Comparativa de los métodos de evComparativa de los métodos de evaluación de la reserva de yodo corporal previamente a la realización de tratamiento con radioyodoaluación de la reserva de yodo corporal previamente a la realización de tratamiento con radioyodo / Comparison of Body Iodine Pool Assessment Methods Before Radioiodine Therapy

Introducción y objetivos: El tratamiento con yodo radiactivo (RAIT) se recomienda para reducir el riesgo de recurrencia y de metástasis en personas con cáncer diferenciado de tiroides (CDT) de riesgo intermedio-alto. En la preparación para la RAIT, la estimulación de la tirotropina y la reducción en la reserva corporal de yodo son elementos importantes para contribuir al éxito de la terapia. Para ello, se pide a los pacientes que reduzcan la ingesta de este mineral antes de la RAIT, y puede evaluarse su reserva corporal midiendo su excreción por la orina (yoduria) antes del tratamiento. El objetivo de nuestro estudio ha sido comparar los métodos utilizados para medir la reserva de yodo corporal en la evaluación de la eficacia de la dieta con bajo contenido en yodo (RID) aplicada a la preparación del paciente para la RAIT. Pacientes y métodos: Suspendieron la levotiroxina tres semanas antes de la RAIT y fueron controlados con una RID durante las dos semanas previas a la realización del tratamiento 80 pacientes con CDT. Tras dos semanas de RID, en todos se llevó a cabo una recolección de orina de 24h el día previo a la fecha de administración de la RAIT. Los sujetos finalizaron dicha recolección en la mañana de la fecha de RAIT y suministraron una muestra puntual de orina. Se calculó la excreción estimada de creatinina en orina de 24 horas de los pacientes. La estimación de la excreción urinaria de yodo o yoduria (UIE) de 24 horas oras se determinó a partir del índice yodo/creatinina (I/C) obtenido en la muestra de orina puntual de los individuos. Se compararon los resultados de la yoduria de 24 horas, la concentración de yodo en la muestra puntual de orina, el cociente I/C en la muestra puntual de orina y la estimación de la yoduria de 24 horas en los pacientes. Resultados: En 99%, la eficacia de la RID fue suficiente según la yoduria de 24 horas obtenida previamente a la RAIT...(AU)

Introduction and Objectives: Radioactive iodine therapy (RAIT) is recommended to reduce the risk of recurrence and metastasis in patients with intermediate-high risk differentiated thyroid cancer (DTC). In preparation for RAIT, stimulation of thyroid-stimulating hormone and reduction of body iodine pool are important for treatment success. For this purpose, patients are asked to reduce their iodine intake before RAIT, and the body iodine pool can be evaluated by measuring iodine excretion in urine before treatment. The aim of our study is to compare the methods used to measure the body iodine pool in the evaluation of the restricted iodine diet (RID) effectiveness applied in the RAIT preparation. Patients and methods: Eighty DTC patients discontinued levothyroxine three weeks before RAIT and followed up with a RID two weeks before treatment. After two weeks of RID, all patients collected their 24-hour urine the day before the RAIT date. Patients completed 24-hour urine samples on the morning of the RAIT date and also provided a spot urine sample. The estimated 24-hour creatinine excretion of the patients was calculated. Estimated 24-hour urinary iodine excretion (UIE) was calculated using the spot urine iodine/creatinine (I/C) ratio of the patients. 24-hour UIE, iodine concentration in spot urine, I/C ratios in spot urine and estimated 24-hour UIE of the patients were analyzed by comparing with each other. Results: In 99% of the patients, RID efficiency was sufficient according to 24-hour UIE before RAIT. The mean 24-hour UIE was 48.81 micrograms/day (mcg/day) in 24-hour urine samples taken from the patients to evaluate the body iodine pool. The patients’ iodine concentrations in spot urine, I/C ratios in spot urine, and estimated 24-hour UIE were all statistically significantly lower than actual 24-hour UIE, which was the reference method (p: 0.026 vs <0.001 vs 0.041)..... (AU)

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects.

INTRODUCTION: Patients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies. Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. MATERIAL AND METHODS: Patients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy. Patients were reclassified in the following 6-18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels. The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. RESULTS: Sixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses. A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). CONCLUSIONS: In selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

Comparison of body iodine pool assessment methods before radioiodine therapy.

INTRODUCTION AND OBJECTIVES: Radioactive iodine therapy (RAIT) is recommended to reduce the risk of recurrence and metastasis in patients with intermediate-high risk differentiated thyroid cancer (DTC). In preparation for RAIT, stimulation of thyroid-stimulating hormone and reduction of body iodine pool are important for treatment success. For this purpose, patients are asked to reduce their iodine intake before RAIT, and the body iodine pool can be evaluated by measuring iodine excretion in urine before treatment. The aim of our study is to compare the methods used to measure the body iodine pool in the evaluation of the restricted iodine diet (RID) effectiveness applied in the RAIT preparation. PATIENTS AND METHODS: Eighty DTC patients discontinued levothyroxine three weeks before RAIT and followed up with a RID two weeks before treatment. After two weeks of RID, all patients collected their 24-h urine the day before the RAIT date. Patients completed 24-h urine samples on the morning of the RAIT date and also provided a spot urine sample. The estimated 24-h creatinine excretion of the patients was calculated. Estimated 24-h urinary iodine excretion (UIE) was calculated using the spot urine iodine/creatinine (I/C) ratio of the patients. 24-h UIE, iodine concentration in spot urine, I/C ratios in spot urine and estimated 24-h UIE of the patients were analyzed by comparing with each other. RESULTS: In 99% of the patients, RID efficiency was sufficient according to 24-h UIE before RAIT. The mean 24-h UIE was 48.81 micrograms/day (mcg/day) in 24-h urine samples taken from the patients to evaluate the body iodine pool. The patients' iodine concentrations in spot urine, I/C ratios in spot urine, and estimated 24-h UIE were all statistically significantly lower than actual 24-h UIE, which was the reference method (p: 0.026 vs <0.001 vs 0.041). Moderate positive correlation between 24-h UIE and iodine concentration in spot urine (r: 0.440), I/C ratio in spot urine (r: 0.493), and estimated 24-h UIE (r: 0.560) found. The strongest correlation was obtained with the estimated 24-h UIE. CONCLUSION: The estimated 24-h UIE obtained by using the I/C ratio in spot urine can be used practically and safely as an alternative to UIE in 24-h urine, which is the gold standard method for evaluating body iodine pool.

