Search

The identification of thyroid tumors with the potential for poor evolution is a major concern, as current management can range from simple active surveillance to aggressive therapeutic measures. MicroRNAs are small non-coding RNAs that play a key role in the regulation of gene expression and therefore in the pathogenesis and progression of different types of cancers. Here we employed several bioinformatics tools to investigate deregulated miRNAs in the lymph node metastasis (LNM) of two different types of thyroid tumors. Using thyroid cancer RNA-seq data available on Gene Expression Omnibus (GEO), we identified 14 common deregulated miRNAs in LNM of both medullary and papillary thyroid carcinomas, three of them still negatively deregulated when compared to their respective primary tumor: miR-199a-3p, miR-199a-5p, and miR-148a-5p. Public data available on TCGA confirmed the downregulation of miR-148a-5p in LNM and tumors with advanced AJCC stage. Looking at their predicted target genes, ITGA3, PVRL1 (also called NECTIN1), SNN, and FBXO28 genes were confirmed as positively deregulated in LNM papillary thyroid carcinomas when compared to normal tissues. Public data available on TCGA once again confirmed higher expression of the ITGA3 gene in LNM, larger and invasive tumors (T4a), and stage III and IV. Similar results were observed for PVRL1 (NECTIN1) and FBXO28, but not for SNN. These bioinformatic analysis findings suggest that miR-199a-3p, miR-199a-5p, and miR-148a-5p dysregulation, leading to epithelial-mesenchymal transition and cell adhesion failure, are associated with thyroid tumors’ LNM. Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.

Abnormalities in the thyroid function and thyroid autoantibodies have been frequently described in patients with autoimmune diseases but seldom in antiphospholipid syndrome patients. In order to determine the prevalence of thyroid function and autoimmune abnormalities, we compared serum thyrotropin (TSH, serum free thyroxine (T4) levels, thyroid antithyroglobulin (TgAb) and antithyroperoxidase (TPOAb) levels of 25 patients with systemic sclerosis, 25 patients with rheumatoid arthritis and 13 patients with antiphospholipid syndrome to a control group of 113 healthy individuals. Evaluation included a thorough clinical examination with particular attention to thyroid disease and a serologic immune profile including rheumatoid factor, antinuclear and anticardiolipin antibody measurements. Subclinical hypothyroidism (4.2Ciertas anormalidades en la función tiroidea y anticuerpos antitiroideos han sido frecuentemente descriptos en pacientes con enfermedades autoinmunes, y más raramente en pacientes con el síndrome antifosfolipídico. Para determinar la prevalencía de anormalidades en la función tiroidea y de autoinmunidad, comparamos los niveles séricos de tirotropina (TSH) tiroxina libre en suero (T4) anticuerpos antitiroglobulina (TgAb) y antitiroperoxidasa (TPOAb) en 25 pacientes con esclerosis sistémica, 25 pacientes con artritis reumatoidea y 13 pacientes con el síndrome antifosfolipídico con un grupo control de 113 individuos aparentemente sanos. La evaluación incluyó un completo examen clínico con particular atención para las enfermedades de la tiroides y una evaluación inmunológica incluyendo dosaje del factor reumatoideo, anticuerpos antinucleares y anticardiolipina. Hipotiroidismo subclínico (4.2

Para avaliarmos o impacto da adesão no controle do hípotiroidismo em nosso meio, estudamos 100 portadores de hipotiroidismo mal controlados (Mo de TSH: 12U/L) acompanhados no HC-UNICAMP e no HUCFF-UFRJ, 80 mulheres e 20 homens de nível sócio-econômico e cultural similar. Após serem examinados e orientados quanto à importância de seu uso adequado, os pacientes recebiam hormônio tiroidiano em uma das 4 apresentações comercialmente disponíveis em nosso meio, de forma aleatória e em dose similar à anteriormente prescrita, por um período médio de 3 meses. Os 25 pacientes de cada grupo possuíam características clínicas e sócio-econômico-culturais semelhantes com renda per capita mensal em torno de U$ 100,00 (X²: NS). Mensalmente os doentes eram examinados por um mesmo médico. Realizávamos um controle do número de comprimidos restantes e embalagens vazias, dosagens de TSH e de T4 livre. Nossos resultados mostram que 82% dos pacientes não aderiam ao tratamento proposto, faltando aos retornos (36% dos casos) e/ou não seguindo corretamente a prescrição médica (66% dos casos). Os níveis de TSH foram controlados em 77 pacientes ao término do estudo, independente da formulação de tiroxina prescrita (X² de pacientes controlados/grupo: NS). Dezesseis pacientes apresentaram níveis de TSH diminuídos no 1o retorno, sugerindo que usavam doses inferiores às prescritas antes do medicamento ser-lhes fornecido. Concluímos que podemos controlar portadores de hipotiroidismo adequadamente com qualquer uma das apresentações disponíveis no mercado nacional quando o paciente adere ao esquema terapêutico proposto.

Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis.This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil.After structuring clinical questions, search for evidence was made available in the literature, initially in the database MedLine, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question.We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis.The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient.

Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial.This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil.After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience.The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH.Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values10 mU/L and for certain patient subgroups.

To investigate the effectiveness of 2 fixed iodine (¹³¹I) doses for the treatment for Graves hyperthyroidism and their impact on eye disease.We prospectively examined 76 patients who received a fixed dose of 370 MBq (group 1) and 52 patients who received 555 MBq ¹³¹I (group 2). Patients were followed up for 12 months and considered in remission when they were in a stable euthyroid or hypothyroid state in the absence of antithyroid drugs 12 months after ¹³¹I administration. Eight patients with active eye disease received a daily dose of 0.5 mg/kg prednisone per kilogram of body weight at the time of radioiodine therapy for 1 month.The remission rate obtained was similar in groups 1 (73.7%) and 2 (80.8%; P = 0.35). Hypothyroidism was diagnosed in 56.5% of the 370-MBq group and 71.1% of the 555-MBq group patients (P = 0.13). There was no correlation among clinical features, thyroid uptake, antibody levels, serum hormones levels, and outcome. However, logistic regression analysis demonstrated that patients with large thyroid glands had 2.4 times less chance to go into remission (odds ratio; 95% confidence interval = 1.18-4.96). None of the patients developed eye disease during any fixed-dose treatment regimen or worsened their previously diagnosed ophthalmopathy.Fixed doses of 370 MBq and 555 MBq ¹³¹I provided similar remission rates; however, outcome was influenced by the thyroid size. We propose that 370 MBq ¹³¹I should be the routine treatment dose for all Graves disease patients, reserving a dose of 555 MBq ¹³¹I to palpable large goiters, without any additional concern to eye disease.

We aimed to investigate the use of NIS mRNA and protein expression as a diagnostic and/or prognostic marker in patients with differentiated thyroid cancer (DTC).This is a case-control study.We studied 397 thyroid nodules tissue samples, including 224 papillary thyroid carcinomas (PTCs), 41 follicular carcinomas, 58 nodular goiters, 56 follicular adenomas and 18 normal tissues assembled in a tissue microarray.NIS protein was identified using a monoclonal antibody that labelled only the follicular cell basolateral membrane of all 397 tissue samples. In addition, NIS mRNA was quantified in 145 DTC patients and 85 PTC cases were screened for BRAF(V600E) mutation.We found low NIS mRNA expression and low or negative NIS protein expression in most DTC. NIS expression was lower in DTC patients over 45 years old and in tumours larger than 2 cm. There was a tendency for lower NIS expression in advanced stages and patients presenting recurrences. All 13 DTC patients who succumbed to the disease were NIS negative at immunohistochemistry and had very low mRNA expression. NIS expression was lower in PTC presenting BRAF(V600E) mutation. However, neither NIS immunohistochemical analysis nor NIS mRNA quantified expression could identify individuals with poor prognosis.Our data suggest that NIS expression may help characterize patients' risk and individuals with a poor response to therapy, but is not useful as a diagnostic or prognostic marker, reinforcing the current concept that an appropriate management of DTC patient is the most important and modifiable prognostic factor.

To investigate the utility of nuclear chromatin texture assessment in the differential diagnosis of follicular patterned lesions, by means of examining 76 samples previously submitted to the immunohistochemical protein analysis of HBME-1, CK-19 and galectina-3.HBME-1 confirmed to be the most sensitive marker of malignancy. A series of morphometric, densitometric and texture variables were useful in the discrimination of the different types of follicular lesions. Among these variables, r(2), a parameter related to the granularity of the nucleus presented the best accuracy, sensitivity, specificity and positive and negative predictive values, distinguishing benign from malignant lesions.The morphometric analysis of nuclear chromatin images may add accuracy to the differential diagnosis of follicular patterned lesions.

