Efficacy of methimazole before the administration of radioactive iodine in the management of Graves' disease: a systematic review and meta-analysis

ABSTRACT BACKGROUND: The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial. OBJECTIVE: To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease. DESIGN AND SETTING: A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria. METHODS: A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021. RESULTS: Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58). CONCLUSIONS: The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease. PROSPERO REGISTRATION: CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.

Graves hyperthyroidism in pregnancy: a rare presentation

Hyperthyroidism in pregnancy is much less common occurring in 0.1-0.2% of women with Grave’s disease being the most common cause accounting for 90% of the cases. It is important to diagnose hyperthyroidism in pregnancy because fetal loss in untreated patients is high and may even be life threatening for the mother. We are presenting a case of 29 years old G3P2L1 who presented to our emergency with amenorrhea of 7 months and history of loose stools for the last 20 days. It was associated with generalized weakness. She also had history of palpitations, weight loss and sleep disturbances. She was a known case of hyperthyroidism for the past 1-2 years and was already taking anti-thyroid drugs. B/L exophthalmos was apparently present. Patient was severly anaemic with haemoglobin of 5.5gms/dl. Ultrasound showed fetal demise at 28weeks. Patient was given 3 units of blood transfusion and was induced with prostaglandins. She delivered a dead male baby weighing 1.2kgs. Her postpartum period was uneventful. Timely diagnosis of graves hyperthyroidism and its optimal treatment throughout pregnancy is vital in reducing maternal, fetal and neonatal complications.

Advances in research on anti-thyroid drugs for recurrence risk factors and predictive models of Graves' disease / 中华内分泌代谢杂志

Graves' disease, also known as diffuse toxic goiter, is an autoimmune disease with increased secretion of thyroid hormone. There are three effective treatments for Graves' disease, which including anti-thyroid drugs ( ATD) , radioactive iodine and thyroidectomy. In general, ATD is the first choice of Graves' disease treatment for domestic physicians, but the high recurrence rate has always been the deficiency of ATD treatment. Recurrence is mainly related to gender, age, smoking, course of disease, goiter and other factors. Among them, the reliability and applicability of single risk factor in evaluating the recurrence rate of Graves' disease after ATD treatment are poor. The prediction model of multi-factor comprehensive score is helpful for the naive patients to choose the best treatment plan, to achieve the goal of precise treatment and to improve the remission rate of Graves' disease drug treatment. In this paper, the reliability of risk factors for Graves' disease recurrence after ATD treatment is evaluated, and the development and application of prediction models such as Graves' recurrent events after therapy ( GREAT) score, GREAT+score, and clinical severity score ( CSS) are reviewed.[Summary] Graves' disease, also known as diffuse toxic goiter, is an autoimmune disease with increased secretion of thyroid hormone. There are three effective treatments for Graves' disease, which including anti-thyroid drugs ( ATD) , radioactive iodine and thyroidectomy. In general, ATD is the first choice of Graves' disease treatment for domestic physicians, but the high recurrence rate has always been the deficiency of ATD treatment. Recurrence is mainly related to gender, age, smoking, course of disease, goiter and other factors. Among them, the reliability and applicability of single risk factor in evaluating the recurrence rate of Graves' disease after ATD treatment are poor. The prediction model of multi-factor comprehensive score is helpful for the naive patients to choose the best treatment plan, to achieve the goal of precise treatment and to improve the remission rate of Graves' disease drug treatment. In this paper, the reliability of risk factors for Graves' disease recurrence after ATD treatment is evaluated, and the development and application of prediction models such as Graves' recurrent events after therapy ( GREAT) score, GREAT+score, and clinical severity score ( CSS) are reviewed.

Advances in research on anti-thyroid drugs for recurrence risk factors and predictive models of Graves′ disease / 中华内分泌代谢杂志

Graves′ disease, also known as diffuse toxic goiter, is an autoimmune disease with increased secretion of thyroid hormone. There are three effective treatments for Graves′ disease, which including anti-thyroid drugs (ATD), radioactive iodine and thyroidectomy. In general, ATD is the first choice of Graves′ disease treatment for domestic physicians, but the high recurrence rate has always been the deficiency of ATD treatment. Recurrence is mainly related to gender, age, smoking, course of disease, goiter and other factors. Among them, the reliability and applicability of single risk factor in evaluating the recurrence rate of Graves′ disease after ATD treatment are poor. The prediction model of multi-factor comprehensive score is helpful for the naive patients to choose the best treatment plan, to achieve the goal of precise treatment and to improve the remission rate of Graves′ disease drug treatment. In this paper, the reliability of risk factors for Graves′ disease recurrence after ATD treatment is evaluated, and the development and application of prediction models such as Graves′ recurrent events after therapy (GREAT) score, GREAT + score, and clinical severity score (CSS) are reviewed.

Treatment options for patients with recurrent Graves hyperthyroidism after anti-thyroid drug treatment / 中华内分泌代谢杂志

Graves'disease (GD) is the most common cause of hyperthyroidism, and its treatment includes anti-thyroid drugs (ATD), radioactive iodine therapy (RAI), and surgical treatment. ATD is the first choice for GD treatment in China, but the high recurrence rate limits its widely clinical application. The therapeutic strategy for patients with recurrent hyperthyroidism after ATD treatment is still controversial.

Changes of thyroid stimulating antibody and thyroid stimulating blocking antibody in treatment of anti-thyroid drugs and combining with levothyrocine to hyperthyroidism / 中华内分泌代谢杂志

Objective Changes of thyroid stimulating antibody(TSAb) and thyroid stimulating blocking antibody(TSBAb) in the treatment of anti-thyroid drugs(ATDs), and the effect of ATDs combining with levothyrocine(LT4) on TSAb and TSBAb were analyzed. Methods Using recombinant Trxfus. TSHRn protein and Trxfus. TSHRc protein as antigens, and TSH receptor antibody(TRAb)-N(TSAb binding hot spots), TRAb-C(TSBAb binding hot spots)in the serum of thyroid disease patients were measured with ELISA. The changes of TRAb-N, TRAb-C over 36 months in 117 TRAb-N positive Graves′ patients with hyperthyroidism were analyzed retrospectively. In the course of treatment, 41 cases as A group with ATDs and LT4 treatment, 76 cases as B group with only ATDs, The changes of TRAb-N and TRAb-C were observed in the two groups. Results (1)According to the change of TRAb-N, 117 TRAb-N positive Graves′ patients with hyperthyroidism were different. In group Ⅰ, 10 patients continued to have persistently positive TSAb and continued to have hyperthyroidism, remission rate 0%. In group Ⅱ, 17 patients showed complicated TRAb-N changes, 12 of 17 patients got relapse, 5 of 17 patients got remission, remission rate 29.4%. And in group Ⅲ, with TRAb-N dropping gradually, 15 of 89 patients got relapse, 74 of the 89 patients got remission, remission rate 83.1%. Three groups were significantly different with x2 test(P0.05). Conclusion TSAb and TSBAb can be used to document TRAb-function, which is significant for us to predict the changes of thyroid function. During ATDs treatment, the temporary early low-dose application of LT4 did not significantly affect TSAb and TSBAb.

Clinical efficacy and ultrasonographic evaluation of anti-thyroid drugs in the treatment of primary hyperthyroidism / 中国生化药物杂志

Objective To investigate the clinical efficacy and ultrasonographic changes treated with anti-thyroid drugs ( ATD ) in patients with primary hyperthyroidism(PHT).Methods 83 cases of PHT patients admitted to the department of ultrasound from February 2013 to August 2015 in Zhuji People's Hospital of Zhejiang Province were selected, the patients were divided into two groups according to the results of ultrasonography, echo nonuniform group 41 cases and echo uniform group 42 cases.ATD therapy was administered to the both groups (were treated with methimazole).The thyroid related indexes and hemodynamics of thyroid right superior diagnosed by color doppler ultrasound, and the curative efficacies of the two groups were analyzed.Results After treatment, the systemic vascular resistance index(RI) of echo uniform group was (0.62 ±0.17), and the echo nonuniform group was (0.65 ±0.18), there was no significant difference between the two groups.The echo uniform group of thyroid artery diameter on the right lobe(D), the peak systolic velocity(Vmax), minimum diastolic blood flow velocity(Vmin), thyroid volume(V) and blood flow volume(Q) were significantly lower than the echo nonuniform group, the difference was statistically significant (P <0.05).The total effective rate of the echo nonuniform group (48.78%) was significantly lower than that in the echo uniform group (85.71%), the difference was statistically significant(P <0.05).Conclusion ATD has a good effect in treating PHT, and can significantly improve the thyroid hemodynamics in patients, it has a positive effect on the regulation of thyroid-related parameters in patients, the clinical treatment is effective, and the effect is better especially in patients with uniform echo.

Sweet's Syndrome Associated with Graves' Disease

Sweet's syndrome, or acute febrile neutrophilic dermatosis, occurs in association with autoimmune diseases such as Hashimoto's thyroiditis but is rare in Graves' disease, in which all cases are induced by propylthiouracil (PTU). We report a case of Sweet's syndrome in a patient with Graves' disease treated with methimazole (MMI) during three weeks. A 34-year-old man presented with the acute onset of high fever, skin rashes on the whole body, arthralgia, and acroparesthesia. Laboratory results showed leukocytosis and elevated C-reactive protein. MMI first stopped and antibiotics and antihistamine therapy started, but his symptoms dramatically improved after oral prednisolone. Graves' disease has again been treated by MMI because of his aggravated ophthalmopathy. After one year of retreatment with MMI, there has been no recurrence of Sweet's syndrome, supporting that Sweet's syndrome in this case was not related to MMI exposure. To our knowledge, this is the first report of Sweet's syndrome associated with Graves' disease per se but not PTU or MMI use.

Managing paediatric Graves’ disease.

Graves’ disease is the most common cause of hyperthyroidism in children. Anti-thyroid drug treatment with carbimazole or its active metabolite methimazole is offered as first line initial treatment but it induces remission in only 30%of children. Propylthiouracil is not recommended in children because of its association with severe hepatic toxicity. For those who relapse after ATD, radioactive iodine can be offered as definitive therapy except in cases with severe Graves’ ophthalmopathy or patients with large goitre who are the candidates for surgery. Total (or near total) thyroidectomy is the surgical procedure of choice for treating paediatric patients with Graves’ disease as it reduces the risk of recurrent hyperthyroidism which was seen in patients undergoing subtotal or partial thyroidectomy.

131I therapy effect on medium and large goiter with goiter with hyperthyroidism / 中国综合临床

Objective To evaluate the effect of 131 iodine(131I) therapy in medium and large goiter with hyperthyroidism in order to investigate the influence of pretreatment with antithyroid drugs (ATD) methimazole(MMI) and propylthiouracide (PTU) on 131I therapy.Methods A total of 338 hyperthyroidism patients (136 cases for male,202 cases for female) with thyroid mass greater than 40 grams were treated with 131I in the People's Hospital of Sichuan Province.Thyroid function,thyroid 131I uptake ratio and thyroid imaging were measured before treatment were measured 1-3 months later after administration of 131I,and they were followed up for 6 months to 4 years.Results There were statistical difference between pretreatment and 3 months later of 131I therapy in terms of free triiodothyronine (FT3),(Free thyroxine) FT4.The level of FT3 decreased from (31.9 ± 16.2) pmol/L to (7.8 ±8.5) pmol/L(t =23.9,P =0.000) and level of FT4 decreased from (58.8 ± 22.2) pmol/L to (19.4 ± 16.9) pmol/L(t =25.4,P =0.000).Among 338 patients,109 patients (32.2％) were developed hypothyroidism,and 91 patients (26.9％) were cured,91patients (26.9％) with improved state,20 patients(5.9％) with ineffective and 27 patients(8.0％) with relapse after administration of 131I.The total effective rate was 94.1％ (318/338).Thyroid weight,levels of FT3,FT4,thyroglobulin antibody(TGA),thyroid microsomal antibody(MCA) in effective group were (49.8 ± 9.97) g,(32.5 ± 16.3) pmol/L,(59.5 ± 22.2) pmol/L,(43.6 ± 35.3) ％,(30.1 ± 22.6) ％ respectively,and were (56.9±15.7) g,(22.8 ± 12.8) pmol/L,(47.9 ±20.3) pmol/L,(22.8±30.0)％,(15.3 ±20.5)％ respectively in ineffective group.There were statistically significant differences between the ineffective group and effective group (t =2.932,2.602,2.287,2.501,2.766 ; P =0.000,0.010,0.023,0.013,0.006).Logistic regression analysis was showed that weight of thyroid and serum FT3 were the most important factors in affecting 1131 therapy.Conclusion 131 I therapy for medium and large-sized goiter with hyperthyroidism is safe and effective.ATD may not reduce the effectiveness of subsequent 131I of hyperthyroidism.Thyroid weight and FT3 are the key influential factors in affecting 131I.

Tratamento clínico com drogas antitireoidianas ou dose terapêutica de iodo-131 no controle do hipertireoidismo na doença de graves: avaliação dos custos e benefícios / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis

Com o objetivo de avaliar os custos e a efetividade das 2 formas de tratamento mais utilizadas em nosso meio para a Doença de Graves, iodo radioativo e tratamento clínico prolongado, analisamos pacientes submetidos a essas terapias na região de Maringá, PR. Foram estudados 23 pacientes, 7 homens e 16 mulheres, com idade média de 35,4 anos, submetidos ao tratamento clínico, e 34 pacientes, 5 homens e 29 mulheres, com idade média de 39,4 anos, submetidos à dose terapêutica com iodeto de sódio (iodo-131). Após 2 anos de tratamento clínico com tiamazol (Tapazol®), 21 pacientes atingiram o eutireoidismo e dois permaneceram hipertireóideos. No grupo da dose terapêutica com iodeto de sódio (iodo-131), 21 pacientes evoluíram para o hipotireoidismo, enquanto que 13 atingiram o eutireoidismo. Para o cálculo do custo de cada modalidade de tratamento, analisamos o número de consultas necessárias durante o seguimento, exames complementares solicitados e medicações utilizadas, como tiamazol e/ou tiroxina. O grupo submetido ao tratamento clínico necessitou de maior número de consultas e exames, sendo que o custo médio foi de R$ 1.345,81 neste período de dois anos, enquanto que no grupo com iodeto de sódio (iodo-131) o valor médio foi de R$ 622,94. Assim, os custos da dose terapêutica com iodeto de sódio (iodo-131) foram 53,7 por cento menores do que o tratamento clínico com drogas antitireoidianas. Este trabalho demonstra que o tratamento com dose terapêutica com iodeto de sódio (iodo-131) apresenta um menor custo, sendo bastante efetivo no controle do hipertireoidismo na doença de Graves.

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R$ 1,345.81, while the RAI group spent a mean amount of R$ 622.94. Therefore, the costs of the RAI treatment were 53.5 percent lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

Anti-thyroid drugs—first choice for Graves' disease / 中国实用内科杂志

Graves' disease,the most common disorder of hyperthyroidism,is an autoimmune disease related with autoantibody (TRAb),with the specific mechanism remaining incompletely understood.The therapies for Graves disease include three conventional methods:anti-thyroid drugs,radioiodine and surgery.Only treatment with anti-thyroid drugs is aimed at the immune factor;they can eliminate TRAb and lead to recovery ultimately.Literatures have drumed in that treatment with anti-thyroid drugs was a basic therapy for Graves' diseases,and they were the first choice to cure hyperthyroidism all over the world (except for the U.S.A).The drugs do not destroy the structure of thyroid follicle,and are safe and efficient;moreover,their effect is reversible and therefore do not cause permanent damage to the thyroid.Anti-thyroid drugs not only can be used alone,it also can be used before radioiodine or surgery.ATA chairman professor Cooper(NEJM,2005) propounded a therapy path for Graves' disease,which is helpful for clinical practice.