RESUMO
Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism. Isolated CD4+CD25+ T cells from spleen of the offspring gestated in Hpx that suffer EAE showed reduced capacity to suppress proliferation of effector T cells (TEff) after being stimulated with anti-CD3 and anti-CD28 antibodies. Moreover, adoptive transfer experiments of CD4+CD25+ T cells from the offspring gestated in Hpx suffering EAE to mice that were induced with EAE showed that the receptor mice suffer more intense EAE pathological score. Even though, no significant differences were detected in the frequency of Treg cells and IL-10 content in the blood, spleen, and brain between mice gestated in Hpx or euthyroidism, T cells CD4+CD25+ from spleen have reduced capacity to differentiate in vitro to Treg and to produce IL-10. Thus, our data support the notion that maternal Hpx can imprint the immune response of the offspring suffering EAE probably due to a reduced capacity to trigger suppression. Such "imprints" on the immune system could contribute to explaining as to why adult offspring gestated in Hpx suffer earlier and more intense EAE.
Assuntos
Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/metabolismo , Hipotireoidismo/complicações , Exposição Materna/efeitos adversos , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Transferência Adotiva , Animais , Biomarcadores , Diferenciação Celular , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/terapia , Feminino , Hipotireoidismo/sangue , Hipotireoidismo/etiologia , Imunofenotipagem , Ativação Linfocitária , Contagem de Linfócitos , Metimazol/administração & dosagem , Metimazol/efeitos adversos , Camundongos , Proteína Básica da Mielina/metabolismo , Fenótipo , Gravidez , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Tireotropina/sangue , Tiroxina/sangueRESUMO
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.
Assuntos
Humanos , Masculino , Adulto , Poliendocrinopatias Autoimunes/diagnóstico , Vitiligo , Tireoidite Autoimune , Metimazol/administração & dosagemRESUMO
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.
Assuntos
Humanos , Feminino , Adulto , Antitireóideos , Antitireóideos/administração & dosagem , Antitireóideos/efeitos adversos , Metimazol/administração & dosagem , Metimazol/efeitos adversos , Agranulocitose , Hipertireoidismo , Preparações FarmacêuticasRESUMO
BACKGROUND: Low doses of antithyroid drugs (ATD) for extended periods may be an alternative for Graves' disease (GD) patients who relapse after a course of ATD. METHODS: Patients with GD relapse (n = 238) after discontinuation of ATD therapy for 12-24 months were retrospectively analyzed in a nonrandomized study. Radioiodine (RAI) treatment and L-thyroxine replacement was used in 114 patients, and a low dose of methimazole (MMI; 2.5-7 mg/daily) was used in 124 patients. Thyroid dysfunction, Graves' ophthalmopathy (GO) evolution, quality of life (QoL), and body weight were evaluated during the follow-up. RESULTS: The mean follow-up was 80.8 ± 35.3 months for the RAI group, and 71.3 ± 40.3 months for the low-dose MMI group. No notable side effects were observed in either group. Thyroid dysfunction was predominant in the RAI group (p < 0.001), and euthyroidism was more common in the MMI group (p < 0.001). GO deterioration was mainly evaluated by clinical activity score (CAS)--it was higher in the RAI group (p < 0.0005) over all periods of follow-up. Multivariate logistic analysis showed that RAI treatment was associated with no improvement in CAS during follow-up (24 months: OR = 3.51 [CI 1.02-12.03], p < 0.05; 36 months: OR = 8.46 [CI 1.47-48.58], p < 0.05; 48 months: OR = 19.52 [CI 1.70-223.10], p < 0.05; 60 months: OR = 21.1 [CI 1.5-298], p < 0.05). Kaplan-Meier survival analysis confirmed this finding (p < 0.0003). Assessment of QoL using the Short Form Health Survey's 36 parameters in stable euthyroid patients (at least six months) was similar in both groups. The RAI group patients gained more weight (p < 0.005), particularly after 24 months of follow-up. CONCLUSIONS: The use of low doses of MMI is efficient and safe, and offers better outcomes for GO than RAI treatment. Prolonged low doses of MMI may be an alternative choice for relapsed GD patients, particularly for GO patients or for patients who refuse a definitive treatment.