The glutathione-S-transferase (GST) gene family has an important role in the biotransformation and detoxification of different xenobiotics and endogenous carcinogens. GST profile has been associated to an increased risk for several types of tumors in different populations, but ethnic stratification makes data interpretation difficult. The Brazilian population represents a unique model in which the types and frequencies of GST gene polymorphisms are less influenced by ethnicity.To evaluate the influence of GST profile in different age and gender groups regarding the risk of developing cancer and its relationship to smoking habit, the GSTT1, GSTM1, and GSTP1 genotypes of 785 Brazilian patients with cancer and 873 cancer-free controls paired on the basis of sex, age, ethnicity, diet and exercise routine, lifetime occupational history, smoking history, general health conditions, and previous diseases were compared.A univariate logistic regression analysis demonstrated that age over 45 years (p=0.0417) and smoking (p=0.0015) were related to cancer. Multivariate analysis confirmed the importance of advanced age in susceptibility to cancer (p=0.0001). It was also observed that smoking significantly increased the risk of cancer among individuals over 45 years old (OR: 1.825, 95%CI: 1.241-2.682). However, no correlation between risk of cancer, smoking habit, age, or gender and any of the studied GST polymorphisms was found.It is suggested that GST profile does not exert an important impact on the influence of tobacco smoking on cancer risk.

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% 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%). Differentiated thyroid carcinoma accounts for 90% 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.

The trend of increasing thyroid cancer has been recognized in Brazil as well as all over the world for several decades. The large use of simple and effective diagnostic tools has significantly contributed to this trend. It is estimated that small carcinomas found at surgery for benign thyroid disorders and by ultrasonography will be identified at greater frequency in the further years. Part of these tumors occurs in low-risk patients that may benefit of less aggressive management strategies. However, the characterization of low-risk patient is still confusing and we lack adequate markers to tell apart patients that may present a troublesome progression of the disease. Furthermore, the use of new follow-up methods has recently changed some guidelines. A multidisciplinary team, including basic scientists, endocrinologists, nuclear medicine physicians, thyroid surgeons and endocrine pathologists reviewed the pertinent literature and, based on their experience, propose some management guidelines for Brazilian patients with low-risk thyroid carcinomas.

Because most differentiated thyroid carcinomas have an excellent prognosis, some authors have claimed that these patients are suffering from over treatment. Grouping patient- and tumor-specific factors have been proposed for prognostic stratification, but no clinicopathologic staging was demonstrated to be useful at the present time. More recently, molecular genetic tools have been used to identify and understand how the primary tumor progresses and many molecular markers have been proposed in order to distinguish the subset of patients at risk of developing metastasis. Here we analyzed some of them, with emphasis on the expression of NIS, a determinant of prognosis since the functional integrity of the iodine transport is essential to assure an uptake of radioiodine high enough to detect and destroy any tumoral thyroid tissue. More recent observations on how some relevant molecular genetics aspects of thyroid cancer impact new potential therapeutic approaches are also discussed.

Germline mutations in the Exostoses-1 gene (EXT1) are found in hereditary multiple exostoses syndrome, which is characterized by the formation of osteochondromas and an increased risk of chondrosarcomas and osteosarcomas. However, despite its putative tumor-suppressor function, little is known of the contribution of EXT1 to human sporadic malignancies. Here, we report that EXT1 function is abrogated in human cancer cells by transcriptional silencing associated with CpG island promoter hypermethylation. We also show that, at the biochemical and cellular levels, the epigenetic inactivation of EXT1, a glycosyltransferase, leads to the loss of heparan sulfate (HS) synthesis. Reduced HS production can be reversed by the use of a DNA demethylating agent. Furthermore, the re-introduction of EXT1 into cancer cell lines displaying methylation-dependent silencing of EXT1 induces tumor-suppressor-like features, e.g. reduced colony formation density and tumor growth in nude mouse xenograft models. Screening a large collection of human cancer cell lines (n=79) and primary tumors (n=454) from different cell types, we found that EXT1 CpG island hypermethylation was common in leukemia, especially acute promyelocytic leukemia and acute lymphoblastic leukemia, and non-melanoma skin cancer. These findings highlight the importance of EXT1 epigenetic inactivation, leading to an abrogation of HS biosynthesis, in the processes of tumor onset and progression.