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Introducción: los medicamentos antitiroideos son una de las alternativas terapéuticas en el tratamiento de la enfermedad de Graves. Sin embargo, pueden generar efectos adversos severos poco frecuentes en el plano hematológico, como la anemia aplásica, la cual se ha asociado con altas dosis de estos medicamentos, aunque con reversión de esta afección ante el retiro del medicamento. Descripción del caso: mujer de 38 años con antecedente de enfermedad de Graves en tratamiento con metimazol, quien consultó por síntomas como epistaxis anterior de difícil control, petequias, astenia e hiporexia. Se documentó pancitopenia en el hemo-grama, con posterior hallazgo en biopsia de médula ósea de aplasia medular, sin respuesta ante el retiro del metimazol y soporte transfusional. Posteriormente, la paciente falleció. Conclusión: la presentación de aplasia medular asociada con metimazol es poco común y se relaciona con altas dosis de este medicamento. En la mayoría de casos, el retiro de este agente genera recuperación clínica y celular. No obstante, en algu-nos pacientes persiste el compromiso hematológico que va desde importantes repercusiones clínicas hasta desenlaces fatales. Por lo tanto, el presente caso busca hace hincapié en la importancia de vigilar este efecto adverso ante el inicio de esta medicación

Introduction: Antithyroid drugs are one of the therapeutic alternatives in the treatment of Graves' dis-ease. However, it can generate severe but infrequent adverse effects at the hematological level, such as aplastic anemia, which has been associated with high doses of these drugs, although with reversal of this hematological condition when the drug is withdrawn. Case description: A 38-year-old woman with a his-tory of Graves' disease treated with methimazole, who consult for symptoms such as anterior epistaxis, petechiae, asthenia, and hyporexia. Pancytopenia is documented in the blood count, with a subsequent finding of bone marrow aplasia in bone marrow biopsy, without response to withdrawal of Methimazole and transfusion support. The patient subsequently died. Conclusion: The methimazole-associated bone marrow aplasia is uncommon and it ́s associated with high doses of methimazole, in most cases with-drawal of methimazole leads to clinical and cellular recovery. However, in some patients hematological involvement persists with significant clinical repercussions up to fatal outcomes. Therefore, this case seeks to highlight the importance of monitoring for this adverse effect before starting this medication

Introdução: as drogas antitireoidianas são uma das alternativas terapêuticas no tratamento da doença de Graves. No entanto, pode causar efeitos adversos graves, mas infrequentes, no nível hematológico, como a anemia aplástica, que tem sido associada a altas doses desses medicamentos, embora com rever-são desse quadro hematológico quando a droga é retirada. Descrição do caso: mulher de 38 anos com história de doença de Graves tratada com metimazol, que consultou por sintomas como epistaxe ante-rior de difícil controle, petéquias, astenia e hiporexia. A pancitopenia é documentada no hemograma, com achado posterior de aplasia da medula óssea na biópsia da medula óssea, sem resposta à retirada do metimazol e suporte transfusional. O doente faleceu posteriormente. Conclusão: a apresentação de aplasia da medula óssea associada ao metimazol é pouco frequente em associação com doses elevadas de metimazol. Na maioria dos casos, a retirada do metimazol conduz à recuperação clínica e celular. No entanto, nalguns doentes, o envolvimento hematológico persiste com repercussões clínicas significati-vas, podendo mesmo ocorrer desfechos fatais. Assim, o presente caso pretende realçar a importância da monitorização deste efeito adverso antes de iniciar esta medicação

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Resumen: Las hormonas tiroideas forman parte fundamental del mantenimiento de la homeostasia, se encuentra particularmente relacionado con la función cardiovascular. Los estados distiroideos clínicos o subclínicos pueden comprometer este sistema en forma significativa durante los procedimientos quirúrgicos. Existen múltiples fármacos que pueden modificar la patología tiroidea en mayor o menor medida, disminuyendo el riesgo de complicaciones en la eventualidad de una cirugía. La utilización de anestesia general, ya sea balanceada o total endovenosa, se ha convertido en el estándar de oro, por la menor tasa de complicaciones asociadas. Durante el período perioperatorio se debe mantener un monitoreo estricto de la función cardiovascular para detectar alteraciones en forma temprana e iniciar las correcciones necesarias.

