ABSTRACT Objective To compare the long-term medical costs of active surveillance (AS), partial thyroidectomy (PT), and total thyroidectomy (TT) in patients with low-risk papillary thyroid microcarcinoma (PTMC) receiving care covered by the Brazilian Public Health System. Materials and methods After reviewing AS cohorts and our own data, we created a model of AS, PT, and TT flow care for low-risk PTMC over 10, 20, and 30 years. The medical costs included those associated with diagnosis, surgery, and follow-up. We considered that 13.3% of the patients on AS would require surgery after a mean of 21.3 months, 4% undergoing TT would develop permanent hypoparathyroidism, and 43% undergoing PT would develop hypothyroidism. Results The most economical alternative was AS. The costs of TT per patient were higher than those of AS by 182.8% over 10 years (866.89 versus 306.49 US dollars [USD], respectively), by 152.9% over 20 years (1,023.66 versus 404.73 USD, respectively), and by 134.7% over 30 years (1,180.42 versus 502.96 USD, respectively). The costs of PT per patient were higher than those of AS by 16.0% over 10 years (355.66 versus 306.49 USD, respectively), by 16.9% over 20 years (473.41 versus 404.73 USD, respectively), and by 17.5% over 30 years (591.17 versus 502.96 USD, respectively). Conclusion The AS approach was less costly than immediate surgery throughout 30 years of follow-up. Hence, the implementation of AS in Brazil should not be hindered by cost considerations. longterm long term , (AS) (PT) (TT lowrisk low risk (PTMC System data 3 diagnosis followup. followup follow up. up follow-up 133 13 13.3 213 21 21. months 4 hypoparathyroidism 43 hypothyroidism 1828 182 8 182.8 1 866.89 86689 866 89 (866.8 30649 306 49 306.4 USD [USD] respectively, respectively respectively) 1529 152 9 152.9 2 1,023.66 102366 023 66 (1,023.6 40473 404 73 404.7 1347 134 7 134.7 1,180.42 118042 180 42 (1,180.4 50296 502 96 502.9 respectively. . 160 16 0 16.0 355.66 35566 355 (355.6 169 16.9 473.41 47341 473 41 (473.4 175 17 5 17.5 591.17 59117 591 (591.1 Hence considerations (AS (PT 13. 18 182. 866.8 8668 86 (866. 3064 306. [USD 15 152. 1,023.6 10236 02 6 (1,023. 4047 40 404. 134. 1,180.4 11804 (1,180. 5029 50 502. 16. 355.6 3556 35 (355. 473.4 4734 47 (473. 17. 591.1 5911 59 (591. 866. (866 1,023. 1023 (1,023 1,180. 1180 (1,180 355. (355 473. (473 591. (591 (86 1,023 102 (1,02 1,180 118 (1,18 (35 (47 (59 (8 1,02 (1,0 1,18 11 (1,1 (3 (4 (5 ( 1,0 (1, 1,1 1, (1

Resumo: Introdução: Repensar os processos de ensino-aprendizagem é tarefa contínua dentro da escola médica, devendo haver aplicação das melhores evidências. Embora as necessidades de mudanças sejam amplamente conhecidas, os meios para realizá-las não o são. Por isso, este relato objetiva descrever a metodologia utilizada por uma faculdade tradicional do ensino em medicina durante seu processo de reforma curricular, o qual contou com a participação ativa da comunidade acadêmica. Relato de experiência: Para a reforma da matriz, foi nomeada uma comissão composta por alunos, docentes e funcionários. Seguindo os princípios do Design Thinking, organizaram-se os conhecimentos prévios e estruturaram-se os processos de escuta dos diferentes sujeitos. Optou-se por desenvolver uma matriz baseada em competências, com disciplinas integradas horizontalmente e priorização de atividades práticas, de modo a permitir uma redução da carga horária global do curso. As reformas implementadas exigiram alterações institucionais complexas para além da matriz, como a mudança da cultura avaliativa, a implementação do portfólio e outras questões de currículo oculto. Discussão: Superou-se o desafio de criar processos flexíveis e sustentáveis porque a comunidade foi capacitada para colaborar na gestão do ensino. Para além de coordenadores e diretores, todos os agentes do processo de aprendizagem devem ser reunidos de forma horizontal com participação ativa na proposição de mudanças. Barreiras e distanciamentos em relação à literatura podem ser enfrentados, devendo-se admitir as limitações para preservar identidades próprias e garantir projetos viáveis. Conclusão: A formação de profissionais competentes é o objetivo dos currículos em medicina, que devem ser revistos continuamente. A reforma descrita permitiu o fortalecimento de vínculos com a comunidade, entregando um projeto representativo e adequado à realidade específica. Resumo Introdução ensinoaprendizagem médica evidências conhecidas realizálas realizá las são isso curricular acadêmica experiência alunos funcionários Thinking organizaramse organizaram se estruturaramse estruturaram sujeitos Optouse Optou competências práticas curso avaliativa oculto Discussão Superouse Superou diretores enfrentados devendose viáveis Conclusão continuamente específica

