TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

CONTEXT: Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. OBJECTIVE: This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. METHODS: Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. RESULTS: From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. CONCLUSION: GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

Thyroid Hormone Homeostasis in Levothyroxine-treated Patients: Findings From ELSA-Brasil.

CONTEXT: The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable. OBJECTIVE: This work aimed to assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study. METHODS: The ELSA-Brasil study follows 15 105 adult Brazilians (aged 35-74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyrotropin (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy. RESULTS: Initiation of therapy with LT4 resulted in an 11% to 19% decrease in TSH, an approximately 19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and antidiabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least 1 serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least 1 serum FT3 below the reference range (<0.23 ng/dL). CONCLUSION: The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.

Differentiated thyroid carcinoma: what the nonspecialists needs to know.

Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

A Cross-Sectional Analysis of Cardiovascular and Bone Health Care Utilization During Treatment With Thyroid Hormone.

CONTEXT: Combination therapy with levothyroxine and liothyronine (LT4 + LT3) and desiccated thyroid extract (DTE) make up >10% of new thyroid hormone (TH) prescriptions in the United States. OBJECTIVE: To assess health care utilization related to cardiovascular disease (CVD) and bone health (BH) events (atrial fibrillation [AF], heart failure [HF], myocardial infarction [MI], stroke, and osteoporosis/fractures [FX]) in participants taking LT4+LT3 or DTE surveyed in the Medical Expenditure Panel Survey database. MATERIALS AND METHODS: Multi-year cross-sectional analysis examining 5437 participants (≥18 years old) treated with LT4, LT4+LT3, or DTE between 2016 and 2020. Health care utilization was assessed through outpatient, emergency, and hospital visits for AF, HF, MI, stroke, FX, and a composite index. A weighted analysis provided national estimates of health care utilization parameters. Utilization was re-analyzed following propensity score-based matching to balance sociodemographic and clinical covariates between treatment groups. Additionally, provider type and specialty data were obtained from visits associated with TH prescriptions. RESULTS: 5106 participants were treated with LT4 monotherapy, 252 with DTE, and 79 with LT4 + LT3. Prevalence of combined outpatient CVD and BH-related care utilization was lower among DTE/LT4+LT3 vs LT4 users (3.5% vs 7.7%; P = .008). There were no differences in emergency/hospital events. After covariate balancing, CVD and BH-related care utilization was similar between groups in outpatient and emergency/hospital settings. LT3 and DTE made up 7.6% of all TH prescriptions. For visits associated with DTE prescriptions, nurse practitioners and alternative medicine professionals were more likely to be identified as the primary provider type. CONCLUSION: No significant differences in CVD- and BH-related health care utilization were identified between LT4 and DTE/LT4+LT3 users after covariate balancing. Non-MD providers were more likely to prescribe DTE.

Differentiated thyroid carcinoma: what the nonspecialists needs to know

ABSTRACT Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Effect of Recombinant Human Growth Hormone Treatment in a Patient with Short Stature Associated with the Ring Chromosome 17 Syndrome.

Background: Ring chromosome 17 syndrome is a rare hereditary disorder whose prevalence is less than 1 : 1.000.000. We present a ten-year-old patient with ring chromosome 17 syndrome who had short stature and was treated with recombinant human growth hormone (rhGH). Case Report. A ten-year-old male scholar had moderate left conductive deafness, left kidney hypoplasia with hypertension, epilepsy, malformations in hands, feet, and abdomen, and disproportionately short stature. Despite no evidence of growth hormone deficiency, rhGH treatment was indicated as a therapeutic test due to his decelerated growth velocity and severe short stature. As a result, his growth velocity increased by 4.2 cm per year and his stature Z-score increased (from -5.87 to -5.23). Conclusion: The patient's severe short stature may be related to genetic, environmental, and hormonal factors and the positive response to rhGH may indicate abnormalities in the somatotropic axis that were mitigated with the treatment. Although rhGH associated with adequate comorbidities controls improved his growth velocity and height Z-score, its effects in the long term are still unclear.

Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism.

