Binge eating disorder, frequency of depression, and systemic inflammatory state in individuals with obesity - A cross sectional study

ABSTRACT Objective: Binge eating disorder (BED) is the most prevalent eating disorder in individuals with obesity. Its association with factors that control hunger and satiety has not yet been elucidated. We evaluated whether levels of inflammatory markers, frequency of psychiatric comorbidities, and appetite-related hormones levels differ between individuals with obesity with and without BED. Materials and methods: The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 - Clinician Version (SCID-5-CV), Binge Eating Scale, and Hospital Anxiety and Depression Scale were evaluated in 39 individuals with obesity. Plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) were measured. Results: Individuals of the BED group exhibited significantly higher percentages of altered eating patterns (hyperphagia, bingeing, post-dinner eating, feeling "stuffed", and emotional eating), higher depressive symptom scores and levels of leptin, CRP, and TNF-α, compared to those from the non-BED group. Logistic regression showed that BED was independently associated with depressive symptoms and CRP levels. Conclusions: Individuals with obesity and BED showed greater psychiatric comorbidity, worse eating patterns and worse inflammatory profile than those without BED. BED should be assessed as an indicator of clinical severity in patients with obesity.

Aggressive nonfunctioning pituitary neuroendocrine tumors.

Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.

Environmentally relevant dose of the endocrine disruptor tributyltin disturbs redox balance in female thyroid gland.

Tributyltin (TBT) is an endocrine disruptor used as a biocide in nautical paints. Even though many TBT effects in marine species are known, data in mammals are scarce, especially regarding the thyroid gland. The present study aimed to evaluate the effect of a subchronic exposure to TBT on thyroid oxidative stress of female Wistar rats. Rats received vehicle (control group), 200 or 1000 ng TBT/kg body weight/day for 40 days. After euthanasia, one part of the thyroids were collected in order to assess iodide uptake; activity and/or mRNA expression of thyroperoxidase (TPO) and dual oxidases (DUOXs); activity and/or mRNA expression of catalase, glutathione peroxidase, superoxide dismutase and NADPH oxidase 4 (CAT, GPx, SOD and NOX4); 4-hydroxynonenal (4-HNE) expression and total thiol groups levels; and mRNA expression of estrogen receptors alpha and beta (ERα and ERß). The remaining part of the thyroid was processed for morphological analysis of estrogen receptor alpha (ERα) and for collagen deposition. Iodide uptake was not changed with treatments. TPO activity and expression were increased in the TBT1000 group (259.81% and 95.17%). The activity, but not mRNA, of CAT (17.36% TBT200; 27.10% TBT1000) and GPx (29.24% TBT200; 28.97% TBT1000) were decreased by TBT. SOD and NADPH oxidase activity, as well as thiol group and 4-HNE levels remained unchanged. Interstitial collagen deposition increased in the TBT200 group (39.54%). The mRNA expression of ERα increased in TBT-treated rats (44.87% TBT200; 36.43% TBT1000), while protein expression was increased but not reaching significance (TBT1000, p = 0.056) by TBT. Therefore, our results show that TBT increases TPO expression and reduces antioxidant enzyme activities in the thyroid gland leading to oxidative stress. Some of these effects could be mediated by the ERα pathway.

The flavonoid quercetin reduces cell migration and increases NIS and E-cadherin mRNA in the human thyroid cancer cell line BCPAP.

Thyroid cancer is the most frequent cancer of the endocrine system. Most patients are treated with thyroidectomy followed by radioiodine therapy. However, in part of the patients, a reduction of the sodium-iodide symporter (NIS) occurs, rendering radioiodine therapy ineffective. Moreover, epithelial-mesenchymal transition (EMT) may occur, leading to more aggressive and invasive features. Herein, we evaluated the effect of the flavonoid quercetin on EMT and NIS expression in BCPAP, a papillary thyroid carcinoma cell line. BCPAP was treated with 100 µM quercetin for 24 h and cell viability, apoptosis, EMT markers and NIS were evaluated. Quercetin decreased cell viability by enhancing apoptosis. The flavonoid also reduced matrix metalloproteinase 9 and increased E-cadherin mRNA levels, inhibiting BCPAP adhesion and migration. Additionally, quercetin increased NIS expression and function. Thus, our results suggest that quercetin could be useful as adjuvant in thyroid cancer therapy, inducing apoptosis, reducing invasion and increasing the efficacy of radioiodine therapy.

