The most effective and primary treatment for thyroid cancer is surgery. The appropriate scope of surgery is the key to the success or failure of the treatment. However, there is no denying that various postoperative non-surgical adjuvant treatments have a great impact on long-term survival and recurrence rates, especially for patients in high-risk groups. Non-surgical treatments for thyroid cancer include thyrotropin suppression therapy, nuclear iodine therapy, radiation therapy, chemotherapy, and biologic therapy. This article describes thyrotropin suppressive therapy for differentiated thyroid cancer.
The correct application of thyrotropin (TSH) suppression therapy after surgery for differentiated thyroid cancer can achieve good results in most papillary and follicular cancers, and the local recurrence rate and distant metastasis rate are significantly reduced. Thirty-year survival rate is also significantly improved.
I. Indications
Since the prognosis of differentiated thyroid cancer in the high-risk group is inferior to that in the low-risk group, and thyroxine increases oxygen consumption in the heart and causes osteoporosis, the best indication for suppressive therapy is differentiated thyroid cancer aged <65 years without cardiovascular disease, especially in the high-risk group and premenopausal women. Secondly, suppressive therapy is also indicated after total thyroidectomy for differentiated thyroid cancer, especially within 5 years after surgery when the cancer is prone to recurrence. Suppressive therapy should be given when there are some poor prognostic factors, such as thyroid cancer without iodine uptake, age >40 years, mass diameter >4 cm, invasion of the envelope, etc.
Choice of agent
Currently, levothyroxine (LT4) is commonly used, with a longer half-life of about 7 days, while the half-life of liothyronien is only 24h, which is beneficial for patients in the high-risk group who need to undergo nuclear scan at any time, in order to shorten the time of stopping the drug before the examination and to perform the scan in time. LT4 (euthyroxine) is a pure preparation with accurate thyroxine content and no risk of allergic reactions, but it is a little more expensive, while the biologic thyroid tablets are crude and have less accurate thyroxine content, but still have value because of their low cost. Once conditions permit, it is convenient to interchange thyroid tablets with LT4. The half-life of both is also similar.
Third, the mastery of the dose
The dose should be determined by the concentration of TSH (S-TSH) and the concentration of T3, T4, FT3, especially FT4, as measured by high-sensitivity immunoassay in serum. It is required that S-TSH is reduced to a certain value, while T3, T4, FT3 and FT4 are maintained within the normal range. Depending on the need, suppressive therapies are divided into two types: total suppressive therapy and partial suppressive therapy. The former requires S-TSH to be below the normal low value, usually <0.3 μIU/ml or even <0.01 μIU/ml. The latter requires S-TSH to be within the normal low value, often 0.3-1 μIU/m1 (normal reference value for S-TSH is 0.3-6.3 μIU/ml).
The American Association of Clinical Endocrinology and the American Thyroid Association recommend a partial suppression regimen for patients in the low-risk group (MACIS score <6.0, AJCC stage I), i.e., TSH < low normal values. For intermediate-risk patients (MACIS score 6.0-6.9, AJCC stage II or stage III papillary carcinoma with lymphatic metastases only), total suppression is recommended, but clinical hyperthyroidism should not be present. In the high-risk group (MACIS score >7.0, AJCC stage IV) hyperthyroidism is allowed with suppressive therapy, but the complications, especially osteoporosis in menopausal women, should be closely monitored. In addition, the dose of thyroxine must be reduced with increasing age in order to reduce osteoporosis and increase myocardial oxygen consumption in rabbits. However, the dose shall be increased when there are the following factors.
1, the gastrointestinal tract malabsorption: such as hepatic sclerosis, short bowel syndrome, etc.
2. Concurrent administration of certain drugs that block T4 absorption: such as aluminum hydroxide, aluminum thioglycollate, ferrous sulfate, lovastatin (, cholesterol-lowering drug), anti-cholestatic gel, etc. 3 Pregnancy, etc.
The effective dose of LT4 is <60 years old: 2.2 μg/kg.d; >60 years old: 1.5-1.8 μg/kg.d. The common initial dose is about 50-100 μg/d of LT4 or 20-40 mg/d of thyroid tablets, but the sensitivity varies individually and the dose should be adjusted with the measurement of thyroid function. The dose should be adjusted according to thyroid function measurements. Patients in the low-risk group should only require partial suppression therapy.
Duration of administration
Patients in the high-risk group should preferably take it for the rest of their lives, while the low-risk group is prone to recurrence during the first 5 years after surgery. Therefore, total suppressive therapy can be administered within 5 years after surgery, with close follow-up and regular imaging such as neck ultrasound, nuclear scan, chest X-ray, CT and ECT. If there is no recurrence, partial suppressive treatment or no treatment can be administered after 5 years. In case of metastasis or recurrence, surgical resection or other non-surgical treatment will be performed. If the initial surgery is a total thyroidectomy or if the residual thyroid gland has been completely destroyed by nuclear iodine ablation, monitoring of serum thyroglobulin (TG) levels at the time of follow-up is of great interest. TG should not increase when suppressive therapy is effective. Once serum TG increases >5 ng/day after 4-6 weeks of cessation of effective suppressive therapy as indicated by the S-TSH assay, one must be alert for tumor recurrence or metastasis. Serum TG levels are more sensitive than nuclear scans after total thyroidectomy for non-functioning thyroid cancer.
Since TG is caused by TSH stimulation of the thyroid follicles, it can be increased by any disease that increases thyroid function, such as nodular goiter and thyroiditis. Therefore, when there is a functioning thyroid follicle, an increase in TG does not imply a malignant tumor.
V. Adverse effects of suppressive therapy
As long as the dose of thyroxine is appropriate, most of the adverse effects are not significant. Once the dose is too high, the following three hazards can be caused and must be prevented.
1, hyperthyroidism (hyperthyroidism) or subclinical hyperthyroidism: as long as the regular review of thyroid function, so that T3, T4, FT3, especially FT4 to maintain within the normal range can avoid this adverse reaction.
2. Osteoporosis: It is characterized by bone pain, increased blood calcium, urinary calcium and osteoporosis, and decreased serum parathyroid hormone, especially in patients with insufficient calcium intake, alcohol consumption, tobacco addiction, hormone dependence and menopausal women.
3, increased myocardial oxygen consumption, promoting angina pectoris, and even myocardial infarction. Therefore, inhibitory therapy must be used with caution or abandoned in patients with coronary arteriosclerotic heart disease, hypertensive heart disease or elderly patients, as well as in patients with atrial fibrillation.
The efficacy of suppression therapy
Inhibition therapy has been shown to reduce the recurrence rate of papillary and follicular adenocarcinoma and the mortality associated with thyroid cancer, even in elderly patients with progressive disease. However, the efficacy of suppressive therapy for advanced lesions is not as good as that of advanced lesions. Recently, a retrospective analysis of 683 cases from 14 centers summarized by international classification suggested a significant reduction in recurrence rate and prolonged survival in both stage III and W and stage I and H papillary carcinomas. In addition, although there was no significant difference in the 10-year survival rate between the suppressive therapy group and the control group, the 30-year survival rate showed that the suppressive therapy group significantly outperformed the control group.