INTRODUCTION: Mutations and single nucleotide polymorphisms (SNPs) in the genes encoding the network of proteins involved in thyroid hormone signaling (TH) may have implications for the effectiveness of the treatment of hypothyroidism with LT4. It is conceivable that loss-of-function mutations or SNPs impair the ability of LT4 to be activated to T3, reach its targets, and ultimately resolve symptoms of hypothyroidism. Some of these patients do benefit from therapy containing LT4 and LT3. METHODS: Here, we reviewed the PubMed and examined gene mutations and SNPs in the TH cellular transporters, deiodinases, and TH receptors, along with their impact on TH signaling, and potential clinical implications. RESULTS: In some mechanisms, such as the Thr92Ala-DIO2 SNP, there is a compelling rationale for reduced T4 to T3 activation that limits the effectiveness of LT4 to restore euthyroidism. In other mechanisms, a potential case can be made but more studies with a larger number of individuals are needed. DISCUSSION/CONCLUSION: Understanding the clinical impact of the genetic makeup of LT4-treated patients may help in the preemptive identification of those individuals that would benefit from therapy containing LT3.

Feasibility of a snowball sampling survey to study active surveillance for thyroid microcarcinoma treatment among endocrinologists and surgeons of Brazil

Abstract Objectives: This study aims to investigate if a sampling method using virtual networks is feasible to survey AS adoption among this "hard-to-reach" population of Brazilian doctors. Methods: An online piloted 11-point structured survey questionnaire (designed using Googleforms®) probed the actual treatment patterns for adult patients with PTMCs, including treatment decision-making nonoperative options, was undertaken between 10 November and 30 November 2020. Participants were reached by the mobile phone Application (APP) and a snowball sampling strategy was used to recruit a total of 4783 members (maximum number of potential reach), which is the total of doctors of the all 21 social media WhatsApp® groups. Results: From a total of 4783 members (maximum number of potential reach), there were 657 (13.7%) doctors (actual reach) who clicked the web link of the questionnaire, out of whom 512 (10.7%) fully completed the online survey. Among the survey respondents, 361 were endocrinologists (70.5%) and 151 were surgeons (29.5%). Overall, for low-risk PTMCs in an elderly patient, 118 responders (23%) recommend AS, while 390 (76%) recommend immediate surgery as the management, including lobectomy (18.5%) and Total Thyroidectomy (58.2%). The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or raised the size during the follow-up. Conclusion: Using snowball sampling strategy as an innovative route to conduct surveys was feasible and applicable but the rate of response was still very low. Our data also suggests the need to investigate if AS is embraced by Brazilian doctors.

Feasibility of a snowball sampling survey to study active surveillance for thyroid microcarcinoma treatment among endocrinologists and surgeons of Brazil.

OBJECTIVES: This study aims to investigate if a sampling method using virtual networks is feasible to survey AS adoption among this "hard-to-reach" population of Brazilian doctors. METHODS: An online piloted 11-point structured survey questionnaire (designed using Googleforms®) probed the actual treatment patterns for adult patients with PTMCs, including treatment decision-making nonoperative options, was undertaken between 10 November and 30 November 2020. Participants were reached by the mobile phone Application (APP) and a snowball sampling strategy was used to recruit a total of 4783 members (maximum number of potential reach), which is the total of doctors of the all 21 social media WhatsApp® groups. RESULTS: From a total of 4783 members (maximum number of potential reach), there were 657 (13.7%) doctors (actual reach) who clicked the web link of the questionnaire, out of whom 512 (10.7%) fully completed the online survey. Among the survey respondents, 361 were endocrinologists (70.5%) and 151 were surgeons (29.5%). Overall, for low-risk PTMCs in an elderly patient, 118 responders (23%) recommend AS, while 390 (76%) recommend immediate surgery as the management, including lobectomy (18.5%) and Total Thyroidectomy (58.2%). The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or raised the size during the follow-up. CONCLUSION: Using snowball sampling strategy as an innovative route to conduct surveys was feasible and applicable but the rate of response was still very low. Our data also suggests the need to investigate if AS is embraced by Brazilian doctors.

Are the anatomical, clinical, and ultrasound characteristics of thyroid nodules with Bethesda III or IV cytology and ACR TI-RADS 3, 4, or 5 able to refine the indications for molecular diagnostic tests?

OBJECTIVE: To analyze the association of clinical, anatomical, and ultrasound (US) characteristics of malignancies in Bethesda III or IV (III-B or IV-B) thyroid nodules. METHODS: The association between malignancies and the following variables were analyzed: III-B or IV-B, age < 55 years and ≥ 55 years, sex, family history of thyroid cancer, history of irradiation, nodule size, and ACR TI-RADS classification in 62 participants who underwent thyroidectomy. RESULTS: Of the 62 participants, 87.1% (54/62) were women, 74.2% were < 55 years old, 95.2% had no family history of thyroid cancer, 56.5% had nodules < 2 cm in size, 62.9% were IV-B, and 69.4% were ACR TI-RADS 4. Thirty-two patients had thyroid carcinoma, and 30 had benign histology. Among all factors associated with malignancy, only ACR TI-RADS 5 classification on US was found to be statistically significant (p = 0.014), while III-B with architectural atypia cytological classification was the only one significantly associated with benign status (p = 0.004). CONCLUSION: Only a high risk of malignancy as assessed using US was able to refine the indication for molecular tests in a group of patients with indeterminate nodules. We found 85% (53/62) of III-B or IV-B thyroid nodules would benefit from available molecular diagnostic tests.