Assuntos
Antitireóideos/administração & dosagem , Doença de Graves/terapia , Oftalmopatia de Graves/terapia , Metimazol/administração & dosagem , Adulto , Feminino , Terapia de Reposição Hormonal , Humanos , Radioisótopos do Iodo/uso terapêutico , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Tiroxina/uso terapêutico , Resultado do TratamentoRESUMO
To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects.
Assuntos
Anormalidades Induzidas por Medicamentos , Antitireóideos/efeitos adversos , Hipertireoidismo/tratamento farmacológico , Metimazol/efeitos adversos , Complicações na Gravidez/tratamento farmacológico , Propiltiouracila/efeitos adversos , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Recém-Nascido , Masculino , Metimazol/administração & dosagem , Razão de Chances , Gravidez , Propiltiouracila/administração & dosagem , RiscoRESUMO
To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects. .
Assuntos
Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Anormalidades Induzidas por Medicamentos , Antitireóideos/efeitos adversos , Hipertireoidismo/tratamento farmacológico , Metimazol/efeitos adversos , Complicações na Gravidez/tratamento farmacológico , Propiltiouracila/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Intervalos de Confiança , Metimazol/administração & dosagem , Razão de Chances , Propiltiouracila/administração & dosagem , RiscoRESUMO
The aim of the present study was to evaluate a new proposal for increasing compliance to the clinical management of patients with Graves' disease (GD) in a large and public University Hospital. The patients were carefully selected (no previous GD treatment, goiter volume less than 6 mL must be living in the metro area of São Paulo), received medication at no cost, were contacted frequently by the social worker and alerted for the date of consultation and only referred to a single endocrinologist during all phases of treatment. We recruited 229 patients with GD that were initially treated with methimazole (MMI--60 mg q.d) in a single daily dose followed by a combination of MMI (20 mg) plus L-T4 (100 microg) daily for 24 months. Only 83 patients (36.2%) completed the protocol and were subdivided in: Group 1 (n= 34) that were in remission for 3 years after discontinuation of the MMI and Group 2 (n= 49) that presented recurrence of GD between 2 and 36 months without MMI. Predictive factors associated with remission were: decrease of the glandular volume, serum TG< 40 ng/mL and normal TRAb values. We concluded that in spite of a careful protocol planned to increase compliance, more than 60% of patients with GD did not complete the therapeutic trial and were referred for radioiodine treatment. The solution for this low therapeutic success for GD should be the possible identification of factors that would indicate patients that are not inclined to follow a long period of clinical therapy.
Assuntos
Antitireóideos/administração & dosagem , Doença de Graves/tratamento farmacológico , Custos de Cuidados de Saúde , Metimazol/administração & dosagem , Adolescente , Adulto , Idoso , Antitireóideos/economia , Protocolos Clínicos , Análise Custo-Benefício , Feminino , Seguimentos , Doença de Graves/sangue , Doença de Graves/economia , Hospitais Públicos , Hospitais Universitários , Humanos , Masculino , Metimazol/economia , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Recidiva , Estudos Retrospectivos , População UrbanaRESUMO
O objetivo do presente estudo foi avaliar esquema terapêutico medicamentoso para aumentar a aderência ao tratamento da moléstia de Graves-Basedow (MGB) em Hospital Público Universitário. Os pacientes foram selecionados segundo critérios rigorosos, que incluíam volume glandular inferior a 60cm³, origem da área urbana de São Paulo e não submetidos a terapia prévia da MGB. Receberam gratuitamente a medicação, eram avisados antecipadamente da data da consulta e acompanhados por um único médico durante todo o tratamento. Foram incluídos 229 pacientes, tratados inicialmente com metimazol (MMI - 60mg/dia) em dose única diária, seguindo-se com combinação de MMI (20mg) com LT4 (100æg) em dose única diária por 24 meses. Apenas 83 pacientes (36,2 por cento) completaram o protocolo quando foram subdivididos em 2 grupos, após a suspensão do MMI+LT4: Grupo 1 (n= 34), que permaneceram em remissão por 3 anos, e Grupo 2 (n= 49), que apresentaram recidiva da doença entre 2 e 36 meses. Os fatores preditivos associados à remissão foram: decréscimo do volume glandular, tireoglobulina sérica < 40ng/ml e valores séricos normais de anticorpos anti-receptor de TSH. Constatamos que apesar do planejamento cuidadoso, mais de 60 por cento dos portadores de MGB não completaram o protocolo e foram encaminhados a tratamento com radioiodo. Admitimos que esse baixo êxito terapêutico poderia ser melhorado mediante identificação dos fatores capazes de indicar quais pacientes estariam propensos a seguir um tratamento de longa duração.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antitireóideos/administração & dosagem , Doença de Graves/tratamento farmacológico , Custos de Cuidados de Saúde , Metimazol/administração & dosagem , Antitireóideos/economia , Protocolos Clínicos , Análise Custo-Benefício , Seguimentos , Doença de Graves/sangue , Doença de Graves/economia , Hospitais Públicos , Hospitais Universitários , Metimazol/economia , Cooperação do Paciente/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Recidiva , Estudos Retrospectivos , População UrbanaRESUMO
The effects of neonatal hypothyroidism on the number of Leydig cells were studied in neonatal Wistar rats. Moderate or severe hypothyroidism were induced during neonatal life by giving different amounts of methimazole (MMI; 0.05% or 0.1%) in the drinking water of pregnant and lactating dams. Rats were sacrificed on day 21 of postnatal life. Severely hypothyroid rats had approximately 45-fold higher serum thyrotropin (TSH) values and demonstrated approximately a 65% decrease in testes weight (p < 0.05) and the number of Leydig cells. However, in moderately hypothyroid rats, in which serum TSH was only approximately 16-fold higher, testicular weight was normal and the number of Leydig cells almost doubled (p < 0.01). There were no significant differences between the serum-free testosterone levels of the moderately and severely hypothyroid rats versus controls. Serum levels of 3alpha-androstanediol glucuronide, although decreased to less than 10% in severely hypothyroid rats (p < 0.01), were not changed by mild hypothyroidism. The number of Sertoli cells was increased in moderately hypothyroid rats versus controls (p < 0.05) and even further increased in severely hypothyroid rats (p < 0.05). We conclude that (1) severe neonatal hypothyroidism impairs the development and function of the testes and (2) moderate neonatal hypothyroidism stimulates the proliferation of Leydig cells.
Assuntos
Animais Recém-Nascidos , Hipotireoidismo/patologia , Células Intersticiais do Testículo/patologia , Androstano-3,17-diol/sangue , Animais , Contagem de Células , Hipotireoidismo/sangue , Hipotireoidismo/induzido quimicamente , Masculino , Metimazol/administração & dosagem , Ratos , Ratos Wistar , Células de Sertoli/patologia , Testículo/patologia , Tireotropina/sangue , Tiroxina/sangueRESUMO
Pancytopenia is a rare complication of the thionamide therapy reported secondary to aplastic anemia, the bone marrow being invariably hypocellular. We present a case of a 16-year-old female with Graves' disease who presented with massive bone marrow plasmocytosis mimicking multiple myeloma. The patient had already been on methimazole for a month when she was admitted to the Pediatric Unit with the diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI was discontinued and the patient was started on broad-spectrum antibiotics, dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo-normocellular marrow, with remaining 6% plasma cells. Myeloma screen was negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months after patient's discharge, her clinical condition, CBC, and bone marrow remained normal. To our knowledge this is the first report of pancytopenia due to MMI, where the usual hypoplasia found is replaced by massive plasmocytosis.
Assuntos
Medula Óssea/patologia , Leucocitose/induzido quimicamente , Metimazol/toxicidade , Plasmócitos/patologia , Adolescente , Antitireóideos/administração & dosagem , Antitireóideos/efeitos adversos , Medula Óssea/efeitos dos fármacos , Doenças da Medula Óssea/induzido quimicamente , Diagnóstico Diferencial , Feminino , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Humanos , Leucocitose/diagnóstico , Metimazol/administração & dosagem , Mieloma Múltiplo , Pancitopenia/etiologia , Plasmócitos/efeitos dos fármacosRESUMO
Radioiodine (131I) is the preferred definitive treatment for Graves' hyperthyroidism. Pretreatment with antithyroid drugs is often used to avoid thyroid hormone discharge after 131I ablation. However, this may represent an unnecessary increase in risk and costs. Fifty-one patients with Graves' disease were randomly assigned to receive 131I alone (28 patients) or 131I plus pretreatment with methimazole (30 mg/day; 23 patients). Methimazole was interrupted 4 days before 131I therapy. Serum T4, free T4 (FT4), and T3 were measured on days -4 and -1, on the day of treatment, and on days 2, 5, 7, 14, 20, and 30. In patients receiving 131I alone, mean serum T4 levels did not change after therapy. Mean serum FT4 and T3 levels decreased significantly 5 days after 131I administration (15% and 18%, respectively). Serum T3 reached its lowest level on day 30 (38%). With pretreatment, mean serum T4, FT4, and T3 levels increased (38%, 39%, and 70%, respectively) after methimazole discontinuation and before 131I administration. After 131I, serum T4 levels peaked on day 7 (23% vs. treatment day; 70% vs. baseline); FT4 levels peaked on day 14 (53% vs. treatment day; 107% vs. baseline). The serum T3 concentration increased 9% on day 2 (85% vs. baseline) and decreased from day 14 (15%) to day 30 (21%). We conclude that interruption of antithyroid drugs causes a short term increase in serum thyroid hormone levels in patients with Graves' hyperthyroidism receiving 131I. Thyroid hormone levels stabilize or decrease during the first 30 days after 131I therapy.
Assuntos
Antitireóideos/uso terapêutico , Doença de Graves/radioterapia , Metimazol/uso terapêutico , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto , Antitireóideos/administração & dosagem , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Metimazol/administração & dosagemRESUMO
En este trabajo se realiza una revisión sistemática de la tirotoxicosis y su relación con trastornos afectivos, especialmente la manía. Se describen las características del cuadro clínico y se alude a las principales hipótesis neurobioquímicas que explican dicha correlación, y se reportan dos casos clínicos. Finalmente se hacen comentarios alusivos, señalando algunas líneas de investigación vinculadas con esta importante condición clínica
Assuntos
Humanos , Feminino , Adulto , Tireotoxicose/diagnóstico , Tireotoxicose/fisiopatologia , Tireotoxicose/psicologia , Transtornos do Humor/psicologia , Metimazol/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Glândula Tireoide/anormalidades , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/etiologia , Transtorno Bipolar/psicologiaRESUMO
In 35 infants of lactating mothers with thyrotoxicosis who were receiving 5 to 20 mg methimazole daily, serum levels of thyroxine, triiodothyronine, thyrotropin were within normal ranges 1 month after the start of breast-feeding. Thyroid function in breast-feeding infants of six lactating mothers receiving methimazole, 20 mg for the first, 10 mg for the second, and 5 mg for an additional 4 months, remained normal. These results suggest the safety of methimazole therapy in lactating mothers.
Assuntos
Antitireóideos/administração & dosagem , Aleitamento Materno , Metimazol/administração & dosagem , Complicações na Gravidez/tratamento farmacológico , Transtornos Puerperais/tratamento farmacológico , Testes de Função Tireóidea , Tireotoxicose/tratamento farmacológico , Adulto , Antitireóideos/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Metimazol/efeitos adversos , Gravidez , Complicações na Gravidez/sangue , Transtornos Puerperais/sangue , Tireotoxicose/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Introducción. La enfermedad de Graves-Basedow es una enfermedad autoinmune con producción de anticuerpos antitiroideos que son inmunoglobulinas del tipo IgG; éstas, durante la gestación pueden atravesar la placenta y producir estimulación anormal de la tiroides fetal ocasionando hipertiroidismo. Presentación del caso clínico. Se presenta el caso de un recién nacido femenino, producto de madre con enfermedad de Graves-Basedow que presentó datos clínicos (peso bajo para la edad gestacional, exoftalmos, taquicardia) y de laboratorio de hipertiroidismo en el periodo neonatal, ameritando tratamiento con metamizol, propanolol y prednisona. Conclusiones. Se analizan las características clínicas del hipertiroidismo transitorio neonatal secundario a paso de anticuerpos antitiroideos durante la gestación
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Hipertireoidismo/congênito , Hipertireoidismo/fisiopatologia , Imunoglobulina G/efeitos adversos , Metimazol/administração & dosagem , Metimazol/uso terapêutico , Propranolol/administração & dosagem , Propranolol/uso terapêutico , Complicações na Gravidez/imunologia , Complicações na Gravidez/terapiaRESUMO
OBJECTIVES: To reduce the number of tablets to be administered daily during antithyroid drug (ATD) treatment of Graves' disease (GD) and to evaluate the effectiveness of adding thyroxine after the patients had become euthyroid during methimazole therapy. PATIENTS AND METHODS: All patients were given gelatin capsules with 30 mg of methimazole 2 times per day for 4-6 weeks, followed by two capsules with 20 mg of methimazole and 75 micrograms of thyroxine to be taken once a day for 18-24 months. Thirty patients with Graves' disease without previous treatment for hyperthyroidism were included. Two were lost to follow-up and 28 (24 women and 4 men; age range 14-53 years; mean 34.2 years) were followed for 18 to 24 months with methimazole and thyroxine medication plus an additional 2 years after the treatment was suspended. After completion of the study the patients were, retrospectively, divided in two groups: group 1 (G1, n = 20) patients considered to be in remission, and group 2 (G2, n = 8) with persistent active Graves' disease. RESULTS: All patients in group 1 had a significant reduction in the glandular mass, as estimated by ultrasonographic studies (mean +/- SD 67 +/- 13 g to 18 +/- 3 g, p < 0.01) whereas subjects in group 2 had no significant reduction in glandular mass (67 +/- 14 g to 53 +/- 16 g). Thyroglobulin levels (mean +/- SD) in G1 were 54 +/- 55 micrograms/L at baseline and decreased to 15 +/- 9 micrograms/L (p < 0.001), and in G2 thyroglobulin concentrations did not decrease significantly after therapy (58 +/- 20 micrograms/L vs 44 +/- 22 micrograms/L). Also, levels of thyroid-stimulating hormone receptor inhibiting antibody (TRAb) only decreased in G1 (49-21% to 8 +/- 5%; p < 0.001). Nineteen patients (all from G1), were euthyroid 2 years after treatment withdrawal, indicating a remission rate of 67.8%. CONCLUSION: The administration of L-thyroxine during anti-thyroid drug treatment, with subsequent inhibition of thyroid-stimulating hormone secretion, may be an important factor in glandular mass reduction, decreasing both the production of antibodies to thyroid-stimulating hormone receptors and the frequency of recurrence of hyperthyroidism.
Assuntos
Doença de Graves/tratamento farmacológico , Metimazol/administração & dosagem , Tiroxina/administração & dosagem , Adolescente , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Doença de Graves/sangue , Doença de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Tireoglobulina/sangue , Glândula Tireoide/patologia , Hormônios Tireóideos/sangue , Tireotropina/sangueRESUMO
We analyzed the evolution of the ophthalmopathy associated with Graves' hyperthyroidism in 45 patients treated with two different antithyroid drug regimens. Group A patients (n = 31) received either methimazole (40-100 mg daily) or propylthiouracil (400-900 mg daily) combined with T3 daily throughout treatment. Group B patients (n = 14) were treated with conventional regimen with lower doses of either methimazole (5-25 mg daily) or propylthiouracil (50-300 mg daily) and no T3 addition. Eye signs and proptosis measurement were evaluated just before the beginning of the treatment and compared with the results after antithyroid drug withdrawal. Improvement of the eye signs considered on grounds of the NOSPECS classification was greater in group A than group B (p less than 0.01). Also, the decrease in proptosis measurement was greater (p less than 0.01) in patients treated with combined regimen (21.5 +/- 2.4 mm to 20.4 +/- 2.3 mm) than in patients receiving conventional therapy (20.4 +/- 1.6 mm to 20.0 +/- 1.7 mm). Serum thyroglobulin concentrations did not correlate with either the severity or the evolution of the ophthalmopathy. Negative serum antithyroglobulin antibody (TgAb) was associated with the improvement of the ophthalmopathy that was noted in 24 out of 27 patients (Chi-Square = 5.84; p less than 0.001). Thus, serum TgAb levels might have some connection with progression of eye signs but serum Tg concentration does not. Our study suggests that in most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves' ophthalmopathy. However, no marked difference can be drawn between the two treatment regimens.