Abstract: Thyroid hormones are a fundamental part of the maintenance of homeostasis, it is particularly related to cardiovascular function. Clinical or subclinical dysthyroid states can significantly compromise this system during surgical procedures. There are multiple drugs that can modify the thyroid pathology to a greater or lesser extent, reducing the risk of complications in the event of surgery. The use of general anesthesia, whether balanced or total intravenous, has become the Gold standard, due to the lower rate of associated complications. During the perioperative period, strict monitoring of cardiovascular function must be maintained to detect alterations early and initiate the necessary corrections.

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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).

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Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusion: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

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ABSTRACT Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusions: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

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Not required for Clinical Vignette.

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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.

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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.

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.

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The association of hyperthyroidism and pregnancy is rare. Its importance resides in the prognosis of mother and fetus. The recognition of thyroid alterations during pregnancy differs from the general population; in this special group, it is necessary to correlate diagnostic tests and normal physiological changes. The main cause of hyperthyroidism is Graves disease, with its autoimmune component. Transient gestational thyrotoxicosis becomes important during pregnancy and is critical in the differential diagnosis, especially during the first trimester. Management of hyperthyroidism during pregnancy has special implications; first-line therapies are contraindicated, and antithyroid drugs become relevant. No therapy is completely safe during pregnancy; possible adverse effects and mother and fetus implications must be evaluated. In this review, we want to consider the physiological changes in thyroid function during pregnancy. Also, we want to point out the best actions for the proper recognition, diagnosis and management of hyperthyroidism during pregnancy, in order to reduce maternal and fetal morbidity and mortality. A review of the literature was performed in PubMed and Science Direct using MeSH words and connectors. We included the most relevant articles published by scientific societies in the last 20 years on the diagnosis and management of hyperthyroidism during pregnancy.

La relación hipertiroidismo y embarazo es poco común. Su importancia recae en el pronóstico de la madre y el feto. El reconocimiento de las alteraciones tiroideas durante el embarazo difiere de la población general. En este grupo poblacional es necesario correlacionar las pruebas diagnósticas con los cambios fisiológicos durante este periodo. La principal causa de hipertiroidismo es la enfermedad de Graves, con su componente autoinmune. La tirotoxicosis gestacional transitoria toma relevancia durante el embarazo y es un diagnóstico diferencial importante durante el primer trimestre. El manejo del hipertiroidismo durante el embarazo tiene implicaciones especiales. Las terapias de primera línea convencionales están contraindicadas, y toman relevancia los medicamentos antitiroideos. Ninguna terapia es totalmente segura durante el embarazo y se deben evaluar los posibles efectos adversos e implicaciones para la madre y el feto. En esta revisión queremos dar a conocer los cambios en la función tiroidea durante la gestación; además, las pautas necesarias para el adecuado reconocimiento, diagnóstico y manejo del hipertiroidismo durante el embarazo, con el fin de disminuir la morbilidad y mortalidad materno-fetal. Se realizó una revisión de la literatura en PubMed y Science Direct utilizando palabras MeSH y conectores. Se incluyeron artículos especiales más relevantes publicados por las sociedades internacionales en los últimos 20 años sobre el diagnóstico y manejo del hipertiroidismo durante el embarazo

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INTRODUCTION: Thyroid dysfunction has often been associated with several psychiatric manifestations. Previous case reports/series suggest the possible role played by acute alteration of thyroid status in the onset of psychotic symptoms. METHODS: Case report and literature review. RESULTS: A 45-year-old woman with no psychiatric antecedents was brought to the ER with a full-blown psychotic episode, marked by paranoid delusions, which developed gradually over two months. She had been treated elsewhere for hyperthyroidism for five years with methimazole 40 mg/d, with poor compliance. One month before the beginning of the psychotic symptoms, methimazole was raised to 60 mg/d and she started taking it correctly. Five months earlier she had TSH: 0.074 uUI/ml and free T4: 1.3 ng/dl. At admission we found a diffuse thyroid goiter, TSH: 70.9 uUI/ml and free T4: 0.03 ng/dl. Brain CT was normal. We hospitalized her with the diagnosis of a psychosis secondary to hypothyroidism, suspended methimazole, and gave her levothyroxine (up to 75 µg/d) and risperidone (2 mg/d). The patient had a quick remission and was discharged after 15 days. Within one month she had TSH: 0.7 uUI/ml and was completely recovered psychiatrically. She has been well since then, with risperidone in the first 8 months, and without it for 10 months now. CONCLUSION: This case report is a reminder of the necessity of checking thyroid status as part of clinical assessment of psychoses. It also supports the hypothesis that antithyroid drugs may have severe psychiatric consequences, especially when they lead to an acute change of thyroid status.