Hydroxyapatite calvaria graft repair in experimental diabetes mellitus in rats.

Among the systemic conditions that impact negatively on the planning and execution of surgical procedures, diabetes mellitus (DM) is the primary clinical condition responsible for complications. This study investigated bone formation in critical defects surgically filled with hydroxyapatite (HA) in diabetic rats. A descriptive, randomized sample and blinded analysis were conducted to test bone regeneration in critical bone defects surgically performed in rat calvaria. Twenty adult male Wistar rats were randomly divided into two groups: control, normoglycemic animals (CG); and test, streptozotocin-induced hyperglycemic animals (TG). A circular bone defect was filled with HA and maintained subperiosteally. The clinical parameters evaluated were body weight, water and food intake, fasting blood glucose, and bone alkaline phosphatase. Bone-grafted area samples were submitted for histomorphometric and stereological analysis. The TG showed a significantly higher rate of new bone formation compared with the CG, sacrificed 15 days after surgery (p < 0.0001). However, at the end of the study, there was no significant difference in the amount of bone formed between groups (p = 0.077). In parallel, with the increase in osteoblastic activity observed in the TG by the measurement of systemic bone alkaline phosphatase (p = 0.016), the analysis of polarized microscopy and stereology demonstrated a lower level collagen maturation and mineralization in the TG. Quantitatively, the TG showed significantly better results for bone gain in the first 15 days. Qualitative assessments, however, showed fewer collagen fibers and bone maturation in the TG compared with the CG both at 15 and 45 days. Therefore, the postoperative evaluation of bone grafts with HA in hyperglycemic situations should consider the systemic and local effects of this condition on the quality of bone repair, rather than identifying the filling or stability of the grafted area after the process. We conclude that clinically detectable bone repair in diabetic animal models submitted to hydroxyapatite grafts may be satisfactory in the early stages. However, hyperglycemia compromises the quality of the newly formed bone and the collagen cross-linking involved in this process.

Perfil da composição corporal de mulheres com obesidade grau III pelo método de bioimpedância multipolar / Profile of body composition in women with class III obesity by multipolar bioimpedance method / Perfil de composición corporal en mujeres con obesidad grado III por el método de bioimpedancia multipolar

RESUMO Objetivo O objetivo do estudo foi analisar um perfil da composição corporal de mulheres com obesidade grau III, através do método de bioimpedância multipolar. Métodos Foram avaliadas 13 mulheres com idades entre 20 e 40 anos e sedentárias. Resultados Os resultados demonstraram que as pacientes possuíam um % de 51,9±1,50 % e massa livre de gordura de 48,1±1,50 %. Em relação à massa gorda e massa magra por regiões do corpo, observou-se que no tronco havia 26,3±3,62 kg e 26,2±2,91 kg, seguido dos membros inferiores com 9,1±0,06 kg e 8,4±0,14 kg e dos membros superiores 3,3±0,02 kg e 7,6±0,01 kg, respectivamente. Os pacientes demonstraram certa simetria entre o lado direito e esquerdo tanto para os membros superiores e inferiores, além disto, à massa muscular foi 32,1±5,08 kg, com um índice de massa muscular de 12,7±1,05 kg/m2. Conclusão Houve um maior acumulo de gordura na região do tronco seguido de membros inferiores e superiores e a massa muscular total estava aparentemente preservada, não sendo verificada a obesidade sarcopênica. Como é um grupo de pessoas que ainda é pouco estudado há a necessidade de uma maior investigação sobre o perfil genético, físico e do gasto calórico em repouso e em exercício.(AU)

ABSTRACT Objective To analyze a body composition profile in women with class III obesity using the multipolar bioimpedance method. Methods Thirteen sedentary women aged between 20 and 40 years were evaluated. Results The results show that the patients had a fat percentage of 51.9±1.50 % and lean mass of 48.1±1.50 %. Regarding fat mass and lean mass per body region, figures of 26.3±3.62kg and 26.2±2.91kg in the upper body, 9.1±0.06kg and 8.4±0.14kg in the lower limbs, and 3.3±0.02kg and 7.6±0.01kg in the upper limbs were obtained. Patients had a good symmetry between the left and right sides in both upper and lower limbs, besides of a muscular mass of 32.1±5.08kg, with a muscular mass index of 12.7±1.05kg/m2. Conclusion Higher fat accumulation was observed in the upper body region, followed by lower and upper limbs. Total muscular mass was apparently preserved, although sarcopenic obesity was not verified. Since this is a group of people that is still understudied, there is a need for further research on genetic and physical profile and caloric expenditure during exercise and rest.

