia mais agressiva em pacientes com este tumor?

Objective To determine whether the currently recommended therapy for papillary thyroid carcinoma (PTC) that show no classical factors indicating a poor prognosis is also effective in cases with a family history of this tumor. Subjects and methods: Forty-two patients were studied; 10 were submitted to lobectomy and 32 to total thyroidectomy, including 23 without lymph node dissection and 9 with lymph node dissection. None of the patients received radioiodine or was maintained under TSH suppression. Results No case of recurrence was detected by imaging methods and there was no increase in thyroglobulin or antithyroglobulin antibodies during follow-up (24 to 72 months). Conclusion The treatment usually recommended for patients with PTC does not need to be modified in the presence of a family history of this tumor if no factors indicating a poor prognosis are present (tumor ≤2 cm, non-aggressive histology, no extensive extrathyroid invasion or important lymph node involvement, complete tumor resection, no evidence of persistent disease after surgery). .

Objetivo Avaliar se a terapia atualmente recomendada para o carcinoma papilífero de tireoide (CPT) sem fatores clássicos de pior prognóstico é efetiva também nos casos em que existe história familiar deste tumor. Sujeitos e métodos: Foram avaliados 42 pacientes; dez foram tratados com lobectomia e 32 com tireoidectomia total, sendo 23 sem dissecção de linfonodos e 9 com dissecção linfonodal. Nenhum paciente recebeu radioiodo ou foi mantido com TSH suprimido. Resultados Nenhuma recidiva nos métodos de imagem foi observada, nem incremento da tireoglobulina ou anticorpos antitireoglobulina durante o seguimento (24 a 72 meses). Conclusão Em pacientes com CPT, sem fatores de pior prognóstico (tumor ≤2 cm, histologia não agressiva, sem invasão extratireoidiana extensa ou acometimento linfonodal importante, ressecção tumoral completa, sem indícios de doença persistente após a cirurgia), o tratamento usualmente recomendado não precisa ser modificado quando há história familiar desse tumor. .

Cáncer tiroideo papilar: reporte de 4 casos familiares / Papillary thyroid cancer: case reports of four family cases

Introducción: El cáncer papilar del tiroides (CPT) es la neoplasia endocrina más frecuente, siendo el 80% de los casos de la variedad papilar; sólo el 10 por ciento se manifiesta antes de los 21 años y tiene una incidencia estimada en este grupo de 0,54:100.000. Su comportamiento en la edad pediátrica se caracteriza por el diagnóstico en una etapa más avanzada de la enfermedad pero con buena respuesta terapéutica y muy baja mortalidad. Objetivo: Presentar 4 casos familiares de CPT, discutir las características particulares y la importancia del diagnóstico precoz en pacientes. Casos clínicos: Se presentan 4 familias con sujetos portadores de un carcinoma papilar familiar de Tiroides, en todas ellas el caso pediátrico se presentó con posterioridad a un caso de un adulto familiar directo, por lo que su búsqueda fue más precoz, y a pesar de un tratamiento oportuno ya tenían enfermedad avanzada al diagnóstico. Los casos pediátricos corresponden a 3 mujeres y 1 varón de edades promedio de 12 años 6 meses al momento del diagnóstico. Discusión: La variedad familiar del carcinoma papilar de tiroides (2 o más familiares de primer grado afectados), representa el 5 por ciento de los cánceres papilares. Se transmite a través de herencia autosómica dominante con penetrancia incompleta y expresividad variable. Se manifiesta a menor edad que el esporádico, es más agresivo con mayor invasión local (32 por ciento), recurrencia (20-50 por ciento) y metástasis linfática (57 por ciento), y se asocia a enfermedades tiroídeas benignas. Con frecuencia es multifocal. Conclusión: El cáncer familiar papilar de tiroides es una patología con peor pronóstico que la variedad esporádica por lo que se requiere una alto índice de sospecha en las familias afectadas para un diagnóstico y tratamiento precoz.