Congenital hypothyroidism and thyroid cancer.

Differentiated thyroid carcinoma (DTC) combined with congenital hypothyroidism (CH) is a rare situation, and there is no well-established causal relationship. CH is a common congenital endocrine, while DTC occurring in childhood represents 0.4-3% of all malignancies at this stage of life. The association of CH with DTC could be related to dyshormonogenetic goiter (DHG) or developmental abnormalities. This review will explore the clinical features and the molecular mechanisms potentially associated with the appearance of DTC in CH: sporadic somatic driver mutations, chronic increase of thyroid-stimulating hormone (TSH) levels, higher concentrations of hydrogen peroxide (H2O2), cell division cycle associated 8 (Borelain/CDC8) gene mutations, and in others genes associated with CH - either alone or associated with the mechanisms involved in dyshormonogenesis. There are some pitfalls in the diagnosis of thyroid cancer in patients with CH with nodular goiter, as the proper cytological diagnosis of nodules of patients with dyshormonogenesis might be demanding due to the specific architectural and cytological appearance, which may lead to an erroneous interpretation of malignancy. The purpose of this article is to suggest an analytical framework that embraces the fundamental relationships between the various aspects of CH and CDT. In face of this scenario, the entire genetic and epigenetic context, the complex functioning, and cross talk of cell signaling may determine cellular mechanisms promoting both the maintenance of the differentiated state of the thyroid follicular cell and the disruption of its homeostasis leading to cancer. Whereas, the exact mechanisms for thyroid cancer development in CH remain to be elucidated.

Are the anatomical, clinical, and ultrasound characteristics of thyroid nodules with Bethesda III or IV cytology and ACR TI-RADS 3, 4, or 5 able to refine the indications for molecular diagnostic tests?

ABSTRACT Objective: To analyze the association of clinical, anatomical, and ultrasound (US) characteristics of malignancies in Bethesda III or IV (III-B or IV-B) thyroid nodules. Subjects and methods: The association between malignancies and the following variables were analyzed: III-B or IV-B, age < 55 years and ≥ 55 years, sex, family history of thyroid cancer, history of irradiation, nodule size, and ACR TI-RADS classification in 62 participants who underwent thyroidectomy. Results: Of the 62 participants, 87.1% (54/62) were women, 74.2% were < 55 years old, 95.2% had no family history of thyroid cancer, 56.5% had nodules < 2 cm in size, 62.9% were IV-B, and 69.4% were ACR TI-RADS 4. Thirty-two patients had thyroid carcinoma, and 30 had benign histology. Among all factors associated with malignancy, only ACR TI-RADS 5 classification on US was found to be statistically significant (p = 0.014), while III-B with architectural atypia cytological classification was the only one significantly associated with benign status (p = 0.004). Conclusion: Only a high risk of malignancy as assessed using US was able to refine the indication for molecular tests in a group of patients with indeterminate nodules. We found 85% (53/62) of III-B or IV-B thyroid nodules would benefit from available molecular diagnostic tests.

TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma.

PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes. RESULTS: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. CONCLUSIONS: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

The Genetics of Papillary Microcarcinomas of the Thyroid: Diagnostic and Prognostic Implications.

Papillary microcarcinoma of the thyroid (mPTC) is defined by the WHO as a papillary thy-roid cancer measuring 10mm or less in diameter and it is nowadays a topic of intense debate among the members of the medical community due to its apparent "epidemic" rise. Although these tumors follow almost always an indolent clinical course and carry an excellent prognosis, it is known that a small sub-set may display a potentially aggressive behavior. Nevertheless, we still lack an accurate way of predict-ing those which will cause significant disease. In an attempt to address this problem, a number of clini-co-pathologic features have been studied as poor prognostic markers in mPTC, and their association with known genetic alterations in thyroid cancer has been evaluated. Herein we review the present knowledge concerning mPTC's genetic profile, namely the prevalence of BRAF (V600E), RAS and TERT promoter mutations and RET/PTC and PAX8-PPARG rearrangements and report the results of the evaluation in the putative prognostic value of these genetic alterations in mPTC.

Simultaneous Papillary Carcinoma in Thyroglossal Duct Cyst and Thyroid.