RESUMEN Objetivo Analizar un perfil de la composición corporal de mujeres con obesidad grado III, a través del método de bioim-pedancia multipolar. Métodos Se evaluaron 13 mujeres de entre 20 y 40 años y sedentarias. Resultados Los resultados demostraron que las pacientes poseían un %G de 51,9 ± 1,50 % y una masa libre de grasa de 48,1 ± 1,50 %. En cuanto a la masa grasa y masa magra por regiones del cuerpo, se observó que en el tronco había 26,3 ± 3,62 kg y 26,2 ± 2,91 kg, seguido de los miembros inferiores con 9,1 ± 0,06 kg y 8 , 4 ± 0,14 kg y de los miembros superiores 3,3 ± 0,02kg y 7,6 ± 0,01 kg, respectivamente. Los pacientes demostraron cierta simetría entre el lado derecho e izquierdo tanto para los miembros superiores e inferiores, además, a la masa muscular fue 32,1 ± 5,08 kg, con un índice de masa muscular de 12,7 ± 1,05 kg/m2. Conclusión Hubo un mayor acúmulo de grasa en la región del tronco seguido de miembros inferiores, superiores y la masa muscular total estaba aparentemente preservada, no siendo verificada la obesidad sarcopénica. Como es un grupo de personas que todavía es poco estudiado hay la necesidad de una mayor investigación sobre el perfil genético, físico y del gasto calórico en reposo y en ejercicio.(AU)

Diabetes mellitus tipo 1 e disfunções tireoidianas / Diabetes Mellitus type 1 and thyroid dysfunction

Os pacientes com diabetes mellitus (DM) apresentam maior prevalência de doenças tireoidianas que a população geral. A autoimunidade certamente é um fator-chave na relação entre essas disfunções endócrinas. Entretanto, outros mecanismos, como redução da captação de iodeto, da atividade tireoperoxidase e aumento do estresse oxidativo na glândula tireoide, também parecem contribuir para este fato. O presente trabalho visa rever aspectos importantes na relação entre DM e doenças tireoidianas, com especial ênfase nos mecanismos envolvidos no aumento do estresse oxidativo na glândula tireoide decorrente do DM...

Diabetes mellitus (DM) patients show a greater prevalence of thyroid disorders than general population. Autoimmunity is a key factor in the relation between these endocrine diseases. However, additional mechanisms, such as reduction of iodide uptake and thyroperoxidase activity, besides increased oxidative stress in the thyroid gland seem to contribute for this fact. The present work aims to review important aspects in the relation between DM and thyroid disease, with special emphasis in the mechanisms involved in the increased oxidative stress in the thyroid gland due to DM...

Zumbido em uma população ribeirinha exposta ao metilmercúrio / Tinnitus in a riverside population exposed to methyl-mercury

Objetivo : Estudar a prevalência de zumbido, verificando se há associação entre a queixa desse sintoma e o teor de mercúrio e mensurar seu impacto na qualidade de vida. Métodos : Estudo seccional em toda a população do Lago do Puruzinho, localizada na margem esquerda do Rio Madeira, cidade de Humaitá, Estado do Amazonas, Brasil. Todos os residentes maiores de 18 anos, de ambos os gêneros, foram submetidos à anamnese, avaliação otorrinolaringológica e exame audiológico. Os indivíduos que apresentaram queixa de zumbido responderam à versão traduzida do questionário Tinnitus Handicap Inventory (THI). Também foram pesquisados os teores de mercúrio total no cabelo desses indivíduos. Resultados: Para análise dos resultados sobre a queixa de zumbido, os sujeitos foram divididos em dois grupos quanto à presença ou não de zumbido. O Grupo 1 foi composto por indivíduos que apresentaram queixa de zumbido e o Grupo 2, por indivíduos sem zumbido. Foi observado que 40% dos indivíduos apresentaram escores do THI compatíveis com handicap leve. A análise da associação da presença de zumbido com os teores de mercúrio total no cabelo mostrou que ambos os grupos apresentaram níveis elevados de mercúrio, porém não ocorreram diferenças entre os grupos. Conclusão : Um quarto dos ribeirinhos apresentou queixa de zumbido e exposição significativa ao mercúrio, mas não houve associação entre o zumbido e os níveis elevados de mercúrio. .

