Anemia aplásica inducida por metimazol: presentación de caso / Methimazole Induced Aplastic Anemia: Case Report / Anemia aplástica induzida por metimazol: relato de caso

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been associated with high doses of these drugs, although with reversal of this hematological condition when the drug is withdrawn.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

Manejo anestésico para cirugía tiroidea. Una revisión no sistemática / Anesthetic management for thyroid surgery. A non-systematic review

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.

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).

Prediction for recurrence following antithyroid drug therapy for Graves' hyperthyroidism

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.

Efficacy of traditional Chinese medicine combined with 131I in the treatment of Graves hyperthyroidism / 中华核医学与分子影像杂志

Objective:To explore the value of traditional Chinese medicine combined with 131I in the treatment of Graves hyperthyroidism. Methods:From March 2020 to July 2021, 90 patients (39 males, 51 females, age (33.2±7.0) years) with Graves hyperthyroidism who were diagnosed and treated in Changshu No.2 People′s Hospital were retrospectively analyzed. Patients were randomly divided into 3 groups ( n=30 in each group), including group A who received treatment of antithyroid drugs (ATD), group B who received treatment of traditional Chinese medicine, and group C who received treatment of 131I combined with traditional Chinese medicine. Thyroid function indicators and inflammatory indicators before treatment and 1, 3, and 6 months after treatment were determined, including free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH) and TSH receptor antibody (TRAb), and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). One-way analysis of variance and χ2 test were used to analyze data. Results:The levels of FT 3, FT 4, TSH, TRAb, CRP, IL-6 and TNF-α in group A, B and C before treatment and 1, 3, 6 months after treatment were significantly different ( F values: 193.27-906.11, all P<0.05). The total effective rate in group C (100.0%, 30/30) was significantly higher than that in group A (86.7%, 26/30) or group B (83.3%, 25/30; χ2 values: 8.24, 9.83, P values: 0.006, 0.037), while there was no significant difference between group A and group B ( χ2=3.02, P=0.124). The incidence of adverse reactions in group B (46.7%, 14/30) was significantly higher than that in group A (30.0%, 9/30; χ2=6.59, P=0.042). And the incidence of adverse reaction in group C (13.3%, 4/30) was significantly lower than that in group A or group B ( χ2 values: 12.05, 7.20, P values: 0.004, 0.038). Conclusion:The curative effect of 131I combined with traditional Chinese medicine is effective and reliable, suggesting that clinical researches should be carried out together and perfected.

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.

Graves' Disease: Can It Be Cured?

Whether or not Graves' hyperthyroidism can be really cured, depends on the definition of “cure.” If eradication of thyroid hormone excess suffices for the label “cure,” then all patients can be cured because total thyroidectomy or high doses of 1¹³¹I will abolish hyperthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a “cure,” which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discontinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves' Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recurrent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibodies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of “cure” would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower.

Hipertiroidismo en el embarazo / Hyperthyroidism in pregnancy

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

Treatment of relapsed hyperthyroidism

Graves disease is the most common disease that causes hyperthyroidism. It is an autoimmune disease characterized by the overproduction of thyroid hormones due to continuous stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibody. Therapeutic modalities for Graves disease include antithyroid drugs (ATDs), radioactive iodine, and thyroidectomy. ATDs are the most preferred therapeutic option by physicians in most countries except North America. However, current treatment strategies are unfortunately aimed at inhibiting thyroid hormone production or ablating the thyroid to induce permanent hypothyroidism, not at inhibiting thyroid-stimulating hormone receptor antibody. ATD therapy has a high relapse rate (more than 50%), and morbidity and mortality increase in cases of relapse. Therefore, the proper and prompt management of relapsed patients is very important.

Methimazole-Induced Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in the Peripheral Nerves

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been reported in Graves' disease patients treated with antithyroid drugs (ATDs), especially propylthiouracil. ATD-induced ANCA-associated vasculitis usually involved the kidneys followed by the respiratory organs and skin. The treatment of ANCA-associated vasculitis induced by ATDs is to stop ATD therapy immediately, which often leads to an overall good prognosis. We report a case of ANCA-associated vasculitis in the peripheral nerves of the lower extremities in a 66-year-old woman who was treated with methimazole (MMI) for Graves' disease. To our knowledge, this is the third case of peripheral nervous system (PNS) involvement of ATD-induced vasculitis and the first case of PNS vasculitis associated with MMI.

