Manejo del paciente con Hipertiroidismo en consulta externa de la Unidad Técnica de Endocrinología del Hospital Carlos Andrade Marín / Management of the patient with hyperthyroidism in the outpatient clinic of the Technical Unit of Endocrinology of the Endocrinology Technical Unit of the Carlos Andrade Marín Hospital

El hipertiroidismo es un trastorno caracterizado por el exceso de hormonas tiroideas. El déficit de yodo es un factor clave en dicha patología y en lugares con suficiencia del mismo se asocian a au-toinmunidad tiroidea. La prevalencia de hipertiroidismo mani-fiesto varía del 0,2% al 1,3% en áreas con suficiencia de yodo, sin embargo, esto puede variar en cada país por diferencias en umbrales de diagnóstico, sensibilidad de ensayo y población se-leccionada. Un reporte de The Third National Health and Nutri-tion Examination Survey (NHANES III) mostró que el hiperti-roidismo manifiesto se presenta en 0,7% de la población general e hipertiroidismo subclínico en el 1,7%1,2.En incidencia, la patología se asocia con la suplementación de yodo, con la mayor frecuencia en áreas de deficiencias, por au-mento de nódulos tiroideos en la población anciana, teniendo a regiones de áreas montañosas como América del Sur, África Central y suroeste de Asia dentro de este grupo. Un meta aná-lisis de estudios europeos mostró una incidencia general de 50 casos por 100000 personas/años1. En Ecuador, según los datos del Instituto Nacional de Estadísticas y Censos (INEC) del 2017, se reportaron 157 casos de hipertiroidismo, de los cuales la En-fermedad de Graves (EG) fue la causa más común, seguida por el bocio multinodular tóxico (BMNT) y finalmente el adenoma tóxico (AT) con una incidencia de 61 %, 24 % y 14 % respecti-vamente3.Los pacientes con esta patología tienen aumento de riesgo com-plicaciones cardiovasculares y mortalidad por todas las causas, siendo falla cardíaca uno de sus principales desenlaces, así el diagnóstico precoz evita estos eventos, principalmente en pobla-ción de edad avanzada.El presente protocolo se ha realizado para un correcto trata-miento de esta patología en el Hospital de Especialidades Carlos Andrade Marín (HECAM).

Hyperthyroidism is a disorder characterized by an excess of thyroid hormones. Iodine deficiency is a key factor in this pa-thology and in places with iodine deficiency it is associated with thyroid autoimmunity. The prevalence of overt hyperthyroidism varies from 0,2% to 1,3% in iodine-sufficient areas; however, this may vary from country to country due to differences in diag-nostic thresholds, assay sensitivity, and selected population. A report from The Third National Health and Nutrition Examina-tion Survey (NHANES III) showed that overt hyperthyroidism occurs in 0,7% of the general population and subclinical hyper-thyroidism in 1,7%1,2.In incidence, the pathology is associated with iodine supplemen-tation, with the highest frequency in areas of deficiencies, due to increased thyroid nodules in the elderly population, having regions of mountainous areas such as South America, Central Africa and Southwest Asia within this group. A meta-analysis of European studies showed an overall incidence of 50 cases per 100000 person/years1. In Ecuador, according to data from the National Institute of Statistics and Census (INEC) in 2017, 157 cases of hyperthyroidism were reported, of which, Graves' di-sease (GD) was the most common cause, followed by toxic mul-tinodular goiter (BMNT) and finally toxic adenoma (TA) with an incidence of 61 %, 24 % and 14 % respectively3.Patients with this pathology have an increased risk of cardiovas-cular complications and all-cause mortality, with heart failure being one of the main outcomes, so early diagnosis avoids these events, mainly in the elderly population.The present protocol has been carried out for the correct treat-ment of this pathology at the Carlos Andrade Marín Specialties Hospital (HECAM).

Dolor y edema de miembros inferiores por dermopatía tiroidea: presentación inusual de la enfermedad de Graves en una paciente adolescente / Lower limb pain and edema due to thyroid dermopathy: an unusual presentation of Graves disease in an adolescent patient

La enfermedad de Graves es un proceso inmunomediado en el que autoanticuerpos se dirigen contra el receptor de tirotrofina. Por su acción estimulante sobre la glándula tiroides, se genera crecimiento glandular difuso y aumento de la hormonogénesis. Se caracteriza por el comienzo subagudo de síntomas constitucionales, neuromusculares, cardiovasculares, gastrointestinales y oculares, seguidos en algunos casos de la aparición de manifestaciones cutáneas como la dermopatía tiroidea o mixedema. En pediatría la enfermedad de Graves es infrecuente (aunque es la causa más frecuente de hipertiroidismo), pero la cronología de aparición de los síntomas está bien descrita; es rara la aparición de dermopatía en ausencia de otros síntomas de hipertiroidismo y sin afectación ocular. Se presenta el caso de una paciente de 15 años con dermopatía tiroidea por enfermedad de Graves sin oftalmopatía ni otros síntomas de hipertiroidismo clínico asociados.

