Management of radioiodine refractory differentiated thyroid cancer: the Latin American perspective.

Radioiodine (RAI) refractory differentiated thyroid cancer is an uncommon and challenging situation that requires a multidisciplinary approach to therapeutic strategies. The definition of RAI-refractoriness is usually a clear situation in specialized centers. However, the right moment for initiation of multikinase inhibitors (MKI), the time and availability for genomic testing, and the possibility of prescribing MKI and selective kinase inhibitors differ worldwide.Latin America (LA) refers to the territories of the world that stretch across two regions: North America (including Central America and the Caribbean) and South America, containing 8.5% of the world's population. In this manuscript, we critically review the current standard approach recommended for patients with RAI refractory differentiated thyroid cancer, emphasizing the challenges faced in LA. To achieve this objective, the Latin American Thyroid Society (LATS) convened a panel of experts from Brazil, Argentina, Chile, and Colombia. Access to MKI compounds continues to be a challenge in all LA countries. This is true not only for MKI but also for the new selective tyrosine kinase inhibitor, which will also require genomic testing, that is not widely available. Thus, as precision medicine advances, significant disparities will be made more evident, and despite efforts to improve coverage and reimbursement, molecular-based precision medicine remains inaccessible to most of the LA population. Efforts should be undertaken to alleviate the discrepancies between the current state-of-the-art care for RAI-refractory differentiated thyroid cancer and the present situation in Latin America.

Correlation between inflammatory parameters and pituitary-thyroid axis in patients with COVID-19.

PURPOSE: Inflammation plays a critical role in the progression of COVID-19. Nonthyroidal illness syndrome (NTIS) has been increasingly recognized in affected patients. We aim to evaluate the correlation of thyroid hormones with markers of inflammation and association with disease outcome in hospitalized patients with COVID-19, and in two profiles of NTIS (low T3-normal/low FT4 vs. low T3-high FT4). METHODS: consecutive patients admitted to a nonintensive care unit for COVID-19 were recruited. Infection was mild in 22%, moderate in 27.1% and severe in 50.8%; 7.41% died. T4, T3, FT4, FT3, and their ratios (T3/T4, FT3/FT4) were correlated with albumin, ferritin, fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer. RESULTS: Fifty five patients (50.9% men, median age 56 years) were included. Albumin correlated positively with T3 and hormones ratios, but negatively with FT4. T3, FT3, T3/T4, and FT3/FT4 correlated inversely with ferritin, fibrinogen, ESR, CRP, LDH, and D-dimer. FT4 showed direct correlation with fibrinogen and ESR. T3/T4 was lower in severe compared to mild/moderate disease [7.5 (4.5-15.5) vs. 9.2 (5.8-18.1); p = 0.04], and lower in patients who died than in those discharged [5 (4.53-5.6) vs. 8.1 (4.7-18.1); p = 0.03]. A low T3/high FT4 profile was associated with lower albumin, higher ferritin, and severity. CONCLUSION: In this cohort, thyroid hormones correlated with inflammation and outcome. T3 and T3/T4 correlated inversely with inflammatory markers; a low T3/T4 ratio was associated with severity and poor prognosis. Patients with low T3 but high FT4 had higher ferritin, lower albumin, and more severe disease at presentation.

Primary aldosteronism: Aldosterone/renin ratio cut-off points. / Hiperaldosteronismo primario: puntos de corte del cociente aldosterona/renina.

