Hyperthyroidism (hyperthyroidism) is a thyrotoxic condition caused by increased synthesis and production of thyroid hormones due to hyperfunction of the thyroid gland itself. There are many causes of hyperthyroidism, including Graves’ disease, multinodular goiter with hyperthyroidism, autonomous hyperfunctional adenoma of the thyroid gland, iodine hyperthyroidism and pituitary hyperthyroidism. In recent years, a large number of clinical practices and theoretical studies and public awareness of radionuclides have led to many new advances in the treatment of hyperthyroidism with 131I, including Graves’ hyperthyroidism and Hashimoto’s hyperthyroidism, refractory severe hyperthyroidism, hyperthyroidism in children and adolescents, subclinical hyperthyroidism, and Graves’ ophthalmopathy, as well as some controversies. This article provides an overview of these. 1.1 131I treatment of Graves’ hyperthyroidism and Hashimoto’s hyperthyroidism Since the first report of the application of radioactive 131I for the treatment of hyperthyroidism in 1942, there has been a history of more than 60 years [1], and a large number of clinical practices and theoretical studies have led to a gradual expansion of the scope of 131I treatment. The United States is the first country to use 131I to treat hyperthyroidism, and 131I has become the treatment of choice for hyperthyroidism, with 2/3 of hyperthyroidism patients currently treated with 131I [2]. In Europe, although the use of synthetic thyroxine replacement therapy after the emergence of hypothyroidism can truly replace the thyroxine secretion of the thyroid gland and still mainly drug therapy [3], but for the increased risk of recurrence, increased thyroid volume, thyroid autoantibody levels of hyperthyroidism patients, has also been used as a first line of treatment with 131l. Since 1958, China began to treat hyperthyroidism with 131I has been hundreds of thousands of cases, in the treatment of refractory severe hyperthyroidism has accumulated rich experience, but Europe and the United States to make pon frequency is still significantly higher than in China and other Asian countries. In the “China Thyroid Disease Diagnosis and Treatment Guidelines” issued by the Endocrinology Branch of the Chinese Medical Association in 2008, the indications, relative indications and contraindications for 131I treatment of hyperthyroidism are as follows [4]. Indications: (1) Graves’ hyperthyroidism with goiter of degree II or above, over 25 years old; (2) ATD treatment failure or allergy; (3) recurrence of hyperthyroidism after surgery; (4) hyperthyroidism heart disease or hyperthyroidism with other etiologies of heart disease; (5) hyperthyroidism and leukopenia and/or thrombocytopenia or thrombocytopenia; (6) hyperthyroidism combined with functional impairment of the liver, kidneys, and other organs; (7) hyperthyroidism of the elderly; (8) hyperthyroidism and diabetes; (9) hyperthyroidism and diabetes, and (10) hyperthyroidism and diabetes, and (11) hyperthyroidism and diabetes. (8) Hyperthyroidism and diabetes mellitus; (9) toxic multinodular goiter; (10) autonomous functional thyroid nodules combined with hyperthyroidism. Relative indications: (1) Hyperthyroidism in adolescents and children who have failed treatment with ATD, refused surgery, or have contraindications to surgery; (2) infiltrative synostosis. For mild and stable moderate and severe infiltrative synostosis can be treated with 131I alone for hyperthyroidism, and for patients with progressive stage, add prednisone before and after 131I treatment. Contraindications: pregnancy, lactation. In 2010, the Chinese Journal of Nuclear Medicine published the consensus of China’s nuclear medicine experts on the treatment of Graves’ hyperthyroidism with 131I, proposing the following indications and contraindications for the treatment of Graves’ hyperthyroidism with 131I [5]. Indications: All patients with Graves’ hyperthyroidism are suitable for treatment. Especially suitable for the following situations: poor ATD efficacy or multiple relapses; long duration of the disease or middle-aged or elderly patients; allergy to ATD or other adverse reactions; hyperthyroidism combined with hepatic impairment; hyperthyroidism combined with leukopenia or thrombocytopenia; hyperthyroidism combined with heart disease; other special types of hyperthyroidism. Contraindications: pregnant and lactating patients. Hashimoto’s hyperthyroidism refers to the coexistence of Hashimoto’s thyroiditis (goitrous Hashimoto’s thyroiditis, GHT) and Graves’ hyperthyroidism, and is suitable for 131I treatment if the rate of thyroid uptake of 131I (radioactive iodine uptake, RAIU) is elevated. However, Hashimoto’s thyroiditis with transient thyrotoxicosis is not suitable for treatment with 131I.Tajiri reported [6] that 13 cases of Hashimoto’s thyroiditis with goiter were treated with 131I, and the mean weight of the thyroid gland was (125.3±57.7) g (42.9~269.4 g) prior to 131I treatment, and then reduced to (49.7±25.8) g (18.3~93.3 g), P<<0.05), and P<0.01). 93.3 g), P<0.001. The average reduction in thyroid weight was 58.7%±14.2%. 1.2 131I treatment for refractory severe hyperthyroidism 131I treatment for hyperthyroidism has been proved to be an effective, safe and economical method, and its application is becoming more and more widespread. However, clinically we may often encounter refractory severe hyperthyroidism patients who are not suitable for ATD and surgery, hyperthyroidism heart disease, hyperthyroidism accompanied by obvious abnormalities in liver function and/or jaundice, hyperthyroidism accompanied by severe hematopoiesis, and so on. Practice has proved that 131I treatment is relatively safe and effective. The reasons are as follows [7-8]: (1) 131I in the body is mainly accumulated in the thyroid gland, and the absorbed dose due to other organs is very small; (2) 131I-induced acute thyroiditis belongs to the deterministic effect of ionizing radiation, and its threshold dose is about 200Gy, while the absorbed dose in the thyroid gland when 131I is used to treat hyperthyroidism is generally not more than 200Gy. Hyperthyroidism with severe hematopoiesis The absorbed dose to the bone marrow and peripheral blood caused by 131I treatment of hyperthyroidism is less than 5 cGy, which does not cause further damage to the bone marrow hematopoietic system. We used 131I to treat patients with hyperthyroidism combined with WBC less than 3.0×109/L and/or PLT less than 60.0×109/L or aplastic anemia [9], and the results were safe and effective. Zhang Zhixiang [10] found in the clinical observation of 46 patients with Graves' hyperthyroidism with hepatic function damage that 6 months after 131I treatment, 42 cases (91.3%) patients had normal or lower than normal thyroid hormones, and 40 cases (87%) patients' liver function recovered significantly compared with the pre-treatment period, and with the lowering of the level of thyroid hormones their liver function indexes were gradually restored to normal, which indicated that the hyperthyroidism thyroid This indicates that there is a close relationship between the fall of thyroid hormone level and the degree of liver function damage. A retrospective analysis of the arrhythmia after 131I treatment in patients with thyroid heart disease [11] found that atrial fibrillation was the most common (65.0%), and the average arrhythmia after 131I treatment was 74.4%, and the rate of cardiac arrhythmia after iodine 131 treatment was higher in younger patients with a relatively shorter course of the disease than in older patients with a longer course of the disease, which may be related to the long-term effect of TH on the heart, aggravating the burden on the heart and leading to cardiomyocyte dysfunction. This may be related to the long-term action of TH on the heart, aggravating the burden on the heart and leading to irreversible pathologic changes in cardiomyocytes. At present, 131I treatment of hyperthyroidism has achieved consensus at home and abroad, especially the treatment of hyperthyroidism accompanied by other comorbidities such as peripheral blood leukopenia, hyperthyroidism heart disease, liver function damage, etc. It is a safe and effective method, and is worthy of clinical promotion and application. 1.3 Treatment of hyperthyroidism in children and adolescents with 131I Although 131I has long been used to treat hyperthyroidism in children and adolescents in the United States and the United Kingdom [2,12], there is a great deal of variation in the understanding of whether or not 131I should be used to treat hyperthyroidism in children and adolescents among physicians in the departments of endocrinology, pediatrics, surgery, and nuclear medicine.In 2007, two articles with opposing views were published simultaneously in the Journal of Clinical Endocrinology and Metabolism (JCEM) in the United States. In 2007, the American Journal of Clinical Endocrinology and Metabolism (JCEM) published two articles with opposing views: Rivkees et al [13] suggested that radioactive iodine is the most appropriate treatment for pediatric Graves' disease, while Lee et al [14] suggested that surgery is the most appropriate treatment for pediatric Graves' disease.15 Glaser et al [15] published the paper "Predicting the likelihood of remission of Graves' disease in children: a prospective multicenter study" in 2008. Likelihood of Predicting Remission in Children with Graves' Disease: A Prospective Multicenter Study", concluded that hyperthyroidism in children responds rapidly to antithyroid medication [with propylthiouracil (PTU)], and that early remission is most likely to be achieved in those who are older (14-15 years of age), and that treatment with antithyroid medication should be continued. If thyroid hormone levels remain above normal after 3 months of antithyroid medication and the original TT3 level is >5.883 nmolL, early remission is unlikely to be achieved and consideration of other methods of treatment may be counseled. The key to the difference in the above views is the safety of 131I treatment of hyperthyroidism in children and adolescents.Read et al [16] did a specific study on this issue, and apart from the fact that almost all developed hypothyroidism, there was no difference in their fertility and growth of their offspring compared with the general population. None of them developed thyroid cancer or leukemia, which again proves that 131I is safe and effective in treating hyperthyroidism in children and adolescents. According to the reports of the United States and the International Commission on Radiological Protection [17], 131I treatment of hyperthyroidism in women of childbearing age or in adolescents and children did not affect the fertility of the patients or increase the incidence of genetic damage. The Endocrinology Branch of the Chinese Medical Association [4] recommended 131I as a second-line drug for the treatment of hyperthyroidism in adolescents and children who are ineffective on antithyroid drugs, refuse surgery, or have contraindications to surgery, according to the national conditions of China. 1.4 131I treatment of subclinical hyperthyroidism Subclinical hyperthyroidism refers to a group of disorders in which serum TSH levels are below the lower limit of the normal reference value and free T4 (FT4) and free T3 (FT3) levels are within the normal reference value range, and the diagnosis is based solely on laboratory test results; many patients are asymptomatic, and there is no consensus opinion on their management. Although evidence from large-scale evidence-based medicine is lacking, studies have confirmed that treatment of subclinical hyperthyroidism results in cardiovascular benefits and improved bone density [18-19]. According to the American Thyroid Association (ATA) and American Academy of Clinical Endocrinologists (AACE) guidelines [20], the principles of treatment of subclinical hyperthyroidism are as follows. 1. Exogenous subclinical hyperthyroidism: For patients treated with thyroid hormone supplementation due to hypothyroidism, the dose of thyroid hormone should be appropriately reduced to normalize the TSH level. 2. endogenous hyperthyroidism: the choice of whether to treat or not and the method of treatment should be based on the patient’s age, whether there is any complication of cardiovascular disease or osteoporosis, the level of TSH decline and the etiology of the thyroid disease. the findings of McDermott [21] and others concluded that subclinical hyperthyroidism due to Graves’ disease is selected as a low-dose anti-hyperthyroid drug. For subclinical hyperthyroidism due to hyperfunctioning thyroid adenoma or toxic multinodular goiter, 131I therapy is recommended. The Royal College of Physicians (RCP) (2007) [22] considered the conditions for 131I treatment of subclinical hyperthyroidism: (1) persistent TSH <0.1 mU/L, (2) comorbid cardiac disease, and (3) presence of underlying thyroid disease.Vaidya et al. [23] presented three dummy cases to 279 British endocrinologists to investigate the opinion of 131I treatment for benign thyroid disease. Virtual case 2 was a 75-year-old female patient with subclinical hyperthyroidism, sinus rhythm, persistent TSH <0.1 mU/L, and normal FT3 and FT4. 63% of respondents recommended 131I treatment. However, it has been reported in the literature that the rate of cardiovascular mortality was significantly higher in hyperthyroid patients treated with radioactive iodine than in the control group, which the investigators attributed to the triggering of a systemic inflammatory response by 131I treatment [24]. One study found [25] that 2668 patients with hyperthyroidism treated with radioactive iodine had a higher risk of death compared with those without radioactive iodine treatment (P<0.01), and the main causes of death were endocrine metabolic diseases, cardiac arrhythmias, and heart failure, while ischemic heart disease and encephalopathy were rare. Therefore, the treatment of subclinical hyperthyroidism with 131I needs further study. 1.5 131I treatment of Graves ophthalmopathy Foreign reports, 131I treatment of hyperthyroidism combined with proptosis, especially smoking hyperthyroidism patients, 15% to 20% of patients may aggravate the original Graves ophthalmopathy (Graves ophthalmopathy, GO) or new occurrence of Graves ophthalmopathy. Smoking, severe hyperthyroidism, elevated thyrotropin receptor antibodies and hypothyroidism after 131I treatment are risk factors for exacerbation of Graves ophthalmopathy or new onset of Graves ophthalmopathy [26].According to Baltalena et al [22], such cases are few and can be prevented with adrenocorticotropic hormone, and recovery from Graves ophthalmopathy is favored after 131I eradication of hyperthyroidism. 