Riesgo de recurrencia y factores de riesgo de invasión del cáncer diferenciado de tiroides / Risk of recurrence and risk factors for invasion of differentiated thyroid cancer

Introducción: El cáncer diferenciado de tiroides (CDT) se encuentra representado por el carcinoma papilar y el carcinoma folicular. Comprende la gran mayoría (>90%) de todos los cánceres de tiroides. Objetivos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Materiales y métodos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Resultados: El 87% fueron del sexo femenino. La edad media fue de 43±14 años. Predominó el riesgo de recurrencia bajo en el 49% de los pacientes, seguido del riesgo intermedio (33%) y riesgo alto (18%). El tamaño tumoral ˃1cm confiere mayor riesgo de ser estratificado como riesgo de recurrencia intermedio/alto (OR 5,7 IC 95% 3,6-9). El sexo masculino representó mayor riesgo de invasión ganglionar (OR 2,8 IC 95% 1,2-6,6); la edad ≥55 años lo fue en la invasión vascular (OR 2,1 IC 95% 1,1-4,1); el tamaño >1cm constituyó un mayor riesgo de manera significativa de invasión capsular (OR 10,5 IC 95% 6,5-17), invasión ganglionar (OR 10,2 IC 95% 3,8-26,9), invasión vascular (OR 30,7 IC 95% 4,2-224) e invasión de tejido peritiroideo (OR 5,2 IC 95% 3,3-8,2). Conclusión: El riesgo de recurrencia inicial más frecuente fue el riesgo bajo. El sexo masculino, la edad ≥55años y el tamaño >1cm constituyen factores de riesgo de invasión a estructuras vecinas.

Introduction: Differentiated thyroid cancer (DTC) is represented by papillary carcinoma and follicular carcinoma. It comprises the vast majority (> 90%) of all thyroid cancers. Objectives: Stratify the risk of initial recurrence of patients with DTC. Relate age, sex, and tumor size to the risk of recurrence, capsular, nodal, vascular, and perithyroid tissue invasion. Materials and methods: Observational, descriptive, retrospective, cross-sectional study with an analytical component. A total of 432 patients with a diagnosis of DTC from Hospital de Clínicas, Instituto de Previsión Social and Instituto Nacional del Cáncer between 2011 and 2015 were included. Results: 87% were female. The mean age was 43 ± 14 years. Low recurrence risk predominated in 49% of patients, followed by intermediate risk (33%) and high risk (18%). Male sex, age ≥55 years and tumor size ˃1cm confer a higher risk of being stratified as intermediate / high recurrence risk, but only size> 1cm was significantly (OR 5.7 95% CI 3.6-9). Male sex represented a higher risk of lymph node invasion (OR 3.1 95% CI 1.4-2.8) and vascular invasion (OR 2.3 95% CI 1.1-4.8); age ≥55 years was in the vascular invasion (OR 2.6 95% CI 1.4-4.9); size> 1cm constituted a significantly higher risk of capsular invasion (OR 10.7 95% CI 6.7-17.3), nodal invasion (OR 10.5 95% CI 4-27.7), vascular invasion (OR 33 95% CI 4.5-244) and invasion of perithyroid tissue (OR 5.1 95% CI 3.2-8.1). Conclusion: The most frequent initial recurrence risk was low risk. Male sex, age ≥55 years, and size> 1cm are risk factors for invasion of neighboring structures.

Modelización del tiempo que tarda un paciente con cáncer diferenciado de tiroides en presentar la primera recaída / Modeling of the Time it Takes for a Patient with Differentiated Thyroid Cancer to Present the First Relapse / Modelagem do tempo que um paciente com câncer diferenciado de tireoide leva para apresentar a primeira recidiva

Introducción: de todos los carcinomas de tiroides, los diferenciados son los predominantes. Según la Asociación Colombiana de Endocrinología, la tasa de recaída puede ser de hasta del 30 %, especialmente en pacientes mayores de 45 años y con características tumorales agresivas. En esta investigación se estimó el tiempo libre de enfermedad que transcurre entre la finalización del tratamiento y la ocurren-cia de la primera recaída. Materiales y métodos: se tomó un archivo de datos con los registros de 469 pacientes con cáncer diferenciado de tiroides (cdt) tratados en una clínica especializada de cuarto nivel de complejidad en Bogotá (Colombia). Los datos se recolectaron entre enero de 1997 y diciembre de 2012 y se analizaron estadísticamente usando modelos paramétricos y no paramétricos para obtener las curvas de supervivencia y riesgo. Resultados: con el método no paramétrico se evidenció que en 8.5 años el 75 % de los pacientes no habrán presentado la primera recaída en cdt; mientras que en el método paramétrico el 50 % de los pacientes que no presentaron una tiroglobulina postratamiento menor o igual a 1 ng/mL y un tamaño del tumor menor o igual a 2 cm, su tiempo estimado de la primera recaída fue 29.2 años. Conclusiones: el tiempo libre de enfermedad y el riesgo de hacer recaída para pacientes con cdt está afectado por la presencia de un tamaño de tumor mayor a 2 cm en el momento de la consulta y una cantidad de tiroglobulina mayor a 1 ng/mL, registrada al terminar el tratamiento.

