Treatment
The main goal of hyperthyroidism treatment is to reduce the concentration of thyroid hormones in the blood and to re-establish the normal metabolic state of the body. There are currently three basic methods for controlling hyperthyroidism syndromes.
①Treatment with anti-thyroid drugs and adjuvant drugs;
② Radioactive iodine (131Ⅰ) therapy;
③Surgical treatment. Each of the three has its own advantages and disadvantages. Before choosing a treatment plan, we must carefully consider the patient’s age, gender, condition, comorbidities and other factors.
1.Anti-thyroid drug (ATD) treatment ATD treatment is currently the most widely used in China. Its advantages are that the dose adjustment is relatively convenient, inexpensive, no special equipment is needed, and the incidence of persistent hypothyroidism after treatment is low; the disadvantage is that the course of treatment is long, the relapse rate is high after stopping the drug, and sometimes more serious drug side effects can be produced.
(1) drug type: anti-thyroid drugs are mainly thiourea derivatives; it is divided into two kinds of thiouracil and imidazole, the former has methylthiouracil (MTU) and propylthiouracil (PTU); the latter has methimazole that is tabazole and carbimazole that is hyperthyroidism. At present, the most used drugs in China are propylthiouracil (PTU) and methimazole (Tabazol).
(2) Pharmacological mechanism of action: The mechanism of action of these drugs has not yet been fully elucidated, and it is currently believed that they act mainly by inhibiting the activity of thyroid peroxidase to prevent the synthesis of thyroid hormones. They act roughly through the following links.
(i) inhibiting the binding of iodine to tyrosine in the thyroid gland, i.e., inhibiting the formation of monoiodotyrosine and diiodotyrosine.
(ii) Blocking the coupling of iodinated tyrosine to T3 or T4.
(iii) Propylthiouracil (PTU) also blocks the conversion of T4 to T3 in peripheral tissues. This effect is positively correlated with dose and is more pronounced when the dose is greater than 600 mg/d.
(4) This group of drugs also mildly inhibits immunoglobulin production, resulting in a decrease in lymphocytes in the thyroid and a decrease in TRAb in the blood circulation.
(3) In vivo processes and effects: Thioureas are rapidly absorbed after oral administration and begin to appear in the blood in 20-30 min, with peak concentrations within 2 h; they can be distributed throughout the body in various tissues, but the highest concentrations are found in the thyroid gland. This drug can pass through the placenta, so use with caution during pregnancy; the concentration in breast milk is also high, so it is prohibited during lactation; it is mainly metabolized in the liver, about 60% is destroyed, and part of it is excreted after combining with glucuronide; the metabolism is fast and the action time is not long. The half-life of propylthiouracil (PTU) in the body is only 90s, and that of methimazole (tabazole) is 6h, but the drug concentration in the plasma is not closely related to the duration of its action, because thioureas are gradually accumulated in the thyroid gland after the effect occurs.
Since thioureas can only inhibit the synthesis of thyroid hormones but not their release, they can only be effective after the hormones originally synthesized in the thyroid gland are gradually released and metabolized after the drug is administered. Iodine can increase the storage of hormones in the thyroid gland, so the use of iodine in the early stage of treatment will delay the effect of thioureas. The use of thioureas sometimes aggravates goiter and proptosis because the concentration of TSH in the blood increases due to the decrease in thyroid hormones. If thiourea is overdosed, it may cause hypothyroidism symptoms.
(4) Indications.
①Adolescent and pediatric patients;
②Mild to moderate hyperthyroidism;
(3) Pregnant women;
④Recurrence after subtotal thyroidectomy and not suitable for radioactive 131I treatment;
⑤Patients with hyperthyroidism with severe proptosis can be treated with small doses first;
⑥Preparation for surgery or radioactive 131I treatment;
(7) Those who cannot be operated because of serious organic diseases, such as serious heart disease and bleeding disease.
(5) Dose and course of treatment: The total course of thiourea treatment is at least 2 years, which can be roughly divided into 3 stages.
(1) Initial treatment stage: The initial treatment dose needs to be determined according to the condition. For patients with severe symptoms or obvious goiter, the dose should be high; for patients with mild symptoms, extremely high titers of TGAb and TMAb, obvious proptosis and combined pregnancy, the dose should be low. In general, methimazole (thiamazole, tapazole, tabazole) 20-60mg/d; PTU 200-600mg/d are suitable for patients with different degrees of symptoms, and are divided into 3 to 4 doses.
The initial treatment phase is usually 1 to 3 months, and symptoms often begin to resolve in 2 to 3 weeks. If symptoms do not improve after 3 months of treatment, consideration should be given to increasing the dose and checking for interfering factors, such as irregular dosing, and stressful situations such as iodine administration and infection.
After 3 months of treatment, most of the patients show significant improvement in symptoms such as hyperphagia, hyperhidrosis and irritability, and weight gain, but whether they can enter the dose reduction phase still needs to be determined according to the specific situation, and the following conditions can be referred to; the above-mentioned symptoms improve significantly, the thyroid gland starts to shrink, the murmur in the neck and precordial area decreases; FT4, TT4 and T3 all drop to the critical range; in the case of discontinuing β-blockers, the heart rate is stable when lying down at 80 beats/s or so.
②Dose reduction phase: After meeting the above conditions and entering the dose reduction phase, the drug dose can be reduced by 1/3 and observed for 2 to 4 weeks after the dose reduction, and then reduced by 1/3 if the condition is stable and closely observed. The dose should not be reduced too rapidly, and when the symptoms rebound, the dose should be increased appropriately and stabilized for 2 to 4 weeks.
After 1 to 3 months of dose reduction, if the condition remains stable, the maintenance phase will be started. The following conditions can be used for reference: the symptoms and signs of hyperthyroidism basically return to normal and are stable for at least 2 weeks; FT4, TT4 and T3 are in the normal range; the ultrasensitive TSH rises to the normal range; the heart rate can be stabilized below 85 beats/s in daily life with the discontinuation of β-blockers.
③Maintenance phase: The size of the maintenance dose needs to be determined on an individual basis, and each patient can explore a dose that is appropriate for him/her. Patients can follow the method of decreasing the dose of medication in the decreasing phase, and when the dose is reduced to a certain dose that can not be further reduced (otherwise the symptoms rebound), it is the maintenance dose for the patient. The maintenance dose for most patients is 2.5-10 mg/d of methimazole and 25-100 mg/d of PTU. The maintenance phase is at least 1 year.
④Discontinuation: Generally, discontinuation is considered only after 2 years of use, and the following conditions must be met when discontinuing the drug; various symptoms and signs have disappeared and the disease has been stable for at least 1 year; FT4, TT4, T3, ultrasensitive TSH and other indicators have completely returned to normal for at least 1 year; at least two consecutive TRAb tests are negative, with an interval of 3-6 months between the two; the usual maintenance dose of methimazole (tabazol) required.