131I is suitable for the treatment of patients with hyperthyroidism combined with proptosis. RCP 2007 suggested [27] that for those with recurrent hyperthyroidism with significant ophthalmopathy after ATD treatment who require 131I for hyperthyroidism, prednisone prophylaxis can be initiated before 131I treatment. The European Study Group on Graves' Orbital Disease published a "consensus statement" in 2008 that in patients with hyperthyroidism and active Graves' ophthalmopathy, prednisone tumors after 131I treatment may have the same effect; in patients with hyperthyroidism and not active Graves' ophthalmopathy, they can be treated with 131I only. The American journal Thyroid commented [28] that the "consensus statement" is also suitable for physicians and patients in North America. Although glucocorticoids and other immunosuppressive agents are effective, their clinical use is limited by their adverse effects and poor patient compliance [29]. It was also found [30] that radioactive iodine therapy was associated with cumulative morbidity and exacerbation of thyroid-associated ophthalmopathy (TAO) compared to antithyroid medications, and its rate of morbidity and exacerbation was found to be higher than that of the Bartalena results after one year of follow-up, which may be explained by the different design of the study protocols and by the characteristics of the patients, the size of the samples, the method of treatment, and the assessment of the efficacy of the treatment. In conclusion, the role of 131I on Graves' ophthalmopathy is controversial and still needs further study. 1.6 Awareness of hypothyroidism after 131I treatment Hypothyroidism is the most common and major adverse reaction of 131I treatment, and the possible complications of combined hyperthyroidism and hypothyroidism are more harmful than those of recurrent hyperthyroidism and long-term use of antithyroid drugs. Hypothyroidism after 131I treatment of hyperthyroidism is classified into early-onset hypothyroidism and late-onset hypothyroidism. The incidence of early-onset hypothyroidism varies widely (5%-40%), and its incidence is closely related to the sensitivity of the patient's thyroid gland to radiation and the dose of 131I. The incidence of late-onset hypothyroidism is reported to be higher in foreign countries, reaching 40% to 70% after 10 years, while it is relatively lower in China (with a large difference in the dose of 131I used at home and abroad) [31]. The causes of late-onset hypothyroidism are currently considered by many scholars to be related to autoimmunity and the natural regression of the disease, as well as excessive iodine intake caused by environmental factors [32]. Experts in nuclear medicine and endocrinology agree that hypothyroidism is an unavoidable consequence of 131I treatment of hyperthyroidism, and at the same time believe that hypothyroidism after 131I treatment of hyperthyroidism is not a serious negative consequence. This is the result of the combination of decades of experience in 131I treatment and in-depth understanding of hypothyroidism. Because hypothyroidism is not unique to 131I-treated hyperthyroidism, it will eventually occur at a rate of 3% per year regardless of the method of treatment [33], and spontaneous hypothyroidism may be part of the natural history of hyperthyroidism. Moreover, measurement of thyrotropin can be sensitive, accurate, and specific for the diagnosis of hypothyroidism, which can be easily corrected with the application of levothyroxine replacement therapy, and can avoid the adverse effects caused by long-term use of ATDs. Therefore, hypothyroidism should not affect 131I as the preferred method of hyperthyroidism treatment, on the contrary, some foreign scholars advocate the use of a single large dose to remove the thyroid gland, followed by replacement therapy, in order to achieve a high cure rate and reduce the risk of thyroid cancer [34]. Replacement therapy for hypothyroidism is relatively simple, effective, and medically inexpensive. The 2011 guidelines for the diagnosis and treatment of hyperthyroidism of the American Thyroid Association and the Association of Clinical Endocrinologists [20] clearly state that 131I treatment is a method that can cure Graves' disease, and that the presence of hypothyroidism after the treatment is the goal of 131I treatment so that hyperthyroidism is considered completely cured. Conclusion 131I treatment of Graves' hyperthyroidism is safe and effective. However, controversy still exists in the selection of patients, the goals of treatment, and the calculation of the therapeutic dose. A univariate analysis of gender, age, disease duration, symptoms, signs, laboratory tests, thyroid mass, thyroid texture, 24-h iodine uptake rate, and 131I dose per gram of thyroid tissue [35] suggests that the disease duration, thyroid mass, 24-h iodine uptake rate, and 131I dose per gram of thyroid tissue are the main factors affecting the effectiveness of 131I therapy. Therefore, when developing an individualized 131I treatment plan, multiple factors need to be considered simultaneously to influence the adjustment of 131I dose in order to improve the 1-time cure rate of 131I.