INTRODUCTION: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, with a prevalence rate of 6-12% in hypertensive patients. Aldosterone/renin ratio (ARR) is the screening test of choice for PA. Because of the variable cut-off points of ARR, reference values related to the populations and methods considered are recommended. OBJECTIVES: (i)To optimize the ARR cut-off points for PA screening with current methods; (ii)to assess the correlation and diagnostic sensitivity of the plasma aldosterone concentration/plasma renin activity (ARR) ratio and the aldosterone concentration/renin concentration (ARC) ratios for PA screening, and (iii)to determine the prevalence of PA in our population. MATERIALS AND METHODS: Plasma aldosterone concentration and plasma renin activity levels were measured using radioimmunoassays (RIAZENco Zentech and RIA DiaSorin respectively), while a chemiluminescence assay (Liaison Diasorin) was used to test renin concentration. ARR and ARC ratios were calculated in 345 subjects (136 healthy subjects and 209 hypertensive patients). RESULTS: Prevalence of PA was 5.9% after diagnostic confirmation. ROC curve analysis suggested an ARR threshold of 48.9(ng/dL)/(ng/mL/h) (100% sensitivity, 93.6% specificity) and an ARC threshold of 2.3(ng/dL)/(µIU/mL) (100% sensitivity, 90.9% specificity). Good correlation was seen between ARR and ARC (ρ=.83, P<.0001), with a presumptive diagnostic concordance of 96.6%. CONCLUSIONS: New cut-off values of ARR and ARC for screening of PA, with high sensitivity and good diagnostic concordance, were determined in the study population. It is important to have valid normal ranges to avoid diagnostic errors.

Related quality of life questionnaire specific to dysthyroid ophthalmopathy evaluated in a population of patients with Graves' disease

ABSTRACT Objective The aim of this study was to measure quality of life (QOL) impairment in individuals currently suffering from Graves' ophthalmopathy (GO) and to determine the correlation of GO-specific QOL scores with disease severity and activity. Subjects and methods Seventy three GO-specific QOL surveys were prospectively analysed and compared with GO status. The GO-specific QOL survey was translated into Spanish and applied to Argentine patients with Graves' disease (GD). Results were compared with presence or absence of GO, Clinical Activity Score (CAS), severity score, age, gender and thyroid function. Results Fifty-six patients answered the survey and underwent complete ophthalmic evaluation, 15 did not have GO and were considered to be a control group. Appearance QOL score for patients with GO (53 ± 31.4) was lower than the control group (88.3 ± 17) (p < 0,000), no difference was observed in functional QOL score. There was a negative correlation between GO severity and both functional (r = -0.575; p < 0.000) and appearance QOL (r = -0.577; p < 0.000). Functional QOL differed between patients with active GO vs control group (p = 0.043). Patients with active and inactive GO had lower appearance QOL scores than control group (p < 0.000, p < 0.001 respectively). Conclusions GO has significant impact on the life of these Argentine patients. QOL was worse in GO patients than in control group, functional QOL was mostly affected by the activity and appearance QOL was mainly altered by the effects of the disease. Patients with more severe GO had lower scores on both QOL scales.

Impacto del compromiso ganglionar en el pronóstico y la evolución del carcinoma papilar de tiroides / Impact of lymph node involvement on prognosis and outcome of paillary thyroid carcinoma

Las metástasis ganglionares regionales del cuello están presentes en un gran porcentaje de los casos con CPT. Sin embargo, en varios trabajos se pudo observar como no todo compromiso ganglionar tiene igual impacto en la evolución de dicha patología. Recientemente en Argentina, Chile y Brasil se modificaron las guías del manejo del CDT y estas recomiendan una estratificación de riesgo y abordaje terapéutico diferente según el número, el tamaño y la extensión del compromiso ganglionar. En esta monografía se analizaron las características de las metástasis ganglionares y su impacto en la evolución del CDT y esto fue realizado previamente a la reciente publicación de las nuevas guías de la ATA. Dada esta situación, se incorporaron a la monografía original algunos aspectos de las guías de ATA

Cervical lymph node metastases are usually present in a high number of cases with papillary thyroid carcinoma. However, many studies have shown that not all lymph node metastases have the same impact on the outcome of this disease. Argentina, Chile, and Brazil have recently changed their differentiated thyroid carcinoma (DTC) guidelines and recommend a different ranking of risk and therapeutic approach according to the number, size, and extension of lymph node metastasis. An analysis of lymph node metastases is presented in this article, which includes their characteristics and impact on DTC. As this analysis was made before the latest publication of the new American Thyroid Association guidelines, some aspects of these guidelines have also been included

Related quality of life questionnaire specific to dysthyroid ophthalmopathy evaluated in a population of patients with Graves' disease.

