Construction and evaluation of recurrence risk model of Graves′ disease treated with antithyroid drugs / 中华内分泌代谢杂志

Objective:To establish and evaluate a predictive model for recurrence risk of Graves′ disease after antithyroid drugs(ATD) withdrawal.Methods:Among 308 patients with newly onset Graves′ disease taking ATD from 2012 to 2019, 170 patients who completed follow-up were enrolled and divided into relapse and remission groups according to whether hyperthyroidism reoccurred within 2 years after ATD withdrawal to establish the discovery cohort. An internal validation cohort was constructed by repeating the sampling with bootstrap. Cox regression analysis was used to screen risk factors and establish a predictive model, named Graves′ Recurrence Evaluation System(GRES). The differentiation and accuracy of GRES model were evaluated and compared with the GREAT score.Results:Of 170 patients, 90 Graves′ disease cases relapsed within 2 years after ATD withdrawal. According to Cox regression analysis, family history of Graves′ disease, younger age(<30 years), grade Ⅱ-Ⅲ goiter, high level of TRAb(≥13 IU/L), large thyroid volume(≥26.4 cm 3) and low 25(OH) D(<14.7 ng/mL) were included in the predictive model: PI=0.672×family history+ 0.405×age+ 0.491×severity of goiter+ 0.808×TRAb+ 1.423×thyroid volume+ 0.579×25(OH) D. PI≥1.449 was associated with a higher risk of recurrence after drug withdrawal. The GRES model has good prediction in assessing Graves′ disease relapse within 2 years after ATD withdrawal and better than GREAT score. Conclusion:GRES model can be used to evaluate the recurrence risk within 2 years for patients with newly onset Graves′ disease after ATD withdrawal, and facilitate clinicians to reasonably select treatment modalities in order to improve the remission rate.

Advance in prognostic factors of Graves disease in children / 国际儿科学杂志

Graves disease(GD) is the most common cause of hyperthyroidism in children.GD is an autoimmune thyroid disease which is based on genetic susceptibility and exacerbated by environmental factors including infection, toxin, drugs and stress.Antithyroid drugs(ATD) are the first-line treatment for GD in children.However, many children relapsed after discontinuing ATD, and the relapse rate between different children varied.Till now, exact cause has not been clarified.Previous studies prove that sex, age, micro-element, goiter size, thyroid hormone level, TRAb level, duration of ATD treatment and genetics may affect prognosis of pediatric GD.Yet predictors precious studies identified were variable.

Study on the prognostic factors of Graves′ disease treated with antithyroid drugs / 中华内分泌代谢杂志

Objective:To investigate the risk factors for recurrence of Graves′ disease after withdrawal of antithyroid drugs (ATD).Methods:This prospective study recruited 285 patients with newly onset Graves′ disease taking ATD from 2012 to 2018 at Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine. A total of 121 patients who completed follow-up were enrolled and were divided into relapse and remission group according to whether hyperthyroidism reoccurred within 2 years after ATD with drawal. Demographics, clinical manifestations, thyroid serological characteristics, and thyroid color doppler ultrasound at baseline and withdrawal were compared between the two groups. Cox regression analysis was used to analyze the correlation between above factors and recurrence of Graves′ disease.Results:Sixty-five patients relapsed within 2 years after drug withdrawal. Patients with early recurrence were characterized by Graves′ disease genetic history and high baseline thyrotrophin receptor antibody (TRAb) levels. Family history, higher serum FT 3(≥18.1 pmol/L), FT 4(≥49.8 pmol/L), and TRAb(≥16.1 mIU/mL) levels, larger goiter(Ⅱ-Ⅲ) and thyroid volume(≥28.6 cm 3), higher peak velocity of superior thyroid artery (STA-PV; ≥0.6 m/s) before treatment, and higher TRAb(≥0.8 mIU/mL) level after ATD withdraw were risk factors for Graves′ disease recurrence. Higher 25-hydroxy vitamin D(≥14.7 ng/mL) level at baseline, as well as high level of TSH(1.4 μIU/mL) at withdrawal may reduce the risk of relapse. Conclusions:Family history of Graves′ disease, clinical manifestations, thyroid serological indicators and imaging characteristics of severe Graves′ disease before treatment all increased the risk of Graves′ disease recurrence. Patients with aforementioned factors should be actively evaluated in order to choose treatment modalities reasonably. We recommended to maintain lower TRAb titer within normal reference range and TSH level between 1.4 μIU/mL and upper limits of normal reference range at ATD withdrawal to reduce the recurrence rate of Graves′ disease.

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.

Update on the safety of antithyroid drugs during pregnancy and lactation / 中华内分泌代谢杂志

Hyperthyroidism in pregnant and breastfeeding women should be adequately treated to prevent maternal and fetal complications. The choice of treatment during pregnancy and lactation is antithyroid drugs ( ATDs) . The risk of embryopathies in fetus and the effect on thyroid function of infants associated with the use of ATDs have been concerned for a long time. Large observational studies have quantified an increased risk of embryopathies associated with the use of methimazole ( MMI) and propylthiouracil ( PTU) during pregnancy, despite the effects of PTU appear less severe. Guidelines recommended PTU as the first-line choice for the first trimester during pregnant. And it is safe for ATDs use in lactating mothers. However, China Food and Drug Administration added the requirement of forbidden use of MMI during lactation this February. Accompanied by the updated guidelines for thyroid disease during pregnancy and the postpartum by American Thyroid Association, the issues of ATDs use during pregnancy as well as postpartum need to be further clarified.

Change of IL-23/IL-17 axis in peripheral blood of patients with Graves disease treated by I or antithyroid drugs therapy / 安徽医科大学学报

Objective To detect the expression level of interleukin-17 (IL-17)/interleukin-23 (IL-23) axis in peripheral blood of patients with Graves disease (GD) before and after 131I or antithyroid drugs (ATD) treatment.Methods The study groups included 40 patients with incipient GD(GD group),20 of whom were treated by 131 I,others were treated by ATD.Forty sex and age matched healthy subjects were recruited as control group.ELISA was uesed to detect interleukin-17 (IL-17),interleukin-23 (IL-23) level before and after the treatment of the GD group and control group.Results ① The expression of IL-23,IL-17 in GD group was significantly higher than the control group(P ＜0.05);②6 months after 131I treatment,the level of serum IL-23,IL-17 were significantly lower than before (P ＜ 0.05),but still higher than the control group (P ＜ 0.05),which was not found in ATD treatment group.Conclusion IL-23/IL-17 axis may play a role in GD which may also be relevant to 131I treatment.

Progress in the study of thyrotoxicosis in pregnancy / 中国综合临床

Thyrotoxicosis in pregnancy is a common endocrine disease,and the incidence is gradually increasing.And thyroid function changes during pregnancy which brings some difficulties to diagnose.It is necessary to further understand the corresponding changes of maternal thyroid hormone levels with the progress of pregnancy.Moreover,the thyroid function in pregnancy is directly related to the pregnancy outcome.If the disease is not well controlled,it will cause damage to both the mother and the fetus,all kinds of adverse pregnancy outcomes make it become the focus of clinical attention.Therefore,this article discusses the etiology of the thyrotoxicosis,thyroid function changes in the period of pregnancy as well as the impact on pregnancy outcomes,and also makes some suggestions of the diagnosis and the treatment of the disease.

Clinical Presentations of 36 Cases of Antithyroid Drug-induced Agranulocytosis / 医学研究杂志

Objective In this article,we report and discuss the clinical presentation of antithyroid drug(ATD)-induced agranulocytosis.Methods We retrospectively studied 36 cases of ATD-induced agranulocytosis over the past 14 years in PUMC hospital.Results ATD-induced agranulocytosis patient's age ranged of 16-62 years old.88.9％ of ATD-induced agranulocytosis occured with a large ATD treatment.91.7％ patients occured in the first three month of drug therapy.A case occured agranulocytosis when 8 months duration.94.4％ patients occurs secondary infections.Conclusion This study showed that ATD-induced agranulocytosis considered to be dose dependent,not irrelevant to sex,age and the drug.

