Immune Response In Thyroid Cancer: Widening The Boundaries.

The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy.201412545

Perioperative assessment guidelines and thyroid disease

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Understanding the Molecular Process of Tumorigenesis

Over the past 25 years, knowledge of the genetic-molecular mechanisms involved in the genesis and progression of cancer have helped to obtain new diagnostic and follow up methods that have drastically redirected the therapeutics used in patients with neoplasia. Some molecular markers are already being routinely used and should provide sensitive and specific tests for early diagnosis, staging and follow up of cancer patients. The molecular characteristics of each tumor should help in predicting its behavior and outlining more effective therapeutic strategies. We have used a didactic manner of presenting the main mechanisms that control the growth and cellular cycle, defined the importance of erroneously activated oncogenes and tumor suppressor genes that are lost or non-functioning, genes involved in programming and maintaining cell life as well as other genes that participate in the tumorigenic process. The mechanisms of tumor progression, invasion and metastasis are reviewed placing an emphasis on the practical application of the knowledge related to these mechanisms. The role of genetic instability and epigenetic changes in the definition of cancer phenotype have been underscored, suggesting the application of molecular genetics in the gene therapy of cancer.Nos últimos 25 anos, o reconhecimento dos mecanismos genético-moleculares implicados na gênese e na progressão do câncer tem permitido obter novos métodos de diagnóstico e de acompanhamento, redirecionando de forma drástica a terapêutica do paciente com neoplasia. Alguns marcadores moleculares já estão sendo utilizados na rotina e deverão prover testes sensíveis e específicos para o diagnóstico precoce, estadiamento e acompanhamento do paciente com câncer. As características moleculares de cada tumor deverão permitir predição do seu comportamento, ajudando a delinear estratégias terapêuticas mais efetivas. Apresentamos de forma didática os principais mecanismos controladores do ciclo celular e do crescimento, definindo a importância de oncogenes erroneamente ativados e de genes supressores tumorais perdidos ou não-funcionantes, dos genes envolvidos na programação e manutenção da vida celular e de outros genes que atuam no processo de tumorigênese. Os mecanismos de progressão tumoral, invasão e metastatização à distância são revistos enfatizando-se a aplicação prática do conhecimento a respeito de tais mecanismos. Lembramos o papel da instabilidade genética e dos fenômenos epigenéticos na definição fenotípica do câncer, sugerindo as aplicações da genética molecular na terapia gênica do câncer.35136

Levothyroxine and the problem of interchangeability of drugs with narrow therapeutic index

The exchange of a prescribed drug by other similar, by generic products and even by custom products has become common practice in our country, often ignoring basic tenets of bioequivalence, interchangeability, stability and characteristics of the pharmaceutical compounds. In the case of drugs of narrow therapeutic index, such as levothyroxine, these problems are intensified, putting the effectiveness of treatment and patient health at serious risk. We review the pertinent legislation, emphasizing the characteristics of levothyroxine and adverse effects that limit the interchangeability of the compound.Tem se tornado prática comum em nosso país a troca de medicamentos prescritos por outros similares, por produtos genéricos e até mesmo por produtos manipulados, muitas vezes ignorando-se preceitos básicos de bioequivalência, permutabilidade, estabilidade e características específicas do composto farmacêutico. No caso de drogas de índice terapêutico estreito, como a levotiroxina, esses problemas se agravam colocando em sério risco a eficácia do tratamento e a saúde do paciente. Revemos a legislação pertinente ressaltando as características da levotiroxina e os efeitos adversos que limitam a permutabilidade do composto.42943

Devemos mudar os valores de referência para TSH normal?

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Câncer da tiróide: aumento na ocorrência da doença ou simplesmente na sua detecção?

15151516Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Thyroid stimulating hormone levels in cord blood are not influenced by non-thyroidal mothers' diseases