OBJECTIVE: The aim of this study was to measure quality of life (QOL) impairment in individuals currently suffering from Graves' ophthalmopathy (GO) and to determine the correlation of GO-specific QOL scores with disease severity and activity. SUBJECTS AND METHODS: Seventy three GO-specific QOL surveys were prospectively analysed and compared with GO status. The GO-specific QOL survey was translated into Spanish and applied to Argentine patients with Graves' disease (GD). Results were compared with presence or absence of GO, Clinical Activity Score (CAS), severity score, age, gender and thyroid function. RESULTS: Fifty-six patients answered the survey and underwent complete ophthalmic evaluation, 15 did not have GO and were considered to be a control group. Appearance QOL score for patients with GO (53 ± 31.4) was lower than the control group (88.3 ± 17) (p < 0,000), no difference was observed in functional QOL score. There was a negative correlation between GO severity and both functional (r = -0.575; p < 0.000) and appearance QOL (r = -0.577; p < 0.000). Functional QOL differed between patients with active GO vs control group (p = 0.043). Patients with active and inactive GO had lower appearance QOL scores than control group (p < 0.000, p < 0.001 respectively). CONCLUSIONS: GO has significant impact on the life of these Argentine patients. QOL was worse in GO patients than in control group, functional QOL was mostly affected by the activity and appearance QOL was mainly altered by the effects of the disease. Patients with more severe GO had lower scores on both QOL scales.

[BRAF V600E mutation in thyroid nodules in Argentina]. / Mutación V600E del oncogén BRAF en nódulos tiroideos en Argentina.

This prospective study analyzed the frequency of V600E mutation of oncogene BRAF in patients operated for benign thyroid nodules and for papillary thyroid cancer in an Argentine population. In patients with papillary thyroid cancer we compared clinicopathological characteristics between those harboring BRAF mutation and those without it. Twenty five consecutive patients operated for benign nodules and for papillary carcinoma were prospectively included. Fresh tissue samples of thyroid nodules and of adjacent thyroid parenchyma were obtained. DNA was extracted and amplified by amplification refractory mutation system polymerase chain reaction (ARMS PCR). Direct sequencing was performed in four samples. Of those patients operated for papillary thyroid cancer, 77% harbored BRAF mutation. All samples from adjacent thyroid parenchyma and from patients operated for benign nodules tested negative for the mutation. Direct sequencing confirmed the results obtained by ARMS PCR. Patients with BRAF mutation were significantly older at the time of diagnosis (BRAF+ 47.7 ± 12.7 years vs. BRAF- 24.7 ± 8.1 years, p < 0.01). Nine out of ten papillary carcinomas with BRAF mutation corresponded to the classic histological subtype, which was not observed in BRAF negative tumors (p < 0.02). In conclusion, we found a high frequency of BRAF V600E mutation in this population of patients operated for papillary thyroid carcinoma in Argentina. These results are consistent with those reported in the literature.

Mutación V600E del oncogén BRAF en nódulos tiroideos en Argentina / BRAF V600E mutation in thyroid nodules in Argentina

Este estudio prospectivo analizó en una población argentina la frecuencia de la mutación V600E del oncogén BRAF en pacientes operados por nódulos tiroideos benignos y por carcinoma papilar de tiroides. En estos últimos se compararon las características clínicas y anatomopatológicas en relación a la presencia o ausencia de la mutación. Se estudiaron prospectivamente 25 pacientes consecutivos operados en nuestra institución. Se obtuvieron muestras histológicas de tejido nodular y el adyacente no nodular en fresco. Se extrajo ADN, se amplificó según técnica amplification refractory mutation system polymerase chain reaction (ARMS PCR). Se efectuó secuenciación directa del gen en 4 muestras. El 77% de los operados por carcinoma papilar resultaron BRAF+. Todas las muestras de tejido adyacente no tumoral y de los nódulos benignos fueron negativas para la mutación. La secuenciación directa confirmó los resultados obtenidos por ARMS PCR en las muestras en que fue efectuada. Los pacientes BRAF+ presentaron mayor edad al diagnóstico vs. aquellos BRAF- (47.7 ± 12.7 vs 24.7 ± 8.1 años, p < 0.01). Nueve de diez carcinomas papilares de tiroides con mutación de BRAF correspondieron a la variante histológica clásica, la cual no se observó en los tumores BRAF- (p < 0.02). En conclusión, comunicamos una elevada frecuencia de mutación V600E del oncogén BRAF en pacientes operados por carcinoma papilar de tiroides en Argentina. Estos resultados son acordes a lo referido en la bibliografía.

