Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox / Vascular Response of Triiodothyronine on Isolated Aortic Rings: Contribution of Redox Mechanisms

Resumo Fundamento A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva ("redox"), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. Objetivos Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. Métodos Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. Resultados A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. Conclusão A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.

Abstract Background Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling. Objective Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms. Methods Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%. Results T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates. Conclusion T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1α After Treatment: A Cell Regulation Study

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Gasto energético en reposo y concentración sérica de lipoproteínas de baja densidad en adultos con hipotiroidismo subclínico leve

La alta prevalencia de hipotiroidismo subclínico en Chile puede deberse a que el límite superior normal de la hormona estimulante del tiroides (TSH) sérica es bajo. Personas con TSH levemente mayor al límite superior pueden ser metabólicamente similares a personas sanas. Se compararon marcadores de acción tiroidea (gasto energético en reposo [GER] y lipoproteína de baja densidad [LDL]) en adultos con hipotiroidismo subclínico leve y con función tiroidea normal con o sin tratamiento con levotiroxina. Se midió GER, perfil lipídico y tiroideo en personas sanas con función tiroidea normal (TSH ≥0,4-<4,5 µUI/ml; n=91); con hipotiroidismo subclínico leve (TSH ≥4,5-≤6,5 µUI/ml; n=5); y con hipotiroidismo clínico tratado con levotiroxina y TSH normal (n=13). Se analizó la LDL en 838 personas sanas con función tiroidea normal y 89 con hipotiroidismo subclínico leve de la Encuesta Nacional de Salud 2016/17 (ENS). El GER, ajustado por peso, sexo y edad, fue similar entre grupos (p=0,71). La LDL fue similar entre personas con función tiroidea normal e hipotiroidismo subclínico leve (91±24 vs. 101±17 mg/dl; p=0,67), y menor en hipotiroidismo tratado (64±22 mg/dl; p<0,01). La LDL no se asoció con TSH pero si inversamente con T4L en mujeres (r=-0,33; p=0,02; n=53). En la ENS, ambos grupos tuvieron similar LDL (p=0,34), la que se asoció inversamente con T4L en mujeres (r=-0,12; p=0,01; n=569) pero no con TSH. Personas sanas con función tiroidea normal y con hipotiroidismo subclínico leve tienen similar GER y LDL. Esto apoya la idea de redefinir el límite superior normal de TSH.

The high prevalence of subclinical hypothyroidism in Chile may be due to the low normal upper limit of serum thyroid-stimulating hormone (TSH). People with TSH slightly higher than the upper limit may be metabolically similar to healthy people. Thyroid action markers (resting energy expenditure [REE] and low-density lipoprotein [LDL]) were compared in adults with mild subclinical hypothyroidism and with normal thyroid function with or without levothyroxine treatment. REE, lipid and thyroid profile were measured in healthy people with normal thyroid function (TSH ≥0,4-<4,5 µUI/ml (n=91); with mild subclinical hypothyroidism (TSH ≥4,5-≤6 µUI/ml; n=5); and with clinical hypothyroidism treated with levothyroxine and normal TSH (n=13). LDL was analyzed in 838 healthy people with normal thyroid function and 89 with mild subclinical hypothyroidism from the 2016/17 National Health Survey (NHS). REE, adjusted for weight, sex and age, was similar between the groups (p=0,71). LDL was similar between people with normal thyroid function and mild subclinical hypothyroidism (91±24 vs. 101±17 mg/dl; p=0,67), and lower in treated hypothyroidism (64±22 mg/dl; p<0,01). LDL was not associated with TSH but was inversely with FT4 in women (r=-0,33; p=0,02; n=53). In the NHS, both groups had similar serum LDL (p=0,34), which was inversely associated with FT4 in women (r=-0,12; p=0,01; n=569), but not with TSH. Healthy people with normal thyroid function and mild subclinical hypothyroidism have similar REE and LDL. These results support the idea of redefining the normal upper limit of TSH.