Purpose : To study the association between the prevalence of tinnitus and mercury exposure and measure the influence of tinnitus on the quality of life. Methods : We conducted a cross-sectional study of men and women aged above 18 years residing in the Lake Puruzinho region, which is located on the left bank of the Rio Madeira, Humaita city, Amazonas state, Brazil. All subjects underwent anamnesis, otorhinolaryngologic evaluation, and an audiology test. Individuals who experienced tinnitus completed the translated Tinnitus Handicap Inventory (THI). We also examined the levels of total mercury in the hair of these individuals. Results : To analyze the results regarding the prevalence of tinnitus, the subjects were divided into two groups according to the presence or absence of tinnitus. Group 1 was composed of subjects with tinnitus and Group 2 was composed of subjects without tinnitus. Consequently, 40% of individuals had scores consistent with mild handicap according to the THI. The analysis of the association between tinnitus and levels of total mercury in hair samples showed that both groups had high levels of mercury. However, this finding was not significantly different between groups. Conclusion : Herein, 25% of the subjects complained of tinnitus and significant exposure to mercury; however, there was no association between the prevalence of tinnitus and high levels of mercury. .

Flavonoid rutin increases thyroid iodide uptake in rats.

Thyroid iodide uptake through the sodium-iodide symporter (NIS) is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO), the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH), and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function.

The mTOR protein as a target in thyroid cancer.

INTRODUCTION: The mammalian target of rapamycin (mTOR) protein is a downstream effector of the phosphatidilinositol-3 kinase (PI3K)/Akt pathway, which regulates not only cell proliferation and viability, but also iodide uptake in thyroid cells. Genetic alterations in the PI3K/Akt/mTOR pathway are common during thyroid cancer progression, and thus, these proteins are attractive targets for cancer therapy. So far, specific mTOR inhibitors, such as rapamycin analogs, have been developed and studied as anti-cancer agents. AREAS COVERED: This review discusses evidence that justifies the potential use of mTOR signaling pathway inhibitors as therapeutic agents for thyroid cancer. EXPERT OPINION: In the near future, mTOR-targeted drugs might represent a new approach for the therapy of thyroid cancer patients; rapamycin analogs have already been developed and are currently being clinically tested. Besides the antiproliferative action of mTOR inhibition, the stimulatory effect on thyroid iodide uptake can also be useful in the treatment of recurrent thyroid cancer. Therefore, if rapamycin analogs are able to increase iodide uptake in thyroid cancer, either alone or in combination with other agents, this will represent a new approach for the treatment of thyroid cancer, which may possibly improve the treatment of patients in which radioiodine therapy is not effective.

Inter-relações entre as funções hormonais do ovário e da tireoide / Interrelations between ovarian and thyroid functions

A relação entre as funções hormonais do ovário e da tireoide vem sendo motivo de interesse da comunidade científica mundial desde o século 19. Ao longo do tempo, diversos estudos objetivaram esclarecer fatos relacionados à interdependência funcional desses sistemas orgânicos. De fato, há evidências da ação direta e indireta do estrogênio na tireoide. Mulheres climatéricas em estado de hipoestrogenismo podem apresentar alterações na função tireoidea. Foram demonstrados efeitos da gonadectomia e da administração de estrogênio na tireoide de animais e de humanos. Por outro lado, alterações da função tireoidea podem causar distúrbios da função reprodutiva feminina. Mulheres portadoras de doenças da tireoide podem apresentar distúrbios menstruais, infertilidade e complicações do ciclo grávido-puerperal. Sendo assim, indicam-se procedimentos para a detecção de distúrbios tireoideos em diversas situações clínicas relacionadas à função reprodutiva feminina. Além disso, a função tireoidea deve ser cuidadosamente avaliada em mulheres com hipotireoidismo durante a gestação ou quando submetidas à estrogenioterapia. Dessa maneira, a função e as doenças da tireoide são assuntos de interesse para o ginecologista. É fundamental a conscientização do profissional que presta assistência à saúde da mulher em relação aos diversos aspectos relacionados às interações entre a tireoide e a função reprodutiva feminina.

Since the 19th century the interrelation between thyroid and sex organs function is recognized. In fact, there are evidences that estrogens act indirectly on the thyroid gland. Postmenopausal women can show altered thyroid function tests. It has been shown in animals and in humans that gonadectomy and estrogens treatment exert effects on thyroid gland. Also, thyroid dysfunction is associated with reproductive dysfunction in women. Both hyper and hypothyroidism may result in menstrual disturbances, infertility, abortion and complicated pregnancy. Tests for detection of thyroid disorders should be performed in women in many situations related to reproductive function. Patients with hypothyroidism should be strictly monitored during pregnancy and hormone replacement therapy with estrogens. Thus, thyroid dysfunction should be a point of interest for gynecologists. Practitioners providing health care for women should be aware of the consequences related to the interactions between these two endocrine systems .

[Clinical repercussion of the 6th edition TNM staging system classification on differentiated thyroid carcinoma]. / Repercussão clínica da reclassificação dos carcinomas diferenciados de tireóide de acordo com a 6a edição do TNM.

The TNM classification of UICC is used for predicting the outcome of thyroid cancer. The 6th edition changed the description of primary tumor (T), regional lymph node (N) and the staging group. The aim of this study was to compare the ability of the 5th and the 6th editions to predict outcome. The two classifications were applied in a retrospective analysis of 90 patients from HUCFF. Sixty-nine patients had papillary carcinoma, 14 follicular, 4 Hürthle cell, and 3 mixed. Patients were followed for a mean period of 58.3 months. At the end of follow-up, 49 patients were disease-free, 23 persisted with disease, 4 had cervical recurrence, 11 had metastases and 3 died. According to the 6th edition, 19 patients were classified as T1, compared to 7 based on the 5th edition; 19 patients were T2 compared to 30; 14 were T3 compared to 10; 22 were T4 compared to 27, and 16 patients were Tx. Both editions showed comparable remissions for stages I, II, and III. For the stage IV there was a significant change in remission, however there was no difference comparing IV and IV C.

New perspectives on the treatment of differentiated thyroid cancer.

Even though differentiated thyroid carcinoma is a slow growing and usually curable disease, recurrence occurs in 20-40% and cellular dedifferentiation in up to 5% of cases. Conventional chemotherapy and radiotherapy have just a modest effect on advanced thyroid cancer. Therefore, dedifferentiated thyroid cancer represents a therapeutic dilemma and a critical area of research. Targeted therapy, a new generation of anticancer treatment, is planned to interfere with a specific molecular target, typically a protein that is believed to have a critical role in tumor growth or progression. Since many of the tumor-initiation events have already been identified in thyroid carcinogenesis, targeted therapy is a promising therapeutic tool for advanced thyroid cancer. Several new drugs are currently being tested in in vitro and in vivo studies and some of them are already being used in clinical trials, like small molecule tyrosine kinase inhibitors. In this review, we discuss the bases of targeted therapies, the principal drugs already tested and also options of redifferentiation therapy for thyroid carcinoma.

Repercussão clínica da reclassificação dos carcinomas diferenciados de tireóide de acordo com a 6ª edição do TNM / Clinical repercussion of the 6th edition TNM staging system classification on differentiated thyroid carcinoma

A classificação TNM segundo a UICC é usada para avaliar os resultados do acompanhamento do carcinoma de tireóide. A 6ª edição modificou a descrição do tumor primário (T), dos linfonodos regionais (N) e dos grupos de estadiamento. O objetivo deste estudo foi comparar a habilidade das 5ª e 6ª edições em predizer resultados. As duas classificações foram aplicadas em uma análise retrospectiva de 90 pacientes do HUCFF. Sessenta e nove pacientes apresentavam carcinoma papilífero, 14 folicular, 4 células de Hürthle e 3 misto. Os pacientes foram acompanhados por um período médio de 58,3 meses. Ao final do acompanhamento, 49 pacientes estavam em remissão, 23 com doença persistente, 4 com recorrência tumoral, 11 com metástases e 3 evoluíram para o óbito. De acordo com a 6ª edição, 19 pacientes foram classificados como T1, comparado com 7 pela 5ª edição; 19 pacientes T2 comparado com 30; 14 classificados como T3 comparado com 10; 22 como T4 comparado com 27, e 16 pacientes como Tx. Ambas as edições mostraram remissões comparáveis para os estágios I, II e III. Para o estágio IV houve uma mudança significativa na remissão, entretanto não houve diferença comparando IV e IV C.