INTRODUÇÃO: Disfunções tireoidianas têm sido frequentemente associadas a diversas manifestações psiquiátricas. Séries e relatos de caso sugerem o possível papel da alteração aguda do status tireoidiano na vigência dos sintomas psicóticos. MÉTODOS: Relato de caso e revisão de literatura. RESULTADOS: Uma mulher de 45 anos sem antecedentes psiquiátricos foi trazida para Unidade de Emergência Referenciada com episódio psicótico, marcado por delírios paranoides, que se desenvolveram gradualmente nos dois meses anteriores. Ela tinha sido tratada, em outro serviço, por hipertireoidismo durante cinco anos com metimazol 40 mg/d, com aderência ruim. Um mês antes do início dos sintomas psicóticos, o metimazol foi aumentado para 60 mg/d, dose que ela estava tomando corretamente. Cinco meses antes ela tinha TSH: 0,074 uUI/ml e T4 livre: 1,3 ng/dl. Na admissão, encontraram-se aumento difuso da glândula, TSH: 70,9 uUI/ml e T4 livre: 0,03 ng/dl. TC de crânio estava normal. Foi hospitalizada por diagnóstico de psicose secundária ao hipotireoidismo, suspenso o metimazol e introduzidas levotiroxina (até 75 µg/d) e risperidona (2 mg/d). A paciente teve rápida remissão e recebeu alta após 15 dias. Um mês após ela apresentava TSH: 0,7 uUI/ml, com remissão completa da psicose. Ela permaneceu bem, com risperidona nos oito meses seguintes e sem a medicação há 10 meses. CONCLUSÃO: Este relato de caso é um alerta para a necessidade de investigar a função tireoidiana como parte do manejo clínico da psicose. Também reforça a hipótese de que drogas antitireoidianas podem ter graves consequências psiquiátricas, especialmente quando levam à mudança aguda do status tireoidiano.

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Los trastornos tiroideos son frecuentes en mujeres en edad reproductiva. Sin embargo, a menudo no se diagnostican porque su sintomatología se confunde con el estado hipermetabólico característico del embarazo. A los cambios fisiológicos en el embarazo de índole cardiovascular, pulmonar, hematológica, inmunológica, etc., se añaden las modificaciones en el eje tiroideo que a lo largo de la gestación presenta diferentes estados, lo que hace aún más difícil el diagnóstico y tratamiento correctos en los casos patológicos. Los trastornos del eje tiroideo tienen repercusiones negativas sobre la madre y el feto, entre otras: preeclampsia, aborto, parto prematuro y trastornos del sistema nervioso central del feto. El tratamiento se debe dirigir a contrarrestar los efectos del aumento o la disminución del funcionamiento de la glándula teniendo en cuenta las diferencias en cuanto a requerimientos y seguridad de los fármacos en el feto. Actualmente es motivo de controversia la tamización de rutina en gestantes para trastornos tiroideos, pues hasta el momento se destinan las pruebas a mujeres embarazadas de alto riesgo.

Thyroid disorders are frequent in women of reproductive age. However, they are often overlooked because their manifestations may be confused with those of the hypermetabolic state that is characteristic of pregnancy. To the physiological changes that occur during pregnancy –cardiovascular, pulmonary, hematological, immunological, etc., it is necessary to add modifications in the thyroid axis that presents different situations during pregnancy; those variations make it difficult to correctly diagnose and treat pathological situations. Disorders of thyroid axis have negative consequences on both mother and fetus, among them: preeclampsia, abortion, premature delivery and disorders of the fetal central nervous system. Treatment must be oriented to counteract the effects of either increased or diminished thyroid function; for that purpose, differences concerning requirements and safety of medicines must be taken into account. Presently there is controversy concerning routine screening of pregnant women for thyroid disorders; so far, the available tests are usually performed only in high-risk women.

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Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.

A 48-year old woman with a recent diagnosis of Graves’ disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf). After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.

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