Thyroglobulin Autoantibodies as Surrogate Biomarkers in the Management of Patients with Differentiated Thyroid Carcinoma

Abstract

Differentiated thyroid cancer is a rare malignancy, but leaves numerous survivors for life-long follow-up. The cornerstone in current guidelines for follow-up is by measuring the thyroid specific tumour marker, thyroglobulin in serum. Most patients can be followed by this method, but some thyroid cancer patients have antithyroglobulin antibodies in serum, both at diagnosis and after treatment, where follow-up is commenced. These antibodies interfere technically in the immunological methods for measuring thyroglobulin, and the antithyroglobulin antibody positive patients are thus eliminated from following current guidelines. In recent years studies have indicated that following the concentration of antithyroglobulin antibodies in serum may be a surrogate marker for recurrence of the thyroid carcinoma. This has recently resulted in publication of an expert position paper, providing a flow scheme for these particular patients. The current review summarises the literature which is the basis for the paper.

Insights into the posttranslational structural heterogeneity of thyroglobulin and its role in the development, diagnosis, and management of benign and malignant thyroid diseases

“…Previous studies have shown that higher titers of anti-Tg antibodies are associated with higher risk of recurrence and have found that the higher the levels of these antibodies, the higher the chances of tumor recurrence (50)(51)(52). Although the presence of antibodies hinders the use of Tg as a followup marker, in some cases the serial TgAb measurements function as a surrogate marker (53). Thus, the majority of patients with DTC and positive TgAb tend to exhibit a progressive decline in titers of these antibodies, and a new increase in antibody levels may be considered a sign of tumor recurrence (52,53).…”

“…Although the presence of antibodies hinders the use of Tg as a followup marker, in some cases the serial TgAb measurements function as a surrogate marker (53). Thus, the majority of patients with DTC and positive TgAb tend to exhibit a progressive decline in titers of these antibodies, and a new increase in antibody levels may be considered a sign of tumor recurrence (52,53). However, anti-Tg antibody positivity itself does not correlate directly with worse prognosis, unless titers increase progressively.…”

“…However, anti-Tg antibody positivity itself does not correlate directly with worse prognosis, unless titers increase progressively. In fact, it is the trend of serum concentration of TgAb, i.e., if it is downward or upward, which will define patient outcomes (53). Regardless of the implications of this phenomenon, the reappearance of anti-Tg antibodies in these patients is an additional indicator of the increased antigenicity of tumor-derived Tg.…”

Early post-treatment risk stratification of differentiated thyroid cancer: comparison of three high-sensitive Tg assays

“…For TgAb-positive patients, the use of serum levels of TgAb as a 'surrogate tumor marker' has been widely adopted in clinical practice (i.e. declining TgAb levels may indicate reduced tumor burden or the absence of disease while the persistence of anti-Tg antibodies, especially if levels are rising, may indicate persistent, recurrent or progressive thyroid cancer) (1,3,4,11). However, the serum levels of TgAbs are not correlated with the tumor load of the patient, but rather indicate the activity of the immune system.…”

Abstracts and short papers from the 5th Congress of the Polish Thyroid Association, Poznan, 3-5 September, 2015

“…In an attempt to elucidate if the presence of TPO.Ab in breast cancer was an expression of a generalised immune response to the cancer or a true indication of autoimmune thyroid disease the author explored the relevance as to the significance of detectable rather than elevated levels of TPO.Ab in breast cancer [15,16]. Examining serum TPO.Ab concentration and its relationship to TSH in patients with postmenopausal breast cancer compared to postmenopausal controls it emerged that there was an association, not only between elevated TPO.Ab (>20.0 kIU/l) and serum TSH but that this association also applied to those patients with breast cancer who had detectable TPOAb (>2.0 < 20.0 kIU/l).…”