Graves disease is an immune-mediated process characterized by the presence of autoantibodies to thyrotropin receptors. Its stimulating action on the thyroid gland causes diffuse glandular growth and increased hormone production. Graves disease is characterized by a subacute onset of non-specific, neuromuscular, cardiovascular, gastrointestinal, and eye symptoms, sometimes followed by skin manifestations, such as thyroid dermopathy or myxedema. In pediatrics, Graves disease is rare (although it is the most frequent cause of hyperthyroidism). However, the chronology of symptom onset has been well described; the development of dermopathy in the absence of other symptoms of hyperthyroidism and without eye involvement is rare. Here we describe the case of a 15-year-old female patient with thyroid dermopathy due to Graves disease without eye disease or other associated clinical symptoms of hyperthyroidism.

Hipertiroidismo por enfermedad de Graves posterior a vacuna contra SARS-CoV-2: reporte de 2 casos / Graves' disease hyperthyroidism following SARS-CoV-2 vaccination: a two cases report

Luego del inicio de las campañas de vacunación masiva contra la infección por COVID-19, se han publicado una serie de reportes que muestran la posible asociación entre la vacuna y alteraciones de la función tiroidea. Desde entonces, múltiples teorías han intentado explicar este hallazgo, en su mayoría de índole autoinmune. Dentro de estas destaca el síndrome autoinmune-autoinflamatorio secundario a adyuvantes (ASIA), que podría generar desórdenes tiroideos de novo o exacerbar los ya existentes. Presentamos dos casos de enfermedad de Graves Basedow posterior al uso de Coronavac. Ambas pacientes presentaron características similares a las descritas en la literatura y cumplen con los criterios de ASIA. No obstante, los beneficios de las vacunas superan los posibles riesgos asociados.

After the beginning of COVID-19 vaccination campaigns, a number of reports have shown the potential association between vaccines and thyroid disfunction. Since then several theories have tried to explain this finding, mostly autoinmmune. One of them is the autoimmune/inflammatory syndrome induced by adjuvants, that could trigger or exacerbate thyroid disease. We present two cases of Graves' disease post Coronavac vaccination. Both pacients share similar features than cases published previously and meet criteria for ASIA syndrome. Nevertheless, the benefts of vaccination largely outweigh any adverse events associated.

Graves' disease, myxedema, and papillary thyroid carcinoma / Doença de Graves, mixedema e carcinoma papilífero de tireoide

Graves' disease (GD) is the leading cause of hyperthyroidism and diffuse toxic goiter in iodine-sufficient geographi-cal areas. GD is associated with classical manifestations such as ophthalmopathy and thyroid dermopathy, in addi-tion to diffuse goiter, which may be the site of carcinomas, as a complication. Case report: A 52-year-old woman presented with goiter and symptoms compatible with hyperthyroidism, such as heat intolerance, weight loss, fati-gue, increased sweat, tachycardia, fine tremors, increased intestinal transit, anxiety, emotional lability, insomnia, exophthalmos, and pretibial myxedema. A complementary investigation confirmed the diagnosis of hyperthyroidism (high free T4 and total T3 levels and low thyroid-stimulating hormone - TSH levels). Ultrasound images showed dif-fuse enlargement of the thyroid lobes by approximately 10 times and the presence of three thyroid nodules, one of which was larger than 2 cm with heterogeneous echogenicity and vascularization throughout the nodule; ultrasoun-d-guided fine needle aspiration revealed cytology compatible with Bethesda IV; scintigraphy revealed a low uptake area (cold nodule) amid a diffuse high-uptake goiter. A thyroidectomy was performed, and the anatomical specimen diagnosis revealed papillary thyroid carcinoma in the right lobe, with adjacent parenchyma compatible with GD. Histopathological examination of the skin showed the presence of myxedema compatible with Graves' dermopathy. The patient evolved with the normalization of TSH levels and a reduction of cutaneous manifestations. Conclusion:GD abnormalities may not be restricted to the classic clinical manifestations, and a careful investigation may reveal the coexistence of carcinomas. (AU)