Guía de práctica clínica para el tratamiento y seguimiento de personas con cáncer diferenciado de tiroides. Parte I: Vigilancia activa

Introducción: El cáncer de tiroides es una enfermedad frecuente en el mundo, con mayor prevalencia del tipo diferenciado. El diagnóstico temprano y manejo pertinente, individualizado y adaptable puede mejorar su pronóstico. Objetivo: Generar recomendaciones basadas en evidencia sobre el tratamiento y seguimiento de personas adultas con cáncer diferenciado de tiroides (CDT). Metodología: Guía de práctica clínica (GPC) a partir de revisión sistemática de literatura (RSL) y consenso de expertos clínicos. El grupo desarrollador definió el alcance y cuatro preguntas que se resolvieron a través de revisión de evidencia de GPC existentes, RSL, estudios primarios publicadas en español o inglés en diferentes fuentes de información desde 2013. Las preguntas de investigación fueron: 1. ¿Cuáles son las indicaciones de la vigilancia activa?, ¿cómo realizarla?, ¿cuándo y con que periodicidad realizarla? 2. ¿Cuál es el tratamiento y su indicación en pacientes con nódulos tiroideos sospechosos de cáncer? 3. ¿Cómo y cuándo realizar seguimiento de pacientes con CDT de acuerdo con el riesgo dinámico? 4. ¿Cuál es el manejo actual de los pacientes iodo refractarios? Se propusieron recomendaciones basadas en la evidencia, y analizadas y discutidas por el colectivo experto en sesiones asincrónicas. Se evalúo la calidad de la evidencia y las recomendaciones fueron gradadas en fuerte o condicional y a favor o en contra a partir del análisis de la calidad de la evidencia, contexto de implementación (disponibilidad e implementación) y la experticia clínica. En el presente documento se desarrollada la primera pregunta, referente a vigilancia activa. Resultados: 86 recomendaciones fueron propuestas y acordadas por el grupo desarrollador, categorizadas en tratamiento y seguimiento para resolver las preguntas planteadas. 10 de las recomendaciones corresponden a vigilancia activa y se incluyen en el presente documento. Recomendaciones claves incluyen, brindar información completa y oportuna a pacientes, conformación de equipos multidisciplinarios, análisis individualizado del paciente para la decisión de tratamiento, estadificación rutinaria de riesgo dinámico para evaluar la respuesta al tratamiento y ajustarlo, minimización de procedimientos fútiles o que aportan poco a la supervivencia y calidad de vida de los pacientes. Conclusión: Se presentan recomendaciones que esperan incidir en la estandarización de la práctica clínica cotidiana de pacientes con CDT y mejores resultados en salud.

Introduction: Thyroid cancer is a common disease in the world, with a higher prevalence of the differentiated type. Early diagnosis individualized and adaptive management can improve prognosis. Objective: Generate evidence-based recommendations on the treatment and follow-up of adults with differentiated thyroid carcinoma (DTC). Methodology: Clinical practice guideline (CPG) based on systematic literature review (RSL) and consensus of clinical experts. The development group defined the range and four questions that were resolved through a review of evidence from existing CPGs, RSLs, primary studies published in Spanish or English in various sources of information since 2013. The research questions were: 1. What are the indications for active surveillance? How to carry it out? When and how often to carry it out? 2. What is the treatment and its indication in patients with thyroid nodules suspicious for cancer? 3. How and when to follow up patients with CDT according to dynamic risk? 4. What is the current management of iodine refractory patients? Evidence-based recommendations analyzed and discussed by the expert group in asynchronous sessions were proposed. The quality of the evidence was evaluated, and the recommendations were graded as strong or conditional and in favor or against based on the analysis of the quality of the evidence, implementation context (availability and implementation) and clinical expertise. In this document, is developed the first question, referring to active surveillance. Results: 86 recommendations were proposed and agreed upon by the development group, categorized into treatment and follow-up to solve the questions raised. 10 of the recommendations correspond to active surveillance and are included in this document. Key recommendations include providing complete and timely information to patients, develop of multidisciplinary teams, individualized patient analysis for treatment decisions, routine dynamic risk staging to evaluate response to treatment and adjust it, minimization of futile procedures or that contribute little to the survival and quality of life of patients. Conclusion: Recommendations are presented that longs to influence the standardization of the daily clinical practice of patients with DTC and better health outcomes.