This prospective study analyzed the frequency of V600E mutation of oncogene BRAF in patients operated for benign thyroid nodules and for papillary thyroid cancer in an Argentine population. In patients with papillary thyroid cancer we compared clinicopathological characteristics between those harboring BRAF mutation and those without it. Twenty five consecutive patients operated for benign nodules and for papillary carcinoma were prospectively included. Fresh tissue samples of thyroid nodules and of adjacent thyroid parenchyma were obtained. DNA was extracted and amplified by amplification refractory mutation system polymerase chain reaction (ARMS PCR). Direct sequencing was performed in four samples. Of those patients operated for papillary thyroid cancer, 77% harbored BRAF mutation. All samples from adjacent thyroid parenchyma and from patients operated for benign nodules tested negative for the mutation. Direct sequencing confirmed the results obtained by ARMS PCR. Patients with BRAF mutation were significantly older at the time of diagnosis (BRAF+ 47.7 ± 12.7 years vs. BRAF- 24.7 ± 8.1 years, p < 0.01). Nine out of ten papillary carcinomas with BRAF mutation corresponded to the classic histological subtype, which was not observed in BRAF negative tumors (p < 0.02). In conclusion, we found a high frequency of BRAF V600E mutation in this population of patients operated for papillary thyroid carcinoma in Argentina. These results are consistent with those reported in the literature.

Tiroideopatías y deficiencia de yodo en una población de embarazadas / Thyroid disorders and iodine deficiency in a pregnant population

INTRODUCCION: La disfunción, autoinmunidad tiroidea (AIT) y el déficit de yodo en embarazo, conllevan a efectos adversos. En ausencia de datos de prevalencia y rangos de Tirotrofina (TSH) en cada trimestre en Argentina, se utilizan las guías internacionales de la American Thyroid Association (ATA).OBJETIVOS: Determinar a) prevalencia de AIT y deficiencia de yodo por pesquisa en embarazadas sanas y b) valores de referencia de TSH por trimestre y prevalencia de disfunción con valores propios. METODOS: Se estudió a 217 embarazadas sanas.Se determinó TSH, T4 y T3 total y libres, Anticuerpos a tiroperoxidasa (ATPO) y yoduria. Excluidas las ATPO positivos y disfunción clínica, se recalculó percentiles 5 y 95 y se establecieron rangos de TSH. Se establecieron porcentajes de valores patológicos de TSH según rangos publicados y propios. RESULTADOS: Los ATPO fueron positivos en 8% de las pacientes. Se halló bocio en 38%. La yoduria fue >150 μgr/dl en 58%. Los valores de TSH (mediana y rango) fueron: 0,95 uUI/ml (0,20-3,30), 1,50 uUI/ml (0,02-7,00) y 1,60 uUI/ml (0,21-4,90) para primer, segundo y tercer trimestre respectivamente. La TSH fue elevada según guías ATA en el 11% y disminuyó a 6,5% con nuestros rangos. Solo 1 paciente presentó hipotiroidismo clínico.CONCLUSIONES: La prevalencia de ATPO fue similar a la referida y casi el 40% presentó bocio leve, considerado adaptativo. Se registróhipotiroidismo clínico en 0,5% y subclínico en 11% según valoresde guías ATA, que descendió al 6,5% acorde a valores de este estudio. La mediana de la yoduria indicó suficiencia de yodo en la población.