Introduction: Between all thyroid carcinomas, the differentiated are predominant. According to the Colombian Association of Endocrinology, the relapse rate can be up to 30%, especially in patients older than 45 years old and with aggressive tumor characteristics. In this investigation, the time that elapses between the initial surgical treatment and the first relapse of the disease was estimated. Materials and methods: A data file was taken with the records of 469 patients with differentiated thyroid cancer (cdt) treated in a specialized clinic of fourth level of complexity iv in the city of Bogotá (Colombia). Data were collected between January 1997 and December 2012 and were statistically analyzed using para-metric and non-parametric models to obtain survival curves and risk. Results: With the non-parametric method, it is evident that in 8.5 years 75% of the patients will not have presented the first relapse in cdt. While applying the parametric method 50% of patients who do not have a postreatment thyroglobulin or one less than or equal to 1 ng/mL and a tumour size less than or equal to 2 cm, their estimated time of First relapse was 29.2 years. Conclusions: Disease-free time and the risk of relapse for patients with cdt is affected by the presence of a tumor size greater than 2 cm at the time of consultation and levels of thyroglobulin greater than 1 ng/mL, recorded at the end of the treatment.

Introdução: de todos os carcinomas da tireoide, os diferenciados são os predominantes. Segundo a Associação Colombiana de Endocrinologia, a taxa de recaída pode ser até 30%, principalmente em pacien-tes com mais de 45 anos e com características de agressividade tumoral. Nesta investigação, estimou-se o tempo decorrido entre o tratamento cirúrgico inicial e a primeira recaída. Materiais e métodos: tomou-se um arquivo de dados com os prontuários de 469 pacientes com câncer diferenciado de tireoide (cdt) atendidos em uma clínica especializada de quarto nível de complexidade na cidade de Bogotá (Colombia). Coletaram-se os dados entre janeiro de 1997 e dezembro de 2012, que depois foram analisados estatisti-camente usando modelos paramétricos e não paramétricos para encontrar curvas de sobrevida e risco. Resultados: com o método não paramétrico, evidenciou-se que, em 8,5 anos, 75% dos pacientes não terão apresentado a primeira recaída na cdt. Enquanto na aplicação do método paramétrico, 50% dos pacientes que não apresentaram tireoglobulina pós-tratamento ou valores menores ou iguais a 1 ng/mL e tamanho do tumor menor ou igual a 2 cm, seu tempo estimado de primeira recaída foi de 29,2 anos. Conclusões: o tempo livre de doença e o risco de recaída, para pacientes com cdt são afetados pela presença de tama-nho de tumor maior a 2 cm no momento da consulta e uma quantidade de tireoglobulina maior a 1 ng/mL, registrada ao terminar o tratamento.

Assessment of the utility of measuring Thyroglobulin mRNA levels by Quantitative Real-Time PCR in the follow-up of differentiated thyroid cancer patients.

INTRODUCTION: The determination of thyroglobulin levels by immunoassay and imaging studies is subject to interference by antithyroglobulin antibodies in up to 30% of cases, suggesting a need to find alternative methods for the follow-up of a significant number of thyroid cancer patients. OBJECTIVES: Assess the sensitivity, specificity, and predictive values of thyroglobulin messenger RNA levels measured by quantitative Real Time-PCR (qRT-PCR) in the blood of patients followed for differentiated thyroid cancer. METHODS: This is a prospective study of Tg-mRNA levels measured with qRT-PCR. A peripheral blood sample was taken in patients with excellent response (69) and with structural incomplete response to treatment (23). Results were analysed using the Unity Real-Time program and expressed as fg/µg RNA. A Receiver Operating Characteristic curve was constructed to assess Tg-mRNA cut-off values. RESULTS: Tg-mRNA levels were not significantly different between the group with excellent response [0.10 fg/µg RNA (0.08-0.17)] and the group with incomplete structural response [0.133 fg/µg RNA (0.07-0.33)] (P < .06). Test sensitivity was 69.6%, specificity was 59.4%, negative predictive value was 85.4% and positive predictive value 36.4% CONCLUSIONS: Our experience shows that this technique could be useful as a rule-out test in selected cases, but its low sensitivity and specificity preclude its usefulness as a first-line test.

Assessment of the utility of measuring Thyroglobulin mRNA levels by Quantitative Real-Time PCR in the follow-up of differentiated thyroid cancer patients. / Evaluación de la utilidad de medir los niveles de ARN mensajero de tiroglobulina por PCR cuantitativa en tiempo real para el seguimiento de pacientes con cáncer diferenciado de tiroides.

