TGA (thyroglobulin antibodies) and MCA (TMA, thyroid microsomal antibodies) are the two main specific thyroid autoantibodies in serum. They are elevated in autoimmune thyroid diseases (e.g., chronic lymphocytic thyroiditis and Graves’ disease) and can also be detected in the blood of other thyroid diseases and healthy people, but at lower titers. TGA is a specific diagnostic indicator for chronic lymphocytic thyroiditis and is often significantly elevated. Thyroglobulin (Tg), a 660 ku glycoprotein secreted by the thyroid follicular epithelium, has about 2 molecules of thyroxine (T4) and 0.5 molecules of triiodothyronine (T3) per Tg and is stored in the follicular lumen. This human protein consists of 2767 amino acid residues and is the storage form of iodine in the body in the thyroid gland, which is hydrolyzed to produce thyroxine and 3,5,3′-triiodothyronine. Normal Tg values Tg can be detected in all normal human serum using sensitive assays, and there is no circadian or seasonal variation in serum Tg. Tg concentration is determined by three main factors: (1) thyroid size. (2) Thyroid damage, such as biopsy, trauma, hemorrhage, radiation damage and inflammation. (3) Hormonal effects, such as TSH, human chorionic gonadotropin and TSH receptor antibodies (TRAb). In the physiological state, thyroid size is the main determinant of Tg level, 5~40 μg/L. Abnormal thyroid function and serum Tg In Graves’ hyperthyroidism (hyperthyroidism) patients, Tg is elevated in almost all patients due to TRAb stimulation. A few have no high or low serum Tg, probably due to TGAb, and Tg returns to normal after hyperthyroidism treatment. In some refractory hyperthyroidism, serum Tg remains at high levels even though T4 and T3 are normal. The relationship between serum Tg and TRAb and recurrence of hyperthyroidism is not very close. Tg peaks on day 1 after hyperthyroidism surgery and decreases to normal after several months; after isotope therapy, Tg can be elevated for 1 to 3 months. Serum Tg is elevated in patients with Plummer’s hyperthyroidism, subacute thyroiditis, and painless thyroiditis, and exogenous thyroid hormone drugs cause low Tg in hyperthyroid patients. Differentiated thyroid cancer and serum Tg The use of Tg as a tumor marker is well established, but whether or not it predicts prognosis and survival in this disease is not well understood, but it is more accurate than radioiodine scans. Serum Tg values before surgery for differentiated thyroid cancer are not meaningful for diagnosis because blood Tg can also be elevated in patients with thyroid disease who do not have thyroid cancer and can be normal in patients with thyroid cancer. Pre-surgical blood Tg levels in differentiated thyroid cancer are positively correlated with tumor size. The biological half-life of Tg in vivo is 65.2 h. It takes 5-10 d after thyroidectomy for Tg to fall below 5-10 μg/L. Ronga et al. retrospectively analyzed 334 patients with differentiated thyroid cancer and measured blood Tg for the first time 40 d after surgery and followed up with regular blood Tg measurements and whole-body scans for 4-16 a. The results showed that blood Tg was elevated in patients with differentiated thyroid cancer for 18 months after surgery. As a result, the first blood Tg values were significantly higher in 79 patients with tumor metastases during 18 months after surgery (258.9±31.1) than in patients without metastases (15.9±19.6) μg/L, p<0.0001]. Therefore, positive blood Tg after surgery suggests tumor recurrence or metastasis. After total thyroidectomy and high-dose 131I therapy in patients with differentiated thyroid cancer, if serum TGAb is negative, then serum Tg should not be measured. If serum TSH is suppressed, elevated serum Tg is often indicative of remaining tumor tissue or metastases. After total thyroidectomy for papillary and follicular thyroid carcinoma, blood Tg should be <10 μg/L. If >10 μg/L indicates the possibility of metastatic foci, the sensitivity of this diagnosis is 100% and specificity is over 80%. negative Tg measurement can reduce unnecessary whole body iodine 131 scans during follow-up. Determination of basal blood Tg and Tg after TSH stimulation is useful to detect the presence or absence of thyroid tissue. An undetectable basal Tg indicates the absence of thyroid tissue; a positive basal Tg with a poor response to TSH indicates a poorly differentiated tumor; a positive basal Tg with a good TSH response indicates the presence of residual thyroid tissue or the presence of differentiated thyroid cancer. When serum TSH concentration is low, Tg values may not be sensitive enough to determine tumor recurrence, and it is necessary to stop levothyroxine T4 (L-T4) treatment for several weeks and measure Tg again when serum TSH is elevated. there is a 10-fold or more increase in blood Tg response to TSH in patients with normal thyroid, and it can be more than 3-fold in patients with well-differentiated thyroid cancer. However, discontinuation of L-T4 can cause discomfort to the patient and may also cause tumor recurrence and metastasis. Tg positive but isotope iodine phase negative often suggests a smaller differentiated cancer, or it may be that iodine agent interferes with isotope scan, or TGAb and other factors interfere with Tg determination, causing Tg false positive. Tg negative but isotope iodine phase positive may be that TGAb interferes causing Tg false negative, or the tumor secreted Tg molecule has abnormal structure and cannot be recognized by Tg antibody. Postoperative follow-up of thyroid cancer: After 2-3 months of initial treatment, thyroid function test should be performed to assess the efficacy of levothyroxine. Follow-up for 6-12 months should determine whether the patient is in the disease-free phase. Assessment includes physical examination, ultrasound, basal and post-rhTSH stimulation serum Tg levels. The latest guidelines of the European Society of Medical Oncology 2012: (1) If the basal serum Tg level is less than or equal to 0.1 ng/ml and the neck ultrasound is unremarkable, the patient is considered to be in the disease-free phase and does not require stimulation testing, and long-term follow-up is only required once a year. (2) When the basal Tg is greater than 0.1ng/ml and also less than 1.0ng/ml, stimulated testing can help detect those patients with elevated Tg to greater than 1.0ng/ml, and these patients require closer follow-up. Imaging is required to find possible lesions, and PET is performed in patients who cannot undergo iodine testing. The prognosis is worse in those with positive imaging.