Methimazole-Induced ANCA Vasculitis: A Case Report.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves' disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m2), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm3, platelets 238,000/mm3, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m2) and negative p-ANCA.

Neutropenia severa inducida por propiltiuracilo / (Severe neutropenia induced by propylthiuracil)

Resumen Los pacientes con hipertiroidismo tienen varias opciones de tratamiento. El tratamiento de la enfermedad de Graves consiste en bloquear el exceso de hormonas tiroideas empleando tionamidas, tiroidectomía o terapia con I131. Los agentes antitiroideos como el metimazol, carbimazole, propiltiuracilo, son efectivos para controlar el hipertirodismo en pacientes con enfermedad de Graves, pero tienen efectos adversos incluyendo, alergias, gastritis, hepatitis y agranulocitosis. Se presenta un paciente hipertiroideo con neutropenia severa durante tratamiento con propiltiuracilo.

Abstract Patients with hyperthyroidism have several treatment options. The treatment of Graves' disease consists of blocking the excess of thyroid hormones using thionamides, thyroidectomy or I131 therapy. Antithyroid agents such as methimazole, carbimazole, propylthiuracil are effective in controlling hyperthyroidism in patients with Graves' disease, but they have adverse effects including, allergies, gastritis, hepatitis and agranulocytosis. We present a hyperthyroid patient with severe neutropenia during treatment with propylthiuracil.

Hipertiroidismo congénito, Reporte de dos casos

Introducción: El hipertiroidismo es una patología tiroidea poco frecuente en neonatos, relacionada con el antecedente materno de enfermedad de Graves, y por lo tanto con el paso transplacentario de inmunoglobulinas estimulantes del receptor de TSH. Presentación de casos: Reportamos dos casos de sexo femenino, que se presentaron en el Hospital Universitario de Santander. El primero de los casos se manifestó en la primera semana; el segundo caso se presentó tardíamente después del primer mes de vida. Los síntomas que presentaron en común fueron taquicardia persistente e hiperactividad. En uno de los casos la presentación clínica fue confundida con una infección bacteriana, debido a la presencia de fiebre. Se confirma el diagnóstico con los niveles de TSH muy suprimidos y T4 libre elevada, al menos al doble del límite superior. Los dos casos observaron medicamentos antitiroideos y propanolol con buena evolución clínica y de laboratorios; no se observamos complicaciones a corto o largo plazo como arritmias o craneosinostosis. Discusión: El hipertiroidismo congénito es una patología poco frecuente y siempre debe ser sospechado en recién nacidos de madres con antecedente de enfermedad de Graves, sus manifestaciones pueden presentarse prenatalmente o postnatalmente, y su diagnóstico y tratamiento deben ser oportunos para evitar secuelas a largo plazo o incluso la muerte.

Introduction: Hyperthyroidism is a thyroidal pathology infrequent in neonates related with maternal history of Graves' disease, and therefore with the transplacental passage of stimulating TSH receptor immunoglobulins. Case report: We report two female gender cases at Hospital Universitario Santander, one of the two cases became manifest during the first week of life, and the other took longer time after the first month of life, as it can happen. Symptoms in common were persistent tachycardia and hyperactivity; one of the cases was mistaken for bacterial infection arising from fever. Diagnose was confirmed of highly suppressed TSH levels and high Free T4, at least twice the limit level. Both cases were treated for some time with antithyroid drugs and ß-blockers, showing good clinical and lab evolution; no complications like arrhythmias or craneosynostosis were observed. Discussion: Congenital hyperthyroidism is a rare condition and should always be suspected in infants of mothers with Graves' disease, its manifestations may occur prenatally or postnatally, and their diagnosis and treatment should be timely to avoid long-term sequelae or death.