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy, representing 80 percent of all thyroid cancers; only 10 percent of cases are manifested before age 21 and have an estimated incidence of 0.54 cases per 100,000 people. In children it is diagnosed at a more advanced stage of the disease but with good therapeutic response and very low mortality. Objective: To present four family cases with PTC, discuss the particular characteristics and the importance of early diagnosis. Case reports: 4 families with members affected by family papillary thyroid carcinoma are presented, all pediatric cases were manifested after a direct member adult case was diagnosed, therefore pediatric patients were early detected, but despite a timely treatment, the disease was advanced at the time of diagnosis. The pediatric cases are 3 females and 1 male with an average age of 12 ½ years old at diagnosis. Discussion: The family variety of papillary thyroid carcinoma (2 or more direct members affected), represents 5 percent of papillary cancers. It is transmitted through autosomal dominant inheritance with incomplete penetrance and variable expressivity. It occurs at a younger age than the sporadic type, and it is more aggressive with greater local invasion (32 percent), recurrence (20-50 percent) and lymphatic metastases (57 percent), and it is associated with benign thyroid diseases and often, it is multifocal. Conclusion: The family papillary thyroid cancer is a disease with worse prognosis than the sporadic variety; therefore, a high index of suspicion is required in affected families for early diagnosis and treatment.

Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus / Nódulo tireoidiano e câncer diferenciado de tireoide: atualização do consenso brasileiro

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

Nódulos tireoidianos são muito frequentes, sobretudo quando se empregam métodos sensíveis de imagem. Embora o câncer seja proporcionalmente raro, sua incidência vem aumentando, especialmente de tumores pequenos, cuja evolução clínica é incerta. A maioria dos pacientes com carcinoma diferenciado de tireoide evolui bem quando adequadamente tratada, com índices de mortalidade similares à população geral. Por outro lado, um percentual não desprezível apresenta recidivas e alguns eventualmente não respondem às terapias convencionais, evoluindo para óbito. Assim, o desafio é distinguir os pacientes merecedores de condutas mais agressivas e, ao mesmo tempo e não menos importante, poupar a maioria de tratamentos e procedimentos desnecessários. Atualizamos o Consenso Brasileiro publicado em 2007, ressaltando os avanços diagnósticos e terapêuticos que os participantes, de diferentes Centros Universitários do Brasil, consideram mais relevantes para prática clínica. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão da literatura pertinente.

Evolution of differentiated thyroid cancer during pregnancy in a community University Hospital in Buenos Aires, Argentina / Evolução do câncer diferenciado de tiroide durante a gestação em um Hospital Universitário de Buenos Aires, Argentina

OBJECTIVE: To analyze the presentation, follow-up and evolution of differentiated thyroid cancer (DTC) detected during pregnancy. SUBJECTS AND METHODS: Twenty nine women with DTC detected during pregnancy were analyzed. Group I (n = 13) was seen during pregnancy and DTC was diagnosed during gestation; detection of the nodule occurred during pregnancy (first trimester). Group II (n = 16) was seen after delivery; detection of the nodule occurred during pregnancy (second or third trimester). Complete thyroidectomy, ablative dose of radioactive iodine, and treatment with levothyroxine were performed. Follow-up: neck ultrasound; TSH, free T4, thyroglobulin, and anti-thyroglobulin antibodies with and without treatment with levothyroxine; and 131I whole body scans. Histological diagnosis, lymph node metastases, tumor size and stage, complications from pregnancy, and DTC evolution were evaluated. RESULTS: 100% of the patients had papillary thyroid carcinoma. Lymph node metastases were detected in 13 (44.8%), and invasion of adjacent extrathyroid tissue in 2 patients. Tumor size was larger in Group II: 22.1 ± 10.9 versus 13.9 ± 3.5 mm; p = 0.03. No differences were found in the tumor stages between groups. All patients had full-term pregnancies and healthy newborns. Follow-up: 5.7 ± 4.3 years; one patient had persistent disease. CONCLUSIONS: DTC detected during pregnancy had a favorable evolution. Surgery may be postponed to the post-delivery period, unless there are risk factors that justify it during pregnancy.