The Recurrence Rate of Graves' Disease among Patients with Subclinical Thyrotoxicosis after Initial Remission with Antithyroid Agents

BACKGROUND AND OBJECTIVES: The recurrence rate of patients with Graves' disease (GD) is estimated to be 50-55% after withdrawal of antithyroid drug therapy, and relapse is frequent in the first year after discontinuing the medication. Follow-up examination of these patients frequently reveals laboratory findings consistent with subclinical thyrotoxicosis in the first year after stopping the antithyroid agents. We investigated the risk of recurrence of GD among patients with resurfacing subclinical thyrotoxicosis state after remission of initial GD with antithyroid treatments. MATERIALS AND METHODS: We reviewed the patients diagnosed with GD who visited the Department of Endocrinology at two tertiary medical centers: Wonju Severance Christian Hospital and Gangneung Asan Hospital. We enrolled patients whose GD was completely treated after initial treatment with antithyroid agents who then developed subclinical thyrotoxicosis after discontinuation of antithyroid agents. RESULTS: We reviewed a total of 44 patients (29 females, 15 males; age, 48.93±18.04; range, 17-85 years). The recurrence rate was 27.3% (12/44 patients), and recurrence occurred 3 months to 12 months later resurfacing of subclinical thyrotoxicosis. Patients with recurred GD was significantly older than non-recurred patients (44.63±17.75 years vs. 58.58±15.48 years, p=0.02). Other clinical parameters measured at the time of initial diagnosis were not different between the two groups. CONCLUSION: The recurrence rate of GD in patients with resurfacing subclinical thyrotoxicosis after initial remission of the disease was less than 30%. A close monitoring is recommended in these subgroup patients, especially in older patients.

Effects of serum level of TPOAb on Graves disease in patients using anti-thyroid drug treatment / 天津医药

Objective To analyse effects of the serum levels of thyroid peroxidase antibodies (TPOAb) on antithyroid drugs (ATD) treatment in patients with incipient Graves disease (GD). Methods A total of 121 patients with incipient GD, who were used anti thyroid drugs for 12 months, were included in this study. Patients were dvided into two groups:TPOAb negative group (TPOAb≤35 IU/mL, n=49) and TPOAb positive group (TPOAb>35 IU/mL, n=72). According to the degree of TPOAb drops the TPOAb positive group was sub-divided into low level positive group (35 IU/mL1 000 IU/mL, n=20). The ATD total dosage for 12 months and thyroid-stimulating hormone (TSH), which returned to normal rate after treatment of 3, 6 and 12 months, were compared between groups. Results ATD total dose was lower in TPOAb positive group (1 743.82±265.38) mg than that of negative group (1 889.18 ±125.51) mg. The ATD total dosages were (1 759.71±230.29) mg, (1 793.75±299.02) mg, (1 731.54± 236.44) mg and (1 710.00 ± 290.73) mg for low level TPOAb positive group, medium level TPOAb positive group, high level TPOAb positive group, and very high level TPOAb positive group respectively. The recovering ratio of TSH was significantly higher in TPOAb positive group than that of TPOAb negative group after 3-month treatment (P<0.05). Conclusion TPOAb positive serum can lead to shorten the course of ATD treatment and reduce the total amount of ATD treatment in GD patients.

Characteristics of Korean Patients with Antithyroid Drug-Induced Agranulocytosis: A Multicenter Study in Korea

BACKGROUND: Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients. METHODS: We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm3. RESULTS: The mean age of the patients (11 males, 43 females) was 38.2+/-14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (> or =6 days) and short recovery time (< or =5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization. CONCLUSION: The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.

The treatment of Graves' disease in children and adolescents

Graves' disease (GD) accounts for 10%-15% of thyroid disorders in children and adolescents. The use of antithyroid drugs as the initial treatment option in GD is well accepted. An average two years remission is achieved in about 30% of children treated with antithyroid drugs. However, the optimal treatment duration and the predictive marker of remission after antithyroid drug therapy are still controversial. Additionally, 131I therapy and surgery are considered the option for treatment in children and adolescents with GD. We review the treatment options for pediatric GD and the possible determinants of remission and relapse on antithyroid drug treatment in children and adolescents.

Diagnóstico y tratamiento de los trastornos tiroideos durante el embarazo: un enfoque para el cuidado integral del binomio madre-hijo / Diagnosis and management of thyroid disorders during pregnancy: an approach to comprehensive care of mother and child

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.