Evaluación de la agudeza diagnóstica de la Ecografía Translaríngea Transcutánea (ETLTC) en la valoración de la movilidad de las cuerdas vocales en cirugía de tiroides y paratiroides / Evaluation of the diagnostic acuity of the Transcutaneous Translaryngeal Ultrasound (TCTLUS) in the assessment of the vocal cords mobility in thyroid and parathyroid surgery

Introducción. La evaluación de la movilidad de las cuerdas vocales en cirugía de tiroides y paratiroides hace parte de la adecuada valoración integral. Aunque la laringoscopia directa es prueba de referencia, su uso real no es rutinario por lo que se propone la ecografía translaríngea como alternativa de evaluación. Métodos. Estudio prospectivo de evaluación de una prueba diagnóstica de la movilidad de las cuerdas vocales pre y posoperatoria, comparando la ecografía translaríngea con la video laringoscopia, en pacientes con cirugía de tiroides y paratiroides, de febrero 1° a noviembre 30 de 2022. Se describieron las variables usando frecuencias absolutas y relativas. En el análisis univariado se calcularon Chi cuadrado y T de Student y en el bivariado, regresión logística binaria. La agudeza diagnóstica se determinó con sensibilidad, especificidad y valores predictivos; se consideró la significancia estadística con p < 0,05. Resultados. Se incluyeron 267 pacientes, 219 mujeres y 48 hombres; 196 pacientes (73,4%) tenían malignidad. Se encontró en el preoperatorio, sensibilidad 100 %, especificidad 99,6 %, VPP 83,3 %, VPN 100 %, odds de probabilidad positiva 83 % y Odds de probabilidad negativa 0,004 %. En el posoperatorio, sensibilidad 82,8 %, especificidad 99,2 %, VPP 92,3 % VPN 97,9 %, odds de probabilidad positiva 92 % y odds de probabilidad negativa 0,2 %. Conclusiones. La ecografía translaríngea en nuestro medio tiene alta agudeza diagnóstica. Podría ser usada en el abordaje inicial de la evaluación de la movilidad de las cuerdas vocales y reemplazar la laringoscopia directa, dejando ésta para cuando la visualización ecográfica no sea adecuada, o en casos de afectación o sospecha de invasión, para su confirmación.

Introduction. The evaluation of the mobility of the vocal cords in thyroid and parathyroid surgery is part of the adequate comprehensive assessment. Altough, direct laryngoscopy is the gold standard, its real use is not routine, so translaryngeal ultrasound approach is proposed as an alternative. Methods. A prospective diagnostic test study was carried out to evaluate the translaryngeal ultrasound compared with video laryngoscopy in visualizing vocal mobility in patients with thyroid and parathyroid surgery from February 1 to November 30, 2022. Patients were described using absolute and relative frequencies. Univariate statistical analysis with Chi-square and Student's t tests. T. Bivariate analysis using binary logistic regression. Diagnostic acuity was calculated with sensitivity, specificity, PPV, NPV. Statistical significance with p< 0.05, 95% confidence interval. Results. 267 patients undergoing thyroid or parathyroid surgery were included, 219 women and 48 men. Malignant: thyroid neoplasm 196 patients (73.4%). The findings were for the preoperative period, 100% sensitivity, 99.6% specificity, PPV 83.33%, NPV 100%, 83% positive probability odds, and 0.004% negative probability odds. For the postoperative period, 82.8% sensitivity, 99.2% specificity, 92.3% PPV, 97.9% NPV, 92% positive probability odds, and 0.2% negative probability odds were found.Conclusions. Translaryngeal ultrasound in our series has high diagnostic acuity. It could be used as the initial approach to evaluate vocal mobility and might replace direct laryngoscopy, leaving it when its visualization is not adequate or in cases of involvement or suspected invasion for confirmation.