Abstract: Introduction: Rethinking the teaching-learning process is a continuous task in medical training, with the constant requirement of applying the best evidence. Although the needs for change are widely known, the means to carry them out are not. Therefore, this report aims to describe the methodology used by a traditional medical school during its curricular reform process, which had the active participation of the academic community. Experience: A committee for curricular reform was appointed, including students, academic and professional staff. Following the principles of Design Thinking, prior knowledge was organized and listening processes were structured. A competency-based matrix was developed, with horizontally integrated disciplines and prioritization of practical activities, allowing for reduced total class hours of the course. The implemented reforms required complex institutional changes beyond the matrix, such as changing the evaluative culture and the implementation of the portfolio, in addition to other hidden curricular issues. Discussion: The challenge of creating flexible and sustainable processes seems to be overcome by empowering the community to collaborate with the educational management. In addition to coordinators and directors, all agents of the learning process must be brought together horizontally with active participation in proposing changes. Barriers and distances in relation to literature can be faced, and limitations must be admitted in order to preserve appropriate identities and guarantee viable projects. Conclusion: Training competent professionals is the goal of curricula, which must be continually reviewed. The reform described allowed for the strengthening of ties between the community, delivering a representative project that was adequate to the specific reality. Abstract Introduction teachinglearning teaching training evidence known not Therefore Experience appointed students staff Thinking structured competencybased competency based developed activities course portfolio issues Discussion management directors faced projects Conclusion curricula reviewed reality

ABSTRACT Objective: Although thyroid microcarcinoma (TMC) usually has a favorable prognosis, some patients present a higher risk of disease recurrence or persistence. Thus, we aimed at identifying possible risk factors associated with an incomplete response to therapy in TMC. Subjects and methods: This was a retrospective study of 517 patients with TMC treated with total thyroidectomy, with or without radioactive iodine (RAI) therapy, reclassified after 1.1 ± 0.4 years according to the response to treatment into “favorable” (excellent/indeterminate) or “unfavorable” (biochemical/structural incomplete) responses. We evaluated participants' age, sex, tumor size, histological variants, multifocality, presence of vascular/lymphatic/perineural invasion, extrathyroidal extension, metastatic lymph nodes (LN), and distant metastasis. The effect of RAI therapy on the response range was analyzed in a given subgroup. Results: The mean age observed was 46.4 ± 12.0 years, and 89.7% were female. We noted 97.5% with papillary carcinoma, 27.8% with multifocality and 11.2% with LN metastasis. Although the majority of patients had a low risk of recurrence/persistence (78%), 75% were submitted to RAI therapy. Incomplete response (20.7%) was associated with multifocality (p=0.041; OR=1.619) and metastatic LN (p=0.041; OR=1.868). These variables were strongly correlated (p=0.000; OR=3.283). No cut-off of tumor size was identified as a predictor of incomplete response by the receiver operating curve analysis. RAI treatment did not influence the response of patients with multifocality or LN metastasis. Conclusion: Multifocality and LN metastasis are independent risk factors for incomplete response in TMC patients and are strongly correlated. Additional RAI therapy was not associated with a more favorable response in these subgroups.

ABSTRACT Objective: The intermediate-risk (IR) category includes tumors with different degrees of aggression. We aimed to identify the risk factors associated with unfavorable response to initial treatment and compare the effect of low/high radioactive iodine (RAI) therapy. Subjects and methods: A total of 614 IR patients were selected from a database, during 1972-2015. All patients underwent total thyroidectomy and RAI therapy and were reclassified after 12-18 months into the favorable (complete/indeterminate) response group and the unfavorable (biochemical/incomplete structural) response group. A total of 92 patients were assessed for late response (mean: 9.19 ± 5.73 years). Age, gender, tumor size, histology, multifocality, vascular invasion, extrathyroidal extension, presence and number of lymph node metastasis, and stimulated thyroglobulin at ablation (sTg) were evaluated. Results: Mean age at diagnosis was 41.47 ± 15.81 years, and 83.6% of the patients were female. Within 12-18 months after initial therapy, unfavorable response was detected in 41.2% of the patients and was associated, in multivariate analysis, with lymph node metastasis (p = 0.041; odds ratio [OR] = 1.9), presence of more than five metastatic lymph nodes (p = 0,017; OR = 2.6), and sTg > 10 ng/mL (p = 0.005; OR = 10.0). For patients with a longer follow-up, sTg >10 ng/mL was associated with unfavorable response (p = 0.002; OR = 6.8). A higher RAI dose was not related to better prognosis at the end of the follow-up. Conclusion: A sTg level of >10 ng/mL and lymph node metastasis were associated with an unfavorable response 12-18 months after initial treatment. A RAI dose below 150 mCi was proven sufficient to treat IR patients.