A doença de Graves (DG) é a principal causa de hipertireoidismo e bócio difuso tóxico em áreas geográficas com iodo suficiente. DG está associada a manifestações clínicas clássicas como oftalmopatia e dermopatia da tireoide, além do bócio difuso, que pode ser sítio de carcinomas, como uma complicação. Relato de caso: Mulher de 52 anos apresentou bócio e sintomas compatíveis com hipertireoidismo como intolerância ao calor, emagrecimento, fadiga, sudorese aumentada, taquicardia, tremores finos, trânsito intestinal aumentado, ansiedade, labilidade emocional, insônia, exoftalmia e mixedema pré-tibial. A investigação complementar confirmou o diagnóstico de hipertireoidis-mo (níveis elevados de T4 livre e T3 total; níveis baixos de hormônio estimulante da tireoide - TSH). As imagens ultrassonográficas mostraram aumento difuso dos lobos tireoidianos em aproximadamente 10 vezes e a presença de três nódulos tireoidianos, um dos quais, maior que 2 cm, com ecogenicidade e vascularização heterogêneas em todo o nódulo, cuja punção aspirativa por agulha fina guiada por ultrassom revelou citologia compatível com Bethesda IV; e a cintilografia evidenciou uma área de baixa captação (nódulo frio) em meio a um bócio difuso de alta captação. Foi realizada tireoidectomia e o diagnóstico da peça anatômica revelou carcinoma papilífero de tir-eoide em lobo direito, com parênquima adjacente compatível com DG. O exame histopatológico da pele mostrou a presença de mixedema compatível com dermopatia de Graves. A paciente evoluiu com normalização dos níveis de TSH e redução das manifestações cutâneas. Conclusão: As anormalidades da DG podem não estar restritas às manifestações clínicas clássicas, e uma investigação criteriosa pode revelar a coexistência de carcinomas, (AU)

Hipertiroidismo en niños y adolescentes: experiencia en un hospital universitario en Colombia / Hyperthyroidism in children and adolescents: Experience in a university hospital in Colombia

Introducción. El hipertiroidismo es una condición heterogénea caracterizada por la producción excesiva de hormonas tiroideas. Su aparición en la edad pediátrica representa un reto diagnóstico y terapéutico. Objetivo. Describir las características clínicas y paraclínicas, así como la evolución y las diferencias entre las principales causas etiológicas de los pacientes con hipertiroidismo atendidos por el Servicio de Endocrinología Pediátrica del Hospital Universitario San Vicente Fundación en Medellín, Colombia, entre el 1° de julio de 2015 y el 30 de junio de 2020. Materiales y métodos. Se hizo un estudio observacional transversal con recolección retrospectiva de la información. Resultados. Se incluyeron 54 pacientes con una edad media de 11,9 años, 72,2 % de ellos mujeres. El 11,1 % tenía antecedentes familiares de enfermedad de Graves y 29,6 % de otras enfermedades tiroideas. El bocio fue la manifestación clínica más frecuente (83,3 %). El 92,6 % había recibido terapia con metimazol, el 79,6 % requirió betabloqueador y el 11,2 % necesitó una terapia farmacológica adicional. Se presentaron reacciones adversas a la medicación en el 16,7 %. En el 20,4 % de los pacientes hubo resolución del hipertiroidismo (espontánea: 9,3 %; posterior a la ablación con yodo radiactivo: 9,3 %, y después de la cirugía: 1,9 %). Conclusión. El hipertiroidismo es una enfermedad con manifestaciones clínicas diversas. La causa más frecuente es la enfermedad de Graves, seguida por la hashitoxicosis. En este estudio, la hashitoxicosis fue más frecuente que en estudios previos. La duración y los efectos secundarios del tratamiento farmacológico fueron similares a los reportados previamente, pero es de resaltar la mayor frecuencia de agranulocitosis en nuestra población.

Introduction: Hyperthyroidism is a heterogeneous condition characterized by the excessive production of thyroid hormones. It represents a diagnostic and therapeutic challenge. Objective: To describe the clinical and paraclinical characteristics and the evolution and differences between the main etiologies in patients with hyperthyroidism treated by the Pediatric Endocrinology Service at the Hospital Universitario San Vicente Fundación in Medellín, Colombia, between July 1st., 2015, and June 30th., 2020. Materials and methods: We conducted a cross-sectional observational study with retrospective data collection. Results: We included 54 patients with a mean age of 11.9 years, 72.2% of whom were female; 85.2% had no history of comorbidities related to autoimmunity; 11.1% had a family history of Graves' disease, and 29.6% of other thyroid diseases. Goiter was the most frequent clinical manifestation (83.3%) and 92.6% of the patients received treatment with methimazole, 79.6% required beta-blockers, and 11.2% additional drug therapy. Adverse drug reactions occurred in 16.7% of the patients and in 20.4% there was a resolution of hyperthyroidism (spontaneous: 9.3%; after radio-iodine ablation: 9.3%, and after surgery: 1.9%). Conclusion: Hyperthyroidism is a disease with diverse clinical manifestations. Its most frequent cause is Graves' disease followed by hashitoxicosis, which in this study had a higher frequency than that reported in the literature. The duration and side effects of pharmacological treatment were similar to those previously reported, but the higher frequency of agranulocytosis is noteworthy.

Doença de Graves e sua recidiva: relato de caso / Grave's disease and its relapse: case repor

A doença de Graves (DG) é uma patologia autoimune que acomete a glândula tireoide e é a causa mais comum de hipertireoidismo. O principal grupo acometido por DG são as mulheres. Sendo assim, relatamos caso de paciente com 52 anos, do sexo feminino, com diagnóstico de Doença de Graves, que caracteriza quadro de hipertireoidismo. A paciente iniciou tratamento com tapazol (tiamazol) durante um ano e realizou pausa, recomendada pelo médico. No entanto, a paciente não retratou melhora e iniciou sintomatologia semelhante a dengue, como mal estar geral e fadiga muscular. Assim, realizou procura médica, e, inicialmente, foi diagnosticada com quadro de dengue, mas não houve melhora dos sintomas e procurou, portanto, endocrinologista. Realizou novos exames e foi confirmado quadro recidivo de Doença de Graves. Dessa maneira, iniciou novo tratamento. O estudo tem como objetivo relatar e discutir quadro de Doença de Graves associada a hipertireoidismo

Grave's disease (DG) is an autoimmune pathology that affects the thyroid gland and it's the most commom cause of hipertireoidism. The main group affected by DG are woman. That way we related a case of patient with 52 years, female with the diagnose of Grave's disease, that shows a patient conditioning of hipertireoidism. The patient began the treatment with tapazol during a year and made a pause recommended by the doctor. Therefore the patient didn't indicate progress and started a symptomatology similar to dengue fever, as general malaise and muscle fatigue. There by the patient searched for a doctor and initially was diagnosed with a patient conditioning of dengue fever, but she didn't manifested a improving of symptoms, and then searched for an endocrinologist. Realized then new exams and a recurrence case of grave´s disease was confirmed. This way the patient started a new treatment. Thus, the present study aims to report and discuss Graves' disease associated with hyperthyroidism.

Perfil clínico e terapêutico dos pacientes com hipertireoidismo do ambulatório de endocrinologia de um hospital universitário do sul do Brasil / Perfil clínico e terapêutico dos pacientes com hipertireoidismo do ambulatório de endocrinologia de um hospital universitário do sul do BrasilClinical and therapeutic profile of patients with hyperthyroidism in an outpatient endocrine clinic at a university hospital in southern Brazil

.Introdução: O hipertireoidismo decorre da elevação sérica dos hormônios tireoidianos, secundária à hiperfunção da glândula tireoide, sendo as principais causas a Doença de Graves (DG) e os Bócios Nodulares Tóxicos (BNT). Objetivos: Avaliar o perfil clínico e modalidades terapêuticas aplicadas em pacientes com diagnóstico de hipertireoidismo acompanhados em um Hospital Universitário no Sul do Brasil. Métodos: Estudo observacional, transversal e descritivo, com inclusão de pacientes com diagnóstico de hipertireoidismo por DG e BNT; foram coletados dados epidemiológicos, clínicos, laboratoriais e de tratamento. Resultados: A maioria dos pacientes foi referenciada pela atenção primária e encontrava-se em uso prévio de droga antitireoidiana (DAT). A variável idade obteve diferença estatisticamente significativa entre as etiologias de DG e BNT; em ambas houve predomínio de incidência no sexo feminino. A DG apresentou maior frequência de sinais e sintomas de tireotoxicose, ao passo que o BNT mostrou mais sinais e sintomas de compressão. Houve remissão da doença em 23,2% dos pacientes com DG tratados com DAT; em 23,2% dos pacientes optou-se pela manutenção de metimazol em baixa dose por mais de 36 meses e em 16,1% foi realizado tratamento definitivo. No BNT foram preferidas terapias definitivas, principalmente a tireoidectomia, em 27,5% dos pacientes. Doses baixas de metimazol por mais de 36 meses foram utilizados também no BNT, em 22,5% dos pacientes. Conclusão: O hipertireoidismo é uma doença heterogênea, desde a clínica inicial até a terapêutica, entre suas etiologias mais prevalentes. Observou-se uma tendência de priorizar as terapias medicamentosas em longo prazo com baixas doses, tanto na DG quanto no BNT. (AU)

Perfil clínico e terapêutico dos pacientes com hipertireoidismo do ambulatório de endocrinologia de um hospital universitário do sul do BrasilClinical and therapeutic profile of patients with hyperthyroidism in an outpatient endocrine clinic at a university hospital in southern Brazil ARTIGO ORIGINALRafael Antonio Parabocz1, Renata Soares Carvalho1, Gianna Carla Alberti Schrut1, Ana Claudia Garabeli Cavalli Kluthcovsky1, Matheo Augusto Morandi Stumpf1Introduction: Hyperthyroidism results from the serum elevation of thyroid hormones, secondary to hyperfunction of the thyroid gland. The main causes are Graves' disease (DG) and Toxic Nodular Goiters (BNT). Objectives: Evaluate the clinical profile and therapeutic modalities applied in patients diagnosed with hyperthyroidism followed up at a University Hospital in Southern Brazil. Methods: Observational, cross-sectional and descriptive study, including patients diagnosed with hyperthyroidism by DG and BNT; epidemiological, clinical, laboratory and treatment data were collected. Results: Most patients were referred by primary care and had been using antithyroid drugs (DAT). The age variable obtained showed a statistically significant difference between the etiologies of DG and BNT; in both, there was a predominance of incidence in females. DG showed a higher frequency of signs and symptoms of thyrotoxicosis, while BNT showed more signs and symptoms of compression. There was remission of the disease in 23.2% of patients with DG treated with DAT; in 23.2% of the patients, low-dose methimazole was maintained for more than 36 months and in 16.1%, definitive treatment was performed. In BNT, definitive therapies were preferred, mainly thyroidectomy, in 27.5% of patients. Low doses of methimazole for more than 36 months were also used in BNT in 22.5% of patients. Conclusion: Hyperthyroidism is a heterogeneous disease, from initial clinic to therapy, among its most prevalent etiologies. There was a tendency to prioritize long-term drug therapies with low doses, both in DG and BNT. (AU)

Características de orbitopatía asociada al tiroides y tasa de requerimiento de cirugía / Thyroid-associated orbitopathy characteristics and surgery requirement rate

RESUMO Objetivo: Conheça as características demográficas e clínicas da Órbita Associada da Tiroide (OAT), bem como a taxa de exigência da cirurgia orbital em pacientes do Centro Médico Nacional do Oeste. Métodos. Estudo observacional, transversal, descritivo e retrospetivo realizado analisando os registos de pacientes diagnosticados com OAT tratados num centro de cuidados de terceiro nível de janeiro de 2005 a julho de 2016. Os resultados. Um total de 236 órbitas de 118 pacientes foram avaliados, com uma idade média de 47,3 (13,2 anos, 74,6% eram do sexo feminino e 25,4% masculinos. 4,2% dos doentes foram tratados com hipotiroidismo, 94,1% com hipertireoidismo e 1,7% com goiter tóxico difuso. 44,9% dos doentes estudados com restrição de movimento ocular,10,2% com queratopatia de exposição e 51,7% com hipertensão intraocular. 34,7% dos doentes avaliados no serviço necessitaram de descompressão orbital, 16,1% de cirurgia palpebral e 8,5% de correção do hatrabisma. Na gestão conservadora destes doentes, 48,3% exigiam o uso de lubrificantes tópicos dos olhos, enquanto 52,5% dos pacientes necessitavam do uso de hipotensivos oculares em número variável. As conclusões. A OAT foi associada principalmente ao hipertiroidismo, sendo mais comum em pacientes do sexo feminino entre os 40 e os 59 anos; mais de 50% dos pacientes necessitaram do uso de hipotensivos oculares. Da mesma forma, a gestão cirúrgica foi realizada em mais de 50% dos pacientes, sendo a descompressão orbital a intervenção mais frequente.

ABSTRACT Objective. To know the demographic and clinical characteristics of Thyroid Associated Orbitopathy (TAO), as well as the requirement rate of orbital surgery in patients of the Orbit Service in the National Medical Center of the West, IMSS. Methods. Observational, cross-cutting, descriptive and retrospective study carried out analyzing the records of patients diagnosed with TAO and treated at a third-level care center from January 2005 to July 2016. Results. A total of 236 orbits of 118 patients were valued, with an average age of 47.3 ± 13.2 years, 74.6% were female and 25.4% male. 4.2% of patients were treated with hypothyroidism, 94.1% with hyperthyroidism and 1.7% with diffuse toxic goiter. 44.9% of patients studied had eye movement restriction,10.2% exposure keratopathy and 51.7% intraocular hypertension. 34.7% of patients valued in the service required orbital decompression, 16.1% palpebral surgery and 8.5% strabism correction. In the conservative management of these patients 48.3% required the use of topical eye lubricants, while 52.5% required the use of eye hypotensives in variable numbers. Conclusions. TAO was mainly associated with hyperthyroidism, being more common in female patients between the age of 40 and 59; more than 50% of patients required the use of eye hypotensives. Likewise, surgical management was performed in more than 50% of patients, with orbital decompression being the most frequent intervention.