Thyroglossal duct cyst (TDC) is a cystic expansion of a remnant of the thyroglossal duct tract. Carcinomas in the TDC are extremely rare and are usually an incidental finding after the Sistrunk procedure. In this report, an unusual case of a 36-year-old woman with concurrent papillary thyroid carcinoma arising in the TDC and on the thyroid gland is presented, followed by a discussion of the controversies surrounding the possible origins of a papillary carcinoma in the TDC, as well as the current management options.

Projeto-piloto de telemonitoramento glicêmico de pacientes com diabete melito tipo 2 na Atenção Primária em Belo Horizonte-MG / A pilot project on glycemic home telemonitoring in type 2 diabetes patients in a Brazilian primary healthcare unit

Introdução: O telemonitoramento aperfeiçoa o controle de doenças crônicas, reduz internações e readmissões hospitalares, possibilita alta mais precoce e aumenta a satisfação do paciente. Objetivo: O estudo objetiva avaliar o impacto de um projeto-piloto de telemonitoramento nos valores da hemoglobina glicada (HbA1C) de pacientes portadores de diabete melito tipo 2 (DM2) com controle glicêmico insatisfatório. Busca, ainda, avaliar a viabilidade dessa ferramenta na Atenção Primária, em relação ao uso e à qualidade da transmissão dos dados, segundo a percepção dos usuários. Materiais e Métodos: Selecionaram-se 28 pacientes insulinizados, entre 30 a 80 anos, com diagnóstico de DM2, assistidos pela equipe de Saúde da Família de uma Unidade Básica de Saúde, localizada em Belo Horizonte. Os pacientes apresentavam duas medidas de HbA1C >7% realizadas dentro dos últimos 360 dias, sendo a medida mais recente realizada até 30 dias antes do início do estudo. Os pacientes foram alocados aleatoriamente em dois grupos, sendo 15 pacientes em telemonitoramento domiciliar e 13 em acompanhamento tradicional. Mensurações das HbA1C dos pacientes foram coletadas ao início e após 90 dias de seguimento. Não houve perdas ou exclusões de pacientes. Resultados: Após 90 dias de intervenção, verificou-se redução significativa das médias dos valores de HbA1C apenas nos pacientes sob telemonitoramento (IC95%; p<0,01 em Teste T). Conclusão: Esse projeto-piloto sinaliza que o telemonitoramento em DM2 é viável, de fácil execução e tem impacto positivo e significativo na melhoria do controle glicêmico dos pacientes. Estudos com um número maior de pacientes se fazem necessários para corroborar esses achados. (AU)

Introduction: Decades of research has issued a lot of data about the cost effectiveness and efficacy of many telemedicine applications. Telemonitoring improves control of chronic diseases, it reduces the need for hospital care, the hospital readmission rate, and it allows earlier hospital discharge and increases patient satisfaction. Objective: We evaluate the impact of a pilot project on glycemic telemonitoring in type 2 Diabetes (DM2) patients on measures of glycated hemoglobin (HbA1C) and evaluate the viability of telemonitoring, about the use and quality of data transmission, in primary health care. Materials and Methods: We had 28 insulinized patients aged 30-80 years diagnosed with DM2, assisted by a Family Health Unit from Horizonte-Brazil. Those patients had at least two HbA1C> 7% within the 360 days prior to the survey and they were randomly divided into two groups, - 15 patients with home telemonitoring and 13 patients with traditional follow-up. The HbA1c values of patients were collected at the beginning and after 90 days. There were no 'loss to follow-up' or exclusions cases. Results: Comparison between HbA1C means of both groups revealed a statistically significant reduction in HbA1C levels only in telemonitored group (IC95%; p<0,01 t-test). Conclusions: This pilot project indicates that home telemonitoring in DM2 is viable, easy to perform, and it has a positive and significant impact on glycemic control of these patients. Larger studies are required to confirm these statements. (AU)

Molecular Markers Involved in Tumorigenesis of Thyroid Carcinoma: Focus on Aggressive Histotypes.