OBJETIVO: Analisar a apresentação, o seguimento e a evolução do câncer diferenciado da tiroide (CDT) durante a gestação. SUJEITOS E MÉTODOS: Vinte e nove mulheres com CDT detectado durante a gestação foram analisadas. O Grupo I (n = 13) foi atendido durante a gestação e o CDT foi diagnosticado durante a gravidez; a detecção do nódulo aconteceu durante a gestação (primeiro trimestre). O Grupo II (n = 16) foi atendido depois do parto; a detecção do nódulo aconteceu durante a gestação (segundo ou terceiro trimestre). Foram feitos a tiroidectomia, dose de iodo radioativo e tratamento com levotiroxina. Acompanhamento: ultrassom de pescoço; TSH, T4 livre, tiroglobulina, e anticorpos antitiroglobulina com ou sem tratamento com levotiroxina e imagens de corpo inteiro com 131I. Foram analisados o diagnóstico histológico, as metástases em linfonodos, estágio e tamanho do tumor e complicações da gestação e a evolução do CDT. RESULTADOS: Cem por cento das pacientes apresentaram carcinoma papilar da tiroide. Foram detectadas metástases em linfonodos em 13 (44,8%) pacientes e invasão de tecidos extratiroidianos adjacentes em duas pacientes. O tumor foi maior no Grupo II: 22,1 ± 10,9 versus 13,9 ± 3,5 mm; p = 0,03. Não foram observadas diferenças nos estágios dos tumores entre os grupos. Não houve partos prematuros e todos os recém-nascidos estavam saudáveis. Acompanhamento: 5,7 ± 4,3 anos; uma paciente apresentou doença persistente. CONCLUSÕES: O CDT detectado durante a gestação tem evolução favorável. A cirurgia pode ser adiada até o momento pós-parto, a não ser que haja fatores de risco que justifiquem a intervenção durante a gestação.

Carcinoma papilar intraquístico asociado a adenocarcinoma ductual infiltrante en un hombre: reporte de un caso / Papillary intra cyst carcinoma associated with ductal adenocarcinoma in a man: case report

El carcinoma papilar intraquístico es un subtipo de carcinoma ductal no invasivo, puede estar asociado o no acarcinoma in situ y a carcinoma infiltrante, es una patología poco frecuente por lo tanto su aparición en hombres es extremadamente rara. El tratamiento en estos casos es equivalente al carcinoma de mama en mujeres, se debate entre mastectomía simple o mastectomía parcial más radioterapia. Presentamos el caso de un hombre a quien se diagnostica preoperatoriamente con un carcinoma papilar y se realiza mastectomía simple más ganglio centinela.

The papillary intra cyst carcinoma is a sub type of ductal no invasive carcinoma, it can be or not associated to in situ carcinoma and to infiltrant carcinoma, is a pathology less frequent, for these reason his apparition in men is extremely rare. The treatment is equivalent to the breast carcinoma in women, debated between simple mastectomy and partial mastectomy with radiation therapy. We present a clinical case of a man with pre operative diagnostic with a papillary carcinoma and realized simple mastectomy with sentinel node.

Postoperative chemoradiation in patients with localized gastric adenocarcinoma: Single center experience.

Background : 5-Flourouracil (FU)-based chemotherapy (CT) and concurrent 45 Gy radiotherapy (RT) is one of the standard postoperative approaches currently used in gastric carcinoma. The high toxicity rates of this treatment leads to interruption of treatment in the majority of patients. In our study, we investigated the rates of toxicity and treatment discontinuation observed during postoperative FU-based chemoradiotherapy (CRT); retrospectively evaluated the effect of CRT and the other prognostic factors on local and distant control and survival. Patients and Methods: A total of 160 patients consisting of 97 total and 63 subtotal gastrectomy receiving postoperative CRT, have been studied retrospectively. Results : Patients who had to discontinue the treatment for a median of 6 (range, 3-13) days experienced toxicity during treatment at a rate of 43%. During the 21 (range, 4-68) months of follow-up local recurrences were observed in 8 (5%) patients and distant recurrences were observed in 41 (25.6%) patients. While the 1-3 year overall survival (OS) rates were 75% and 42%, 13-year disease-free survival (DFS) rates were 63% and 42%, respectively. In the univariate analysis for OS and DFS demonstrated statistical significance for below those 60 years of age, D1-D2 dissection type, negative surgical margin, early treatment beginning, the absence of invasion, and early stage disease. D1D2 dissection type, early treatment begining, age below 60 years and early stage disease significantly improve OS and DFS in multivarite analysis. Conclusions: Survival is worse in patients older than 60 years, had late treatment begining, advanced stage and D0 dissection.