ABSTRACT Objective We aimed to evaluate the impact of minimal extrathyroidal extension (mETE) alone on the risk of recurrence of papillary thyroid carcinoma (PTC). The impact of other factors, including multifocality, age, tumor size, and stimulated thyroglobulin (sTg) values was also assessed. Subjects and methods We retrospectively analyzed 1,108 PTC patients from a medical institution, who presented tumors ≤ 4 cm without any adverse characteristics other than mETE. Patients were classified according to their response to initial treatment 12 to 24 months after surgery as proposed by the 2015 American Thyroid Association (ATA) guideline. Statistical analysis was performed using multivariate logistic regression and receiver operating characteristic (ROC) curve. Results In the multivariate logistic regression analysis, mETE did not have an impact on the response to initial treatment (p = 0.44), similar to multifocality, age, and tumor size. Initial Tg value was the only variable associated with a poor response (p < 0.01, odds ratio = 1.303, 95% confidence interval 1.25-1.36). The ROC analysis revealed that Tg was significant (area under curve = 0.8750); the cutoff value of sTg as a predictor of poor response was 10 ng/mL (sensitivity = 72.2%, specificity = 98.5%). Conclusion For low-risk PTC presenting mETE as the only aggressive feature, the initial sTg value is essential to identify patients who may have a poor response after initial treatment and benefit from further treatment. Arch Endocrinol Metab. 2020;64(3):251-6

Resumo Objetivo: Avaliar a utilidade da elastografia (usando compressão manual) como uma ferramenta adicional de diagnóstico em crianças e adolescentes com nódulos da tireoide. Materiais e Métodos: Este foi um estudo prospectivo realizado entre setembro de 2012 e agosto de 2013 em um hospital no Brasil. Realizamos elastografia, ultrassonografia e biópsia por aspiração com agulha fina em 32 pacientes com idade entre 6 e 18 anos que tinham, no total, 38 nódulos tireoidianos. Resultados: Os achados da elastografia em relação ao histopatológico foram corretos em 78,5% dos casos. A elastografia poderia ter evitado a tireoidectomia desnecessária de três pacientes. Apenas um nódulo maligno da tireoide foi classificado como E1. Conclusão: Nossos resultados sugeriram que a alta elasticidade de um nódulo na elastografia está associada a um baixo risco de câncer de tireoide. Caso se confirme em outros estudos, a elastografia pode ser útil como teste de triagem complementar de nódulos tireoidianos em crianças.

Abstract Objective: To evaluate the usefulness of elastography (using manual compression) as an additional diagnostic tool for children and adolescents with thyroid nodules. Materials and Methods: This was a prospective study conducted between September 2012 and August 2013 at a hospital in Brazil. We performed elastography, ultrasound, and fine-needle aspiration biopsy in 32 patients between 6 and 18 years of age who had, in total, 38 thyroid nodules. Results: The elastography findings correlated with the histopathological diagnosis in 78.5% of cases. In three patients, an unnecessary thyroidectomy could have been avoided if the elastography results had been prioritized. Only one malignant thyroid nodule was found to show high elasticity. Conclusion: Our results suggest that high elasticity of a nodule on elastography is associated with a low risk of thyroid cancer. If further confirmed in other studies, elastography may prove useful as a complementary test for screening thyroid nodules in children.