Doble tormenta tiroidea y arrítmica en una gestante con múltiples taquicardias refractarias mediadas por un haz de kent intermitente ablacionado exitosamente

La tormenta tiroidea es un estado crítico y poco frecuente que condiciona la disfunción de múltiples órganos por el efecto del exceso de las hormonas tiroideas, esta disfunción endócrina tiene una elevada mortalidad y genera manifestaciones típicas como la taquicardia, fiebre, alteraciones gastrointestinales, cardiovasculares y del sistema nervioso central. El embarazo se ha asociado con un incremento en la incidencia de arritmias. Necesitan un tratamiento inmediato con drogas antiarrítmicas, cardioversión eléctrica o cesárea de urgencia. El WPW es una anormalidad cardiaca congénita que consiste en la presencia de un haz anómalo (Haz de Kent) que evita el sistema normal de conducción uniendo directamente aurículas y ventrículos. Veremos el caso de una gestante de 32 semanas que presenta un cuadro de tormenta tiroidea y múltiples episodios de taquicardia paroxística supraventricular (TPS), de tórpida y sombría evolución clínica mediada por un haz anómalo de Kent intermitente. Es evidente que la tormenta tiroidea en el contexto de la gestación produjo cambios en las propiedades electrofisiológicas del haz anómalo de Kent intermitente lo cual propició el desarrollo de múltiples taquicardias paroxísticas supraventriculares refractarias a la cardioversión eléctrica y farmacológica. Tampoco mejoró con la tiroidectomía total, solamente cedió por completo con la ablación por catéter de radiofrecuencia del haz anómalo de Kent.

Thyroid storm is a critical and infrequent state that conditions the dysfunction of multiple organs due to the effect of excess thyroid hormones. This endocrine dysfunction has a high mortality and generates typical manifestations such as tachycardia, fever, gastrointestinal, cardiovascular and heart disorders, and the central nervous system. Pregnancy has been associated with an increased incidence of arrhythmias. They need immediate treatment with antiarrhythmic drugs, electrical cardioversion, or emergency caesarean section. WPW is a congenital cardiac abnormality that consists of the presence of an abnormal bundle (Kent bundle) that prevents the normal conduction system, directly joining the atria and ventricles. We will see the case of a 32-week pregnant woman who presented symptoms of thyroid storm and multiple episodes of paroxysmal supraventricular tachycardia (PST), with a torpid clinical course mediated by an abnormal intermittent Kent bundle. It is evident that the thyroid storm in the context of pregnancy produced changes in the electrophysiological properties of the intermittent Kent bundle, which led to the development of multiple PST refractory to electrical and pharmacological cardioversion. Moreover, it also did not improve with total thyroidectomy, only resolved completely with radiofrequency catheter ablation of the Kent bundle.

Diagnostic value of a computer-assisted diagnosis system for the ultrasound features in thyroid nodules

ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in "aspect ratio" were 95.6%, 96.2%, and 95.4%, in "margin irregularity" were 90.7%, 90.5%, and 90.9%, in "margin smoothness" were 85.8%, 88.5%, and 83.0%, in "calcification" were 83.6%, 81.7%, and 82.0%, in "homogeneity" were 88.9%, 90.6%, and 82.2%, in "major echo" were 85.3%, 88.0%, and 85.4%, and in "contains very hypoechoic echo" were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.

Correlation of 18F-sodium fluoride uptake and radiodensity in extraosseous metastases of medullary thyroid carcinoma

ABSTRACT Objective: Although 18F-sodium fluoride (18F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, it can also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of 18F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable. Subjects and methods: Extraosseous metastatic lesions of 15 patients with MTC were evaluated using 18F-NaF positron-emission tomography (PET)/computed tomography (CT) and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values. Results: Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01). Conclusion: The findings of the present study suggest that there is an association between 18F-NaF uptake and calcium deposition in extraosseous metastases of MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for 18F-NaF uptake in regions without visible calcium deposition.