INTRODUCTION: The dysfunction, thyroid autoimmunity (AIT) and iodine deficiency in pregnancy, leading toadverse effects. In the absence of prevalence data and ranges of Thyrotropin (TSH) in each quarter in Argentina, international guidelines of American Thyroid Association (ATA) are used. OBJECTIVES: To determine a) prevalence of AIT, thyroid dysfunctionand iodine deficiency by screening in healthy pregnant b) TSH reference values per quarter and prevalence of dysfunction with own values. METHODS: We studied 217 healthy pregnant. TSH, T4 and T3 total and free, antibodies to thyroid peroxidase (ATPO) and urinary iodine was determined. Excluding positive ATPO and clinical dysfunction, 5th and 95th TSH percentiles wasrecalculated and established own TSH ranges. Percentage of pathological TSH values was established according to published ranges and with own values. RESULTS: ATPO were positive in 8% of patients. Goiter was found in 38%. The iodine level was> 150 μgr / dl in 58%. TSH values (median and range) were: 0.95 mIU / ml (0.20- 3.30), 1.50 mIU / ml (0.02-7.00) and 1.60 mIU / ml (0.21-4.90) for the first quarter, the second and third respectively. The TSH was elevated as guides ATA in 11% and in 6.5% as own values. Only one patient had clinical hypothyroidism. CONCLUSIONS: The prevalence of ATPOwas similar to that reported, and almost 40% had mild goiter, considered adaptive. Clinical hypothyroidism was recorded at 0.5% and subclinical in 11% as guides ATA, which fell to 6.5%as own values. The median urinary iodine indicated iodine sufficiency in the population.

Negative correlation between bone mineral density and TSH receptor antibodies in long-term euthyroid postmenopausal women with treated Graves' disease.

BACKGROUND: Thyrotoxicosis is a cause of secondary osteoporosis. High concentrations of triiodotironine (T3) in Graves' disease stimulate bone turnover, but it is unclear if euthyroidism will always normalize bone metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism through the TSH receptor and TSH receptor antibodies (TRAb) may have an important role in bone turn-over.The aim of our study was to determine, in pre and postmenopausal euthyroidism patients with previous overt hyperthyroidism due to Graves' disease the bone mineral density (BMD) as well as factors that could affect BMD in each group, including TRAb. METHODS: Cross-sectional, non-interventional study. Fifty-seven patients with previous hyperthyroidism due to Graves' disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid for at least 6 months prior to study were included and compared with fifty- two matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured. RESULTS: Only euthyroid postmenopausal patients with a history of hyperthyroidism due to Graves' disease showed lower whole body BMD than matched controls. The BMD expressed as Z-score was less in whole body and lumbar spine in postmenopausal in relation to premenopausal women with previous overt hyperthyroidism due to Graves' disease.In the postmenopausal patients, the Z-score of lumbar spine BMD correlated negatively with TRAb (r = -0,53, p < 0.008), positively with the time of evolution of the disease (r = +0.42, p < 0.032) and positively with the time of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD (F = 3. 90, p < 0.01). CONCLUSIONS: In euthyroid women with a history of Graves' hyperthyroidism, BMD was only affected in the postmenopausal group. The negative correlation of Z-score of lumbar spine BMD with TRAb suggests that this antibody may affect the bone metabolism.

Tratamiento del hipertiroidismo por Enfermedad de Graves en pacientes adultos no embarazadas

La tirotoxicosis tiene múltiples etiologías y manifestaciones clínicas, así como distintas opciones terapéuticas. El apropiado tratamiento dependerá de un diagnóstico certero y también de la preferencia y características clínicas de cada paciente individual. En este artículo se describe una guía clínica basada en la evidencia para el tratamiento del hipertiroidismo por Enfermedad de Graves, dirigida a médicos generalistas, clínicos, endocrinólogos y otros especialistas que traten a pacientes con Enfermedad de Graves. Métodos: El desarrollo de la guía se llevó a cabo por expertos médicos endocrinólogos miembros de la Sociedades filiales de la Federación Argentina de Endocrinología y Metabolismo. El grupo de trabajo conformado examinó la literatura utilizando una búsqueda sistemática en Pubmed y Cochrane. La evidencia recolectada junto con la experiencia y conocimiento de los expertos fue utilizada para el desarrollo de cinco tópicos principales con sus respectivas recomendaciones. La fuerza de las recomendaciones y la calidad de la evidencia que respalda a cada una de ellas fueron clasificadas en forma sistemática por el grupo de expertos y se detalla en el texto. Resultados: Los cinco tópicos principales desarrollados en esta guía para la Enfermedad de Graves incluyen el tratamiento con drogas antitiroideas y sus efectos adversos, el tratamiento con Iodo 131 y el tratamiento quirúrgico, así como el tratamiento adyuvante con b-bloqueantes, compuestos iodados, corticoides, litio y perclorato. Conclusiones: Se desarrollaron en total 47 recomendaciones basadas en la evidencia para el tratamiento de los pacientes con Enfermedad de Graves hipertiroideos.