Alteraciones tiroideas en la infancia y en la adolescencia. Parte 1: hipertiroidismo / Thyroid disorders in childhood and adolescence. Part 1: Hyperthyroidism

El hipertiroidismo es el cuadro clínico resultante del exceso de hormonas tiroideas debido a hiperfunción glandular. Es una enfermedad rara en niños y adolescentes, pero con una alta morbilidad. La causa más frecuente es la enfermedad de Graves. El objetivo de esta publicación es realizar una revisión y actualización del hipertiroidismo infantojuvenil para guiar su detección y derivación temprana al endocrinólogo pediatra. Debe ser considerado cuando el niño o adolescente presente síntomas asociados a esta patología y bocio de grado variable. Se confirma con el perfil bioquímico característico.El tratamiento consiste, inicialmente, en bloquear los efectos del exceso de hormonas tiroideas con betabloqueantes y, además, disminuir su producción con drogas antitiroideas como primera elección. Ante efectos secundarios a su administración, recidivas o ausencia de remisión de la enfermedad, se optará por el tratamiento definitivo: yodo radioactivo o cirugía con el objetivo de lograr el hipotiroidismo o eutiroidismo

Hyperthyroidism is a serious and rare disorder in childhood characterized by the overproduction of thyroid hormones by the thyroid gland. Graves disease is the most common cause. The objective of this paper is to review and update hyperthyroidism in children and adolescents aiming to guide its early detection and referral to the pediatric endocrinologist. The disease should be suspected if typical symptoms and goiter are present and has to be confirmed with the characteristic biochemical profile. Initially, treatment to block the effect of the thyroid excess is needed. Antithyroid drugs are the recommended first-line treatment to diminish hormone production. Alternative treatments, such us radioactive iodine or thyroidectomy, are considered in cases of adverse effects to drugs, relapse or non-remission of the disease, in order to achieve hypothyroidism or euthyroidism.

The polymorphic inheritance of DIO2 rs225014 may predict body weight variation after Graves' disease treatment

ABSTRACT Objective: We aimed to investigate the role of DIO2 polymorphisms rs225014 and rs12885300 in Graves' disease patients, mainly for controlling body weight following treatment. Subjects and methods: We genotyped 280 GD patients by the time of diagnosis and 297 healthy control individuals using a TaqMan SNP Genotyping technique. We followed up 141 patients for 18.94 ± 6.59 months after treatment. Results: There was no relationship between the investigated polymorphisms with susceptibility to GD and gain or loss of weight after GD treatment. However, the polymorphic inheritance (CC+CT genotype) of DIO2 rs225014 was associated with a lower body weight variation after GD treatment (4.26 ± 6.25 kg) when compared to wild type TT genotype (6.34 ± 7.26 kg; p = 0.0456 adjusted for the follow-up time). This data was confirmed by a multivariate analysis (p = 0.0138) along with a longer follow-up period (p = 0.0228), older age (p = 0.0306), treatment with radioiodine (p-value = 0.0080) and polymorphic inheritance of DIO2 rs12885300 (p = 0.0306). Conclusion: We suggest that DIO2 rs225014 genotyping may have an auxiliary role in predicting the post-treatment weight behavior of GD patients.

The change in the clinical presentation of Graves disease: a 30 years retrospective survey in an academic Brazilian tertiary center

ABSTRACT Objective Graves' disease (GD) is the main cause of hyperthyroidism among adults. It is an autoimmune condition classically marked by the Merserburg Triad (goiter, thyrotoxicosis, and orbitopathy), but the change in presentation of GD over time has rarely been studied. To determine changes in the clinical presentation of patients with GD in the last 30 years. Subjects and methods The study evaluated 475 patients diagnosed with GD between 1986 and 2016 in a single center. Patients were evaluated regarding epidemiological aspects, thyroid function, inflammatory activity of the eyes evaluated by the Clinical Activity Score; CAS, severity evaluated by NOSPECS classification and thyroid volume estimated by ultrasonography. Results Patients assessment identified an increase in the mean age of diagnosis of GD (p < 0.02), a reduction in thyroid volume (p < 0.001) and less intense orbital involvement from 2007-2016 compared to 1986-2006 (p = 0.04). The number of smoking patients was smaller from 2007 to 2016 (28.7%) than 1986 to 2006 (42.8% p = 0.001). The TSH and TRAb values did not had significant changes. Conclusion GD presentation appears to be changed in the last years compared to the typical initial presentation. There is a less frequent inflammatory involvement of orbital tissue, smaller goiters, a lower number of smokers and diagnosis at older age.