ABSTRACT Objectives: We sought to assess the relationship between stimulated thyroglobulin (sTg) before radioactive iodine therapy (RIT), and the dynamic risk stratification 1 year after treatment, and to establish the utility of the sTg as a predictor of response to therapy in these patients. A retrospective chart review of patients with differentiated thyroid cancer (DTC) who underwent RIT after surgery and were followed for at least 1 year, was carried out. Subjects and methods: Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The sTg values before RIT were compared among the groups. ROC curve analysis was performed. Results: Fifty-six patients were enrolled (mean age 44.7 ± 14.4 years, 80.7% had papillary carcinoma). Patients with excellent response had sTg = 2.1 ± 3.3 ng/mL, those with indeterminate response had sTg = 8.2 ± 9.2 ng/mL and those with incomplete response had sTg = 22.4 ± 28.3 ng/mL before RIT (p = 0.01). There was a difference in sTg between excellent and incomplete response groups (p = 0.009) while no difference was found between indeterminate and either excellent or incomplete groups. The ROC curve showed an area under the curve of 0.779 assuming a sTg value of 3.75 ng/mL. Conclusion: Our study results suggest that the higher the sTg before RIT, the greater the likelihood of an incomplete response to initial treatment. A sTg cut-off of 3.75 ng/mL was found to be a good predictor of response to initial treatment in patients with DTC.

OBJETIVO: Investigar a associação entre parâmetros histológicos do carcinoma papilífero da tireoide (CPT) e a presença de tireoidite de Hashimoto (TH). MATERIAIS E MÉTODOS: Amostra de tecidos de CPT foi revista por um médico patologista. Os seguintes parâmetros foram avaliados: presença de TH concomitante, multicentricidade, metástase linfonodal, tamanho tumoral, invasão vascular, infiltração perineural, variante histológica e estadiamento patológico. Os dados clínicos incluíam gênero e idade ao diagnóstico. RESULTADOS: Um total de 94 casos de CPT foi revisto. Houve predomínio do sexo feminino (85,1% vs. 14,9%) e a idade média de apresentação foi de 45,13 anos. A presença de TH foi associada a maior ocorrência de tumores multifocais (p = 0,004), estágios iniciais de estadiamento (p = 0,02) e tumores menores (p = 0,025). CONCLUSÃO: O CPT associado a TH apresentou-se com menor dimensão, maior ocorrência de multifocalidade e em estadiamentos mais iniciais do que os casos de CPT sem TH associada. Um melhor entendimento da resposta imune envolvida nesses tumores pode ser útil para estratégias futuras de prevenção e para o desenvolvimento de novas abordagens terapêuticas para esse tipo de neoplasia.

OBJECTIVE: To investigate the association between the histological parameters of papillary thyroid cancer (PTC) and the presence of Hashimoto's thyroiditis (HT). MATERIALS AND METHODS: Histological samples from patients with PTC were reviewed by an endocrine pathologist. The following parameters were analyzed: presence of concomitant HT, multifocality, presence of nodal metastasis, tumor size, vascular invasion, perineural infiltration, histological variant, and pathological staging. Clinical data included gender and age at the time of the diagnosis. RESULTS: A total of 94 cases of PTC were reviewed. There was a predominance of women (85.1% vs. 14.9%) and median age at presentation was 45.13 years. The presence of HT was significantly associated with greater occurrence of multifocal tumors (p = 0.004), early pathological stage (p = 0.02), and smaller tumor size (p = 0.025). CONCLUSIONS: Patients with PTC associated with HT had significantly smaller tumors, more often multifocal and in an earlier stage than their counterparts without HT. A better understanding of the immune response involved in these tumors may be useful for future strategies on the prevention and for the development of new therapeutic approaches for this group of neoplasms.

A Doença de Graves constitui a forma mais comum de hipertireoidismo e três abordagens terapêuticas são atualmente utilizadas: uso de medicamentos antitireoideanos, cirurgia e iodo radioativo (I 131). Os efeitos do o I 131 e a indução precoce de hipotireoidismo são conseqüências da destruição induzida do I131 sobre o parênquima tireoideano. São poucos relatos encontrados na literatura acerca dos efeitos da radioioterapia sobre a laringe e conseqüentemente na produção vocal. OBJETIVO: Avaliar os efeitos agudos sobre a voz da radioiodoterapia em pacientes com hipertireoidismo por Doença de Basedow Graves. MATERIAL E MÉTODO: Estudo de corte contemporâneo longitudinal, prospectivo. Procedimentos: Investigação vocal, mensuração do tempo máximo fonatório de /a/ e relação s/z, análise freqüência fundamental (Software Praat), laringoscopia e análise perceptivo-auditiva em três momentos: pré-dose, 4 dias e 20 dias pós dose. Momentos baseados no perfil inflamatório do tecido tireoideano. RESULTADOS: Não houve mudanças estatisticamente significantes nos aspectos vocais e laringológicos nos três momentos avaliados. CONCLUSÃO: A radioiodoterapia não afeta a qualidade vocal.

Graves's disease is the most common cause of hyperthyroidism. There are three current therapeutic options: anti-thyroid medication, surgery, and radioactive iodine (I 131). There are few data in the literature regarding the effects of radioiodine therapy on the larynx and voice. The aim and the AIM: os this study was: to assess the effect of radioiodine therapy on the voice of Basedow-Graves patients. MATERIAL AND METHOD: A prospective study was done. Following the diagnosis of Grave's disease, patients underwent investigation of their voice, measurement of maximum phonatory time (/a/) and the s/z ratio, fundamental frequency analysis (Praat software), laringoscopy and (perceptive-auditory) analysis in three different conditions: pre-treatment, 4 days, and 20 days post-radioiodine therapy. Conditions are based on the inflammatory pattern of thyroid tissue (Jones et al. 1999). RESULTS: No statistically significant differences were found in voice characteristics in these three conditions. CONCLUSION: Radioiodine therapy does not affect voice quality.

OBJETIVO: Caracterizar a qualidade vocal, por meio de análise computadorizada e perceptivo-auditiva, de pacientes com hipertireoidismo (grupo A) e hipotireoidismo (grupo B). MÉTODOS: Vinte mulheres não fumantes, com idades entre 18 e 55 anos, atendidas no Ambulatório de Endocrinologia da instituição, foram avaliadas após o diagnóstico clínico e laboratorial de hipertireoidismo ou hipotireoidismo. Os parâmetros investigados foram: tempo da doença, presença de queixa vocal, tempos máximos de fonação /a/, /s/ e /z/, freqüência fundamental (F0), ruído glótico (GNE). Os aspectos avaliados na análise perceptivo-auditiva, foram: coordenação pneumo-fonoarticulatória (coordenada ou incoordenada), pitch, loudness, ataque vocal, ressonância, velocidade de fala e qualidade vocal, que poderia ter até duas das seguintes classificações: neutra, rouca, soprosa, áspera ou tensa, e grau: leve, moderado ou severo. Os dados foram tabulados e analisados estatisticamente através do programa EPI-INFO 6.04b, método qualitativo Fisher, com nível de significância menor do que 0.05. RESULTADOS: A análise perceptivo-auditiva mostrou que sete pacientes hipotireoideos e nove pacientes hipertireoideos apresentaram alteração na qualidade vocal. Oito pacientes em ambos os grupos apresentaram incoordenação pneumo-fonoarticulatória. Oito pacientes do grupo A e seis pacientes do grupo B referiam queixas vocais como rouquidão e voz grossa, respectivamente. Na análise acústica, nove pacientes apresentaram o ruído glótico alterado. CONCLUSÃO: Os resultados evidenciaram grande incidência de alteração vocal nos grupos estudados (grupos dos pacientes com hipertireoidismo e com hipotireoidismo), o que demonstra a relação entre disfonia e disfunções tireoideanas.

PURPOSE: To characterize the vocal quality of subjects with hyperthyroidism (group A), and hypothyroidism (group B) through a computer-aided and auditory-perceptive analysis. METHODS: Twenty non-smoking women with ages between 18 and 55 years from the Endocrinology Ambulatory of the institution were evaluated after clinical and lab diagnosis for hyperthyroidism or hypothyroidism. The parameters investigated were: period bearing the disease, vocal complaint, maximum phonation time /a/, /s/, and /z/, fundamental frequency (F0), glottal noise (GNE). The aspects evaluated in the auditory-perceptive analysis were: pneumo-phono-articulatory coordination (coordinated or uncoordinated), pitch, loudness, vocal attack, resonance, speech speed and vocal quality, that could be classified as one or two of the following: neutral, hoarse, whispered, coarse, or tense, and degree: light, moderate or severe. Data were statistically analyzed through the EPI-INFO 6.04b software, Fisher qualitative method, considering a significance level of 0.05. RESULTS: The auditory-perceptive analysis showed that seven patients with hypothyroidism and nine with hyperthyroidism presented changes in vocal quality. Eight subjects from both groups presented pneumo-phono-articulatory incoordination. Eight subjects from group A and six from group B referred vocal complaints, such as hoarseness and thick voice, respectively. In the acoustic analysis, nine subjects presented change in glottal noise. CONCLUSION: The results showed great incidence of vocal changes on the studied groups (both hyper and hypothyroidism groups), which evidences the relation between dysphonia and thyroidal dysfunctions.