Assuntos
Oftalmopatias/tratamento farmacológico , Doença de Graves/tratamento farmacológico , Metimazol/administração & dosagem , Propiltiouracila/administração & dosagem , Tri-Iodotironina/administração & dosagem , Adolescente , Adulto , Autoanticorpos/sangue , Quimioterapia Combinada , Oftalmopatias/sangue , Oftalmopatias/etiologia , Feminino , Doença de Graves/sangue , Doença de Graves/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tireoglobulina/sangue , Tireoglobulina/imunologiaAssuntos
Metimazol/efeitos adversos , Propiltiouracila/efeitos adversos , Adulto , Agranulocitose/induzido quimicamente , Doença de Graves/tratamento farmacológico , Humanos , Fígado/efeitos dos fármacos , Metimazol/administração & dosagem , Metimazol/uso terapêutico , Propiltiouracila/administração & dosagem , Propiltiouracila/uso terapêuticoRESUMO
The authors studied 389 Graves' hyperthyroid patients receiving either high propylthiouracil (PTU) or methimazole (MMI) daily doses or low doses to evaluate whether adverse effects were related to the thionamide drugs or its daily dose regimen. Group 1 patients (n = 286) received high PTU (728 +/- 216 mg/day, n = 92) or MMI (60 +/- 19 mg/day, n = 94) doses, and group 2 patients (n = 103) were treated with low PTU (255 +/- 85 mg/day, n = 39) or MMI (23 +/- 10 mg/day, n = 64) doses. Major adverse effects were observed in 11 (2.8%) patients. Of these, four (1.0%) had agranulocytosis, two (0.5%) were granulocytopenic and five (1.3%) had hepatotoxicity. Agranulocytosis occurred in two patients from each group, 0.7% and 1.9%, respectively from group 1 and group 2. There was no significant difference between the groups or the types of thionamide. There also was no correlation with the patients' age. All of the patients were hyperthyroid, and its onset occurred in the first to third month of treatment. Full recovery was achieved in all cases after drug withdrawal. Four of 5 patients with hepatotoxicity were treated with high PTU doses, and one patient received low MMI doses (p less than .05). All patients were euthyroid. Arthralgias, skin rash and gastric intolerance, the minor adverse effects of thionamides studied, were observed in 52 (13.4%) of the patients. Although no significant differences were found, most of the patients experiencing side effects were from group 1 an received MMI therapy. These adverse effects did not demand drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doença de Graves/tratamento farmacológico , Hipertireoidismo/tratamento farmacológico , Metimazol/efeitos adversos , Propiltiouracila/efeitos adversos , Adolescente , Adulto , Idoso , Agranulocitose/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas , Criança , Relação Dose-Resposta a Droga , Toxidermias , Humanos , Articulações/efeitos dos fármacos , Metimazol/administração & dosagem , Pessoa de Meia-Idade , Dor/induzido quimicamente , Propiltiouracila/administração & dosagem , Gastropatias/induzido quimicamenteRESUMO
Os autores sintetizam um pouco da história do emprego dos antitireoidianos na prática clínica, especificamente em relaçäo ao tratamento do hipertireoidismo da doença de Graves, apresentando razöes para seu uso. Na experiência do Instituto de Endocrinologia da Santa Casa do Rio de Janeiro, as taxas de remissäo do hipertireoidismo, 1 ano após a interrupçäo da medicaçäo foram melhores no grupo de doentes que fez uso da medicaçäo por período superior a 1 ano do que naquele de pacientes que receberam a medicaçäo por período inferior a 1 ano (taxas respectivamente de 44,28% e 12,96%). Os antitireoidianos devem continuar sendo empregados como primeira opçäo no tratamento do hipertireoidismo da doença de Graves. Em caso de impossibilidade de controle da doença, deve-se recorrer às formas ablativas de tratamento, uso do lado radioativo ou cirurgia