Decreased serum levels of IL-27and IL-35 in patients with Graves disease

ABSTRACT Objectives Graves' disease (GD) is an autoimmune disease causing the overproduction of the thyroid hormone from thyroid gland. This disease is mainly the result of the production of antibodies against TSH receptors. Cytokines play an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The regulatory role of IL-12 on TH1 cells has been proven. IL-27 and IL-35, members of IL-12 cytokine family, are two cytokines that have been newly discovered. IL-35 has been identified as a novel immunosuppressive and anti-inflammatory cytokine while IL-27 has both inflammatory and anti-inflammatory functions. The objective of the current study was to examine the changes in the serum level of the foregoing cytokines in GD patients in comparison to healthy controls. Materials and methods In this study, serum levels of IL-27 and IL-35 were determined by an ELISA method; anti TPO and anti Tg were measured by an RIA method in 40 new cases of Graves's disease. The findings were compared with 40 healthy controls. Results The results showed a significant difference between IL-27 and IL-35 regarding their serum levels with P values of 0.0001 and 0.024, respectively; anti TPO and anti Tg levels of the cases were also significantly different from controls (p < 0.001). Conclusion The reduction in the serum levels of IL-27 and IL-35 in GD patients compared to normal subjects suggests the possible anti-inflammatory role of these cytokines in GD.

Successful therapeutic approach in a patient with elephantiasic pretibial myxedema

Abstract Localized pretibial myxedema is a dermopathy whose treatment is a challenge in dermatology, occurring in 0.5-4% of patients with Graves' disease. This autoimmune thyroid condition stimulates the production of hyaluronic acid and glycosaminoglycans that are deposited particularly in the pretibial region. Clinically, it presents as a localized, circumscribed, and non-depressible infiltrate in plaques. Several treatment modalities have been proposed, and their results vary, with worse response observed in severe cases. This report presents the case of a patient with elephantiasic pretibial myxedema who was subjected to intralesional corticosteroid applications, resulting in an excellent and encouraging therapeutic response that was maintained.

Intrathyroid injection of dexamethasone inhibits Th2 cells in Graves disease

ABSTRACT Objective Intrathyroid injection of dexamethasone (IID) was used for decrease the relapse rate of hyperthyroidism in the treatment of Graves' disease (GD), but the mechanism is still unclear. We aimed to explore the effect of IID on T help (Th)1/Th2 cells and their chemokine in patients with GD. Subjects and methods A total of 42 patients with GD who were euthyroidism by methimazole were randomly divided into IID group (n = 20) and control group (n = 22). Thyroid function and associated antibody, Th1/Th2 cells proportion, serum CXCL10 and CCL2 levels, and CXCR3/CCR2 mRNA expression in peripheral blood mononuclear cells before and after 3-month IID treatment were tested by chemiluminescence assay, Flow cytometry, ELISA, and real-time PCR, respectively. Thyroid follicular cells were stimulated by IFN-γ and TNF-α and treated with dexamethasone in vitro. CXCL10 and CCL2 levels in supernatant were determined. Results After 3-month therapy, the proportion of Th2 cells and serum CCL2 levels, as well as TPOAb, TRAb levels and thyroid volume decreased in IID group (p < 0.05). However, the proportion of Th1 and CXCL10 levels had no change in IID group and control (p > 0.05). The CXCR3/CCR2 ratio had no change in both groups (p > 0.05). Conclusion IID therapy could inhibit peripheral Th2 cells via decreasing CCL2 level in peripheral blood, and this result partly explain the effects of IID therapy on prevention of relapse of GD. Arch Endocrinol Metab. 2020;64(3):243-50

Acquired reactive perforating collagenosis in association with prostate adenocarcinoma, chronic lymphocytic leukemia, and Graves disease

Abstract Acquired reactive perforating collagenosis is a rare skin disorder characterized by the presence of umbilicated pruritic papules and nodules. Transepidermal elimination of altered and perforating bundles of basophilic collagen from the epidermis is a characteristic histologic feature of acquired reactive perforating collagenosis. Along with its well-known association with systemic diseases such as diabetes mellitus, chronic renal failure, and dermatomyositis, there are reports of acquired reactive perforating collagenosis being associated with malignancies. Herein, we present a case of acquired reactive perforating collagenosis associated with chronic lymphocytic leukemia, prostate adenocarcinoma, and Graves's disease. Clinicians are required to be more vigilant in evaluating patients with acquired reactive perforating collagenosis due to its unique association with malignancies and other systemic diseases.