Fractura de Cadera en los hospitales públicos de la Argentina / Hip Fracture in Public Hospitals of Argentina

La fractura de cadera en población añosa constituye un problema creciente para los sistemas de salud a nivel mundial debido a su elevado impacto econámico y social. Objetivos: Evaluar los egresos por fractura de cadera en adultos mayores de 55 años informados al Ministerio de Salud de la Nación durante los años 2000, 2006, 2007 y 2008. Analizar el efecto de la edad y sexo sobre la incidencia de fracturas de cadera, los tipos de fractura y su variabilidad en el tiempo. Materiales y Métodos: Se obtuvieron los datos de egresos por fracturas de cadera en pacientes mayores de 55 años registrados en el Ministerio de Salud de la Nación. Se calculá la Tasa de Egresos (TE) por fracturas de cadera, la TE estratificada por sexo (♀: mujer, ♂: varán) y edad; Tasa de Crecimiento Interanual (TCI). Estadística: test de Chi cuadrado y test T de Student para datos no apareados. Resultados y Conclusiones: La fractura de cadera en los hospitales públicos de la Argentina durante los años evaluados, alcanzá un promedio de 5700 egresos/año, con una TE 280/100000. La relación ♀/♂ fue de 2,3. La edad de egreso promedio fue de 78,7 años siendo significativamente menor en los hombres en relación a las mujeres. La relación ♀/♂ aumentá tres veces con la edad. La edad fue un fuerte determinante de las fracturas, siendo la TE de 2800/100000 en los individuos mayores de 75 años. La TCI fue de 1,4 %. La fractura cervical de fémur fue la más frecuente, y fue aumentando progresivamente con la edad; la fractura de trocánter se mantuvo estable en los grupos de menor edad y solo aumentá en los mayores de 75 años. Ambos tipos de fractura predominaron en las mujeres. Este es el primer trabajo que establece datos sobre fractura de cadera en la Argentina. Con el envejecimiento de la población, la fractura de cadera se convertirá en una carga progresivamente mayor para los sistemas de salud.

Hip fracture in the aged population constitutes a growing problem for health systems at a global level because of its economic and social impact. Objectives: to assess discharges for hip fracture in adults over the age of 55 reported to the Ministry of Health of Argentina during the years 2000, 2006, 2007 and 2008; analyze the effect of age and sex on the incidence of hip fractures and its variability over time. Materials and Methods: The discharge data for hip fractures in patients over 55 years were obtained from registers of the Ministry of Health of Argentina. We calculated the Discharge Rate (DR) by hip fractures, DR of fractures stratified by sex (♀: female, ♂: male) and age; the Annual Growth Rate (AGR). Statistics: Student test and Chi square test. Results and Conclusions: Hip fracture in public hospitals in Argentina in the evaluated years reached an average of 5700 discharges per year, with a DR 280/100000. The.♀/♂ ratio was 2.3. The average discharge age was 78.7 years, significantly lower in men in relation to women. The relationship ^/c? increased three times with age. The age was a strong determinant of fracture so the DR was 2800/100000 in people older than 75 years. The AGR was 1.4 %. Cervical fracture was the most frequent, and increased progressively with age; the trochanteric remained stable in the younger age groups and increased in people over 75 years. Both were more common in women. This is the first trial on hip fracture data in Argentina. Given population aging hip fracture will become a progressively larger burden on public health.

Latin American Thyroid Society recommendations for the management of thyroid nodules / Recomendações da Sociedade Latino-Americana de Tireoide no manejo de nódulos tireoideos

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries.