Psychosis associated with methimazole-induced hypothyroidism: a case report / Psicose associada com hipotireoidismo induzido por metimazol: um relato de caso

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.

Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso / Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report

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.

Relevant factors in predicting the relapse of Graves disease after treatment with antithyroid drugs / 中华全科医师杂志

Objective To evaluate the prognostic factors of predicting the outcome of Graves disease (GD) after treatment with antithyroid drugs.MethodsA retrospective audit was performed for 306 consecutive patients with newly diagnosed GD.They were divided into successful and failure groups (including recurrent and non-stop subgroups )according to the treatment outcomes.Different prognostic factors after treatment with antithyroid drugs were compared and the state of thyrotropin suppression was observed as the euthyroid state at Months 3,6 and 12 respectively.ResultsAmong them,141patients (46.1％ ) were cured and 165 patients (53.9％) had treatment failures.Age at the time of diagnosis was (46 ±10) years in the successful group and (36 ±9) years in the failure group(t =3.152,P =0.002).Free T3 ( FT3 ) was (25.2 ±8.9) and ( 18.7 ±9.4) pmol/L in the failure and successful groups respectively (t =3.326,P =0.001).The FT3 to FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were higher in the failure group ( t =3.331,3.389,P =0.001).Logistic regression analysis showed that thyroid size,FT3 to FT4 ratio and TRAb at the time of diagnosis were associated with failure outcomes.The ratio of continuing thyrotropin suppression in the recurrent subgroup was more than that in the successful group ( X2 =77.515,114.441,136.232,all P ＜ 0.01).ConclusionsThe GD patients with a large thyroid size and high pre-mediation levels of TRAb and FT3 to FT4 ratio are more prone to respond unfavorably to antithyroid drug treatment.And those with a large thyroid size and post-medication ophthalmopathy and continuing thyrotropin suppression have a high rate of recurrence.

The Clinical Course and Prognostic Factors to Medical Treatment of Graves' Disease in Children and Adolescents

PURPOSE: The aim of this study was to observe clinical course including remission rate during antithyroid medication for Graves' disease in children and adolescents, and to evaluate factors related to remission. METHODS: This is a retrospective study of 42 patients (8 males), who were diagnosed at pediatric endocrine clinic in Chungbuk National University Hospital from January 1994 to December 2009. They were treated with antithyroid drugs only and were followed for at least 2 years. Their average age at diagnosis was 11.5 +/- 3.4 years, and average follow-up period was 4.5 +/- 2.2 years. RESULTS: At diagnosis, 64.3% of the subjects were in puberty, 87.8% showed goiter which was significantly prevalent in females (P < 0.05), and 38.9% manifested exophthalmos. Thyrotropin receptor antibody was positive in all the patients, whereas anti-microsomal antibody was positive in 88.1% and anti-thyroglobulin antibody in 81.0%. Twenty two (52.4%) patients remitted with 4.3 +/- 2.5 years' medication, and the others were continuously medicated at the last follow-up of 4.8 +/- 1.8 years. By quartile estimate for the remission time, 25 percentile was remitted at 3.7 years, 50 percentile at 7.1 years, and 75 percentile at 9.2 years. Among the factors for the remission, initial thyroid stimulating hormone level was significantly lower in non-remission group compared to remission group (P < 0.05). CONCLUSION: In pediatric Graves' disease treated only antithyroid drugs, the time required for remission is so long that it is necessary to establish fixed medication period and to choose definitive treatment modality as in adult Graves' disease through multicenter clinical study.

Recent review on medical treatment of thyroid disease

Thyroid disorder is a common disease. Graves' disease is the most frequent cause of thyrotoxicosis and pharmacological treatment is current trends worldwide. Because of the severe adverse effects of propylthiouracil, methimazole or carbimazole should be selected as the drug of choice except for special situations such as women in the first trimester of pregnancy, thyroid storm, or in patients with severe side effects to methimazole. Treatment should continue for 12 to 18 months, but duration can be adjusted depending on the patient. For hypothyroidism, synthetic levothyroxine is the mainstay of treatment. In order to avoid overtreatment, the dosage of levothyroxine should be determined in consideration of the patient's age, sex, bodyweight, general condition, and comorbidities. In subclinical hypothyroidism, thyroid hormone replacement is suggested in patients with thyroid stimulating hormone concentrations >10 mIU/L. For non-elderly patients with high titers of thyroid autoantibodies, patients with dyslipidemia, pregnant patients, and women with infertility or ovulatory dysfunction, treatment with levothyroxine can be considered.