A Prospective Clinical Follow-up Study of Drug Treatment in Patients With Graves' Disease
Conditions: Graves´ Disease
Sponsor: First Hospital of China Medical University

 
 
Study Protocol 
 
 
 
A Prospective Clinical Follow-up Study of Drug Treatment in 
Patients with Graves’ Disease 
 
 
 
 
 
 
NCT number: not yet assigned 
Date of the document: June 17, 2019 
 
 

I. 
Research Content 
Graves’ disease (GD) is a common disease in endocrinology department, its prevalence rate 
is as high as 1.5%. Antithyroid drugs (ATD) are the first choice for GD treatment. However, there 
are some problems in drug treatment of GD: 1. ATD treatment cycle is long, the rate of loss to 
follow-up is high, and the recurrence rate is high. Foreign guidelines recommend that ATD 
treatment should be stopped for about 1.5-2 years. Foreign literature reports that the recurrence 
rate varies from 10-60% after drug withdrawal. GD recurrence was closely related to race, 
inclusion criteria, study nature (prospective or retrospective), and thyrotropin receptor antibody 
(TRAb) titers at discontinuation. 2. ATD treatment may lead to leukopenia and liver function 
impairment, but when these side effects occur, their severity and which factors are related to them, 
China still lacks prospective clinical studies with large sample size in this respect. 
This study was a prospective follow-up study of newly diagnosed and relapsed Graves’ 
disease patients in the Endocrinology Clinic of the First Affiliated Hospital of China Medical 
University. The following aspects will be studied: 1. Through the prospective follow-up study of 
GD patients, we will get the relapse rate and remission rate of GD patients treated with drugs, 
explore the risk factors of GD patients relapsing after drug treatment, and make GD relapse risk 
prediction software; 2. To compare the effects of high dose and low dose methimazole on the 
remission rate, liver side effects, leukopenia and other adverse drug reactions, and to summarize 
the incidence and risk factors of liver side effects, leukopenia and other adverse drug reactions 
caused by drug treatment; 3. To investigate the sensitivity and specificity of TRAb in the diagnosis 
of GD in China and its role in predicting recurrence; 4. After taking ATD, the serum alkaline 
phosphatase of GD patients will increase first and then decrease. This study will focus on 
analyzing the dynamic changes of this index before and after methimazole treatment, and analyze 
the relationship between it and thyroid function index. 
II. 
Research objectives 
By utilizing the leading position of this discipline in the research field of thyroid science in 
China, we can accumulate the treatment experience of Graves’ disease in China and provide our 
own experience for the formulation of hyperthyroidism guidelines in China. 

III. 
Research technique 
1. Patient inclusion criteria 
① Newly diagnosed GD and GD relapses. 
② Patients with active infiltrative exophthalmos in GD were excluded. 
③ Patients with other autoimmune diseases affecting thyroid function were excluded. 
④ Excluding patients with combined malignancies and other serious diseases. 
2. GD patients were recruited according to the above inclusion criteria. Follow-up records 
were established for GD patients identified for enrollment. According to the guidelines, 
outpatient follow-up is required every month until the patient has normal thyroid 
function; after the thyroid function is normal, outpatient follow-up is required every 2-3 
months. 
3. GD patients enrolled were identified and thyroid function, liver function, TRAb and 
blood routine tests were performed during outpatient follow-up to observe the treatment 
effect and give medication guidance. 
4. To determine the GD patients enrolled, record the laboratory test results at each follow-
up visit and enter them into the database established in this study. At each follow-up 
visit, the GD patients enrolled should collect and retain blood samples and store them 
frozen at-80℃ for subsequent study. 
5. To investigate the risk factors of GD relapse and drug-induced side effects, genetic, 
epigenetic and proteomic studies were performed on preserved blood samples of GD 
patients. 
IV. 
Statistical analysis plan 
Continuous variables were presented as median (25th–75th percentile) or mean±standard 
deviation and compared using the Mann–Whitney U test or independent sample t-test. Categorical 
variables were presented as frequency and percentage and compared using the chi-square or 
Fisher’s exact tests. Univariate and multivariate Logistic regression analyses were used to estimate 
the odds ratio and 95% confidence intervals for potential risk factors for recurrence of 
hyperthyroidism and adverse reaction under MMI treatment. P<0.05 was considered statistically 
significant. 

V. 
Experimental Feasibility Analysis 
The Department of Endocrinology of the First Affiliated Hospital of China Medical 
University is in the leading position in the field of thyroid research in China. The outpatient 
volume of thyroid diseases accounts for about 50% of endocrine diseases. It is fully capable of 
conducting prospective clinical follow-up observation of Graves’ disease. The research direction 
of the project leader is thyroid diseases, and he has accumulated rich clinical experience in the 
diagnosis and treatment of thyroid diseases. 
VI. 
Expected experimental results 
1. To obtain and analyze the remission rate, recurrence rate and related risk factors of 
Graves’ disease patients. 
2. To obtain and analyze the prevalence of side effects and associated risk factors of drug 
therapy in patients with Graves’ disease. 
3. To evaluate the sensitivity and specificity of TRAb in the diagnosis of Graves’ disease 
and its role in predicting recurrence. 
4. Through the implementation of this project, a standardized management model for GD 
treatment follow-up has been established. After that, relying on our leading role in the 
national thyroid field, we will further carry out a national multicenter clinical study of 
GD.