Thyroglobulin and Thyroglobulin Antibodies

Differentiated thyroid cancer (DTC) is the most common endocrine cancer, and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131 depending on post-operative risk stratification. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up of DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous thyrotropin (TSH) is suggested to detect occult disease with maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has been incorporated into more recent clinical guidelines; thus, the cornerstone in current guidelines for long-term follow-up is by measuring serum basal (i.e. unstimulated) Tg, and most patients can be followed by this method. However, some thyroid cancer patients have serum anti-thyroglobulin antibodies (TgAb), both at diagnosis and after treatment, when follow-up is started. As these antibodies interfere technically in the immunological methods measuring Tg, current guidelines cannot be implemented in the follow-up of TgAb-positive patients. However, many studies have indicated that following the concentration of TgAb in serum could serve as a “surrogate marker” for recurrence of the thyroid carcinoma. Additionally, in recent years, complementary laboratory methods such as Tg mini-recovery test and Tg measurement by tandem mass liquid spectrometry were proposed to overcome interferences when measuring Tg. The present chapter reviews the biological basis, advances and challenges in Tg and TgAb measurement techniques, as well as their impact on clinical management of DTC patients.