Vários consensos têm sido publicados acerca do diagnóstico e do tratamento de nódulos e câncer da tireoide. Entretanto, as recentes recomendações nem sempre são apropriadas para diferentes regiões ou países. O objetivo deste trabalho foi oferecer uma série de recomendações para a avaliação e conduta de pacientes portadores de nódulos tireoideos aplicáveis a todos os países da América Latina. O trabalho foi realizado por um comitê composto por 13 membros da Sociedade Latino-Americana de Tireoide envolvidos com pesquisa e manejo de pacientes portadores de nódulos e carcinoma diferenciado da tireoide, de diferentes centros médicos da América Latina. As recomendações foram estabelecidas, após consenso, utilizando as opiniões especializadas de cada membro e os princípios da medicina baseada em evidência. Após a primeira reunião do grupo, um primeiro documento foi elaborado e encaminhado a todos os membros para revisão. Posteriormente, o documento foi enviado aos membros da Sociedade Latino-Americana de Tireoide para avaliação, sugestões e comentários. A versão final, elaborada após refinada revisão de todos os autores, representa o estado da arte no diagnóstico e na conduta de nódulos tireoideos, aplicáveis a todos os países da América Latina.

Recommendations of the Latin American Thyroid Society on diagnosis and management of differentiated thyroid cancer.

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries.

Recommendations of the Latin American Thyroid Society on diagnosis and management of differentiated thyroid cancer / Recomendações da Sociedade Latino-Americana de Tireoide para diagnóstico e manejo do carcinoma diferenciado de tireoide

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries.

Estas recomendações tiveram por objetivo o desenvolvimento de diretrizes para avaliação e manejo de pacientes com câncer diferenciado da tiroide em países latino-americanos. Um painel composto por 13 membros da Sociedade Latino-Americana de Tireoide (SLAT) - que estavam envolvidos em pesquisas, e eram peritos no cuidado do paciente com câncer da tiroide e provenientes de diferentes centros médicos latino-americanos - utilizou os princípios da Medicina Baseada em Evidências para produzir esse consenso. Após uma primeira reunião, um texto inicial foi elaborado, baseado em evidências e opiniões dos especialistas do painel e, posteriormente, circulado entre os membros do painel, para revisão. Após a revisão, o documento foi enviado aos membros da SLAT para comentários e considerações e, finalmente, revisado e refinado pelos autores. As recomendações finais aqui apresentadas demonstram o estado da arte no manejo do câncer diferenciado da tireoide aplicadas aos países latino-americanos.

Genotyping of resistance to thyroid hormone in South American population. Identification of seven novel missense mutations in the human thyroid hormone receptor beta gene.

Thyroid Hormone Receptor beta (THRB) defects, typically transmitted as autosomal dominant traits, cause Resistance to Thyroid Hormone (RTH). We analyzed the THRB gene in thirteen South American patients with clinical evidence RTH from eleven unrelated families. Sequence analysis revealed seven novel missense mutations. Four novel mutations were identified in exon 9. The first, a c.991A>G transition which originates a substitution of asparagine by aspartic acid (p.N331D). The second nucleotide alteration consists of a guanine to cytosine transversion at position 1003 (c.1003G>C) and results in substitution of the alanine at codon 335 by proline (p.A335P). The third mutation, a c.1022T>C transition produces a change of leucine by proline (p.L341P). The fourth mutation detected in exon 9 was a c.1036C>T transition which replaces the leucine at codon 346 by phenylalanine (p.L346F). The sequencing of the exon 10 detected three novel missense mutations. The first, a c.1293A>G transition changing isoleucine 431 for methionine (p.I431M). The second, the cytosine at position 1339 was replaced by adenine (c.1339C>A) resulting in the replacement of proline by threonine (p.P447T). The third mutation detected in exon 10 was a c.1358C>T transition resulting in the substitution of proline at codon 453 by leucine (p.P453L). Finally, sequencing analysis of the THRB gene revealed three substitutions previously described (p.A268G, p.P453T and p.F459C). The p.P453T was found in two patients. In conclusion, we report thirteen patients with RTH caused by heterozygous mutations of the THRB gene. Seven of the identified mutations correspond to novel substitutions.

Latin American thyroid society recommendations for the management of thyroid nodules.

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries.

Graves' disease: evolution and prognosis after eight months of treatment with methimazole

We studied 26 patients with Graves' disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1% of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60% and a specificity of 100%. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse