In 1942, Hamilton et al. reported the use of iodine-131 for the treatment of hyperthyroidism (mainly Graves’ disease (GD)) (hereafter referred to as hyperthyroidism). Over the past half century, more than 2.5 million cases of hyperthyroidism have been treated with iodine-131. Extensive practice and systematic long-term follow-up data have elucidated and reconceptualized many of the concerns and expanded the scope of iodine-131 treatment for hyperthyroidism. Iodine-131, drugs and surgery are all effective treatments for hyperthyroidism, each with its own characteristics. How to better carry out the iodine-131 treatment of hyperthyroidism and the optimization of the treatment plan are still controversial both at home and abroad. The new understanding and progress in this area is introduced in the relevant literature. First, iodine-131 treatment of hyperthyroidism did not increase the incidence of thyroid cancer and leukemia and other cancers. The U.S. Hyperthyroidism Follow-up Research Collaborative Group published three follow-up results in 1968, 1974 and 1998. Through the investigation of 23,000 hyperthyroidism patients treated with iodine-131 from 1946 to 1964, it was proved that the incidence of thyroid cancer and leukemia and other cancers did not increase in these patients. Sweden and other countries, experts reported on the acceptance of iodine-131 diagnosis or treatment of 46,988 patients survey results, the bone marrow of these patients by the iodine-131 caused by the average absorbed dose of 14mGy, did not find that the incidence of leukemia increased. China’s use of iodine-131 treatment of hyperthyroidism has been more than 200,000 cases, so far only 2 cases of thyroid cancer and 5 cases of leukemia were reported, respectively, lower than the incidence of the general population of 3.9/100,000 and 2.98~3.90/100,000. II. Iodine-131 is safe and effective in treating hyperthyroidism in adolescents. Whether iodine-131 treatment of hyperthyroidism causes genetic damage is a common concern. Foreign countries began to report the long-term results of iodine-131 treatment of hyperthyroidism in children and young people in 1964, and in 1998, Rivkess et al. reviewed the iodine-131 treatment of hyperthyroidism in children, and after comparing the effects of antithyroid drugs (ATDs), surgery, and iodine-131 treatment, they especially emphasized that iodine-131 treatment of hyperthyroidism was safe and effective, not only did the incidence of cancer not increase, but also the incidence of congenital malformations in the offspring of the offspring of the offspring. Not only is there no increase in the incidence of cancer among them, but the incidence of congenital malformations in their offspring is also not significantly different from that of the general population. Studies by experts such as Xing Jiayi, Zhong Shangzhi, Shen Youmou, and Chen Tanghua have shown that iodine-131 treatment of hyperthyroidism in children and young people has no effect on fertility and does not increase the incidence of genetic damage. Therefore, the age limit of Iodine-131 treatment of hyperthyroidism has been relaxed. Third, in the United States, iodine-131 has become the drug of choice for most physicians in the treatment of hyperthyroidism. In view of more than 50 years has been fully proved that iodine-131 treatment of hyperthyroidism has the advantages of simple method, wide range of application, safe and effective, short cure time, low cost and very few relapses, in addition to hypothyroidism, no other long-term adverse consequences, there have been more and more doctors and patients are willing to use iodine-131 treatment of hyperthyroidism. According to Solomon et al. survey, for a hypothetical hyperthyroidism patients, 197 American Thyroid Association (ATA) members, 69% preferred iodine-131 treatment, 30% preferred ATD, only 1% preferred surgical treatment. The American Association of Clinical Endocrinologists (AACE) and the ATA published guidelines for the treatment of hyperthyroidism and hypothyroidism in 1995, respectively, and made iodine-131 the first choice for the treatment of hyperthyroidism. the ATA pointed out that: “in the United States, iodine-131 has been the most commonly used treatment for hyperthyroidism. Iodine-131 treatment does not reduce fertility, is not carcinogenic, and has no adverse effects on offspring when used before pregnancy. For patients under 20 years of age, although there is still controversy, but the use has become more common”. Fourth, the scope of application of iodine-131 treatment of hyperthyroidism has been expanded. 1. Age selection: The issue of debate is now the treatment of women of childbearing age, young people and children. Age restrictions are justified by the potential risk of cancer and leukemia, as well as the risk of congenital anomalies and hypothyroidism in the offspring. However, 60 years of experience and data show that no risks related to cancer and leukemia have been found with iodine-131 treatment. Long-term follow-up data at home and abroad show that fertility and offspring development are not affected by the prolonged period of time, that the rate of spontaneous abortions does not increase, and that fetal malformations do not exceed the natural incidence. Therefore, blanket exclusion of young patients from iodine-131 treatment is not justified. With the exception of pregnant and lactating women, iodine-131 is a safe treatment for all age groups, including women of childbearing age and children. However, in adolescents and children with hyperthyroidism, it should be applied with caution and should be used as a second-line drug therapy. 2. Hyperthyroidism with infiltrative proptosis: Whether hyperthyroidism with infiltrative proptosis is an indication for iodine-131 treatment has been a controversial issue. The main reason is that some scholars believe that iodine-131 treatment increases the risk of exacerbation of proptosis. Currently, most scholars support the treatment of hyperthyroidism with infiltrative proptosis with iodine-131. It has been demonstrated that there is no difference between ATD, surgery and iodine-131 treatment in terms of exacerbation of the eye or the development of new eye disease. Some scholars reported that, with ATD, surgery and iodine-131 treatment, there was no statistical difference between those who had no ophthalmopathy before treatment and those who had ophthalmopathy after treatment (6.7%, 7.1%, and 4.9%), and those who had ophthalmopathy before treatment and those who had ophthalmopathy aggravated after treatment (18.9%, 19.2%, and 22.7%), respectively. However, the basic impression is that after iodine-131, surgery and ATD treatment, there is indeed a possibility of exacerbation of ophthalmopathy or the emergence of new ophthalmopathy, and there does not seem to be a significant difference between the three treatments. Therefore, iodine-131 treatment is not a contraindication for hyperthyroidism with infiltrative proptosis. How to effectively prevent and treat Graves’ ophthalmopathy, on the other hand, is a topic worth exploring and researching. 3. Hashimoto’s disease combined with hyperthyroidism: out of the concern of hypothyroidism, this kind of patients traditionally do not advocate iodine-131 treatment. However, because Hashimoto’s disease and hyperthyroidism may be different stages of the same disease, such patients may continue for several years, and clinical identification is difficult, and the effect of other therapies is also poor, coupled with hypothyroidism is not a serious negative consequences, in recent years, the iodine-131 treatment is gradually increasing, but in the dosage should strive to be cautious. V. Auxiliary drugs and comprehensive treatment of hyperthyroidism. 1. The application of ATD: general hyperthyroid patients should not take ATD or stop taking drugs for a period of time before receiving iodine-131 treatment, to avoid the effect on the iodine uptake rate. It has been proved that the application of ATD (especially PTU) before iodine-131 treatment has an important effect on the cure rate. However, for patients with severe hyperthyroidism and elderly hyperthyroidism, especially those with cardiovascular complications (such as heart failure and atrial fibrillation) or other related diseases, they should be treated with a sufficient dose of ATD for a short period of time, and then, when the clinical symptoms are alleviated and the thyroid function improves, the drug should be discontinued for 72 hours, and the iodine uptake rate should be re-determined, and then the iodine-131 treatment should be given accordingly. The purpose is to make iodine-131 treatment safer and to avoid thyroid crisis or exacerbation of hyperthyroid symptoms. After taking iodine-131, for those with severe symptoms, failure or large dose of iodine-131, depending on the situation, they can continue to take the appropriate dose of ATD for 4-6 weeks 2-4 days after taking iodine-131, so that the patients can safely pass through the period in which iodine-131 produces sufficient therapeutic effect, and it can play a role in preventing thyroid crisis, alleviating radiothyroiditis, and enhancing the near-term effect of iodine-131 treatment. 2. β2 receptor blocker application: many of the manifestations of hyperthyroidism are caused by β2 adrenergic receptor. β2 receptor blocker can’t inhibit the formation and secretion of thyroid hormone by itself, but it can competitively antagonize the effect of catecholamines at adrenergic receptor, so that the symptoms of hyperthyroidism can be improved, so it is often used in the adjuvant treatment of hyperthyroidism. Iodine-131 treatment of hyperthyroidism, due to the destruction of the thyroid follicles, the release into the blood of T3, T4 increase, can make the symptoms of hyperthyroidism aggravated, the choice of appropriate β2 receptor blocker is very important. 3. Comprehensive treatment for patients with hyperthyroidism and proptosis: Iodine-131 induces new ophthalmopathy rarely (3%~5%), but there is a risk of aggravation of the existing ophthalmopathy. It is generally believed that those who do not have or only have mild eye disease before treatment should not be treated with special treatment during iodine-131 treatment, otherwise, comprehensive treatment measures should be taken. Sixth, on the understanding and management of hypothyroidism after iodine-131 treatment. It is an indisputable fact that the incidence of hypothyroidism is high in isotopic iodine-131 treatment of hyperthyroidism. However, hypothyroidism is not unique to iodine-131 treatment; it also occurs after ATD and surgical treatment. It has been reported that in 5221 cases of hyperthyroidism, permanent hypothyroidism was found in 24.8% at 2.7 years of follow-up. The incidence of late-onset hypothyroidism is not related to the size of the iodine-131 dose, and there is no substantial difference in the frequency of abnormal immune responses between post-surgical hypothyroidism and hypothyroidism after iodine-131 treatment. It has been reported that regardless of the method of treatment, ultimately hypothyroidism will occur at a rate of 3% per year. Therefore, many scholars believe that late-onset hypothyroidism may not necessarily be a side effect of iodine-131 treatment. Modern thyroid-stimulating hormone analyses can diagnose hypothyroidism very sensitively and specifically and can physiologically regulate hormone replacement. Therefore, the development of hypothyroidism with iodine-131 therapy is not a serious negative consequence. On the contrary, the impact of prolonged ineffective treatment of hyperthyroidism on the patient’s health and quality of life will be enormous. Any improvement in treatment can only reduce early-onset hypothyroidism, and there is no good solution to reduce or prevent late-onset hypothyroidism. In conclusion, hyponatremia after iodine-131 treatment exists objectively, but it is not a serious negative consequence. Ensuring a high cure rate while reducing early-onset hyponatremia to an acceptable level has always been the goal pursued by nuclear medicine practitioners. The presence of hypothyroidism does not affect the use of iodine-131 as a safe and effective treatment for hyperthyroidism. Early diagnosis of hypothyroidism and timely replacement therapy are important. Thyroxine (eugenol) replacement therapy is given early for subclinical hypothyroidism and mild hypothyroidism to give rest to the more fragile cells after iodine-131 irradiation, to prevent final cellular failure, and to help prevent the emergence or exacerbation of new ophthalmopathies after treatment, as well as to reduce the incidence of thyroid cancer, and also to perform tests at the end of the first year after replacement when the medication is discontinued for 4-6 weeks to rule out temporary hypothyroidism.