Lithium as pre-radioablative treatment of Graves’ Disease Complicated by Thyroid Storm and Methimazole-induced Agranulocytosis: A case report

@#Thyroid storm and thionamide-induced agranulocytosis are both rare and serious medical emergencies. We report a case of a patient in which these two rare events simultaneously occurred. A 33-year-old male, maintained on Methimazole for Graves’ Disease, presented with fever, throat pain, and uncontrolled thyrotoxic symptoms. Methimazole was promptly discontinued. Thyroid storm was alternatively treated with lithium, hydrocortisone, and propranolol. Agranulocytosis was managed supportively with GCSF and empiric antibiotics. Lithium was maintained until after radioablation. When thionamides are contraindicated, lithium is a viable option for the acute management of thyroid storm and a bridge to definitive therapy.

Endocrinopatías por inmunoterapia oncológica / Endocrinopathies by oncological immunotherapy

La relación entre inmunidad y cáncer es compleja. Las células tumorales desarrollan mecanismos de evasión a las respuestas del sistema inmunitario. Esta capacidad permite su supervivencia y crecimiento. La inmunoterapia ha transformado el tratamiento oncológico mejorando la respuesta inmunitaria contra la célula tumoral. Esta se basa en el bloqueo de los puntos de control inmunitario mediante anticuerpos monoclonales contra la molécula inhibidora CTLA-4 (antígeno 4 del linfocito T citotóxico [CTLA-4]) y la proteína 1 de muerte celular programada y su ligando (PD-1/PD-L1). Aunque los inhibidores de los puntos de control inmunitario (ICIs) son fármacos bien tolerados, tienen un perfil de efectos adversos conocido como eventos adversos inmunorrelacionados (EAI). Estos afectan varios sistemas, incluyendo las glándulas endocrinas. Los eventos adversos endocrinos más frecuentes son la disfunción tiroidea, la insuficiencia hipofisaria, la diabetes mellitus autoinmune y la insuficiencia suprarrenal primaria. El creciente conocimiento de estos efectos adversos endocrinos ha llevado a estrategias de tratamiento efectivo con el reemplazo hormonal correspondiente. El objetivo de esta revisión es reconocer la incidencia de estas nuevas endocrinopatías, la fisiopatología, su valoración clínica y el manejo terapéutico. (AU)

The relationship between immunity and cancer is complex. Tumor cells develop evasion mechanisms to the immune system responses. This ability allows their survival and progression. Immunotherapy has transformed cancer treatment by improving the immune response against tumor cells. This is achieved by blocking immune checkpoints with monoclonal antibodies against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 and its ligand (PD-1 / PD-L1). Although the immune checkpoint inhibitors (ICIs) are well tolerated drugs, they have a profile of adverse effects known as immune-related adverse events (irAES). These involve diverse systems, including the endocrine glands. The most frequent endocrine immune-related adverse events are thyroid and pituitary dysfunction, autoimmune diabetes mellitus and primary adrenal insufficiency. The increasing knowledge of these irAES has led to effective treatment strategies with the corresponding hormonal replacement. The objective of this review is to recognize the incidence of these new endocrinopathies, the physiopathology, their clinical evaluation, and therapeutic management. (AU)

Reversal of Olfactory Disturbance in Allergic Rhinitis Related to OMP Suppression by Intranasal Budesonide Treatment

PURPOSE: We evaluated the severity of olfactory disturbance (OD) in the murine model of allergic rhinitis (AR) and local allergic rhinitis (LAR) in mice. We also investigated the therapeutic effect of an intranasal steroid on OD. METHODS: Forty BALB/c mice were divided into 5 groups (n = 8 for each). The control group was sensitized intraperitoneally (i.p.) and challenged intranasally (i.n.) with saline. Mice in the AR group got i.p. and i.n. ovalbumin (OVA) administration for AR induction. The LAR group was challenged i.n. with 1% OVA for inducing local nasal allergic inflammation, without inducing the systemic allergy. The OD group got an i.p. methimazole administration (75 mg/kg) to induce total destruction of olfactory mucosa. Mice in the intranasal budesonide group received i.n. budesonide (12.8 μg per time, 30 minutes after the i.n. OVA challenge) while using OVA to cause systemic allergies. We conducted a buried-food pellet test to functionally assess the degree of OD in each group by measuring the time taken until finding hidden food. We evaluated the damage to olfactory epithelium using histopathologic evaluation and compared the degree of olfactory marker protein (OMP) expression in olfactory epithelium using immunofluorescent staining. RESULTS: Mice of the AR (81.3 ± 19.8 seconds) and LAR groups (66.2 ± 12.7 seconds) spent significantly more time to detect the pellets than the control group (35.6 ± 12.2 seconds, P < 0.01). After treatment, the intranasal budesonide group exhibited significantly better results (35.8 ± 11.9 seconds) compared with the AR and LAR groups (P < 0.01). The AR and LAR groups showed considerable olfactory epithelial damage and suppression of OMP expression compared with the control group. In the intranasal budesonide group, the olfactory lesions and OMP expression had improved substantially. CONCLUSIONS: OD may be caused by olfactory epithelial damage and suppression of OMP expression in nasal allergic inflammation and could be reversed using an intranasal steroid.

Embarazo y lesión hepática inducida por medicamentos. Reporte de un caso y revisión de la literatura / Pregnancy and drug-induced liver injury. Case report and literature review

La lesión hepática inducida por medicamentos o DILI (del inglés, Drug-Induced Liver Injury) es una condición relativamente rara, y más aún durante el embarazo. Usualmente es subdiagnosticada, y cuando se presenta en nuestro medio, pocas veces es notificada a los sistemas de registros nacionales, con un importante subregistro a nivel nacional y de Latinoamérica. Su forma de presentación clínica, tiempo de latencia, patrón de lesión hepática y reacciones idiosincráticas dificultan el diagnóstico oportuno, así como la ausencia tanto de pruebas diagnósticas objetivas, como de cambios histológicos patognomónicos que confirmen esta entidad. Se presenta el primer caso reportado en la literatura de una mujer en primer trimestre de gestación, quien cursó con DILI secundario al uso de tionamidas por sospecha clínica de hipertiroidismo.

Drug-induced liver injury (DILI) is a relative rare condition among general population and among pregnant women. It is usually underdiagnosed, and when identified, it is rarely notified to the national registry systems, especially locally, and in general in Latin America. Clinical presentation, time before symptom onset, patterns of liver injury and idiosyncratic reactions make an early diagnosis difficult, as well as the absence of diagnostic tests or histological changes that are unique to this pathology to confirm the diagnosis. We present the first case reported in the literature of a woman, who during the first trimester of pregnancy presented with DILI, secondary to the use of thionamides due to suspected hyperthyroidism.

Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study / Anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol: um estudo prospectivo brasileiro

Abstract Introduction: The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations. Objective: To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole. Methods: This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n = 36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n = 33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n = 13). Results: ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis. Conclusion: This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.

Resumo Introdução: Os efeitos adversos de drogas antitireoidianas são conhecidos. Vasculite associada a anticorpos anticitoplasma de neutrófilos é uma reação adversa grave. A maioria dos estudos que avaliam anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas envolveu pacientes tratados com propiltiouracil, entretanto menos informação se encontra disponível para o metimazol. Além disso, a maioria dos estudos que investigaram anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas foi conduzida em populações asiáticas. Objetivo: Avaliar a frequência de anticorpos anticitoplasma de neutrófilos e vasculite anticorpos anticitoplasma de neutrófilos-positivo em uma população adulta de pacientes brasileiros tratados com metimazol. Método: Este foi um estudo prospectivo. Avaliamos pacientes ≥ 18 anos com doença de Graves com o uso de metimazol há pelo menos seis meses (Grupo A, n = 36); com doença de Graves previamente tratados com metimazol, mas que não usaram esse medicamento por pelo menos seis meses (Grupo B, n = 33) e com doença nodular em uso de metimazol há pelo menos seis meses (Grupo C, n = 13). Resultado: Anticorpos anticitoplasma de neutrófilos foram detectados em 17 pacientes (20,7%). Quatro pacientes (4,9%) tinham anticorpos anticitoplasma de neutrófilos fortemente positivos. A frequência de anticorpos anticitoplasma de neutrófilos foi semelhante nos grupos. Quando os Grupos A e B foram somados e comparados ao Grupo C para avaliar a influência da doença de Graves, e quando os Grupos A e C foram somados e comparados ao Grupo B para avaliar a influência da interrupção do metimazol, não foi encontrada diferença na frequência de anticorpos anticitoplasma de neutrófilos. Não houve diferença em relação a sexo, idade, etiologia do hipertireoidismo, anticorpos antirreceptor de TSH, dose ou tempo de uso de metimazol entre pacientes com e sem anticorpos anticitoplasma de neutrófilos. Os títulos desses anticorpos não se correlacionaram com dose ou tempo de uso de metimazol. Nenhum paciente anticorpos anticitoplasma de neutrófilos-positivo apresentou evento clínico resultante de vasculite. Conclusão: Este estudo clínico de uma população brasileira apresenta frequência considerável de anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol, mas a repercussão clínica desse achado permanece indefinida.

Neutropenia febril asociada a la ingesta de metimazol: reporte de caso / Febrile neutropenia associated with methimazole ingestion: case report

La neutropenia se define como un recuento absoluto de neutrófilos menor a 1500 células /µL. Se debe a la disminución en la producción de granulocitos o al aumento en su destrucción, ya sea a nivel medular o periférico. Según la clasificación de la Organización Mundial de la Salud (OMS) los grados de neutropenia van de 0 a IV, de acuerdo a la magnitud de la disminución del recuento de neutrófilos. El grado IV es el de mayor riesgo y corresponde a recuentos por debajo de 500 células/µL. El impacto en la morbimortalidad asociada a la neutropenia no está vinculado con la disminución directa del recuento celular, sino con los procesos infecciosos asociados a los que son propensos los pacientes que la presentan. Existen diversas condiciones por las que se puede desarrollar neutropenia, entre las que se encuentran las infecciones, las malignidades y los fármacos. Estos últimos pueden generar eventos adversos por mecanismos dosis dependiente, como en el caso de la quimioterapia citotóxica o por una reacción idiosincrática. Se presenta el caso de una paciente femenina de 37 años de edad, con antecedentes de tirotoxicosis, tratada con propanolol y metimazol durante cuatro semanas, quien además de manifestaciones tóxicas, presentó neutropenia febril muy grave, que mejoró luego de suspensión del antitiroideo. Se pretende resaltar la asociación de neutropenia febril como complicación de uso de tionamidas y la importancia del seguimiento con exámenes de laboratorios para un diagnóstico oportuno(AU)

Neutropenia is defined as an absolute neutrophil count less than 1500 cells / μL. It is due to the decrease in the production of granulocytes or increase in their destruction, either at the medullary or peripheral level. According to the classification of the World Health Organization (WHO) the degrees of neutropenia range from 0 to IV, taking into account the magnitude of the decrease in the neutrophil count. Grade IV is the highest risk and corresponds to counts below 500 cells /μL. The impact on morbidity and mortality associated with neutropenia is not linked to the direct reduction of the cell count, but to the associated infectious processes to which patients who present it are prone. There are several conditions under which neutropenia can develop, including infections, malignancies and drugs. The latter can generate adverse effects by dose-dependent mechanisms, as in the case of cytotoxic chemotherapy or an idiosyncratic reaction. Next, the case of a female patient of thirty-seven years of age, with a history of thyrotoxicosis, treated with propanolol and methimazole for four weeks, who in addition to toxic manifestations, presents very severe febrile neutropenia that improves after suspension of the antithyroid. We aim to highlight the association of febrile neutropenia as a complication of thionamide use and the importance of follow-up with laboratory tests for an opportune diagnosis(AU)

Debilidad muscular con hipokalemia e hipertiroidismo en un adolescente con síndrome de Down / Muscle weakness with hypokalemia and hyperthyroidism in an adolescent with Down syndrome

La hipokalemia aguda es una causa poco frecuente de debilidad muscular. La parálisis periódica tirotóxica es una complicación infrecuente de la tirotoxicosis, en sus diferentes etiologías, en la cual se produce hipokalemia por un flujo masivo de potasio al compartimiento intracelular, que provoca parálisis muscular, que afecta, principalmente, la musculatura proximal de los miembros inferiores. Es importante reconocer esta entidad para instaurar un tratamiento adecuado que incluya el rápido suplemento de potasio y el uso de beta-bloqueantes no selectivos. El tratamiento del hipertiroidismo subyacente y el retorno al estado eutiroideo es imprescindible para la resolución de los episodios de parálisis periódica tirotóxica. Aquí se presenta a un paciente de 13 años de edad con síndrome de Down que consultó por debilidad muscular de los miembros inferiores y trastorno de la marcha, asociada a hipokalemia aguda, en el que se realizó el diagnóstico de hipertiroidismo por enfermedad de Graves.

Acute hypokalemic paralysis is a rare cause of acute weakness. Thyrotoxic periodic paralysis (TPP) is an unusual complication of hyperthyroidism. It is characterized by sudden onset of hypokalemia condition resulting from a shift of potassium into cells and paralysis that primarily affects the lower extremities. Failure to recognize TPP may lead to improper management. Treatment of TPP includes replacing potassium rapidly, using nonselective beta-blockers and correcting the underlying hyperthyroidism as soon as possible. TPP is curable once euthyroid state is achieved. We describe a 13-year-old male with Down syndrome who presented with acute onset of lower extremity weakness secondary to acute hypokalemia and was found to have new onset Graves' disease.

Methimazole-induced aplastic anemia with concomitant Hepatitis in a young Filipina with Graves' disease / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;">A 34-year-old Filipino with Graves' disease on methimazole came in due to fever, sore throat and jaundice. Patient was initially diagnosed with methimazole induced agranulocytosis and drug induced liver injury. She was treated with intravenous broad spectrum antibiotic and granulocyte colony stimulating factor. On day 4 of admission, patient had pancytopenia and was managed as methimazole induced aplastic anemia and was started on steroid therapy and 1 unit of packed red blood cell was transfused. The jaundice also increased hence she was given ursodeoxycholic acid. On day 9 of admission, with the consideration of "lineage steal phenomenon," biopsy was done and eltrompobag was started. Patient was discharged stable at 12th day of hospital admission. This case presents the 3 rarest, life threatening complication of methimazole: agranulocytosis, aplastic anemia and hepatitis. </p>

Encefalopatía asociada a enfermedad tiroídea, un diagnóstico a tener en mente / Encephalopathy associated with thyroid disease, a diagnosis to take into account

Mujer de 54 años con antecedentes de Hipertensión arterial e Hipotiroidismo. Historia de aproximadamente 3 meses de evolución caracterizado al inicio por ánimo bajo, cambios en el comportamiento con aparición progresiva de conductas extraña, ideas delirantes y alucinaciones visuales y auditivas, junto con disminución en requerimientos de hormonas tiroídeas hasta la suspensión. Consulta en varios centros donde se cataloga como Trastorno depresivo severo con síntomas psicóticos, Síndrome confusional, Síndrome Psicótico. En este contexto se pesquisa Hipertiroidismo con títulos elevados de Anticuerpos Antitiroídeos e inicia tratamiento con Metimazol y Betabloqueo. Tras extenso estudio que descartan causas infecciosas, neoplásicas y autoinmunes; se inicia tratamiento con pulsos de Metilprednisolona con excelente y rápida respuesta clínica, la cual mantiene durante el curso del seguimiento con dosis decrecientes de corticoides.

A 54-year-old woman with a history of arterial hypertension and hypothyroidism. History of approximately 3 months of evolution characterized at the beginning by low mood, changes in behavior with progressive appearance of bizarre behaviors, delusional ideas and visual and auditory hallucinations. Consultation in several centers where it is classified as severe Depressive disorder with psychotic symptoms, Confusional syndrome, Psychotic syndrome. Hyperthyroidism is investigated with high titers of Antithyroid Antibodies and initiates treatment with Methimazole and Betablock. After extensive study that ruled out infectious, neoplastic and autoimmune causes; Treatment with Methylprednisolone pulses is initiated with excellent and rapid clinical response, which is maintained during the course of follow-up with decreasing doses of corticosteroid.

Patrones de prescripción de medicamentos antitiroideos en una población de Colombia / Patterns of prescription of antithyroid drugs in a Colombian population

Resumen Introducción: en Colombia no se conoce la prevalência de los trastornos asociados a tirotoxicosis ni se dispone de estudios fármacoepidemiológicos acerca de la prescripción de los medicamentos antitiroideos. Objetivo: determinar los patrones de prescripción de los antitiroideos y variables asociadas a su uso en una población de pacientes en Colombia. Métodos: estudio de corte transversal, realizado entre enero 1 y marzo 30 de 2015 sobre los hábitos de prescripción de medicamentos antitiroideos en una población afiliada al sistema de salud colombiano. Se midieron variables sociodemográficas, farmacológicas y de comedicación. Se diseñó una base de datos sobre el consumo de medicamentos y se utilizaron pruebas t de student, X 2 y modelos de regresión logística. Resultados: un total de 327 pacientes en tratamiento con medicamentos antitiroideos fueron incluidos. La edad media fue de 53.7±18.1 años y 78.3% de pacientes correspondió a mujeres. El metimazol se prescribió en 95.4% de los pacientes, el propiltiouracilo en 4.6%. En 76.8% de pacientes se presentó comedicación; en particular con antihipertensivos (38.2%) y adicionalmente con propranolol (34.3%). Conclusiones: la tendencia de prescripción de medicamentos antitiroideos en Colombia es similar a lo reportado en diferentes estudios a nivel mundial. El principal medicamento antitiroideo es metimazol, con una tasa de uso mayor a la reportada en Norteamérica y en estudios europeos. Las dosis del metimazol y de propiltiouracilo reportadas en este estudio se ajustan a las recomendaciones de la Asociación Americana de Endocrinología Clínica.

Abstract Introduction: the prevalence of disorders associated with thyrotoxicosis is not known in Colombia, nor pharmacoepidemiological studies are available on the prescription of antithyroid drugs. Objective: to determine the prescription patterns of antithyroid drugs and variables associated with their use in a population of Colombian patients. Methods: cross-sectional study, conducted between January 1 and March 30, 2015 on the prescription habits of antithyroid drugs in a population affiliated with the Colombian Health System. Sociodemographic, pharmacological and comedication variables were measured. A database on drug consumption was designed and student t-tests, X 2 and logistic regression models were used. Results: a total of 327 patients in treatment with antithyroid drugs were included. The mean age was 53.7 ± 18.1 years and 78.3% of patients corresponded to women. Methimazole was prescribed in 95.4% of patients, propylthiouracil in 4.6%. In 76.8% of patients, comedication was present in particular with antihypertensive agents (38.2%) and additionally with propranolol (34.3%). Conclusions: the prescription tendency of antithyroid drugs in Colombia is similar to that reported in different studies worldwide. The main antithyroid drug is methimazole, with a rate of use higher than that reported in North America and in European studies. The doses of methimazole and propylthiouracil reported in this study are in accordance with the recommendations of the American Association of Clinical Endocrinology.

Síndrome poliglandular autoinmune tipo iii c: reporte de caso / Autoimmune polyglandular syndrome type iiic: case report

El síndrome poliglandular autoinmune comprende un grupo de enfermedades autoinmunes de las glándulas endócrinas, y que afecta órganos no endócrinos, puede ser de tipo I, II y III. Paciente masculino de 26 años presenta palpitaciones, debilidad, y disnea de esfuerzos de 2 meses de evolución. Al examen físico, índice de masa corporal 29,6 kg/m², obesidad central, con acromía en cara, axilas y cuello. Los estudios muestran TSH 0,01 uUl/ml,T4 libre 3,67 ng/dl, antitiroperoxidasa 505,70 Ul/ml, insulina en ayunas 32,77 U/l, y a las 2 horas 77 U/l, glicemia en ayunas 101 mg/dl, curva tolerancia oral a la glucosa a las 2 horas de 140 mg/dl. La ecografía tiroidea revela bocio multinodular. Diagnósticos: tiroiditis autoinmune, vitíligo, prediabetes, sobrepeso. Manejo con metimazol 5 mg c/12 h, y metformina 850 mg en la noche. El paciente baja de peso y la glicemia mejora. El diagnóstico definitivo fue Tiroiditis autoinmune y vitíligo compatible con síndrome poliglandular tipo IIIC.

Autoimmune Polyglandular Syndrome comprises a group of autoimmune diseases of the endocrine glands, and affecting non-endocrine organs, there are type I, II and III. Male patient, aged 26 years old has palpitations, weakness, and exertional dyspnea for 2 months. The physical examination found body mass index 29,6 kg/m², central obesity, with acromia on face, armpits and neck. Studies show TSH 0,01 uUl/ml, freeT4 3,67 ng/dl, antithyroperoxidase 505,70 U/ml, fasting insulin 32,77 U/l, after 2 hours 77 U/l, fasting glycemia 101 mg/dl, glucose tolerance at 2 hours 140 mg/dl. Thyroid ultrasound reveals multinodular goiter. Diagnoses: autoimmune thyroiditis, vitiligo, prediabetes, overweight. It prescribed metimazole 5 mg every 12 hours, and metformin 850 mg at night. Patient with weight reduction and glucose improvement. Definitive diagnoses patient with autoimmune thyroiditis and vitiligo, compatible with polyglandular syndrome type IIIC.

Thyroid dysfunction during pregnancy

Thyroid dysfunction during pregnancy can result in serious complications for both the mother and infant. However, these complications can be prevented by the optimal treatment of overt maternal thyroid dysfunction. The serum thyroid-stimulating hormone (TSH) concentration is the most reliable measure of thyroid function during pregnancy. Due to the physiologic changes in TSH levels during pregnancy, the correct interpretation of thyroid function requires knowledge of the gestational week and the appropriate population-based reference interval. In addition to a TSH test, the measurement of thyroid peroxidase antibody helps determine whether to treat subclinical hypothyroidism during pregnancy. Since the use of antithyroid drugs during pregnancy is associated with birth defects, it is recommended to discontinue the medication and to perform repeated thyroid function testing during the first trimester. If therapy is needed during the first trimester, propylthiouracil is preferred over methimazole.

Case of Raynaud Syndrome after the Use of Methimazole

Raynaud syndrome is a medical condition that causes pain, numbness, and changes in skin color at the distal extremities. Raynaud syndrome can be subdivided into primary Raynaud's and secondary Raynaud's. The former is diagnosed when the cause is unknown and the latter is caused by an underlying condition, such as connective tissue diseases, injury, smoking, or certain medications. Both cancer chemotherapy and β-blockers are relatively common causes of Raynaud syndrome but there are no reports of its association with methimazole administration. The authors encountered a 43-year old woman with hyperthyroidism who developed digital ulcers associated with Raynaud syndrome after a methimazole treatment. Her digital ulcers and Raynaud syndrome were improved after methimazole was replaced with propylthiouracil and conventional therapy. This paper reports this case along with a review of the relevant literature.

Prevalence and Annual Incidence of Thyroid Disease in Korea from 2006 to 2015: A Nationwide Population-Based Cohort Study

BACKGROUND: The incidence of thyroid nodules has increased worldwide in recent years. Thyroid dysfunction is a potential risk factor for hypercholesterolemia, cardiovascular disease, osteoporosis, arrhythmia, and neuropsychiatric disease. This study investigated the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism in Koreans. METHODS: In this nationwide population-based cohort study, 51,834,660 subjects were included using the National Health Information database from 2006 to 2015, after the exclusion of subjects with thyroid cancer. RESULTS: The prevalence in Korea in 2015 of thyroid nodules, hypothyroidism in patients taking thyroid hormone, and hyperthyroidism in patients undergoing treatment was 15.82/1,000 population, 15.94/1,000 population, and 2.76/1,000 population, respectively. All these diseases were more prevalent among women than among men. The number of incident cases of these three thyroid diseases steadily increased from 2006 to 2012, and then decreased through 2015. The incidence of thyroid nodules, hypothyroidism treated with thyroid hormone, and treated hyperthyroidism was 6.79/1,000 population, 1.76/1,000 population, and 0.55/1,000 population, respectively, in Korea in 2015. The use of methimazole continuously increased, from 33% of total antithyroid drug prescriptions in 2006 to 74.4% in 2015, and it became the most frequently prescribed antithyroid drug in Korea. In contrast, the use of propylthiouracil continuously decreased. CONCLUSION: This was the first nationwide study of the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism to take into account recent changes and to include the current status of patients receiving treatment.

A Case of Graves' Disease Accompanied with Acute Hepatitis A Virus Infection / 대한소화기학회지

Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves' disease has not been reported in literature worldwide. Although there is no well-established mechanism that explains the induction of Graves' disease by HAV to date, our case suggests that HAV infection may be responsible for inducing Graves' disease. A healthy 27-year-old female presented fever, palpitation, and diarrhea, and she was subsequently diagnosed as acute HAV infection. Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves' disease. She had never had symptoms that suggested hyperthyroidism, and previous thyroid function test was normal. Acute HAV infection was recovered by conservative management, however, thyroid dysfunction was maintained even after normalization of liver enzymes. Methimazole was used to treat Graves' disease. We report a case of concurrent acute HAV infection and Graves' disease in a patient without preexisting thyroid disease. This suggests that HAV infection may be a trigger for an autoimmune thyroid disease in susceptible individuals.

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.

RE: Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease

No abstract available.

Efectos adversos severos del Metimazol. Comunicación de dos casos y revisión de la literatura / Severe adverse effects of Methimazole. Communication of two cases and review of the literature

Los fármacos antitiroideos constituyen uno de los pilares del tratamiento del hipertiroidismo. En nuestro país solo se encuentra disponible el metimazol. Estas drogas han sido asociadas a múltiples reacciones adversas, la mayoría leves. Efectos adversos infrecuentes pero potencialmente letales como la agranulocitosis, hepatitis y el síndrome de artritis por antitiroideos, obligan a suspender el tratamiento. Comunicamos dos casos de complicaciones infrecuentes del tratamiento con metimazol.

Antithyroid drugs are one of the cornerstones in the management of hyperthyroidism. In our country, only methimazole is available. These drugs have been related to a variety of adverse reactions, most of them minor. Infrequent but potentially lethal side effects such as agranulocytosis, hepatitis and the antithyroid arthritis syndrome, demand drug cessation. We report two cases of infrequent complications of methimazole.

Adenoma de tiroides de células bizarras, a propósito de un caso / Thyroid adenoma of bizarre cells: with regard to a case

Introducción: El adenoma folicular de núcleos bizarros es un tipo de adenoma folicular de tiroides, con apariencia histológicamente preocupante pero de curso clínico benigno. Caso: Presentamos una paciente con antecedentes de hipertiroidismo en tratamiento con tiamazol. Debido a la presencia de un nódulo tiroideo se le practicó punción con aguja fina de la glándula. El estudio histopatológico demostró la presencia de células de Hürthle e identificó células características de adenoma folicular de núcleos bizarros. En el Ecuador no se reportó ningún caso similar. Discusión: Las células que tienen mutaciones en el gen p53 podrían considerarse como un estadio temprano de carcinoma anaplásico.

Introduction: A follicular adenoma of the thyroid gland is a kind of adenoma having bizarre nuclei with a histological worrisome appearance, though with a benign clinical evolution. Case: We present the case of a female patient with a past history of hyperthyroidism treated with tiamazol. A fine needle aspiration of the thyroid gland was performed; the cytology showed Hürthle's cells atypia, although, the specimen displayed features of follicular adenoma with bizarre nuclei. Up to now, there have not been reports of this entity in Ecuador. Discusion: Cells showing p53 mutations should be considered an early stage of anaplastic thyroid carcinoma.