CONTEXT: Screening programs not only offer the opportunity to trace and treat almost all cases of congenital hypothyroidism but also mean large savings to the health system. However, carefully planned strategies are necessary to extend their benefits and reduce costs. OBJECTIVE: To determine the possible influence of maternal diseases that affect maternal-fetal placenta dynamics on primary thyroid stimulating hormone (TSH) screening for congenital hypothyroidism. DESIGN: Prospective non-randomized clinical trial with at least 3 months of follow-up. SETTING: A public university referral center [CAISM/Hospital das Clínicas, Faculty of Medicine, University of Campinas, Campinas, SP]. PARTICIPANTS: 415 neonates divided into 5 groups: eighty-three infants born from cardiac mothers; 98 from mothers that had toxemia; 54 of the mothers had diabetes mellitus; 40 were HIV positive and 140 had no diseases. INTERVENTION: All newborns had cord blood samples collected on filter paper at birth. MAIN MEASUREMENTS: TSH was measured from dried blood spots using a homemade immunofluorescence assay (sensitivity in dried blood spots = 0.1 mU/L). RESULTS: There was no significant difference in the mean TSH levels among the 5 groups. Moreover, TSH levels were around 5 mU/L in 48% of the newborns, indicating that our region is severely deficient in iodine. CONCLUSIONS: Our results indicate that primary TSH screening programs using cord blood are not affected by maternal diseases. We suggest that, besides its technical advantages over heel punctures with T4 primary approaches, neonatal screening using primary cord blood TSH may also be used as a monitoring tool for evaluation and control of iodine deficiency disorders (IDD).CONTEXTO: Os programas de detecção precoce trazem economias ao sistema de saúde e oferecem a oportunidade de rastrear e tratar precocemente casos de hipotiroidismo congênito. OBJETIVO: Determinar influências de doenças que afetam a dinâmica materno-fetal-placentária sobre programas de detecção precoce de hipotiroidismo congênito que se baseiam na dosagem do hormônio tirotrófico (TSH). TIPO DE ESTUDO: Ensaio clínico prospectivo não-randomizado com, ao menos, três meses de seguimento. LOCAL: Centro Universitário Público de Referência - Centro de Atendimento Integrado a Saúde da Mulher (CAISM). PARTICIPANTES: 415 recém-nascidos de 5 grupos de parturientes: 83 crianças eram filhas de mães cardiopatas; 98 de mães com toxemia gravídica; 54 de mães diabéticas; 40 de mães portadoras de imunodeficiência adquirida (HIV); e 140 de mães hígidas. PROCEDIMENTOS: Todos os recém-nascidos tiveram amostras de sangue de cordão umbilical coletadas em papel de filtro ao nascimento. VARIÁVEIS ESTUDADAS: Dosagem de TSH em sangue coletado em papel de filtro usando um ensaio imunofluorométrico próprio (sensibilidade em manchas de sangue seco = 0.1 mU/L). RESULTADOS: Não encontramos diferença na média de TSH dos 5 grupos. Além disso, os níveis de TSH estavam acima de 5 mU/L em 48% dos bebês, sugerindo que nossa região é severamente deficiente em iodo. CONCLUSÕES: Nossos resultados demonstram que programas de detecção precoce de hipotiroidismo congênito, que utilizam primariamente TSH, não são afetados por doenças maternas não-tiroidianas. Sugerimos que, além das vantagens técnicas sobre a punção de calcanhar com dosagem primária de T4, os programas de detecção precoce que utilizam primariamente TSH de cordão umbilical também podem ser usados como instrumento de avaliação e controle da carências de iodo.State University of Campinas Faculty of Medical Sciences Department of MedicineUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of MedicineUNIFESP, EPM, Department of MedicineSciEL

Allelic Imbalance Studies Of Chromosome 9 Suggest Major Differences In Chromosomal Instability Among Nonmelanoma Skin Carcinomas.

Loss of heterozygosity in the 9p21-p22 region, has been frequently described in a wide range of human malignancies, including familial melanomas. Also, losses and gains in other regions of chromosome 9 have frequently been observed and may indicate additional mechanisms for basal cell tumorigenesis. To investigate allelic imbalance in the 9p21-p22 region, among basal cell carcinomas. Microsatellite analysis. Two dermatology services of public universities in São Paulo and the Laboratory of Cancer Molecular Genetics of Universidade Estadual de Campinas (Unicamp). 13 patients with benign skin lesions consecutively referred to the outpatient dermatology clinics of Unicamp and Universidade Estadual de São Paulo (Unesp) and 58 with malignant skin tumours. MEAN MEASUREMENTS: We examined 13 benign cases including four of solar keratosis, three keratoachanthomas, three melanocytic nevi, two of Bowen's disease and one of neurofibroma, and 58 malignant skin tumors: 14 of squamous cell, 40 basal cell carcinomas and four melanomas. Participating patients had the main tumor and a normal portion of non-adjacent skin surgically removed. DNA was extracted from the tumor and matching normal tissue. We used four sets of primers to amplify polymorphic microsatellite repeats on chromosome 9, two of them targeting the 9p21-p22 region. We identified eight cases (20%) of allelic imbalance among basal cell carcinomas, two cases of loss of heterozygosity and six cases of microsatellite instability in the 9p21-p22 region. Additional markers were also involved in three of these tumors. No events were detected among the benign or the other malignant cases. This phenotype dependency suggests that there is a major distinction between the two most important forms of nonmelanoma skin cancers in their tendency to present microsatellite instability in chromosome 9. Since the CDKN2a/p16INK4a, p19ARF and p15INK4b tumor suppressor genes do not appear to be responsible for the observed abnormalities, other genes at 9p21-p22 may be involved in the pathogenesis and progression pathway of basal cell carcinomas.12218-2

Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis. CONCLUSIONS: We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness

The clinical use of thyroid function tests

Laboratory tests are essential for accurate diagnosis and cost-effective management of thyroid disorders. When the clinical suspicion is strong, hormonal levels just confirms the diagnosis. However, in most patients, symptoms are subtle and unspecific, so that only biochemical tests can detect the disorder. The objective of this article is to do a critical analysis of the appropriate use of the most important thyroid function tests, including serum concentrations of thyrotropin (TSH), thyroid hormones and antithyroid antibodies. Through a survey in the MedLine database, we discuss the major pitfalls and interferences related to daily use of these tests and recommendations are presented to optimize the use of these diagnostic tools in clinical practice.Exames laboratoriais são fundamentais para o diagnóstico acurado e o monitoramento custo-efetivo das disfunções tireoidianas. Quando há alta suspeita clínica, as dosagens hormonais apenas confirmam o diagnóstico. No entanto, na maioria dos pacientes, a sintomatologia é sutil e inespecífica, de forma que apenas testes bioquímicos podem detectar o transtorno. O objetivo deste artigo é fazer uma análise crítica do uso apropriado dos principais testes de função tireoidiana, entre eles a dosagem sérica do hormônio estimulante da tireoide (TSH), dos hormônios tireoidianos e dos anticorpos antitireoidianos. Mediante um levantamento na base de dados do MedLine, são discutidas as principais armadilhas e interferências relacionadas ao uso cotidiano desses testes e apresentadas recomendações para otimizar a utilização dessas ferramentas diagnósticas na prática clínica.19320