The TNM classification of UICC is used for predicting the outcome of thyroid cancer. The 6th edition changed the description of primary tumor (T), regional lymph node (N) and the staging group. The aim of this study was to compare the ability of the 5th and the 6th editions to predict outcome. The two classifications were applied in a retrospective analysis of 90 patients from HUCFF. Sixty-nine patients had papillary carcinoma, 14 follicular, 4 Hürthle cell, and 3 mixed. Patients were followed for a mean period of 58.3 months. At the end of follow-up, 49 patients were disease-free, 23 persisted with disease, 4 had cervical recurrence, 11 had metastases and 3 died. According to the 6th edition, 19 patients were classified as T1, compared to 7 based on the 5th edition; 19 patients were T2 compared to 30; 14 were T3 compared to 10; 22 were T4 compared to 27, and 16 patients were Tx. Both editions showed comparable remissions for stages I, II, and III. For the stage IV there was a significant change in remission, however there was no difference comparing IV and IV C.

New perspectives on the treatment of differentiated thyroid cancer

Even though differentiated thyroid carcinoma is a slow growing and usually curable disease, recurrence occurs in 20-40 percent and cellular dedifferentiation in up to 5 percent of cases. Conventional chemotherapy and radiotherapy have just a modest effect on advanced thyroid cancer. Therefore, dedifferentiated thyroid cancer represents a therapeutic dilemma and a critical area of research. Targeted therapy, a new generation of anticancer treatment, is planned to interfere with a specific molecular target, typically a protein that is believed to have a critical role in tumor growth or progression. Since many of the tumor-initiation events have already been identified in thyroid carcinogenesis, targeted therapy is a promising therapeutic tool for advanced thyroid cancer. Several new drugs are currently being tested in in vitro and in vivo studies and some of them are already being used in clinical trials, like small molecule tyrosine kinase inhibitors. In this review, we discuss the bases of targeted therapies, the principal drugs already tested and also options of redifferentiation therapy for thyroid carcinoma.

Apesar de o carcinoma diferenciado da tireóide ser considerado uma doença de curso indolente e geralmente curável, recorrência tumoral ocorre em aproximadamente 20 a 40 por cento e desdiferenciação celular, em até 5 por cento dos casos. A quimioterapia convencional e a radioterapia apresentam apenas um modesto efeito sobre o câncer de tireóide avançado. Dessa forma, o carcinoma da tireóide desdiferenciado representa um dilema terapêutico e uma importante área de pesquisa. A terapia direcionada, uma nova geração de tratamento para o câncer, tem como objetivo interferir com um alvo molecular específico, geralmente uma proteína considerada fundamental para o crescimento e progressão tumoral. Como muitos eventos iniciadores do processo de carcinogênese tireoideana já foram identificados, a terapia direcionada representa uma promissora opção terapêutica para o carcinoma da tireóide avançado. Várias drogas novas estão em estudos in vitro e in vivo e algumas já estão sendo testadas em estudos clínicos, como as pequenas moléculas inibidoras de tirosina cinase. Nesta revisão, as bases moleculares da terapia direcionada, as principais drogas utilizadas e as opções terapêuticas de rediferenciação do carcinoma da tireóide serão discutidas.

Amplificação de mRNA de tireoglobulina no sangue de pacientes com carcinoma diferenciado da tireóide: qual o seu verdadeiro significado? / Thyroglobulin mRNA amplification in peripheral blood of patients with differentiated thyroid carcinoma: what does it really mean?

Apesar do excelente prognóstico, aproximadamente 20-40 por cento dos pacientes com carcinoma diferenciado da tireóide (CDT) evoluem com recidiva tumoral e o prognóstico está relacionado principalmente à detecção precoce da doença. Desta forma, o acompanhamento permanente dos pacientes com exames sensíveis é fundamental. A tireoglobulina (Tg) sérica já demonstrou importância como marcador de recidiva. Entretanto, sua dosagem apresenta ainda algumas dificuldades, como a interferência com anticorpo anti-Tg, e a sensibilidade dependente do nível de TSH. A amplificação de mRNA tumor-específico extraído a partir de células neoplásicas na corrente sangüínea apresentou resultados iniciais promissores. No entanto, após quase uma década de estudo da detecção do mRNA de Tg no sangue, ainda não foi estabelecida sua real contribuição no acompanhamento dos pacientes com CDT. Após análise crítica dos estudos publicados, verifica-se a enorme diversidade de protocolos empregados e resultados conflitantes. Desta forma, até o momento, a amplificação de mRNAs tireóide-específicos não é superior à dosagem de Tg sérica existente. A possibilidade de transcrição ilegítima e splicing alternativo são fatores que podem interferir com a especificidade do método.