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, which are stored in the follicular lumen. Lysosomes hydrolyze Tg surface T4 and T3 and release them into the blood, while a small amount of Tg is also released into the blood, and some Tg is secreted into the blood via the thyroid lymphatics. Tg in the blood circulation is cleared by macrophages in the liver. The secretion rate of Tg is 100 mg/(60 kg・d) and its plasma half-life is (29.6±2.8) h. Yang Hui, Department of Nuclear Medicine, Henan Cancer Hospital
1 Tg determination Tg determination has undergone hemagglutination, release immunoassay (RIA) and release immunoassay (IMA), but it was not until the current sensitive luminescence method for Tg determination, which can distinguish between normal values of Tg and low values after thyroidectomy, that Tg determination was used clinically.
The interference of serum thyroglobulin antibody (TGAb) on the determination of serum Tg is not proportional to the concentration of serum TGAb, and the degree of interference is related to the nature and affinity of the antibody, specificity and serum volume. when TGAb is positive, the Tg value determined by IMA method is easy to be low, causing false negatives and masking patients with recurrent and metastatic thyroid cancer; the Tg value determined by RIA method is easy to be high, causing false positives. The Tg value determined by RIA method is likely to be high and cause false positives.
Tg concentration is mainly determined by 3 factors: (1) thyroid gland size. (2) Thyroid damage, such as biopsy, trauma, hemorrhage, radiation damage and inflammation. (3) Hormonal influences, such as TSH, human chorionic gonadotropin and TSH receptor antibodies (TRAb). In the physiological state, the size of the thyroid gland is the main determinant of Tg levels, with normal values of Tg ranging from 5 to 40 μg/L.
3 Abnormal thyroid function and serum Tg In Graves’ hyperthyroidism (hyperthyroidism) patients, Tg is elevated in almost all patients due to the stimulation of TRAb. In a few people, serum Tg is not high or is low, probably due to the effect of 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 patients with hyperthyroidism.
4 Differentiated thyroid cancer and serum Tg 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, while blood Tg can also 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, and it takes 5-10 d after thyroidectomy for Tg to fall below 5-10 μg/L. Ronga et al [6] 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. 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 131I scans during follow-up.
Determination of basal blood Tg and Tg after TSH stimulation is beneficial in detecting 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 remaining thyroid tissue or the presence of differentiated thyroid cancer. When serum TSH concentration is low, Tg value 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 after serum TSH is elevated. blood Tg response to TSH increases more than 10-fold in patients with normal thyroid and can increase more than 3-fold in patients with well-differentiated thyroid cancer. 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 indicates 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 TGAb interference causing Tg false negative, or the tumor secreted Tg molecule has abnormal structure and cannot be recognized by Tg antibody.
—- From Dai Weixin Bai Yao, Determination and clinical aspects of thyroglobulin, Foreign Medical Journal of Endocrinology, Vol. 22, No. 6, November 2002, 364-365