Accuracy of ultrasound in predicting thyroid malignancy: a comparative analysis of the ACR TI-RADS and ATA risk stratification systems

ABSTRACT Objective: Thyroid nodules are very common in clinical practice, and ultrasound has long been used as a screening tool for their evaluation. Several risk assessment systems based on ultrasonography have been developed to stratify the risk of malignancy and determine the need for fine-needle aspiration in thyroid nodules, including the American Thyroid Association (ATA) system and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). The aim of this study was to compare the performance of the ATA and ACR TI-RADS systems in predicting malignancy in thyroid nodules based on the nodules' final histopathology reports. Materials and methods: We performed a retrospective review of medical records to identify patients who underwent thyroid surgery at King Abdulaziz University from 2017 to 2022. The ultrasound features of the nodules with confirmed histopathology (benign versus malignant) were evaluated. Both ATA and ACR TI-RADS scores were documented. Results: The analysis included 191 patients who underwent thyroid surgery and fulfilled the inclusion criteria. Hemithyroidectomy was performed in 22.5% of the patients, and total thyroidectomy was performed in 77.0% of them. In all, 91 patients (47.6%) were found to have malignant nodules on histopathology. We then compared the histopathology reports with the preoperative ultrasonographic risk scores. The estimated sensitivity and specificity in identifying malignant nodules were, respectively, 52% and 80% with the ATA system and 51.6% and 90% with the ACR TI-RADS system. Conclusion: Both ATA and ACR TI-RADS risk stratification systems are valuable tools for assessing the malignancy risk in thyroid nodules. In our study, the ACR TI-RADS system had superior specificity compared with the ATA system in predicting malignancy among high-risk lesions.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Predictors of recurrence after total thyroidectomy in 1,611 patients with papillary thyroid carcinoma: postoperative stimulated serum thyroglobulin and ATA initial and dynamic risk assessment

ABSTRACT Objective: Despite a favorable prognosis, some patients with papillary thyroid carcinoma (PTC) develop recurrence. The objective of this study was to examine the impact of the combination of initial American Thyroid Association (ATA) risk stratification with serum level of postoperative stimulated thyroglobulin (s-Tg) in predicting recurrence in patients with PTC and compare the results with an assessment of response to initial therapy (dynamic risk stratification). Subjects and methods: We retrospectively analyzed 1,611 patients who had undergone total thyroidectomy for PTC, followed in most cases (87.3%) by radioactive iodine (RAI) administration. Clinicopathological features and s-Tg levels obtained 3 months postoperatively were evaluated. The patients were stratified according to ATA risk categories. Nonstimulated thyroglobulin levels and imaging studies obtained during the first year of follow-up were used to restage the patients based on response to initial therapy. Results: After a mean follow-up of 61.5 months (range 12-246 months), tumor recurrence was diagnosed in 99 (6.1%) patients. According to ATA risk, recurrence was identified in 2.3% of the low-risk, 9% of the intermediate-risk, and 25% of the high-risk patients (p < 0.001). Using a receiver operating characteristic curve approach, a postoperative s-Tg level of 10 ng/mL emerged as the ideal cutoff value, with positive and negative predictive values of 24% and 97.8%, respectively (p < 0.001). Patients with low to intermediate ATA risk with postoperative s-Tg levels < 10 ng/mL and excellent response to treatment had a very low recurrence rate (<0.8%). In contrast, higher recurrence rates were observed in intermediate-risk to high-risk patients with postoperative s-Tg ≥ 10 ng/mL and indeterminate response (25%) and in those with incomplete response regardless of ATA category or postoperative s-Tg value (38.5-87.5%). Using proportion of variance explained (PVE), the predicted recurrence using the ATA initial risk assessment alone was 12.7% and increased to 29.9% when postoperative s-Tg was added to the logistic regression model and 49.1% with dynamic risk stratification. Conclusions: The combination of ATA staging system and postoperative s-Tg can better predict the risk of PTC recurrence. Initial risk estimates can be refined based on dynamic risk assessment following response to therapy, thus providing a useful guide for follow-up recommendations.