Analysis of 60 Cases of ADR Caused by Methimazole and Propylthiouracil in Our Hospital / 中国药房

OBJECTIVE:To provide reference for rational use of antithyroid drugs (ATD) in the clinic. METHODS:Retro-spective analyzed 60 cases of adverse reaction caused by Methimazole and Propylthiouracil in terms of age,gender,incubation peri-od,organ or system involved and clinical manifestation,which were searched from 2004 May-2014 Dec. in First Affiliated Hospital of Soochow University. RESULTS:Among 60 ADR cases,male was more than female,and the ratio of male to female was 1∶2.75;average age was(39.7 ± 13.4)years old,and 83.3%ADR occurred between 20 and 59 years old;66.7%ADR occurred within 30 days. Most common clinical manifestations were drug-induced liver disease(66.7%,40/60)and neutropenia(25%,15/60). There was statistical significance in the proportion of drug-induced liver disease caused by methimazole and propylthiouracil in all ADR cases(P0.05). CON-CLUSIONS:Before and after the treatment of antithyroid drugs,it’s necessary to check hepatic function and the number of neutro-phile granulocyte,and we should monitor and follow up it to ensure the safe use of drugs.

Elevation of serum creatine kinase during methimazole treatment of Graves disease in a 13-year-old girl and a literature review of similar cases

We report a 13-year-old girl with Graves disease, who showed an increased level of serum creatine kinase (CK) accompanied by myalgia after methimazole (MMI) treatment. This patient developed muscular pain two weeks after MMI administration, along with increased CK levels. The level of thyroid hormone was within the normal range when she showed increased CK levels. After the MMI dose was decreased and levo-thyroxine was added, serum CK levels decreased to normal and the myalgia improved. The pathophysiologic mechanism of this effect has not yet been elucidated. An acute relatively hypothyroid state occurs secondary to antithyroid drug (ATD) administration in chronic hyperthyroidism, which may cause changes in the CK levels. In this report, we present a rare pediatric case, along with a literature review of similar cases. In the initial state of MMI treatment, myalgia should be detected and when it occurs, CK levels should be measured. The clinical strategy of monitoring CK levels with the aim of normalizing thyroid hormones is helpful in case of the development of adverse reactions, such as myalgia, during ATD treatment for Graves disease in children.

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.

Approach to the patient with pulmonary-renal syndrome caused by antithyroid drug-induced ANCA-associated vasculitis / 中华内分泌代谢杂志

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) refers to the groups of potentially life-threatening autoimmune disease.Antithyroid drug is one of the causes.Usually the involved organs are skin,kidney,and (or) lung.Early diagnosis and treatment of AAV is essential.Timely cessation of antithyroid drugs is the first step.If necessary,glucocorticoids and (or) immunosuppressive agents should be used to delay the progression of the disease.

Regulation of TSH Receptor Autoantibodies by a long Non-Coding RNA (Heg) and Cdk1- A Review.

Aims: A substantial part of the genome is transcribed in non-coding RNAs. We review our finding of a long non-coding RNA (designated Heg) in mononuclear cells (MNC) and regulation of TSH receptor autoantibodies (TRAb). Results: The Heg RNA transcript in MNC is negatively correlated with TRAb in patients with early and untreated Graves’ disease. In treated patients and in controls Heg correlated negatively with CD14 mRNA. Transfection studies with fragments of Heg added to MNC (exogenous Heg) decreased CD14 mRNA in MNC and increased gene expression of RIG-I, TLR7 and IFN-γ. Heg is likely to activate TLR7 receptors. CD14 is a co-receptor of TLR7. Decrease in gene expression of CD14 after Heg is a sign of differentiation of MNC to dendritic cells. This may reduce surface expression of CD14, cytokine responses and the responsiveness to TSH receptor antigens. Thus the relationship between TRAb and lnc Heg RNA is most likely explained by receptor crossinterference. Cdk1 mRNA (an index of cell cycle activity) is positively related with TRAb. Cdk1 mRNA and TRAb but not Heg decreased significantly during antithyroid treatment. Cdk1 decreased to values below normal. Conclusion: Thus both Heg RNA and Cdk1 may regulate the level of TRAb but by two different mechanisms.

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.

Association of HLA-DRB1 allele polymorphism and ANCA with the susceptibility to antithyroid drug-induced leucocytopenia in patients with Graves' disease / 中华内分泌代谢杂志

ObjectiveTo investigate the relationship of HLA-DRB1 allele polymorphism and antineutropil cytoplasmic antibody ( ANCA ) with the susceptibility to antithyroid drug ( ATD ) -induced leucocytopenia in the patients with Graves' disease (GD) in Anhui Han Chinese.MethodsThe HLA-DRB1 * 08032,DRB1 * 1501,and DRB1 * 0901 allele frequencies were determined by the polymerase chain reaction-based sequence-specific primer (PCR-SSP) method in 76 patients with Graves' disease who had ATD-induced leucocytopenia and 98 patients with Graves' disease treated with ATD,who were free from leucocytopenia.The other230 healthy subjects served as controls.Indirect immunofluorescence assay (IIF) was used to detect ANCA positive rate.Result( 1 ) Compared with the controls and the GD patients without leucocytopenia,the allele frequencies ofDRB1 * 08032 and DRB1 * 1501 in patients with ATD-induced leucocytopenia were significantly increased ( OR were 3.06,1.77,4.03,and 2.28,all P＜0.05),while that of HLA-DRB1 * 0901 was decreased ( OR were 0.33 and 0.43,both P＜0.05 ).(2)The ANCA frequencies were significantly increased in the GD patients with methimazole-induced leucocytopenia compared with those without leucocytopenia (x2 =4.878,P＜0.05 ).( 3 ) Compared with the GD patients not carrying DRB1 * 08032,DRB1 * 1501,and DRB1 * 0901 alleles,the ANCA positive rates were significantly increased in the GD patients carrying these alleles(x2 were 5.682,5.429,4.009,and 4.549,all P＜0.05).ConclusionsThe DRB1 * 08032 and HLA-DRB1 * 1501 alleles may be susceptible to ATD-induced leucocytopenia in Anhui Hans,while HLA-DRB1 * 0901 alleles may be protective or resistant gene.Immune response may be involved in the development of leucocytopenia.The occurrence of immune response is based on the genetic susceptibility.

Update on the side effects of antithyroid drugs / 中华内分泌代谢杂志

Antithyroid drugs(ATD)is the main treatment for hyperthyroidism and its adverse reactions have been much concerned by physicians. Methimazole(MMI)and propylthiouracil(PTU)are the two common antitithyroid drugs used currently. Generally, the ATD are safe and effective, though their clinical adverse reactions are also relatively common. The toxic effects include liver damage and leukocytopenia, antineutrophil cytoplasmic antibody-associated pulmonary small-vessel vasculitis, hypoglycemia, allergic reactions, muscle impairment,and so on. They are usually reversible and disappear spontaneously when the drug is discontinued. However,the serious rare side effects can also occur and there may have potentially deadly threatening effects which need to be cautious for the clinicians. MMI is usually preferred over PTU because it has significantly fewer side effects. And unlike the dose-dependent side effects of MMI, there has no significant correlation between adverse reaction and drug dosage in using PTU. Moreover, PTU has more severe hepatotoxity than MMI, even fatal liver impairment and liver failure. The risk of liver damage from PTU is an important concern, particularly in children. For this reason, MMI is the first choice for treating children with hyperthyroidism.

