scholarly journals Antithyroid Drug Therapy for Graves’ Disease and Implications for Recurrence

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jia Liu ◽  
Jing Fu ◽  
Yuan Xu ◽  
Guang Wang

Graves’ disease (GD) is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD), radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors. Of these influencing factors, some are modifiable but some are nonmodifiable. The recurrence risk can be reduced by adjusting the modifiable factors as much as possible. The titration regimen for 12–18 months is the optimal strategy of ATD. Levothyroxine administration after successful ATD treatment was not recommended. The addition of immunosuppressive drugs might be helpful to decrease the recurrence rate of GD patients after ATD withdrawal, whereas further studies are needed to address the safety and efficacy. This paper reviewed the current knowledge of ATD treatment and mainly focused on influencing factors for recurrence in GD patients with ATD treatment.

Author(s):  
Pei-Wen Wang

Context: Antithyroid drugs (ATD) are the first-line treatment for Graves’ disease (GD); however, relapse following treatment is approximately 30% - 40% in the first year, and 50% - 60% in the long term. Identification of risk factors that predict relapse, after discontinuing ATD, plays an important role in guiding therapeutic options. Evidence Acquisition: PubMed was used to search for studies published in English between 1995 and 2019. The following search terms were used: Graves’ disease, antithyroid drugs, relapse, recurrence, and outcome. The reference lists from review articles were also included in the search in order to find older journals. Results: Factors associated with a high recurrence rate, as reported in most studies, were divided into phenotype and genotype predictors. Phenotype factors included large goiter size, persistence of high TSH receptor antibody (TRAb), severe hyperthyroidism, smoking, younger age, male sex, and prior history of recurrence. Genotype factors included human leukocyte antigen (HLA), CD40, CTLA-4, PTPN22, Tg, and TSHR genes. In a subgroup analysis by age, genetic factors were better predictors in the younger group, while clinical signs were more useful in the older group. The reliability of using individual baseline risk factors to predict subsequent relapse is poor; however, predictive scores calculated by grouping single risk factors might help to predict future outcomes. Conclusions: Longer normalization time of TRAb, the persistence of a palpable goiter, and harboring genetic risk factors in younger patients are associated with high recurrence rate of GD. Multi-marker prediction models have been proposed and validated to improve the predictive value of relapse after ATD withdrawal.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245978
Author(s):  
Imam Subekti ◽  
Gracia Jovita Kartiko ◽  
Zahra Farhanni Suhardi ◽  
Muhadi ◽  
Wismandari Wisnu

Graves’ disease (GD) has a high recurrence rate despite various and adequate treatment. Numerous studies have been performed to identify the predictor of disease recurrence. This report aims to investigate the role of thyroid stimulating hormone (TSH) level as a thyrotropin in predicting the recurrence of Graves’ disease within 1 to 2 years following antithyroid drug (ATD) withdrawal. Literature searching was conducted on PubMed, Scopus, Cochrane, Proquest, EBSCO in August 2019 and Google Scholar in October 2020. The study criteria include the study that evaluates TSH level 4 weeks following ATD withdrawal, with subjects ≥18 years old who are retrospectively or prospectively followed up after 1 to 2 years following ATD withdrawal. Four eligible studies were selected based on inclusion/exclusion criteria, all of which measured TSH level at 4 weeks following ATD withdrawal. All studies had 1 to 2 years follow up. One study was an RCT, two studies were done in prospective cohort and another in retrospective cohort. All studies had comparable validity and applicability. Three out of four studies suggested that low TSH level measured 4 weeks following treatment withdrawal was associated with higher risk of disease recurrence. In conclusion, low TSH level obtained 4 weeks after ATD withdrawal was associated with higher rate of recurrence rate in GD.


1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S312-S317 ◽  
Author(s):  
G. Benker ◽  
D. Reinwein ◽  
H. Creutzig ◽  
H. Hirche ◽  
W. D. Alexander ◽  
...  

Abstract. In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.


Author(s):  
Danilo Villagelin ◽  
Roberto Bernardo Santos ◽  
João Hamilton Romaldini

Context: Graves’ disease is an autoimmune disease caused by thyrotropin receptor antibodies (TRAb). These antibodies can be measured and used for the diagnosis, prediction of remission, and risk of Graves’ orbitopathy development. There are three treatments for Graves’ disease that have remained unchanged for the last 75 years: Antithyroid drugs, radioiodine, and surgery. Antithyroid drugs are the first treatment option worldwide and are usually used for 12 - 18 months. Recent reports suggest the use of antithyroid drugs for more than 18 months with better outcomes. This review focuses on two aspects of treatment with antithyroid drugs: The impact of using antithyroid drugs for more than 12 - 18 months on remission rates and the trend of TRAb during prolonged antithyroid drug treatment. Evidence Acquisition: A review was performed in Medline on the published work regarding the duration of ATD treatment and remission of Graves' disease and also ATD treatment and TRAb status during the 1990 - 2019 period. Results: Remission rates are variable (30% - 80%), and many clinical and genetic factors serve as predictors. The long-term use of antithyroid drugs appears to increase remission rates. TRAb values usually decline during ATD treatment, but the trend could occur in two ways: Becoming negative or showing a fluctuating pattern. However, approximately 10% of the patients will remain TRAb-positive after five years of treatment with antithyroid drugs. Conclusions: Antithyroid drugs can be used for long periods with an increase in remission rates, and a gradual decrease in TRAb levels, with the disappearance of TRAb in 90% of the patients after 60 months.


2013 ◽  
Vol 23 (2) ◽  
pp. 76-80
Author(s):  
Dalia Daukšienė ◽  
Narseta Mickuvienė

Graves‘ disease is an autoimmune thyroid disorder characterized by the presence of autoantibodies against thyrotropin receptor. Antithyroid drugs are effective in controlling hyperthyroidism, but only one-third of patients achieve long-term remission after antithyroid drug treatment withdrawal. Influence of demographic factors (such as age and gender) on clinical features and outcome of Graves’ disease remains unclear despite decades of scientific research. The aim of the study was to determine the influence of age and gender on clinical features and outcome of Graves’ disease. Matherial and methods. We performed a retrospective study of 194 adult patients with newly diagnosed Graves’ disease. Outcome after antithyroid drugs was defined as remission or failed. Results. The mean age of males was greater than females (p=0,022). Males and females had the same outcome after medical therapy. The presence of large goiter was associated with lower mean age at diagnosis in both females and males. Patients less than 40 yr. of age were more likely to have large goiter (grade III) than smaller goiter (grade I/II) compared with older patients (OR 2.81, 95% CI 1.35 –5.84). Age at disease onset had no significant relationship with the medical treatment failure. Conclusions. Age less than 40 yr. is a significant predictor for the presence of large goiter at diagnosis. Age and gender did not predict the outcome of Graves’ disease.


1974 ◽  
Vol 19 (4) ◽  
pp. 165-169 ◽  
Author(s):  
I. R. McDougall ◽  
J. P. Kriss

The ocular manifestations of Graves' disease are probably due to autoimmunity. Thyroglobulin and complexes of thyroglobulin and antithyroglobulin have a predilection to attach to extraocular muscle membranes in vitro. It is suggested that in vivo these molecules are directed, probably via lymphatics, to the orbit where they attach to the muscle cell membranes. B lymphocytes, which have been shown to be capable of combining with both thyroglobulin and complexes, attach on to these molecules. The tissue damage is probably caused by the complexes, the lymphocytes, or both. Treatment of hyperthyroidism in a patient with ophthalmopathy should be cautious and with antithyroid drugs. This will reduce, though not completely eliminate, the possibility of a post-treatment exacerbation. If for some reason definitive treatment of the hyperthyroidism is essential, worsening of the ophthalmopathy may be prevented by prescribing steroids or immunosuppressive drugs at the time of surgical or radioiodine treatment. When progressive eye disease has arisen, orbital radiotherapy is a safe effective alternative to high dose corticosteroid treatment or surgical decompression.


2020 ◽  
pp. 1-4
Author(s):  
MosabNouraldein Mohammed Hamad

Agranulocytosis is an infrequent and serious side effect of antithyroid drugs characterized by a noticeable reduction in granulocyte and neutrophil count, it usually occurs within the first 2-3 months of treatment. There is a variety of mechanisms by which ATD can induce agranulocytosis, direct drug effects, and immunological mechanisms. We present 33 years old female attended Atbara teaching hospital who has developed agranulocytosis 2 weeks after starting ATD to treat relapsed Graves' disease. What was unusual about this patient is that symptoms have occurred in a period less than 15 days of starting treatment and with a dose of 45 mg /day. The physician must educate the patient about the possibility of early onset of serious side effects of ATD and to seek medical advice as soon as possible.


1990 ◽  
Vol 29 (04) ◽  
pp. 158-165 ◽  
Author(s):  
G. Berding ◽  
H. Schicha

In 200 patients follow-up examinations were performed up to one year after radioiodine therapy (RITh) with individual dose calculation. The mean applied dose was significantly lower in patients with immunogenic hyperthyroidism (Graves’ disease) as compared to patients with non-immunogenic hyperthyroidism (disseminated/multifocal autonomy, HYDA). In Graves’ disease the rate of recurrent hyperthyroidism was significantly higher and that of posttreatment hypothyroidism lower. Considering the high recurrence rate in Graves’ disease a higher dose, e. g. 150 Gy, seems to be appropriate. In patients with HYDA who received antithyroid drugs during RITh, recurrence of hyperthyroidism appeared slightly more, and posttreatment hypothyroidism slightly less, frequent. The efficiency of RITh was not significantly reduced by additional treatment with antithyroid drugs. Posttreatment hypothyroidism in patients with euthyroid goiter and disseminated/multifocal autonomy (EUDA) occurred significantly more frequent if the basal TSH level was ≥0.5 µlE/ml before therapy. The goiter size was reduced independent of the basal TSH level. In this group protection by thyroxine could avoid posttreatment hypothyroidism without impairing the reduction of goiter. In HYDA patients after thyroid surgery recurrence appeared less, and in those with EUDA posttreatment hypothyroidism significantly more, frequent. A lower dose seems to be suitable in patients who underwent thyroid surgery before. In patients with focal autonomy after RITh no recurrence of hyperthyroidism was observed. In 9% a suppressed basal TSH level indicating persistent autonomy was seen. Posttreatment hypothyroidism in focal autonomy appeared only in patients without manifest hyperthyroidism before RITh and was significantly more frequent in this group as compared to the other groups of patients. In patients with focal autonomy who developed hypothyroidism the dose calculation was based on a significantly higher volume of the adenoma. In 3 cases cystic parts of the adenoma were not subtracted. This caused a higher radiation dose to the paranodular tissue, which might have been one reason for the high rate of posttreatment hypothyroidism in this group of patients.


2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Ai Yoshihara ◽  
Jaeduk Yoshimura Noh ◽  
Natsuko Watanabe ◽  
Kenji Iwaku ◽  
Sakiko Kobayashi ◽  
...  

The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves’ disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low.


1991 ◽  
Vol 14 (10) ◽  
pp. 847-851 ◽  
Author(s):  
Enio Martino ◽  
S. Balzano ◽  
L. Bartalena ◽  
A. Loviselli ◽  
V. Sica ◽  
...  

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