CircSEMA6A upregulates PRRG4 by targeting MiR-520h and recruiting ELAVL1 to affect cell invasion and migration in papillary thyroid carcinoma

ABSTRACT Objective: As the most prevalent type of thyroid malignancy, papillary thyroid carcinoma (PTC) accounts for over 80% of all thyroid cancers. Circular RNAs (circRNAs) have been found to regulate multiple cancers, including PTC. Materials and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyse RNA and protein levels. Fluorescence in situ hybridization (FISH) was used to detect the distribution of the target genes. Functional experiments and animal experiments were implemented to analyse the biological functions of target genes in vitro and in vivo. Luciferase reporter, RNA pulldown, RNA binding protein immunoprecipitation (RIP) and mRNA stability assays were used to probe the underlying mechanisms. Results: CircSEMA6Awas found to be upregulated in PTC tissues and cells, and its circular structure was verified. CircSEMA6A promotes PTC cell migration and invasion. Moreover, circSEMA6A functions as a competing endogenous RNA (ceRNA) to upregulate proline rich and Gla domain 4 (PRRG4) expression by sponging microRNA-520h (miR-520h). CircSEMA6A recruits ELAV1 to stabilize PRRG4 mRNA and drives PTC progression via PRRG4. Conclusion: CircSEMA6A upregulates PRRG4 by targeting miR-520h and recruiting ELAVL1 to affect the invasion and migration of PTC cells, offering insight into the molecular mechanisms of PTC.

Differentiated thyroid carcinoma: what the nonspecialists needs to know

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

Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy

ABSTRACT Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LN growth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusions: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

Surgical safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy: a systematic review and meta-analysis

Abstract Objectives To assess the safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy in thyroid tumor. Methods Bilateral axillo-breast approach robotic thyroidectomy and other approaches (open thyroidectomy, transoral robotic thyroidectomy, and bilateral axillo-breast approach endoscopic thyroidectomy) were compared in studies from 6 databases. Results Twenty-two studies (8830 individuals) were included. Bilateral axillo-breast approach robotic thyroidectomy had longer operation time, greater cosmetic satisfaction, and reduced transient hypoparathyroidism than conventional open thyroidectomy. Compared to bilateral axillo-breast approach endoscopic thyroidectomy, bilateral axillo-breast approach robotic thyroidectomy had greater amount of drainage, lower chances of transient vocal cord palsy and permanent hypothyroidism, and better surgical completeness (postopertive thyroblobulin level and lymph node removal). Bilateral axillo-breast approach robotic thyroidectomy induced greater postoperative drainage and greater patient dissatisfaction than transoral robotic thyroidectomy. Conclusion Bilateral axillo-breast approach robotic thyroidectomy is inferior to transoral robotic thyroidectomy in drainage and cosmetic satisfaction but superior to bilateral axillo-breast approach endoscopic thyroidectomy in surgical performance. Its operation time is longer, but its cosmetic satisfaction is higher than open thyroidectomy.

Coexistence of Hashimoto's thyroiditis and papillary thyroid carcinoma revisited in thyroidology, an experience from an endemic region: fad or future?

SUMMARY OBJECTIVE: Papillary thyroid carcinoma, per se, is the most common type of thyroid cancer, and Hashimoto's thyroiditis is the most frequent autoimmune disease of the papillon gland. The liaison between Hashimoto's thyroiditis and thyroid cancers is still an ongoing debate in thyroidology. The aim of the study was to discuss the frequency of the co-occurrence of Hashimoto's thyroiditis and papillary thyroid carcinoma. METHODS: This study is designed as a retrospective analytical cohort study. The institutional database and archive of histopathology scanning identified the patients who had undergone thyroidectomy between January 2022 and January 2016. The Statistical Package for Social Sciences v21.0 program was used for statistical purposes. Descriptive and chi-square tests were applied, and a p<0.05 was considered significant. RESULTS: Of 498 patients who had undergone thyroidectomy for 4 years, 99 (20%) were male and 399 (80%) were female. Of note, papillary thyroid carcinoma was revealed in 160 (32%) patients, and Hashimoto's thyroiditis was recognized in 178 (35.74%) patients. The prevalence of Hashimoto's thyroiditis in cases with papillary thyroid carcinoma was 43.8%, while the prevalence in patients with Hashimoto's thyroiditis was 41.1%. CONCLUSION: A debate still remains on the propriety of these two phenomena. Herewith, we recognized a correlation between the presence of papillary thyroid carcinoma and Hashimoto's thyroiditis. Providers should be vigilant about the coexistence of these phenomena. We might postulate the so-called total thyroidectomy for cases with a cytologic diagnosis of Hashimoto's thyroiditis with a papillary thyroid carcinoma. As a matter of fact, this issue merits further investigation.