INTRODUCTION: The determination of thyroglobulin (Tg) levels by immunoassay is subject to interference by antithyroglobulin antibodies in up to 30% of cases, suggesting a need to find alternative methods for the follow-up of a significant number of thyroid cancer patients. OBJECTIVES: Assess the sensitivity, specificity, and predictive values of thyroglobulin messenger RNA (Tg-mRNA) levels measured by quantitative Real Time-PCR (qRT-PCR) in the blood of patients followed for differentiated thyroid cancer. METHODS: This is a prospective study of Tg-mRNA levels measured with qRT-PCR. A peripheral blood sample was taken in patients with excellent response (n=69) and with structural incomplete response to treatment (n=23). Results were analysed using the Unity Real-Time program and expressed as fg/µg RNA. A Receiver Operating Characteristic curve was constructed to establish Tg-mRNA cut-off values. RESULTS: Tg-mRNA levels were not significantly different between the group with excellent response [0.10fg/µg RNA (0.08-0.17)] and the group with incomplete structural response [0.133fg/µg RNA (0.07-0.33)] (p<0.06). Test sensitivity was 69.6%, specificity was 59.4%, negative predictive value was 85.4% and positive predictive value was 36.4%. CONCLUSIONS: Our experience shows that this technique could be useful as a rule-out test in selected cases, but its low sensitivity and specificity preclude its usefulness as a first-line test.

Metástasis raras de cáncer papilar de tiroides en músculo esquelético: serie de casos / Rare metastases of papillary thyroid cancer in skeletal muscle: case series

Las metástasis del carcinoma papilar de tiroides (CPT) generalmente son a nivel locorregional, la diseminación a distancia es poco habitual, sin embargo la invasión de tejidos blandos aunque inusual puede ocurrir, y afecta negativamente la supervivencia. El presente estudio describe una serie de casos de Metástasis Musculares de CPT. Se realizó un estudio transversal de un solo centro que evaluó diez pacientes con CPT con metástasis en músculo. La edad de los pacientes fue entre 46 a 77 años, siendo la edad promedio de 60 años, 7 de los cuales fueron de sexo masculino que corresponde al 70%, todos con antecedente de CPT con respuesta estructural incompleta, además de las metástasis en músculo presentaron afectación de tres o más órganos, con necesidad de varios tratamientos, cada paciente registró entre 1 a 8 cirugías, recibieron entre 100 a 780mCi de I131 (yodo radiactivo), ocho ameritaron radioterapia, todos tuvieron indicación de tratamiento con ITK, sin embargo solo cuatro pacientes tuvieron acceso a dicho medicamento. La mayoría de las metástasis del CPT en músculo fueron diagnosticadas en los estudios de imagen PET/ CT, después de la tiroidectomía el tiempo de su presentación fue muy variable entre 1 a 18 años, el número de músculos comprometidos se reporta entre uno a cuatro, siendo el glúteo (4 casos) el músculo metastásico más frecuente. La presencia de metástasis musculares empeora el pronóstico en nuestra serie de pacientes.

Metastases of thyroid papillary carcinoma (CPT) are generally at the locoregional level, the dissemination from a distance is unusual, however the invasion of soft tissues, although rare can occur, and it negatively affects survival. The present study describes several Muscular Metastases of CPT cases. A transversal study in one only center was performed and assessed ten patients CPT metastases in muscles.The patients age ranged from 46 to 77, being the average age of 60, and 7 of them were male, corresponding to the 70%, everyone with CPT records with an incomplete structural response. Besides muscular metastases they also presented issues with three or more organs, needing many treatments. Each patient registered between 1 to 8 surgeries, they received between 100 to 780mCi of I131. Eight required radiotherapies, everyone required treatment with ITK, however, just four patients had access to that medication. Most of the CPT metastases in muscles were diagnosed in PET/CT image studies, after the thyroidectomy, the time for its presentation was very variable between 1 to 18 years, the number of compromised muscles is reported between one to four, being the buttock (4 cases) the most frequently muscle with metastases. The presence of muscular metastases aggravates the prognosis in our series of patients.

Detección ecográfica de remanentes del conducto tirogloso luego de tiroidectomía por cáncer de tiroides / Thyroglossal duct remnants detected by ultrasonography after total thyroidectomy for thyroid carcinoma

Resumen Existen numerosas comunicaciones de hallazgo incidental de remanentes del conducto tirogloso (CTG) posteriores a una tiroidectomía total, pero se desconoce su implicancia en pacientes con cáncer diferenciado de tiroides (CDT). Nuestro objetivo fue determinar frecuencia de detección ecográfica de remanentes del CTG posterior a la tiroidectomía total en pacientes con CDT y evaluar el impacto del hallazgo en la respuesta al tratamiento. Se incluyeron 377 pacientes con CDT tratados con tiroidectomía total entre enero 1994 y enero 2017, con seguimiento de al menos un año posterior a la cirugía. Se detectó la presencia de remanente del CTG en 16/377 (4.2%): 15 de bajo riesgo de recurrencia y uno de riesgo intermedio. Trece recibieron radioyodo. Todos tuvieron un estado sin evidencia de enfermedad al final del seguimiento, excepto uno con riesgo intermedio que presentó una respuesta inicial estructural incompleta e indeterminada posterior al vaciamiento ganglionar. La mediana del tiempo de diagnóstico del remanente del CTG luego de la tiroidectomía fue de 5 años (rango 1-16). Dos pacientes con remanentes del CTG fueron intervenidos quirúrgicamente, ambos presentaron tumoraciones de aparición súbita en región suprahioidea, 2.4 y 4 cm, detectados a los 9 y 16 años luego de la tiroidectomía, respectivamente. La prevalencia de esta condición parece ser poco frecuente. Sin embargo, la aparición de una masa quística en el seguimiento de un paciente con CDT puede ser confundido con enfermedad metastásica y generar ansiedad. El hallazgo de remanentes del CTG parecería no tener ningún impacto en la respuesta al tratamiento.

Abstract There are numerous reports of incidental findings of thyroglossal duct remnants (TGDR) after total thyroidectomy, but its implication on the outcome of patients with differentiated thyroid cancer (DTC) is unknown. The aim of this study was to determine the frequency of TGDR detected by ultrasonography after total thyroidectomy in patients with DTC and to evaluate the impact of this finding on the response to treatment. A total of 377 records of patients with DTC who received total thyroidectomy between January 1994 and January 2017 were reviewed. Patients with less than one year of follow-up after surgery were excluded. TGDR was diagnosed in 16 out of 377 (4.2%). Fifteen had a low risk of recurrence DTC and 13 of them were treated with radioactive iodine. All low risk patients had an excellent response to treatment. Only one with an intermediate risk of recurrence DTC had an initial structural incomplete response which changed to an indeterminate response after a modified central lymph node dissection. The median time of TGDR diagnosis after thyroidectomy was 5 years (1-16). Two patients underwent TGDR surgery due to the presence of a rapidly growing neck mass, 2.4 and 4 cm in size, detected 9 and 16 years after thyroidectomy, respectively. The prevalence of this condition seems to be rare. However, the appearance of a cystic mass during the follow-up of a patient with DTC cancer could be confused with metastatic disease. The diagnosis of TGDR seems not to have an impact on the response to treatment.

Variación de dosis de radioyodo en pacientes con cáncer diferenciado de tiroides post implementación de guías ATA 2015 / Variation of radioiodine dose in patients with differentiated thyroid cancer after implementation of the ATA 2015 guidelines

Introducción: El cáncer diferenciado de tiroides (CDT), es actualmente la neoplasia endocrina más frecuente. Su tratamiento estándar es la resolución quirúrgica, asociado a ablación con radioyodo (RI) según la clasificación propuesta por la American Thyroid Association (ATA). Las indicaciones y dosis de este último, han ido variando en los últimos años según avanzan las investigaciones en este ámbito. Objetivo: En el siguiente estudio se compararon las dosis de RI utilizadas previo y posterior a la implementación de las últimas guías de la ATA. Materiales y métodos: Estudio retrospectivo observacional de 70 pacientes con diagnóstico de CDT del Hospital Clínico de la Universidad de Chile entre 2012 y 2017. Se agruparon los pacientes en dos cohortes, los operados entre los años 2012-2015 y los 2016-2017 clasificándolos según riesgo ATA, TNM y riesgo de recurrencia. Se consignaron las dosis de RI utilizadas y se compararon entre las cohortes. Análisis estadístico: Mann Whithney. Resultados: Al comparar la dosis de RI entre ambas cohortes, según TNM y riesgo ATA, se obtuvo los siguientes resultados: los pacientes T1b de la cohorte 2012-2015 presentaron dosis de RI significativamente mayores que los de la cohorte 2016-2017; también se evidenció que en pacientes N0 hubo una diferencia estadísticamente significativa, mostrando una tendencia a disminuir la dosis de RI; además, en los pacientes de la cohorte 2012-2015 con riesgo ATA intermedio, se obtuvo que las dosis de RI fueron significativamente mayores que las utilizadas en la cohorte 2016-2017. Conclusión: Se concluye que las variaciones de las dosis de RI utilizadas en pacientes con CDT en un hospital universitario van acorde a las recomendaciones internacionales actuales, particularmente la publicación de la guía ATA 2015, aplicándose radioablación con menor dosis de RI. Dado este cambio, se ha evidenciado igualdad de efectos con dosis menores de RI y consecuentemente menos efectos adversos.

Introduction: Differentiated thyroid cancer (CDT) is currently the most frequent endocrine neoplasia. Its standard of care is surgical treatment, associated with radioiodine ablation (IR) according to the classification proposed by the American Thyroid Association (ATA). The indications and doses of the latter have changed in recent years as research in this area advances. Objective: In the following study, the doses of IR used before and after the implementation of the latest ATA guidelines were compared. Materials and methods: Retrospective observational study of 70 patients with a diagnosis of CDT from the Clinical Hospital of the University of Chile between 2012 and 2017. Patients were grouped into two cohorts, those surgically intervened between the years 2012-2015 and 2016-2017, classifying them according to ATA risk, TNM and recurrence risk. The IR doses used were reported and compared between the cohorts. Statistical analysis: Mann Whithney. Results: When comparing the IR dose between both cohorts, according to TNM and ATA risk, the following results were obtained: T1b patients in the 2012-2015 cohort had significantly higher IR doses than those in the 2016-2017 cohort; It was also evidenced that N0 patients showed a statistically significant tendency to decrease the IR dose; In addition, the 2012-2015 cohort with intermediate ATA risk, revealed IR doses significantly higher than those used in the 2016-2017 cohort. Conclusion: It is concluded that the variations in IR doses, used in patients with CDT in a university hospital, are in accordance with current international recommendations, particularly the publication of the ATA 2015 guidelines, applying radioablation with a lower dose of IR. Given this change, equality of effects has been evidenced with lower doses of IR and consequently fewer adverse effects.

Radioiodine treatment of differentiated thyroid cancer related to guidelines and scientific literature. / Tratamiento del cáncer diferenciado de tiroides con radioyodo a la luz de las guías y de la literatura científica.

In differentiated thyroid cancer (DTC), radioiodine is administered to eliminate residual normal thyroid tissue after thyroidectomy (ablative treatment), to treat residual microscopic disease (adjuvant treatment), and to treat macroscopic or metastatic disease. Currently, treatment of DTC with 131I is still a matter of controversy due to the absence of prospective clinical trials assessing its benefit in terms of overall survival and recurrence-free interval. The current recommendations of the experts are based on observational retrospective data and on their interpretation of the literature. Pending the results of the prospective trials that are currently underway, the use of 131I seems to be justified not only in high-risk patients, but also in intermediate-risk and low-risk patients. The guidelines of The American and British Thyroid Association, European and American Societies of Nuclear Medicine, The European Consensus Group and the latest edition of National Comprehensive Cancer Network (NCCN) were considered in drawing up this continuing education document, we also undertook a review of the related scientific literature.

Comparación de la respuesta inicial luego de la ablación con 30 mCi de 131I versus no ablación en pacientes con cáncer diferenciado de tiroides de bajo riesgo de recurrencia. Estudio prospectivo multicéntrico / Comparison of initial response to treatment after remnant ablation (RA) with 30 mCi of 131 I versus no RA in patients with differentiated thyroid cancer with low risk of recurrence. Multicentric prospective study

RESUMEN Material y métodos Estudio prospectivo multicéntrico. Se incluyeron 174 pacientes con CDT tratados consecutivamente desde junio 2014 hasta mayo 2015. Se los dividió en 2 grupos (ablacionados y no ablacionados) con 87 pacientes incluidos en cada uno. La respuesta inicial al tratamiento se determinó con la medición de tiroglobulina, anticuerpos anti-tiroglobulina y ecografía de cuello. Resultados Se compararon las características basales de ambos grupos y no se evidenciaron diferencias estadísticamente significativas: sexo femenino 84% y 88% (p = 0,5); edad promedio de 46,8 y 47,5 años (p = 0,7); carcinoma papilar variedad clásico 68% y 75,9% (p = 0,15), respectivamente. El resto de las características basales como tamaño tumoral, bilateralidad, multifocalidad, tiroiditis de Hashimoto y estadio tumoral tampoco mostraron diferencias significativas. La evaluación de la respuesta inicial al tratamiento se realizó en 64 pacientes del grupo ablacionado y en 76 del grupo no ablacionado. Se observó una respuesta excelente en 81% de pacientes ablacionados vs. 87% del grupo no ablacionado, con una frecuencia de respuesta estructural incompleta de 1,6% y 1,4%, respectivamente, (p = 0,9). Un 17% de los ablacionados y 12% de los no ablacionados presentaron una respuesta indeterminada. Conclusión: Los pacientes de bajo riesgo, ablacionados o no, presentan similares frecuencias de respuesta inicial excelente y estructural incompleta. El seguimiento a largo plazo podrá definir si estas respuestas iniciales se mantienen en el tiempo, lo que permitirá reducir la indicación de ablación con radioyodo en este grupo de pacientes con CDT.

ABSTRACT Patients and methods We included 174 patients; 87 patients in each group (ablated and nonablated). Assessment of the initial response to treatment was performed by measurement of thyroglobulin and anti-thyroglobulin antibodies and by neck ultrasonography. Results Baseline characteristics of both groups were compared, and no statistically significant differences were found: female sex 84% and 88,5%, respectively, (p = 0.5); mean age of 46.8 and 47.5 years, respectively (p = 0.7); papillary carcinoma classic variant 68% and 75.9%, respectively (p = 0.15). The remaining of the baseline characteristics such as tumor size, presence of bilaterality, multifocality, Hashimoto's thyroiditis and tumor stage were not statistically significant, either. The evaluation of the response to treatment was finally performed in 64 patients from the ablated group and in 76 from the non-ablated group. An excellent response to treatment was observed in 81% of ablated patients vs. 87% of the non-ablated group, with a frequency of structural incomplete response of 1.6% and 1.4%, respectively (p = 0.9). On the other hand, 17% and 12% of patients in each group had an indeterminate response. Conclusion Low-risk ablated and non-ablated patients have a similar frequency of excellent initial and structural incomplete response to treatment. Long-term follow-up is needed to establish whether these initial responses are maintained over time, and thus further refine the indications of RA in this group of patients with DTC.

Respuesta parcial a lenvatinib como segunda línea de tratamiento en cáncer diferenciado avanzado de tiroides / Partial response to lenvatinib as a second line of treatment in advanced differentiated cancer of thyroid

RESUMEN Las metástasis a distancia ocurren en alrededor del 10% de los pacientes con cáncer diferenciado de tiroides (CDT), y cerca de la mitad de estos casos serán refractarios al radioyodo (RAIR). Sorafenib fue el primer inhibidor multicinasa (IMK) aprobado por la FDA para su uso en cáncer diferenciado de tiroides RAIR avanzado y progresivo, y hasta el momento es el único aprobado por la ANMAT en nuestro país para esta indicación. Lenvatinib es el segundo IMK aprobado por la FDA para este grupo de pacientes, y es una alternativa terapéutica que debe ser considerada, debido a su disponibilidad como fármaco de uso compasivo en nuestro país. Presentamos nuestra experiencia con el uso de lenvatinib como segunda línea de tratamiento en una paciente con CDT progresivo previamente tratado con sorafenib.

ABSTRACT Distant metastases occur in around 10% of patients with differentiated thyroid cancer (DTC), and half of these cases will become refractory to radioiodine therapy (RAIR). Sorafenib was the first multikinase inhibitor (MKI) approved by the FDA for patients with differentiated advanced and progressive RAIR thyroid cancer, and it is the only one approved by ANMAT in our country for this indication. Lenvatinib is the second MKI approved by the FDA for this group of patients, and is a therapeutic alternative that should be considered, due to its availability as a compassive use drug in our country. We present our experience with the use of lenvatinib as a second line of treatment in a patient with DTC with advanced and progressive disease under treatment with sorafenib.

Métodos de tiroglobulina de primera y segunda generación: su utilidad en pacientes con cáncer diferenciado de tiroides / First and second generation thyroglobulin measurement methods: Their usefulness in patients with thyroid cancer

El cáncer diferenciado de tiroides (CDT) es el cáncer endocrinológico más frecuente y en las últimas décadas su incidencia ha aumentado. El seguimiento de la enfermedad se efectúa con la medición de tiroglobulina (Tg) sérica, ecografía cervical y barrido corporal total diagnóstico. Los métodos de Tg han evolucionado a través del tiempo. Actualmente, los ensayos inmunométricos de Tg se clasifican en 1.ª y 2.ª generación (1.ª G y 2.ª G). Comprobamos que los ensayos de 2.ª G alcanzan una precisión adecuada para medir valores del orden de 0,1 ng/ml y los de 1.ª G de 1 ng/ml. La bibliografía señala que en el caso de los pacientes de bajo riesgo, una Tg bajo levotiroxina indetectable por un método de 2.ª G puede evitar la realización de Tg estimulada, sea por la suspensión de la terapia hormonal como por el empleo de la TSH recombinante humana, debido a su mayor sensibilidad. Sin embargo, por su menor especificidad, un valor detectable no asegura la presencia de enfermedad, y debería confirmarse. Para optimizar la utilidad clínica de dicha medición se podrían emplear valores de cortes de acuerdo con la población y el método en lugar de la sensibilidad funcional o límite de cuantificación del mismo. Se señalan también otros aspectos críticos en la medición de Tg como son la discordancia entre distintas metodologías y las interferencias en su medición, principalmente por anticuerpos antitiroglobulina. En presencia de interferencias pierden utilidad los ensayos de Tg de 1.ª y 2.ª G. El seguimiento de los pacientes con Tg interferida tiene limitaciones todavía no resueltas. Es importante consensuar entre médicos y bioquímicos las dificultades técnicas y los criterios de interpretación de los valores de Tg en el seguimiento de los pacientes con CDT.

Differentiated thyroid cancer (DTC) is the most common endocrine cancer (tumour) and its incidence has risen in the past decades. Its follow-up includes measuring serum thyroglobulin (Tg), performing neck ultrasound and a diagnostic whole-body scan. Tg assays have evolved with time. At present immunoassays for Tg are classified as 1 st and 2 nd generation assays (1 st G and 2 nd G). 2 nd G assays show an adequate (good) precision at levels close to 0.1 ng/ml and 1 st G assays at levels close to 1 ng/ml. The literature shows that for low risk patients on levothyroxine treatment, who undetectable levels by 2 aG assays can avoid the stimulation test performed by thyroid hormone withdrawal or after recombinant human TSH, due to better sensitivity. However, due to lower specificity, detectable levels do not confirm the presence of disease (tumour), and should be confirmed. To optimise the clinical usefulness of the test, cut-off values specific for population and method should be used, instead of functional sensitivity or quantification limit. Critical issues for measuring Tg are discussed, such as non-harmonisation of methods, and interferences, mainly by antithyroglobulin antibodies (ATg). 1 st and 2 nd G assays are less useful in presence of ATg, and follow up of such patients is limited. Consensus between physicians and the laboratory on technical issues and interpretation criteria of Tg values is of outmost importance in the follow-up of DTC patients.

Thyroid cancer in lingual thyroid and thyroglossal duct cyst.

Ectopy is the most common embryogenetic defect of the thyroid gland, representing between 48 and 61% of all thyroid dysgeneses. Persistence of thyroid tissue in the context of a thyroglossal duct remnant and lingual thyroid tissue are the most common defects. Although most cases of ectopic thyroid are asymptomatic, any disease affecting the thyroid may potentially involve the ectopic tissue, including malignancies. The prevalence of differentiated thyroid carcinoma in lingual thyroid and thyroglossal duct cyst is around 1% of patients affected with the above thyroid ectopies. We here review the current literature concerning primary thyroid carcinomas originating from thyroid tissue on thyroglossal duct cysts and lingual thyroid.

Individualised dosimetry in patients with differentiated thyroid cancer based on external dose-rate. Optimisation of the number of measurements.

OBJECTIVES: To compare the results of individual dosimetry in differentiated thyroid cancer patients treated with (131)I at our centre with the established limits and dosimetry results of published studies. Analysis of the optimal number of measurements necessary to reduce the impact of dosimetry for the comfort of the patient and, secondly, on the workload of health workers. MATERIAL AND METHODS: Dosimetry was performed in the Nuclear Medicine Department of the University and Polytechnic Hospital La Fe, on 29 patients suffering from differentiated thyroid cancer and treated with activities between 1.02 and 5.51 GBq (mean 2.68 GBq) of (131)I. The Spanish Society of Medical Physics (SEFM) protocol was used, based on measurements of external dose rate adjusted to a bi-exponential curve according to a two compartment model. Different dosimetries were performed on each patient, taking different selections of the available measurements in order to find the optimal number. RESULTS: Results are well below the dosimetry limits, and are consistent with those obtained in other centres. The number of measurements can be reduced from 5, as proposed in the SEFM protocol, to 4 without significant loss of accuracy. Further reducing measures may be justified in individual cases. CONCLUSIONS: The values obtained for the dosimetry quantities are significantly below the established limits. A reduction in measurements can be assumed at the cost of a moderate increase in uncertainty, benefiting the patient.