Thyroid cancer derived from follicular cells (TCDFC) comprises well-differentiated (papillary and follicular) carcinoma, poorly differentiated carcinoma, and anaplastic carcinoma. Papillary thyroid carcinoma is the most common endocrine cancer, and its incidence is steadily increasing. Lethality and aggressiveness of TCDFC is inversely correlated with differentiation degree. In this review, an emphasis has been put on molecular markers involved in tumorigenesis of thyroid carcinoma with a focus on aggressive histotypes and the role of such biomarkers in predicting thyroid cancer outcome. Genetic rearrangements in TCDFC (RET/PTC, PAX8/PPARG) and mutations in RAS, BRAF, TERT promoter (TERTp), TP53, PIK3CA, and AKT1 are discussed. The majority of the studies to date indicate that TERTp mutations can serve as a marker of more aggressive disease in all the subtypes of thyroid carcinoma, being the best current marker of poor prognosis, due to its independent association with distant metastases and increased disease-specific mortality. Some studies suggested that a more accurate prediction of thyroid cancer outcome may be possible through a more extensive genetic analysis. The same is true concerning the identification of other mutations that are only relatively frequent in advanced tumors (e.g., TP53, PIK3CA, or AKT1). A better understanding of the prognostic role of TERTp mutation (together with additional ones like BRAF, RAS, PIK3CA, AKT1, or TP53) and the clarification of their putative role in fine-needle aspiration biopsies are likely to allow, in the future, an early refinement of the stratification risk in patients with well-differentiated carcinomas. It is worth noting that, as with any categorical staging system, the risk evaluation within each category (low, intermediate, and high) varies depending on the specific clinicopathologic features of individual patients and the specific biological behavior of the tumor. Finally, besides the diagnostic and/or prognostic significance of the above-mentioned mutations, it is crucial to understand that the molecular pathways and epigenetic alterations will likely turn into interesting targets for new therapies.

Avaliação do emprego de videoconferências para a capacitação à distância dos médicos das equipes de saúde da família dentro do projeto nacional telessaúde / Evaluation of the use of videoconferencing for distance training of doctors in the family health teams within the national telehealth project

Introdução: o Programa Nacional de Telessaúde visa à atualização e capacitação dos médicos das Equipes de Saúde da Família por meio de videoconferências (VCs), com potencial impacto na melhoria da atenção à saúde em locais remotos e redução do deslocamento dos pacientes. Ainda, propõe mais interação da atenção primária com centros especializados. Objetivos: apresentação e avaliação do emprego desse sistema de videoconferências, possibilitando melhor planejamento das ações do projeto. Métodos: analisados 916 questionários de avaliação/retroalimentação preenchidos pelos participantes ao término de 84 VCs de Medicina, no período de 2009 até 2013. As VCssão um braço do Projeto Nacional de Telessaúde e alcançam 50 municípios em Minas Gerais, sob a coordenação da FM-UFMG. Elas realizam-se via web, exigindo aparelhagem mínima no centro difusor e receptor. Resultados: no período do estudo, obteve-se média de 12,64 municípios e 19,42 conferencistas por VC. Destes, a média de médicos foi 12,97. Quanto aos parâmetros de qualidade das VC, alcançaram avaliação positiva (?ótimo? ou ?bom?) o som em apenas 62% delas e a qualidade de imagem em 84%. O tema foi considerado ?interessante? ou ?muito interessante? em 98%. Conclusões: as VCs têm se fortalecido como alternativa para instituições educacionais. Porém, a participação de conferencistas e municípios nesse projeto foi aquém da almejada. Análises comparativas com VCs de outras áreas revelam, ainda, reduzida adesão dos médicos. Entre os problemas detectados, especialmente quanto à qualidade do som, a baixa qualidade de internet nos municípios pode ter contribuído para esse resultado.

Introduction: the National Telehealth Program aims at updating and training doctors in the Family Health Teams by means of videoconferencing (VCs), with potential impact on improving the health care in remote locations and reducing the displacement of patients. In addition, it proposes increased primary care interaction with specialized centers. Objectives: presentation and evaluation of the use of the videoconferencing system allowing for better planning of action in the project. Methods: 916 evaluation /feedback questionnaires were analyzed, completed by participants at the end of 84 VCs in Medicine, between 2009 and 2013. The VCs are a branch of the National Telehealth Project and reach 50 municipalities in Minas Gerais under the coordination of the FM-UFMG. They are held via web, requiring minimal equipment in diffuser and receiver centers. Results: in the study period, an average of 12.64 municipalities and 19.42 speakers were identified. Of these, the average number of doctors was 12.97. The quality parameters achieved positive assessment (?great? or ?good?) in just 62% for the sound, and 84% for the image. The theme was considered ?interesting? or ?very interesting? by 98%. Conclusions: the VCs have been strengthened as an alternative to educational institutions. However, the participation of speakers and municipalities in this project was lessthan desired. The comparative analysis of VCs from other areas also reveals a reduced adhesion of doctors. Among the problems detected, especially regarding the sound quality, the low quality of internet connection in the municipalities may have contributed to this result.