Avaliação da mortalidade associada ao status tireoidiano em uma coorte de pessoas idosas eutireoidianas de ambulatório de geriatria em hospital universitário / Assessment of mortality associated with thyroid status in a cohort of euthyroid older adults from a geriatric outpatient clinic at a university hospital

Resumo Objetivo Avaliar associações entre a média da tireotropina (TSH) e tiroxina livre (T4L) mantida durante follow-up, e mortalidade em pacientes idosos eutireoidianos definidos de acordo com a faixa de referência específica para a idade (FR-e) do TSH. Método Coorte retrospectiva tipo análise de sobrevivência incluindo pacientes idosos eutireoidianos acompanhados no ambulatório de hospital universitário entre 2010 e 2013. Todos os participantes haviam sido avaliados quanto ao risco de incapacidade funcional como critério para admissão nesse ambulatório. As médias dos valores de TSH e T4L foram calculadas através das dosagens obtidas no período de acompanhamento. Cada FR-e de TSH foi dividida em quatro partes iguais, considerando níveis mais baixos como variável de exposição (≤1,75 mUI/L para <80 e ≤2,0 mUI/L para ≥80 anos). Os níveis de T4L foram dicotomizados em duas categorias (< e ≥1,37 ng/dL). O desfecho foi o tempo até a morte. A regressão de risco proporcional de Cox foi empregada para estimar a hazard ratio (HR) e o intervalo de confiança (IC) de 95% Resultados 285 participantes (73% mulheres, idade média =80,4 anos) seguidos pela mediana de 5,7 anos (IQR =3,7-6,4; máximo =7), sendo que 114 faleceram. Após o modelo final ajustado, a mortalidade esteve associada ao TSH no limite inferior (HR=1,7; IC=1,1-2,7; p=0,016) e ao T4L mais elevado. (HR=2,0; IC=1,0-3,8; p=0,052). Conclusão Níveis médios de T4L mais altos e de TSH mais baixos foram associados ao risco de morte em coorte de idosos eutireoidianos usando FR-e de TSH.

Abstract Objective To assess the associations between the mean thyrotropin (TSH) and mean free thyroxine (FT4), detected during follow-up, and mortality in a group of older euthyroid patients according to age-specific reference range (as-RR) for TSH. Method Retrospective survival analysis cohort including euthyroid elderly patients who were being monitored at the outpatient clinic of a university hospital from 2010 to 2013. All participants had been assessed for the risk of functional disability as a criterion for admission to this outpatient clinic. Mean TSH and FT4 values were calculated using hormone dosages obtained during the follow-up period. Each as-RR for TSH was divided into four equal parts, considering the lower levels as the main exposure variable (≤1.75 mlU/L for <80, and ≤2.0 mlU/L for ≥80 years). FT4 levels were explored according to two categories (< e ≥1.37 ng/dL). The outcome was time to death. We used Cox proportional hazard regression to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results 285 participants (73% females, mean age =80.4 years) followed by a median of 5.7 years (IQR =3.7-6.4; maximum =7), of which 114 died. After the adjusted final model, mortality was associated with the lowest mean TSH (HR=1.7; CI=1.1-2.7; p=0.016) and with the upper mean of FT4 (HR=2.0; CI=1.0-3.8; p=0.052). Conclusions Higher FT4 and lower TSH mean levels were associated with risk of death in a cohort of euthyroid older adults using an as-RR of TSH.