Consenso brasileiro para o diagnóstico e tratamento do hipertireoidismo: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia / The Brazilian consensus for the diagnosis and treatment of hyperthyroidism: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism

INTRODUÇÃO: O hipertireoidismo é caracterizado pelo aumento da síntese e liberação dos hormônios tireoidianos pela glândula tireoide. A tireotoxicose refere-se à síndrome clínica decorrente do excesso de hormônios tireoidianos circulantes, secundário ao hipertireoidismo ou não. Este artigo descreve diretrizes baseadas em evidências clínicas para o manejo da tireotoxicose. OBJETIVO: O presente consenso, elaborado por especialistas brasileiros e patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia, visa abordar o manejo, diagnóstico e tratamento dos pacientes com tireotoxicose, de acordo com as evidências mais recentes da literatura e adequadas para a realidade clínica do país. MATERIAIS E MÉTODOS: Após estruturação das questões clínicas, foi realizada busca das evidências disponíveis na literatura, inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO - Lilacs. A força das evidências, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão. RESULTADOS: Foram definidas 13 questões sobre a abordagem clínica inicial visando ao diagnóstico e ao tratamento que resultaram em 53 recomendações, incluindo investigação etiológica, tratamento com drogas antitireoidianas, iodo radioativo e cirurgia. Foram abordados ainda o hipertireoidismo em crianças, adolescentes ou pacientes grávidas e o manejo do hipertireoidismo em pacientes com oftalmopatia de Graves e com outras causas diversas de tireotoxicose. CONCLUSÕES: O diagnóstico clínico do hipertireoidismo, geralmente, não oferece dificuldade e a confirmação diagnóstica deverá ser feita com as dosagens das concentrações séricas de TSH e hormônios tireoidianos. O tratamento pode ser realizado com drogas antitireoidianas, administração de radioiodoterapia ou cirurgia de acordo com a etiologia da tireotoxicose, as características clínicas, disponibilidade local de métodos e preferências do médico-assistente e paciente.

INTRODUCTION: Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis. OBJECTIVE: This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil. MATERIALS AND METHODS: After structuring clinical questions, search for evidence was made available in the literature, initially in the database MedLine, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question. RESULTS: We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis. CONCLUSIONS: The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient.

Avaliação da radioiodoterapia com doses fixas de 10 e 15 mCi em pacientes com doença de graves / Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with graves’ disease

As opções terapêuticas para a hipertireoidismo da doença de Graves são as drogas antitireoidianas, a cirurgia e o radioiodo, porém nenhuma delas é considerada ideal pois não atuam diretamente na etiopatogênese da doença. O radioiodo vem sendo cada vez mais utilizado como primeira escolha, sendo um tratamento definitivo, seguro e de fácil administração. Há autores que preferem doses mais altas para induzir deliberadamente o hipotireoidismo, enquanto outros recomendam doses mais baixas que, a curto prazo, implicam menor incidência de hipotireoidismo e maior de eutireoidismo. Não há consenso sobre o melhor esquema de doses fixas a ser utilizado, sendo esse o principal enfoque deste estudo, no qual comparamos doses de 10 e 15 mCi. Dos 164 pacientes analisados, 61 (37,2 por cento) foram submetidos a 10 mCi e 103 (62,8 por cento), a 15 mCi de 131I. Na análise longitudinal, observou-se que a remissão do hipertireoidismo foi estatisticamente diferente no sexto mês (p < 0,001), sendo maior no grupo em que foi empregada a dose de 15 mCi. Contudo, foi semelhante nos dois grupos após 12 e 24 meses. É possível concluir que doses fixas de 10 e 15 mCi promovem semelhante remissão do hipertireoidismo após 12 meses de tratamento. A remissão do hipertireoidismo não teve associação com idade, sexo ou uso prévio de drogas antitireoidianas.

The treatment options for the hyperthyroidism of Graves’ disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of 131I were compared. Among the 164 patients analyzed, 61 (37.2 percent) were submitted to 10 mCi and 103 (62.8 percent) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of 131I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs.