Graves’ disease is an autoimmune thyroid disease, also known as toxic Diffuse goiter, diffuse goiter with hyperthyroidism, and the clinical term hyperthyroidism is used to refer to Graves’ hyperthyroidism.
(I) Pathogenesis.
Graves hyperthyroidism is a disorder of immune balance in patients, which is a manifestation of autoimmune thyroid disease. The thyrotropin receptor antibodies produced by the patient’s B lymphocytes are an important cause of this disease, and also the reason why this disease is always delayed and repeated.
(ii) Clinical manifestations.
The main manifestations are hyperthyroid hormoneemia and increased sympathetic excitability, such as: palpitations, fear of heat, excessive sweating, anxiety, irritability, hyperphagia, weight loss, hand tremors, weakness, proptosis, increased frequency of stools, insomnia, fever, and lower limb edema. According to clinical observation, fear of heat, excessive sweating, weight loss, tachycardia and arrhythmia are common symptoms of hyperthyroidism.
In detail, the main changes of the body during hyperthyroidism are.
1. Abnormal energy and substance metabolism: increased basal metabolic rate, irritable fever, excessive sweating, weight loss, etc. Accelerated decomposition of liver glycogen and muscle glycogen, increased blood glucose, abnormal glucose tolerance, and often accompanied by diabetes.
2. Disorders of water and salt metabolism: thyroid hormones promote diuresis and increase potassium excretion, making it easy for hypokalemic periodic paralysis to occur. Hyperthyroidism hypokalemic paralysis manifests as sudden onset of bilateral lower limb flaccid paralysis, but the sensory nerve response is normal. It usually occurs at night or early in the morning. The blood potassium level is low, and recovery is rapid after potassium supplementation. In severe cases, respiratory muscle paralysis and difficulty in breathing can be life-threatening if not treated in time.
3. Cardiovascular system: Thyroid hormone excites the sympathetic nerve of the heart muscle and enhances the effect of catecholamines, which may lead to tachycardia, increased heart beat volume, arrhythmia, heart enlargement, increased pulse pressure difference, apical systolic murmur, atrial fibrillation, heart failure and hyperthyroid heart disease.
4. Mental and nervous system: excitation of neuromuscular by thyroid hormone, nervousness, irritability, hand tremor, increased excitability of plant nerves, hyperthyroidism psychosis, etc.
5. Digestive system: thyroid hormones increase intestinal motility, increase appetite, increase bowel movements, indigestion diarrhea, poor absorption of nutrients, etc.
6. Proptosis and ocular signs are important signs of Graves’ hyperthyroidism: When Graves first described the disease, he proposed three major signs: proptosis, nail swelling and mucinous edema in front of the tibia. Proptosis can be unilateral or bilateral. Hyperthyroidism and proptosis can occur simultaneously, or hyperthyroidism can occur after ophthalmopathy. A few cases only show proptosis with normal thyroid function, called Graves’ ophthalmopathy with normal thyroid function, also known as ophthalmic Graves’ disease.
Restricted mucinous edema in front of the tibia: mucinous edema in the soft tissues in front of the tibia, rough skin, pigmentation, thickening of soft tissues and toughness, no pressure pain. It is generally bilateral and symmetrical, and is a more specific sign of Graves’ hyperthyroidism, which is meaningful for diagnosis and less common in recent years.
(C) Diagnosis.
1. Hypermetabolic and sympathetic excitation symptoms: fear of heat, excessive sweating, wasting, cardiovascular symptoms, i.e. the presence of thyrotoxicosis, are common clinical manifestations of hyperthyroidism.
2. Increased blood T3, T4, FT3, FT4 and decreased TSH are important bases for the diagnosis of thyrotoxicosis.
3. Signs include goiter, proptosis, and pretibial mucinous edema. A positive one of these, combined with a positive 1 or 2 above, is an important basis for the diagnosis of Graves’ hyperthyroidism.
4. Increased thyroid uptake of 131 iodine and diffusely enhanced uptake of nuclear thyroid imaging are important bases for the diagnosis of Graves’ hyperthyroidism.
5. Positive blood thyroid antibodies support the diagnosis of autoimmune thyroid disease (Graves’ hyperthyroidism).
6. Other tests: ultrasound of the thyroid gland can be used for reference.
(iv) Treatment.
There are three types of treatment for hyperthyroidism: antithyroid drugs, 131 iodine and surgery. each of the three methods has its own characteristics, advantages and disadvantages, and there is no perfect one. The most traditional method is subtotal thyroidectomy, for which the surgeon who invented the procedure was awarded the Nobel Prize in 1909. 131 iodine and antithyroid drugs were then gradually established, and the U.S. Food and Drug Administration approved propylthiouracil and 131 iodine as treatment drugs for hyperthyroidism in 1947 and 1951, respectively. At present, thyroid surgery is generally only used when the thyroid gland is huge leading to obvious pressure symptoms or when hyperthyroidism is accompanied by nodules suspected of thyroid cancer, and hyperthyroidism is generally treated by internal medicine.
1. Anti-thyroid drug therapy.
Anti-thyroid drugs are still the first-line drugs for hyperthyroidism treatment because of their easy application and better clinical effect. However, the treatment course is long and the relapse rate is high after discontinuation (long-term remission rate <50%), and there are side effects such as liver, kidney and blood damage.
The common clinical antithyroid drugs are isopyrazoles (methimazole, tapazole) and thioureas (propylthiouracil).
The pharmacological mechanisms include: inhibition of thyroid peroxidase activity; inhibition of iodide activation, affecting iodination of tyrosyl residues; inhibition of MIT iodination; and inhibition of iodinated tyrosine coupling to generate thyroid hormones.
Therapeutic course: In the case of tabazol, the starting dose of 10 mg 3 times daily is gradually reduced until the blood levels of thyroid hormones are normal and clinical symptoms are relieved. Because it takes two weeks to release thyroid hormone stored in the thyroid gland and the plasma half-life of T4 is 7 days, the effect of the drug mostly appears in about 4 weeks. The reduction period is about 2-3 months, which is determined by the condition. The maintenance dose is 5-10mg/day. The total duration of treatment is 1.5-2 years.
It is common for patients to take antithyroid drugs for several years without stopping, which can easily lead to liver damage and hypocellularity, so a long course of treatment should be avoided. In cases of relapse, it is best to switch to 131 iodine therapy if relapse is still possible with antithyroid drugs. In cases of relapse after treatment with one antithyroid drug (e.g., tabazol), it is best to switch to 131 iodine treatment if the effect is often unsatisfactory when switching to another antithyroid drug (e.g., propylthiol).
During the treatment of hyperthyroidism, attention should be paid to the use of adjuvant drugs such as improving heart rate, protecting blood picture, protecting liver function, glucocorticoids, etc. For severe hyperthyroidism, Lugol’s solution can be used to control the hyperthyroidism for a period of time.
2.131 iodine therapy.
Indications: The indications for 131 iodine treatment abroad are simply one, that is, the disease suffered is Graves’ hyperthyroidism. With the popularization and deepening of 131 iodine treatment for Graves’ hyperthyroidism, the indications in China will be further simplified. At present, we choose 131 iodine treatment more often in the following cases: patients with poor efficacy of antithyroid drugs or multiple relapses, patients with long duration of disease or middle-aged or elderly patients, patients with allergy or other adverse reactions to antithyroid drugs, Graves’ hyperthyroidism combined with liver function impairment, Graves’ hyperthyroidism combined with leukopenia or thrombocytopenia, Graves’ hyperthyroidism combined with heart disease, patients with contraindication to surgery or high risk of surgery, patients with history of neck surgery or external irradiation, etc.
Contraindications: Pregnant and lactating patients, Graves’ hyperthyroidism with concomitant diagnosis or high suspicion of thyroid cancer (when surgery is the preferred treatment). Age is not a contraindication.
Features: easy method, positive efficacy, high cure rate, low recurrence rate, significant reduction in thyroid volume, safe and non-invasive, lower treatment cost and high benefit.
1) Preparation before 131 iodine treatment
A. Stop taking drugs and food that affect the effect of 131 iodine treatment for 2 weeks: drugs include anti-thyroid drugs, thyroxine tablets, perchlorate, iodine-containing contrast agents, etc.; food mainly refers to seafood rich in iodine.
B. Specialized examinations and related systemic tests: thyroid hormone levels, thyroid stimulating hormone levels, thyroid-related antibodies, thyroid ultrasound (to determine the weight of the thyroid gland, which is required for the 131 iodine dose formula), thyroid uptake rate and effective half-life (which is required for the 131 iodine dose formula and has a differential diagnostic role), thyroid static imaging (to estimate the weight of the thyroid gland, which also has a differential diagnostic role), and thyroid imaging (to estimate the weight of the thyroid gland, which is required for the 131 iodine dose formula). It is also useful for differential diagnosis.
C. Ask for detailed history of current illness, past history, family history, etc. The physical examination should also be done carefully, including physical examination of the thyroid, eyes, heart, lungs, liver, spleen, and limbs.
D. Patient’s informed consent should be signed.
2) Calculation of 131 iodine dose
The dose of 131 iodine should be calculated based on the principle of individual optimization, and at present there are many formulas, mainly two.
①Fixed dose method.
② Calculation of 131 iodine activity based on the absorbed dose required to achieve the therapeutic target thyroid or the planned amount of 131 iodine required per gram of thyroid.
Most experts in North America believe that the goal of 131 iodine treatment for Graves’ hyperthyroidism is hypothyroidism, so the fixed-dose method is mostly used, and for adults, treatment is given more than once.
The calculation method generally requires the determination of three important parameters: thyroid weight (or thyroid volume), maximum thyroid uptake rate (or 24-hour uptake rate) and effective half-life. The maximum thyroid uptake rate is generally a calculated value, so some formulas use the 24-hour uptake rate instead of the maximum 131 iodine uptake rate. The thyroid absorbed dose is chosen more often as 100Gy, and the amount of 131 iodine required per gram of thyroid is planned more often as 100μCi. Although the calculation method undergoes more experimental steps and fine calculations, the index of patients’ sensitivity to treatment cannot be estimated precisely, which is the main reason for the great difference in efficacy after treatment for patients with similar various parameters.
3) Method of drug administration
In order to ensure adequate absorption of 131 iodine by patients, it is advisable to take 131 iodine orally on an empty stomach or after 2 hours after a meal; in addition, food should be taken only 2 hours after taking 131 iodine.
4) Adjustment of 131 iodine treatment dose
Regardless of which dosage method is used, the 131 iodine dose can be adjusted before treatment with reference to the following factors
Factors for increasing the dose of 131 iodine: large and hard thyroid gland; old age, long medical history, poor effect of long-term anti-thyroid drugs; short effective half-life; poor or ineffective first 131 iodine treatment; Graves’ hyperthyroidism with comorbidities such as hyperthyroid heart disease and hyperthyroid myopathy.
Factors for reducing the dose of 131 iodine: young age, short medical history, small thyroid gland; those who have not undergone any treatment or relapsed after surgery; those who have obvious efficacy of the first 131 iodine treatment but are not in complete remission; those who have a long effective half-life.
5) Evaluation of the efficacy of 131 iodine therapy and patient follow-up
The efficacy of 131 iodine treatment for Graves’ hyperthyroidism is certain, generally speaking, the remission rate is 50-80% and the total effective rate is up to 95%. The overall efficiency of 131 iodine treatment is high and the cost-effectiveness ratio is high compared to other treatment methods. Symptoms and signs of hyperthyroidism do not resolve immediately after 131 iodine treatment, but generally begin to resolve 2-3 weeks after treatment, with symptoms disappearing and thyroid hormone levels gradually returning to normal in about 3-6 months.
In about 25% of patients, hyperthyroidism worsens after treatment and gradually resolves after 3-4 weeks. Patients can be followed up for 1 year at 1 month, 3 months, 6 months and 12 months after taking 131 iodine. The follow-up includes changes in the patient’s serum thyroid hormone levels, blood work, liver function and changes in the signs and symptoms of hyperthyroidism.