Since Hertz et al. pioneered radioactive iodine (RAI) for the treatment of Graves disease (GD) in 1942, nearly 70 years have passed since then, and more than 2 million cases of GD have been treated with Iodine-131 worldwide, and hundreds of thousands in China. Because of its safety, effectiveness, low side effects, simplicity and low cost, iodine-131 treatment has been gaining more and more clinical attention and is being used more and more widely. In North America, iodine-131 therapy has become the preferred treatment for adults with GD. In China, more and more GD patients are choosing iodine-131 treatment.
Safety of iodine-131 treatment: A large number of long-term clinical studies have shown that iodine-131 treatment does not lead to an increase in the incidence of malignant tumors and leukemia, and no increase in the incidence of thyroid cancer; no adverse effects on fertility and offspring development, no increase in the rate of spontaneous abortion, and no more than the natural incidence of fetal malformations.
Principle: The thyroid gland is highly iodophilic and iodine-131 is taken up by thyroid follicular cells through sodium/iodine cotransporter (Na+/I-symporter, NIS). thyroid follicular cells in GD patients overexpress NIS and the uptake of iodine-131 is significantly higher than that of normal thyroid tissue. iodine-131 has an effective half-life of 3.5~4.5 days in the thyroid gland and can stay in the The effective half-life of iodine-131 in the thyroid gland is 3.5-4.5 days, and it can stay in the thyroid gland for a sufficient time. The average range of B-rays released during the decay of iodine-131 in the thyroid tissue is 0.8 mm, and almost all of them are absorbed by the thyroid tissue, while the effect on the normal tissues around the thyroid gland is minimal. Due to the “cross-fire” effect of iodine-131, the central part of the thyroid gland receives a higher dose of irradiation than the peripheral part of the gland. This reduces the synthesis and secretion of thyroid hormones and normalizes the function of the thyroid gland to cure hyperthyroidism.
Indications
1. Adult patients with Graves’ hyperthyroidism.
2. Patients with Graves’ hyperthyroidism who have not recovered from regular antithyroid treatment for more than 2 years and have an enlarged thyroid gland of 2 degrees or more.
3. Adult and adolescent patients with Graves’ hyperthyroidism who are allergic to antithyroid medication, or have poor efficacy, or have relapsed several times after antithyroid medication, or have relapsed after surgery.
4. Patients with Graves’ hyperthyroidism with granulocytopenia or thrombocytopenia.
5. Patients with Graves’ hyperthyroidism with atrial fibrillation.
6. Patients with Graves’ hyperthyroidism with impaired liver function.
Contraindications
1. Patients during pregnancy and lactation.
2. Patients with acute myocardial infarction.
3. Patients with severe renal insufficiency.
Patient preparation
1. Avoid eating iodine-containing foods (mainly seafood) for three weeks, and stop taking anti-thyroid drugs for two weeks (one week if the condition is severe).
2. Routine physical examination, blood and urine routine, electrocardiogram and liver function. For patients with rapid heart rate and nervousness, give b-blockers or sedatives.
3. Check FT3, FT4, TSH levels, TgAb, TPOAb, thyroid iodine uptake, thyroid imaging or thyroid ultrasound.
4. Estimation of thyroid weight by thyroid imaging or thyroid ultrasound combined with clinical consultation.
5. In severe cases, patients should be treated with anti-thyroid medication first and then treated with iodine-131 after the condition has subsided.
6. Health education. Before treatment, introduce to patients the main methods of treatment for hyperthyroidism and their advantages and disadvantages, answer patients’ questions, introduce in detail the precautions, efficacy, recent treatment reactions and long-term complications of iodine-131 treatment, and patients sign the informed consent form.
7. Patients with hyperthyroidism combined with periodic paralysis, hyperthyroid heart disease and proptosis should be given appropriate treatment before iodine-131 treatment.
Iodine-131 Dose Calculation
There are three main methods of iodine-131 dose calculation: fixed dose method, semi-fixed dose method and calculated dose method. The first two methods are more commonly used in North America and some European countries, while the calculated dose method is used in China.
The calculated dose method calculates the iodine-131 dose based on the weight of the thyroid gland and the 24-hour thyroid uptake rate, so that the dose is individualized.
Iodine-131 dose (mCi) = planned amount (uCi / g thyroid tissue) * thyroid weight (g) / 24-hour iodine uptake rate of thyroid (%)
The planned amount of iodine-131 is usually given at 70-120 uCi per gram of thyroid tissue.
The calculated dose method has a lower incidence of early onset hypothyroidism, but also has a relatively low one-time cure rate.
Adjustment of iodine-131 dose
1. Factors for increasing the dose: ① Large and hard thyroid gland. (2) Old age, long duration of disease, and poor efficacy of long-term anti-thyroid drug therapy. ③People with poor or ineffective first iodine-131 treatment.
2. Factors for dose reduction: ①Short duration of disease, young age, small thyroid gland. (2) Those who have not been treated with anti-thyroid drugs. (3) Those who have not recovered from the previous iodine-131 treatment.
Method of administration and precautions
1. Drug administration method: Use the one-time oral method. Iodine-131 should be given orally on an empty stomach, and food should be taken only after 2 hours.
2. Precautions after iodine-131 treatment: Consult patients to take rest, prevent infection and avoid mental stimulation, do not rub or squeeze the thyroid gland. Avoid close contact with pregnant women or infants for one week. Female patients should not get pregnant within six months, and male patients should also take contraceptive measures within six months. Those who are not cured after 3~6 months of iodine-131 treatment can consider iodine-131 treatment again.
Treatment reactions and treatment
1. Early reactions: Some patients have reactions such as weakness, nausea, itchy skin and swollen thyroid gland within one week after taking iodine-131, but most of the symptoms are mild and do not require special treatment, and can disappear on their own after a few days. For patients with serious conditions or those who are infected after taking iodine-131, attention should be paid to prevent the occurrence of hyperthyroidism crisis, and once it occurs, it should be treated according to the treatment of hyperthyroidism crisis in internal medicine.
2. Hypothyroidism: The main complication of iodine-131 treatment for hyperthyroidism is divided into early-onset hypothyroidism and late-onset hypothyroidism.
Early-onset hypothyroidism: It occurs within one year after iodine-131 treatment. It occurs because of the direct destruction of thyroid follicular cells by radiation, and is related to the dose of iodine-131 given by iodine and the sensitivity of individuals to radiation. The occurrence of early-onset hypothyroidism cannot be prevented or predicted medically, and even the use of low-dose iodine-131 treatment for hyperthyroidism cannot eliminate early-onset hypothyroidism. The main purpose of iodine-131 treatment is to control hyperthyroidism as soon as possible, not to avoid the occurrence of hypothyroidism. If thyroxine replacement therapy is given promptly after the onset of hypothyroidism, patients can grow and have children normally and maintain a normal quality of life. Some patients with early onset hypothyroidism are temporary and can recover on their own.
Late onset hypothyroidism: It occurs one year after iodine-131 treatment and increases at a rate of 2~3% per year. The cause of late onset hypothyroidism is not well understood and may be related to autoimmune dysfunction, but not to the dose of iodine-131. Late onset hypothyroidism is not unique to iodine-131 treatment, but can also occur after antithyroid medication and surgical treatment. Some patients with GD even develop spontaneous hypothyroidism without any treatment, so it can be considered that hypothyroidism is a natural progression of the disease course of GD.
Whether early onset hypothyroidism or late onset hypothyroidism is detected, it should be promptly replaced by treatment. Patients should be informed that most early-onset hypothyroidism and all late-onset hypothyroidism are permanent and require long-term thyroxine replacement therapy to enhance compliance.
Follow-up visits
In general, patients should be reviewed 3 to 6 months after iodine-131 treatment, or monthly if needed. The review should include symptoms and signs of hyperthyroidism, FT3, FT4, TSH and blood count. The follow-up interval can be gradually extended after the cure of hyperthyroidism. A reliable sign of successful iodine-131 treatment is a significant reduction in thyroid volume. In case of hypothyroidism, thyroxine replacement therapy should be promptly administered.
Evaluation of efficacy
1. Efficacy of treatment of hyperthyroidism: Iodine-131 treatment starts to show effect 2~3 weeks after treatment, which is manifested by reduction of symptoms of hyperthyroidism, thyroid gland shrinkage and weight gain, and after 2~3 months, the condition is basically controlled. The thyroid gland shrinkage is the most obvious among the signs. Most GD patients have basic relief of hyperthyroidism symptoms within 3 months after treatment, and all symptoms and signs disappear in 6 months to 2 years. The primary cure rate of iodine-131 is 50~80%, the total effective rate is over 95%, the relapse rate is 1~4%, and the inefficiency rate is 2~4%. The cure rate is positively correlated with the dose of iodine-131, with a low cure rate and low incidence of early-onset hypothyroidism for small doses, and a high cure rate and high incidence of early-onset hypothyroidism for large doses. The scale of iodine-131 treatment is to keep the incidence of early-onset hypothyroidism at an acceptable level while ensuring a high cure rate.
According to the changes of FT3 and FT4 and the improvement of clinical manifestations in GD patients, the evaluation criteria of the efficacy of iodine-131 treatment for hyperthyroidism are divided into four types.
Cured: The patient’s hyperthyroidism symptoms and signs completely disappeared, and FT3, FT4 and TSH returned to normal levels.
Improvement: The patient’s hyperthyroidism symptoms are reduced, the signs do not disappear completely, and the serum FT3 and FT4 do not drop to the normal range, or once dropped to the normal range and then rebounded.
Ineffective: The patient’s symptoms and signs of hyperthyroidism do not change or worsen, and the serum FT3 and FT4 concentrations are always higher than normal.
Hypothyroidism: Patients show symptoms of hypothyroidism, serum FT3 and FT4 are lower than normal, and TSH is higher than normal.
2. Efficacy of treatment of hyperthyroidism complications
① Hyperthyroidism myopathy: including myasthenia gravis, periodic paralysis and myasthenia gravis. After curing hyperthyroidism with iodine-131, myasthenia or myasthenia gravis mostly improves or recovers, and periodic paralysis usually does not occur anymore, but iodine-131 treatment does not help much to improve myasthenia gravis.
② Hyperthyroid heart disease: Its treatment lies in controlling hyperthyroidism. After hyperthyroidism is treated with iodine-131, atrial fibrillation disappears automatically, the enlarged heart gradually returns to normal, and cardiac function gradually improves.
③Graves’ ophthalmopathy: also known as thyroid-related ophthalmopathy (GO), it is one of the common manifestations of GD. It can be protruding in one eye or both eyes. Common symptoms include foreign body sensation in the eye, blurred vision, photophobia, tearing, and diplopia. Typical signs include proptosis, extraocular muscle dysfunction, perifoveal and eyelid edema conjunctival congestion and edema, epiretinal contracture, and exposure keratitis. the pathogenesis of GO has not been fully elucidated and may be related to thyroid stimulating hormone receptor antibodies (TRAb).
Approximately 13-45% of patients with GD have GO. Most patients are asymptomatic and do not require special management.
GO and hyperthyroidism are both independent and interrelated. GO can occur in patients with normal thyroid function, in patients several years after treatment of hyperthyroidism, or even in patients with hypothyroidism. GO occurs in 39% of patients with hyperthyroidism, 20% before hyperthyroidism, and 41% after hyperthyroidism. Mild proptosis usually decreases or disappears gradually 3-6 months after iodine-131 treatment.
In patients with hyperthyroidism without proptosis, the chance of inducing proptosis after iodine-131 treatment is very small. In patients with hyperthyroidism with proptosis, most of them return to normal, improve or remain stable after iodine-131 treatment, while very few patients have worsening proptosis. Iodine-131 therapy combined with glucocorticoids, early detection of hypothyroidism and timely thyroxine replacement can effectively prevent the occurrence and aggravation of proptosis.
(4) Hyperthyroidism combined with impaired liver function: Whether the liver function is abnormal due to hyperthyroidism or hyperthyroidism combined with other liver diseases (e.g. chronic hepatitis, cirrhosis), early iodine-131 treatment is emphasized, i.e. iodine-131 treatment is administered before the patient’s liver function has failed to the extent that it cannot withstand iodine-131 treatment. After hyperthyroidism is cured, liver function improves, especially the improvement of liver damage caused by hyperthyroidism is more obvious.
⑤ Others: In patients with hyperthyroidism combined with diabetes mellitus, iodine-131 treatment can improve diabetes mellitus while curing hyperthyroidism; in patients with hyperthyroidism psychosis, psychiatric symptoms can be controlled after iodine-131 treatment.