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.

Treatment of hyperthyroidism in pregnancy and lactation with antithyroid drugs / 医学研究生学报

Management of hyperthyroidism in pregnancy and lactation has been the topic for many years. This article has discussed the use of antithyroid drugs(ATDs) in pregnancy and lactation, including the choice, the safety, as well as the influences of ATDs to infants.

A Case of Transient Granulocytopenia during Treatment of a Patient with Graves' Disease and Type 1 Diabetes Mellitus - Differential Diagnosis from Agranulocytosis by a Single Injection of G-CSF / 대한내분비학회지

Granulocytopenia, which can be seen in patients with Graves' disease during treatment with antithyroid agents, could be a self resolving transient episode or can imply the beginning of life threatening agranulocytosis requiring a change in treatment modality. Transient granulocytopenia could be a manifestation of hyperthyroidism itself, or a mild side effect of antithyroid drugs. Aganulocytosis is a rare, but major complications of the termination drug, propylthiouracil (PTU), requiring prompt termination of the medication, and intensive care. Therefore, differentiation of agranulocytosis and transient granulocytopenia, is important, but is not practically easy. We introduce a case of transient granulocytopenia, which was detected in a patient with Graves'Disease, accompanied by underlying type 1 diabetes mellitus, during treatment with PTU. Diagnosis of transient granulocytopenia was made by a normal granulocyte count following a single injection of G-SCF, and the patient was treated with conservative therapy. This case confirms a diagnostic tool for differentiating transient granulocytopenia and PTU-induced agranulocytosis.

Hepatic Injury during Treatment with Antithyroid Drugs in Patients with Hyperthyroidism / 대한내분비학회지

BACKGROUND: Propylthiouracil (PIV) and methimazole (MMI) were widely used for the treatment of hyperthyroidism. Hepatic injury caused by these agents is a rare but serious complication. This study is to investigate the clinical features of hepatotoxicity from antithyroid drugs. METHODS: We reviewed 17 cases of hepatic injury during treatment with antithyroid drugs in patients with hyperthyroidism. Included were 6 cases we experienced and 11 cases reported in Korean literature from 1986 to 1999. We analyzed the clinical features of hepatic injury. RESULTS: Of 17 cases of hepatic injury, 12 were PTU cases and 5 MMI cases. The mean age of PTU cases was 40 years with 6/12 patients over 40 years old and 2/5 MMI cases were over 40 years old. The dose of PTU was 300 mg/d or more in 10/12 cases (83%) and the dose of MMI was 30 mg/d in 3/5 cases (60%). The hepatic injury occurred within 3 months in 8/12 PTU cases (67%) and within 2 months in 4/5 MMI cases (80%). The duration of hepatic injury tended to be longer in MMI cases than in PTV cases (median; 80 vs 41 days, p=0.102). In PTU cases, the duration of hepatic injury was correlated with the duration of drug use before hepatic injury (p<0.05). All of 8 biopsied cases who took PTU had predominantly hepatocellular necrosis. Two biopsied cases who took MMI had cholestatic jaundice and nonspecific abnormality, respectively. Biochemical findings of all MMI cases were compatible with cholestatic jaundice. As to the treatment of hyperthyroidism after hepatic injury, 4/12 PTU cases were treated with RAI therapy, 5 with MMI and one with surgery, and treatment was unknown in two. On the other hand 3/5 MMI cases interestingly entered into spontaneous remission after hepatic injury and 2/5 had RAI therapy. Hepatic dysfunction recurred in each one whom treatment by changing to MMI or PTU was tried on. CONCLUSION: Most of hepatic injury during treatment with antithyroid drugs developed within two to three months of drug use. The hepatic injury related to PTU was mainly cytotoxic whereas that related to MMI was cholestatic. Since there is a cross-reaction between PTU and MMI in hepatotoxicity, RAI therapy or operation shoud be considered as an alternative treatment of hyperthyroidism after hepatic injury.