Câncer de tireoide na infância e na adolescência: estudo de casos e revisão da literatura / Thyroid cancer in childhood and adolescence: case study and literature review

Introdução: As neoplasias malignas da tireoide não são comuns na faixa etária pediátrica. O objetivo deste trabalho foi realizar um levantamento epidemiológico e clínico dos casos de câncer de tireoide (CT) atendidos no Hospital Universitário de Santa Maria (HUSM) entre 1993 e 2008, com descrição do diagnóstico e da terapêutica, acompanhado de uma revisão de literatura dessa patologia. Métodos: Estudo de demanda retrospectivo a partir do registro do Serviço de Patologia do Hospital Universitário de Santa Maria, RS (HUSM), no período de 1/1/1993 a 31/12/2008. Resultados: Nos 15 anos avaliados, foram encontrados 10 pacientes com diagnóstico de CT. Este estudo de casos inclui sete dos 10 pacientes; os demais foram excluídos devido à insuficiência de dados nos prontuários. O sexo feminino foi o mais acometido. Seis dos sete pacientes foram submetidos à tireoidectomia total com esvaziamento ganglionar. O tipo histológico predominante foi o carcinoma papilífero e o tamanho médio dos tumores foi de 2 cm. As metástases linfonodais foram encontradas em seis casos no momento do diagnóstico e o número médio de linfonodos acometidos foi quatro. Conclusão: Os resultados encontrados são consistentes com os achados epidemiológicos e clínicos encontrados na literatura para esta faixa etária. Destaca-se a importância do seguimento de um protocolo de manejo do CT dentro de um hospital universitário

Introduction: Malignant neoplasms of the thyroid are not common in pediatric patients. The aim of this study was to carry out an epidemiological and clinical survey of the cases of thyroid cancer (TC) treated at the University Hospital of Santa Maria (HUSM) between 1993 and 2008, with a description of diagnoses and treatment, together with a literature review of this disorder. Methods: A retrospective, demand study based on the registry of the Department of Pathology, University Hospital of Santa Maria-RS (HUSM) from 1/1/1993 to 31/12/2008. Results: Over the past 15 years, there were 10 patients diagnosed with TC. This case study includes seven of the 10 patients, the others were excluded because of insufficient data in the charts. Females were more affected. Six of seven patients underwent total thyroidectomy with lymph node dissection. The predominant histological type was papillary carcinoma and the average size of tumors was 2 cm. Lymph node metastases were found in six cases at diagnosis and the mean number of affected lymph nodes was four. Conclusion: The results are consistent with epidemiological and clinical findings in the literature for this age group. The study highlights the importance of following a management protocol of CT within a university hospital

Papillary thyroid carcinoma: Debate at rest.

Introduction: Papillary thyroid cancer (PTC) is the most common well-differentiated cancer of the thyroid and is one of the fastest growing group of cancers probably because of the increased use of ultrasound (HRUSG) in the evaluation of the thyroid in recent years. Materials and Methods: A MEDLINE and OVID database search was performed to collect information on papillary thyroid carcinoma. Recently published consensus guidelines were also used as an additional resource. Conclusions: The controversy regarding the extent of thyroidectomy in patients of PTC is relatively settled, with total thyoidectomy being the preferred approach with nodules >1.5 cm in size. Lymph node (LN) metastases do not seem to affect the overall survival, but they do increase the recurrence rate. It is worthwhile to offer LN dissection at initial surgery if LNs are ultrasonologically diagnosed to harbor malignancy. In experts hands, the rate of recurrent laryngeal nerve injury and hypoparathyroidism is negligible in a neck dissection in initial surgery and remains negligible if carried out in a redo or completion scenario.

Protocol for thyroid remnant ablation after recombinant TSH in thyroid carcinoma / Protocolo para ablación de remanentes tiroideos luego de TSH recombinante en el cáncer diferenciado de tiroides

In some countries, in order to perform rhTSH-aided thyroid remnant ablation (TRA) after surgery, it is generally necessary to confirm that thyroidectomy has been almost complete. Otherwise, the nuclear medicine specialist will not administer a high radioiodine dose because it might be hazardous due to the possibility of thyroid remnant actinic thyroiditis. Considering this, it would be necessary to use two rhTSH kits (one for diagnostic purposes and the other one to administer the 131I dose). In this study, we used an alternative protocol for TRA with the use of one kit of rhTSH in twenty patients diagnosed with low risk papillary thyroid carcinoma. All patients had negative titers of anti-thyroglobulin antibodies. Successful thyroid remnant ablation was confirmed with an undetectable rhTSH stimulated thyroglobulin level (< 1 ng/ml) in all 20 patients between 8 to 12 months after radioiodine administration. The use of this protocol combining scintigraphy with the subsequent administration of a therapeutic dose following the administration of one kit of rhTSH would avoid the need of using 2 kits to perform the ablation and would decrease the costs associated with its use while significantly enhancing the quality of life of patients with thyroid cancer.

En algunos países, para realizar la ablación de los remanentes tiroideos con radioyodo después de la cirugía, generalmente se requiere confirmar que la tiroidectomía fue casi completa, ya que de otra manera el especialista en medicina nuclear no administrará una dosis elevada de radioyodo, considerando que esto puede ser dañino para el paciente debido a la posibilidad de generar una tiroiditis actínica. De acuerdo con esto, sería necesario administrar 2 kits de rhTSH (uno para diagnóstico y otro para la dosis de radioyodo). En este estudio, empleamos un protocolo alternativo para la ablación luego de la administración de un único kit (2 ampollas) de rhTSH en 20 pacientes con antecedentes de un carcinoma papilar de bajo riesgo. Todos los pacientes presentaban títulos negativos de anticuerpos anti-tiroglobulina. La ablación exitosa de remanente tiroideo se confirmó con un nivel no detectable de tiroglobulina (<1 ng/ml) al estímulo por rhTSH en los 20 pacientes, entre 8 a 12 meses luego de la ablación. El uso de este protocolo que combina la posibilidad de realizar un centellograma diagnóstico y la ablación luego del uso de un solo kit de rhTSH, facilita su empleo, disminuye los costos asociados, a la vez que permite una mejor calidad de vida de los pacientes con cáncer de tiroides.

Cáncer papilar de tiroides a la luz de las evidencias actuales / Papillary thyroid cancer: an update

The new screening and diagnostic tools for thyroid cancer lead to a higher prevalence of the disease. This requiresa new approach to the therapy of thyroid cancer, that usually has an indolent and slow evolution. The incidence of microcarcinoma is increasing since the vast majority of thyroid cancers are diagnosed during a screening ultrasonography. In papillary thyroid cancer there is a familial aggregation and close relatives of an index patient have three to six times more risk of having the disease. Exposure to radiation, older age and association with other thyroid diseases are external risk factors for the disease. Thyroid cancer is staged using TNM classification, that allows to establish prognosis. There is still discussion about the best treatment in early stages of the disease. Our working group always recommends total thyroidectomy and radioiodine ablation to obtain a better control and survival and reduce the risk of relapse.

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.

A glândula tireóide tem capacidade de captar e concentrar iodeto, etapa fundamental na biossíntese dos hormônios tireóideos. O uso de iodo radioativo para fins de diagnóstico e terapia das doenças da tireóide vem sendo feito há muitos anos. Entretanto, somente após a clonagem do gene que codifica o co-transportador de sódio/iodeto (NIS) houve aumento significativo dos estudos relacionados ao mecanismo de transporte de iodeto. Os estudos sobre a regulação da expressão do NIS e a possibilidade de terapia gênica visando à transferência do gene NIS para células que normalmente não expressam esse transportador, foram também viabilizados. Na maior parte dos nódulos tireóideos hipofuncionantes, tanto benignos quanto malignos, a expressão do gene do NIS está presente, mas a proteína NIS fica retida no compartimento intracelular. A transferência do gene usando-se promotores tecido-específicos possibilitou a expressão do NIS em células tumorais não-tireóideas in vivo. Além do seu uso terapêutico, o NIS também vem sendo usado para a localização de metástases tumorais através da cintilografia ou do PET-scan usando-se 124I. Em conclusão, a clonagem do NIS possibilitou enorme avanço na área de fisiopatologia tireóidea e foi também fundamental para estender o uso do radioiodo para tumores não tireóideos.

Carcinoma de tireóide na infância e adolescência / Thyroid carcinoma in children and adolescents

Aproximadamente 10 por cento das neoplasias de tireóide aparecem abaixo dos 21 anos e representam 3 por cento das neoplasias da infância, com predomínio em meninas (2F:1M). São papilíferos em 90 por cento casos e mais freqüentemente bilaterais, multifocais e de maior dimensão. Invasão de cápsula e metástases ganglionar ou pulmonar são mais freqüentes que no adulto. O efeito carcinogênico da radiação é especialmente importante na criança pré-púbere. Em 5 por cento dos casos de PTC existe história familial. Genes como o RET/PTC, RAS e BRAF estão habitualmente envolvidos na gênese do processo. A apresentação clínica pode ser nódulo cervical (90 por cento casos) sem que represente um fator de pior prognóstico. O US e a PAAF são procedimentos diagnósticos valiosos. O tratamento deve ser cirúrgico (tireoidectomia total com esvaziamento ganglionar) seguido de PCI e radioterapia ablativa. A substituição com L-tiroxina deve objetivar a supressão crônica do TSH. O prognóstico ao longo prazo é melhor que no adulto. A quantificação da Tg plasmática também é útil na detecção da doença residual.

Approximately 10 percent of thyroid cancers are present in patients less than 21 years of age, representing 3 percent of all cancers of children and adolescents, with predominance in females 2:1 in relation to males. Thyroid cancers in this age group are usually papillary (90 percent), bilateral, multifocal and bigger in size compared to adults. Capsule invasion and lymphatic and pulmonary metastases are more frequent in children. Radiation sensitivity seems to represent an important factor in prepubertal patients. Familial history is reported in 5 percent of the cases. Genes such as RET/PTC, RAS and BRAF are usually involved in thyroid carcinogenesis in this age group. Cervical adenomegaly is a common clinical presentation, but does not represent a poor prognostic factor in children. Ultrasound and fine needle aspiration biopsy are valuable diagnostic procedures. Surgery is the preferred treatment including thyroidectomy and ganglionary excision, followed by ablative radioiodine therapy. L-thyroxine replacement with suppressive dosage should be employed targeting chronic TSH suppression. Long-term prognosis is usually better in children when compared with adults. Plasma thyroglobulin measurement is also useful to detect residual thyroid cancer disease.

Carcinoma não medular familiar da tiróide / Familial nommedullary thyroid cancer

O carcinoma diferenciado da tiróide, papilífero ou folicular, origina-se da célula folicular tiroideana, sendo a neoplasia maligna mais freqüente desta glândula. Desde 1955 têm sido relatados casos de agrupamento familiar deste carcinoma, e atualmente estima-se que 4,2 por cento de todos os carcinomas diferenciados da tiróide tenham origem familiar. Esses casos costumam ser mais agressivos, incidem em idade mais precoce, são multifocais e apresentam maior taxa de recorrência. Parecem ser transmitidos por herança autossômica dominante com penetrância variável, mas os genes exatos responsáveis pela doença ainda não foram totalmente identificados. Os pacientes devem ser tratados com tiroidectomia total e freqüentemente também com esvaziamento linfonodal cervical, seguidos de ablação com iodo radioativo e terapia supressiva do TSH com levotiroxina. Alguns autores recomendam rastreamento de familiares de primeiro grau dos pacientes afetados através da ultrassonografia cervical, com objetivo de realizar diagnóstico precoce, possibilitando melhores resultados terapêuticos.

Nonmedullary thyroid carcinoma, originating from thyroid epithelial cells, is the most frequent thyroid malignant neoplasia. Since 1955, there has been increasing evidence that this cancer may have a familial predisposition. It is now established that around 4.2 percent of all nonmedullary thyroid carcinomas occurs on the background of familial predisposition. These cases are often more aggressive, due to early onset, multifocality and a higher percentual of recurrences. An autossomal dominant inheritance pattern appears likely in most families, although the exact genes responsible for this syndrome have not yet been identified. Patients affected by this cancer should be treated with total thyroidectomy routinely and, in most cases, lymph node dissection, followed by iodine ablation and TSH suppressive therapy with levothyroxine. Some authors also recommend that first-degree relatives of patients with nonmedullary thyroid cancer (especially women) should be submitted to neck ultrasound for thyroid cancer screening, aiming early diagnosis for better treatment results.