Cholestasis secondary to hyperthyroidism in Graves disease: report of one case / Colestasia en un paciente con hipertiroidismo por enfermedad de Graves: informe de un caso

ABSTRACT Hyperthyroidism can induce elevation in several liver function tests including aminotransferases, alkaline phosphatases and, less frequently, serum bilirubin. These alterations are usually mild and asymptomatic. We report a 26 year-old male presenting with palpitations, progressive jaundice, choluria and generalized itching. Laboratory tests were compatible with hyperthyroidism and a mild elevation of bilirubin, alkaline phosphatases and gamma glutamyl transpeptidase. A liver biopsy showed portal hepatitis with canalicular cholestasis. The patient was treated temporarily with glucocorticoids, cholestyramine and betablockade. Thereafter, he was treated with radioactive iodine, after which serum bilirubin decreased steadily until normalization in ten weeks.

El hipertiroidismo puede producir elevación de aminotransferasas, fosfatasas alcalinas y, menos frecuentemente, de bilirrubina sérica. Habitualmente, estas alteraciones son leves y asintomáticas. Reportamos un hombre de 26 años con hipertiroidismo secundario a enfermedad de Basedow-Graves, que debutó con un cuadro colestásico, inicialmente estudiado por sospecha de patología hepática autoinmune que incluyó biopsia hepática. Posteriormente, se diagnosticó hipertiroidismo que fue tratado con glucocorticoides, colestiramina y beta bloqueo como puente a terapia definitiva con radioyodo. La evolución mostró disminución progresiva hasta la normalización de bilirrubina sérica.

Resultados de la tiroidectomía total en el tratamiento del hipertiroidismo / Results of total thyroidectomy in the treatment of hyperthyroidism

INTRODUCCIÓN: En el tratamiento del hipertiroidismo se recurre a la cirugía en casos de bocio grande, fracaso del tratamiento médico o indicación social de tratamiento definitivo. OBJETIVO: Analizar los resultados en cuanto a función tiroidea del tratamiento del hipertiroidismo mediante tiroidectomía total (TT). MATERIAL Y MÉTODO: Estudio retrospectivo de 26 pacientes con hipertiroidismo, intervenidos en el Hospital de la Plana durante 2015-2018, con seguimiento de 36 meses. Tras estudio estadístico descriptivo e inferencial, se analizó la probabilidad de recidiva del hipertiroidismo mediante el método de Kaplan-Meier, y se utilizó el modelo de Cox para ajustar los efectos sobre la recidiva de las diferentes variables. RESULTADOS: El 73,1% tenían normofunción tiroidea; el 19,2%, hiperfunción, y en otro 7,7% existía hipofunción. El tiempo medio de supervivencia (normofunción) fue de 25,87 meses (IC: 17,52-34,21). En el estudio de supervivencia con el log-rank en función de la variable anatomía patológica y complicaciones, no hay diferencias estadísticamente significativas en la supervivencia de ambos grupos. DISCUSIÓN: Coincide con otros trabajos publicados. CONCLUSIÓN: La TT es un método efectivo de tratamiento para el hipertiroidismo, con baja incidencia de complicaciones. Sin embargo, no hemos encontrado ninguna variable que nos permita predecir el resultado.

INTRODUCTION: Surgery is used in the management of hyperthyroidism in cases of large goiter, failure of medical treatment or social indication of definitive treatment. AIM: To analyze the results of the treatment of hyperthyroidism by total thyroidectomy (TT) regarding to thyroid function. MATERIAL AND METHODS: Retrospective study of 26 patients with hyperthyroidism, operated on the Hospital de la Plana during 2015-2018, with a follow-up of 36 months. After a descriptive and inferential statistical study, the probability of recurrence of hyperthyroidism was analyzed using the Kaplan-Meier method, and the Cox model was used to adjust the effects on recurrence of the different variables. RESULTS: 73.1% had thyroid normofunction; in 19.2% there was hyperfunction, and in another 7.7% there was hypofunction. The average survival time (normofunction) was 25,87 months (CI: 17,52-34,21). In the study of survival with the log-rank depending on the pathological results and complications, there are no statistically significant differences in the survival of both groups. DISCUSSION: This coincides with other published works. CONCLUSION: TT is an effective method of treatment for hyperthyroidism, with a low incidence of complications. However, we have not found any variable that allows us to predict the result.

Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves disease

BACKGROUND: Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves' disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. METHODS: Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. RESULTS: There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. CONCLUSIONS: hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves' disease.