Síndrome metabólico e hipotiroidismo: un estudio transversal en una población ecuatoriana

Introducción: el síndrome metabólico y el hipotiroidismo son condiciones muy frecuentes y a menudo superpuestas. Ambos son precursores bien establecidos de la enfermedad cardiovascular aterogénica. Objetivo: evaluar la asociación entre el hipotiroidismo y el síndrome metabólico en pacientes que asisten a la consulta de medicina interna del Hospital IESS de Riobamba, Ecuador. Metodología: se realizó una investigación de tipo descriptiva, correlacional con un diseño no experimental de corte transversal desde enero de 2022 hasta julio de 2023. Se incluyeron 985 sujetos de ambos sexos, mayores de 25 años. A todos los pacientes se les realizó un exhaustivo examen físico y se tomaron muestras de sangre para la realización de pruebas bioquímicas y hormonales. Resultados: 84,97% de los participantes eran eutiroideos, 1,93% presentaron hipotiroidismo manifiesto y 4,97% hipotiroidismo subclínico, mientras que 32,99% tenían síndrome metabólico. Se encontraron diferencias significativas en la edad, peso, circunferencia de cintura, colesterol total, LDL colesterol, triglicéridos, glucosa postpandrial y HOMA-IR entre los sujetos con hipotiroidismo manifiesto y los eutiroideos (p<0,05). Se observó una correlación positiva entre la TSH y todos los componentes del síndrome metabólico (p<0,05). La prevalencia de síndrome metabólico fue significativamente mayor en los sujetos con hipotiroidismo manifiesto (p < 0,05) que en los demás grupos. Se observó que los niveles de T4L (OR 8,82; IC 95% 1,56-49,8) y TSH (OR 1,61; IC 95% 1,19-2,18) son factores de riesgo para el desarrollo de síndrome metabólico. Conclusión: el hipotiroidismo y el síndrome metabólico están altamente asociados. Es recomendable que los sujetos con hipotiroidismo sean examinados para detectar síndrome metabólico y viceversa. La evaluación de la función tiroidea en pacientes con este síndrome puede ayudar a identificar y prevenir el riesgo de eventos cardiovasculares y cerebrovasculares.

Introduction: Metabolic syndrome and hypothyroidism are widespread and often overlapping conditions. Both are well-established precursors of atherogenic cardiovascular disease. Objective: To evaluate the association between hypothyroidism and metabolic syndrome in patients attending the internal medicine consultation at the IESS Hospital in Riobamba, Ecuador. Methodology: A descriptive, correlational research study was conducted with a non-experimental cross-sectional design from January 2022 to July 2023. Nine hundred eighty-five subjects of both sexes and over 25 years of age, were included. All patients underwent a thorough physical examination and blood samples were taken for biochemical and hormonal tests. Results: Eighty-four-point ninety-seven percent of the participants were euthyroid, 1.93% presented overt hypothyroidism, 4.97% had subclinical hypothyroidism, and 32.99% had metabolic syndrome. Significant differences in age, weight, waist circumference, total cholesterol, LDL cholesterol, triglycerides, postprandial glucose, and HOMA-IR were found between subjects with manifest hypothyroidism and euthyroid subjects (p<0.05). A positive correlation was observed between TSH and all components of the metabolic syndrome (p<0.05). The prevalence of metabolic syndrome was significantly higher in subjects with overt hypothyroidism (p < 0.05) than in the other groups. It was observed that the levels of FT4 (OR 8.82; 95% CI 1.56-49.8) and TSH (OR 1.61; 95% CI 1.19-2.18) were risk factors for the development of the metabolic syndrome. Conclusion: Hypothyroidism and metabolic syndrome are highly associated. It is recommended that subjects with hypothyroidism be screened for metabolic syndrome and vice versa. Evaluation of thyroid function in patients with this syndrome can help identify and prevent the risk of cardiovascular and cerebrovascular events.

Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics

ABSTRACT Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusions: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.

Bilateral choroidal metastasis of follicular thyroid carcinoma 7 years after total thyroidectomy: a case report

ABSTRACT Follicular thyroid cancers account for 15%-20% of all thyroid tumors. Choroidal metastases secondary to follicular thyroid cancer rarely occur. Herein, we report the case of an 85-year-old woman who presented choroidal metastasis from a follicular thyroid carcinoma in the right eye 7 years after total thyroidectomy and underwent enucleation. To confirm the diagnosis and primary tumor site, histopathological, and immunohistochemical examinations were performed. One year later, she presented metastasis in the contralateral eye. Few similar cases have been described in the literature.