Uso do TSH humano recombinante no câncer diferenciado de tireóide / Recombinant human TSH use in differentiated thyroid cancer

O seguimento imediato após tireoidectomia total (TT), em pacientes com câncer diferenciado de tireóide (CDT), tradicionalmente é feito com a ablação de remanescentes tireoidianos (RT) com 131I, na vigência de hipotireoidismo. O seguimento tardio do CDT inclui o uso de doses supressivas de T4, dosagem seriada da tireoglobulina (Tg), pesquisa de corpo inteiro (PCI) com 131I e ultra-sonografia (US) cervical. Nos últimos anos, tem-se mostrado que a ablação de RT com a ajuda do TSH recombinante humano (rhTSH) tem a mesma eficácia que a ablação de RT observada com a elevação endógena do TSH, mas sem os sintomas e piora de qualidade de vida descritos no hipotireoidismo. A dosagem da Tg estimulada com TSH endógeno ou exógeno, 9 a 12 meses após o tratamento inicial do CDT, associado à US cervical, pode identificar pacientes de baixo risco potencialmente curados de sua doença e nos quais a supressão do TSH não necessita ser tão intensa, evitando as complicações cardíacas e ósseas da tireotoxicose exógena prolongada. Finalmente, apesar de não existirem estudos randomizados que avaliem o papel do rhTSH no tratamento do CDT metastático, os resultados do tratamento combinado do rhTSH e 131I mostram um benefício clínico na maioria dos pacientes tratados.

Traditionally, the immediate treatment of patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy (TT) is thyroid remnant ablation (TRA) with 131I, during hypothyroidism. Late follow-up of DCT includes suppressive doses of T4, serial measurements of thyroglobulin (Tg), whole body scan (WBS) with 131I and cervical ultrasound (US). In the last years, TRA with the aid of recombinant human TSH (rhTSH) has shown not only to avoid symptoms of hypothyroidism and a lower quality of life, but also to have the same efficacy as TRA during endogenous TSH elevation. Stimulated Tg with endogenous or exogenous TSH, 9 to 12 months after the initial treatment of DTC, associated with cervical US, is able to identify low-risk patients virtually cured of their disease, in whom TSH suppression does not need to be so strict, avoiding the heart and bone complications of prolonged exogenous thyrotoxicosis. Finally, in spite of the absence of randomized studies designed to evaluate the role of rhTSH in metastatic DTC disease, results of the combined treatment of rhTSH and 131I show a clinical benefit in the majority of treated patients.

Nódulos de tireóide e câncer diferenciado de tireóide: consenso brasileiro / Thyroid nodules and differentiated thyroid cancer: brazilian consensus

Os nódulos tireoidianos constituem a principal manifestação clínica de uma série de doenças da tireóide com uma prevalência de aproximadamente 10 por cento na população adulta. O maior desafio é excluir o câncer da tireóide, que ocorre em 5 a 10 por cento dos casos. Os carcinomas diferenciados respondem por 90 por cento dos casos de todas as neoplasias malignas da tireóide. A maioria dos pacientes com carcinoma diferenciado apresenta, geralmente, um bom prognóstico quando tratada adequadamente, com índices de mortalidade similares à população geral. No entanto, alguns indivíduos apresentam doença agressiva, desafiando o conhecimento atual e ilustrando a complexidade do manejo dessa neoplasia. No presente trabalho, reunimos 8 membros do Departamento de Tireóide da Sociedade Brasileira de Endocrinologia & Metabologia, para elaborarmos, por consenso, as diretrizes brasileiras no manejo dos nódulos tireoidianos e do câncer diferenciado da tireóide. Os membros participantes representam diferentes Centros Universitários do Brasil, refletindo diferentes abordagens diagnósticas e terapêuticas. Inicialmente, cada participante ficou responsável pela redação de determinado tema a ser enviado ao Coordenador, que, após revisão editorial e elaboração da primeira versão do manuscrito, enviou ao grupo para sugestões e aperfeiçoamentos. Quando concluído, o manuscrito foi novamente enviado e revisado por todos. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão pertinente da literatura.

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that ~10 percent of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10 percent). Differentiated thyroid carcinoma accounts for 90 percent of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.