In this study, the dose of methimazole was adjusted according to the different states of thyroid function, and the effects of conventional therapy and intensive therapy on the cumulative recurrence of Graves' hyperthyroidism after two years of drug withdrawal were evaluated. At the same time, the changes of immune indexes and inflammatory factors in the regulation process were evaluated. This study is a phase IV clinical study designed and carried out by the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), which is a randomized, open and routine treatment group with parallel control.

The results show that the high recurrence rate of antithyroid drugs may be related to the insufficient treatment time, the fact that thyroid autoantibodies did not turn negative when the drugs were stopped, and the thyroid volume did not shrink after treatment. However, individual differences are large, and there is no clear conclusion yet. Graves hyperthyroidism is a common organ-specific autoimmune disease, and its diagnosis mainly depends on the detection of thyroid autoantibodies, especially thyroid-stimulating receptor (TRAb). The antigens in thyroid gland include thyroglobulin (Tg), thyroid peroxidase (TPO) and sodium iodide symporter (NIS) besides thyroid stimulating receptor (TR). Graves hyperthyroidism patients were not only positive for TRAb, but also some patients were positive for anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb). At present, the traditional antithyroid drug treatment scheme is to adjust the dosage according to whether the thyroid function returns to normal or not, and observe the antibody turning negative at the same time, and only pay attention to whether TRAb turns negative or not. It has been found that whether TPOAb turns negative when stopping the drug can predict the recurrence after stopping the drug, suggesting that it is not only necessary to observe whether TRAb turns negative, but also to pay attention to whether other thyroid autoantibodies turn negative during the treatment of hyperthyroidism. The negative conversion of all antibodies may indicate that autoantigens are no longer exposed, and the immune balance is stable.

Methimazole (MMI) is one of the most important antithyroid drugs in the treatment of Graves' disease. It mainly blocks the synthesis of thyroid hormone by inhibiting the activity of peroxidase and reduces the production of thyroid hormone. At the same time, some studies have found that methimazole has immunomodulatory effect. Methimazole is recommended for initial treatment of first-time Graves' hyperthyroidism. 30mg/d is suitable for severe Graves' hyperthyroidism and 15mg/d is suitable for mild and moderate Graves' hyperthyroidism. Research has used blocking alternative methods to treat hyperthyroidism patients, maintaining the moderate or high dose of methimazole without decreasing, such as adding levothyroxine to treat hypothyroidism when hypothyroidism occurs, in order to suppress the immune state of Graves' disease patients. However, the research results have not found that it can reduce the recurrence rate of hyperthyroidism. Analyzing the results of these clinical studies, it is found that the use time of methimazole in some studies of blocking replacement therapy is short, and the total treatment time is only one year, and all antibodies are not required to turn negative at the end of treatment. Some studies only focus on the negative conversion of TRAb antibody, but not on the negative conversion of other antibodies such as TgAb and TPOAb.

Therefore, in this study, the intensive treatment group was treated with the inhibition substitution method of fixed middle dose methimazole plus levothyroxine, and the antibody was reduced after all turned negative, while the conventional treatment group was reduced according to whether the thyroid function was normal, so as to evaluate the effects of intensive treatment and conventional treatment on the cumulative recurrence of Graves' hyperthyroidism after two years of drug withdrawal. At the same time, the changes of immune indexes and inflammatory factors during the regulation process were evaluated. To provide evidence for improving the clinical remission rate of Graves' hyperthyroidism and exploring the etiology of Graves' hyperthyroidism.

Inclusion Criteria:

• Graves hyperthyroidism (responsible for doctors' clinical diagnosis)
• Age 18-65, for both men and women
• Thyroid receptor antibody (TRAb) was positive
• Take part in this research voluntarily and sign the informed consent form

Exclusion Criteria:

• Those who have used glucocorticoid or other immunosuppressants for a long time within 3 months before being selected
• Those who have participated in any other drug trials within 3 months before being selected
• Subjects who are participating in clinical research of other drugs
• Patients with a history of malignant tumors
• Ill-controlled hypertension: diastolic blood pressure≥100mmHg, systolic blood pressure ≥160 mmHg
• Blood routine: the total number of white blood cells < 3.0×109 or neutrophils < 1.5× 109
• Other thyroid diseases: such as subacute thyroiditis, thyroid nodules, high-function adenoma
• Alanine aminotransferase(ALT) or aspartate amino transferase(AST) is greater than 2 times of the normal upper limit; When ALT or AST is less than 2 times of the normal upper limit, and the test of hepatitis B two half-and-half positive
• Renal insufficiency: serum creatinine is higher than the upper limit of normal value
• Patients with heart failure
• Patients with coronary heart disease
• Patients with other autoimmune diseases
• Patients who are known to be allergic to any component of this medicine are allergic to the active ingredients or any auxiliary materials in the prescription
• Patients with multiple drug allergies, allergic diseases, people with high sensitivity and drug addicts
• Alcoholism, mental disorder or other observers who are not suitable for drug testing
• Pregnant and lactating women cannot rule out the possibility of pregnancy
• Taking any medicine with unknown ingredients or using traditional Chinese medicine, the researcher judges the medicine that may affect the curative effect of hyperthyroidism
• According to the researcher's judgment, other medical history that reduces the possibility of joining the group or complicates the joining of the group, such as frequent changes in the working environment, may easily lead to lost follow-up.

Rejection Criteria:

• The compliance of this clinical trial protocol is < 80% or > 120%;
• Those who did not meet the inclusion criteria or the exclusion criteria were found during the experiment;
• Those who can't cooperate, including those who can't complete the whole course of treatment, don't complete the follow-up as planned, and increase or decrease adjuvant drugs at will;
• During the trial, use other drugs that may affect the curative effect of this trial.

Termination of Research Criteria:

• Those who are allergic or intolerant to this drug;
• Adverse reactions or serious adverse events that patients can't tolerate occur;
• Pregnant women of childbearing age in the experiment;
• Other diseases appear during the treatment, and the treatment of accompanying diseases will interfere with the clinical observers of this medicine;
• The researcher thinks it is inappropriate to continue the experiment.

The medical records of the subjects (research medical records , laboratory sheets, etc.) will be kept intact in the hospital. The project researchers, ethics committee and project funding department will be allowed to consult the medical records of the subjects. Any public report on the results of this study will not disclose the personal identity of the subjects. We will make every effort to protect the privacy of the subjects' personal medical data within the scope permitted by the laws of the People's Republic of China.