Spanish consensus for the management of patients with advanced radioactive iodine refractory differentiated thyroid cancer.

BACKGROUND: Approximately one third of the patients with differentiated thyroid cancer (DTC) who develop structurally-evident metastatic disease are refractory to radioactive iodine (RAI). Most deaths from thyroid cancer occur in these patients. The main objective of this consensus is to address the most controversial aspects of management of these patients. METHODS: On behalf of the Spanish Society of Endocrinology & Nutrition (SEEN) and the Spanish Group for Orphan and Infrequent Tumors (GETHI), the Spanish Task Force for Thyroid Cancer, consisting of endocrinologists and oncologists, reviewed the relevant literature and prepared a series of clinically relevant questions related to management of advanced RAI-refractory DTC. RESULTS: Ten clinically relevant questions were identified by the task force. In answering to these 10 questions, the task force included recommendations regarding the best definition of refractoriness; the best therapeutic options including watchful waiting, local therapies, and systemic therapy (e.g. kinase inhibitors), when sodium iodide symporter (NIS) restoration may be expected; and how recent advances in molecular biology have increased our understanding of the disease. CONCLUSIONS: In response to our appointment as a task force by the SEEN and GHETI, we developed a consensus to help in clinical management of patients with advanced RAI-refractory DTC. We think that this consensus will provide helpful and current recommendations that will help patients with this disorder to get optimal medical care.

Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

OBJECTIVES: To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT. MATERIAL AND METHODS: Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi). RESULTS: Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands. CONCLUSION: Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands.

[Postoperative radioiodine ablation in patients with low risk differentiated thyroid carcinoma]. / Ablación posquirúrgica con radioyodo en pacientes con carcinoma diferenciado de tiroides de bajo riesgo.

Most patients with newly diagnosed differentiated thyroid carcinoma have tumors with low risk of mortality and recurrence. Standard therapy has been total or near total thyroidectomy followed by postoperative radioiodine remnant ablation (RRA). Although RRA provides benefits, current clinical guidelines do not recommend it universally, since an increase in disease-free survival or a decrease in mortality in low risk patients has not been demonstrated so far. Advancements in our understanding of the biological behavior of thyroid cancer have been translated into the clinic in a personalized approach to the patients based on their individual risk of recurrence and mortality. Current evidence suggests that RRA is not indicated in most low-risk patients, especially those with papillary carcinomas smaller than 1cm, without extrathyroidal extension, unfavorable histology, lymph node involvement or distant metastases. Follow-up of these patients with serial measurements of serum thyroglobulin and neck ultrasound is adequate. Careful evaluation of all risk factors of clinical relevance will allow a more realistic assessment of each individual patient.

Anticuerpos antitiroglobulina en el monitoreo del carcinoma diferenciado de tiroides en pacientes del Instituto Nacional de Enfermedades Neoplásicas. Enero - junio 2015 / Antithyroglobulin antibodies in the monitoring of differentiated thyroid cancer in patients of the National Institute of Neoplastic Diseases. January-June 2015

Introducción: el cáncer diferenciado de tiroides es la neoplasia endocrina más común, en esta neoplasia se consideran a 2 subtipos el cáncer papilar y el cáncer folicular, ambas neoplasias son de buen pronóstico, el tratamiento es la tiroidectomía y ablación con 131I, el monitoreo se realiza mediante el dosaje de tiroglobulina (Tg), que tiene como principal interferente la presencia de anticuerpos anti-tiroglobulina (Ac-Tg) que invalidan su medición. Objetivos: Detectar la presencia de Ac-Tg durante el monitoreo de pacientes del INEN con cáncer diferenciado de tiroides. Diseño: Estudio descriptivo transversal retrospectivo. Institución: Instituto Nacional de Enfermedades Neoplásicas Lima, Perú. Material: registros de las historias clínicas con monitoreo, de enero-junio 2015. Principales medidas de resultados: Presencia de Ac-Tg. Resultados: del total de 196 registros, 190 correspondieron carcinoma papilar (96,9 por ciento) y un total de 6 correspondieron al carcinoma folicular (3,1 por ciento) con una relación hombre mujer 1:6, se reportaron 35 pacientes (17,9 por ciento) con anticuerpos positivos (>115 UI/mL). Conclusiones: Con los resultados se demuestra que existe una similitud en cuanto a los datos epidemiológicos reportados; en comparación con los datos reportados en la literatura internacional, también es sugerente continuar con los estudios de los Ac-Tg como posible marcador tumoral.

Introduction: differentiated thyroid cancer is the most common endocrine malignancy, consider this neoplasia 2 subtypes papillary and follicular cancer, both neoplasms are good prognosis, treatment is thyroidectomy and 131I ablation, monitoring is performed by the dosage of thyroglobulin, whose main interfering the presence of thyroglobulin antibodies that invalidate measurement. Objectives: To detect the presence of thyroglobulin antibodies for monitoring INEN patients with differentiated thyroid cancer. Design: Retrospective cross-sectional study. Institution: National Institute of Neoplastic Diseases Lima, Peru. Material: records of medical records with monitoring, from January to June 2015. Main outcome measures: Presence of thyroglobulin antibodies. Results: total of 196 records, 190 were for papillary (96.9 per cent) carcinoma and a total of 6 corresponded to follicular carcinoma (3.1 per cent) with a male female ratio 1:6, 35 patients were reported (17.9 per cent) antibody-positive (>115 UI/mL). Conclusions: The results demonstrate that there is a similarity in terms of the epidemiological data reported; compared with data reported in the international literature, it is also suggestive continue with studies of tumor marker antithyroglobulin antibody as possible.