A recent review of 1500 consecutive DTC patients with more than 2 years postoperative follow-up found that although 22.7% were currently TgAb-positive, an additional 12.7% had a past history of TgAb-positivity but had become TgAb-negative during the postoperative period [27,37▪▪,98,99]. Thus, approximately one-third of DTC patients have TgAb detected at some time in their course, and clearly the TgAb status of a patient can change over time necessitating TgAb measurement with every thyroglobulin test [1,2,14▪,16▪▪,30▪▪,44]. Although the most common change in TgAb status is positive to negative in response to successful treatment [27,37▪▪,98,99], the persistence of TgAb, a rising TgAb trend, the failure of TgAb to fall or a de-novo TgAb appearance is highly suspicious for active disease [7,14▪,37▪▪,89,92,100,107]. However, a rising TgAb concentration is not specific for recurrence but can also result from any thyroid injury causing thyroglobulin release (RAI treatment, lymph node biopsy or additional surgery) . It is now apparent that TgAb concentrations respond to changes in the mass of thyroglobulin-secreting thyroid tissue so that the trend in TgAb concentrations can be used as a surrogate tumor-marker [7,14▪,30▪▪,37▪▪,65,89,90,98,100,107]. Thus, TgAb measurement is not merely a qualitative (positive versus negative) test for validating that a Tg2GIMA measurement is free from TgAb interference but acts as an indicator for thyroglobulin antigen sensed by the immune system. Unfortunately, given the difference in numeric values reported by different TgAb methods, and the time needed to establish the TgAb trend (TgAb half life ∼10 weeks ), it is critical that postoperative TgAb monitoring be performed using the same manufacturer's method [29,30▪▪,36,90]. Alternatively, when a change in TgAb method is necessary, the patient-specific ratio between the new versus the old TgAb test can be used to rebaseline TgAb testing to the new method, as previously described [37▪▪,90].
The clinical utility of monitoring TgAb trends as a surrogate tumor-marker is illustrated in Fig. 4, in which serum TgAb monitoring of four PTC patients without disease is shown in the upper panels, to contrast with four PTC patients with persistent or recurrent disease shown in the lower panels. Figure 4a shows that TgAb-positive patients rendered disease-free by thyroidectomy may display a transient early rise in TgAb in response to the thyroglobulin released by the surgery and/or RAI treatment, but thereafter TgAb progressively declines and may become undetectable during the early years of follow-up, especially if the initial TgAb concentration was low. Disease-free patients with high TgAb concentrations typically display a slow progressive TgAb decline over years but may not achieve full TgAb-negativity, possibly because of the long-lived memory of plasma cells . The left-hand panels show the TgAb concentrations expressed as percentage of an initial (0–3 month) value. Figure 4b shows that when patients are disease-free, TgAb concentrations typically fall by more than 50% during the first postoperative year [26▪,30▪▪,34,100] and thereafter continue to fall to less than 10% of initial value over subsequent years. These TgAb trends contrast with those of the PTC patients with persistent or recurrent disease shown in the lower panels. Figure 4c shows that when there is active disease, TgAb concentrations may show a decline in the early months following thyroidectomy that is not sustained, or may be followed by a progressive TgAb rise or even a de-novo TgAb appearance sometimes years after TgAb absence, necessitating concurrent TgAb measurement with every thyroglobulin test [30▪▪,44,107]. Figure 4d illustrates that although some patients with active disease have a 50% TgAb decline in the first postoperative year, TgAb rarely declines to less than 10% unless the disease is successfully treated.
Now that RAI treatment is no longer considered necessary to treat low-risk DTC, postoperative serum thyroglobulin monitoring will primarily be made for disease-free patients who have functioning thyroid remnants that typically give rise to serum basal Tg2GIMA concentrations in the 0.05–0.5 μg/l or less range when TSH is suppressed. When TgAb is absent (∼75% of DTC), the serum basal Tg2GIMA trend and doubling time are important prognostic parameters. However, when TgAb is present, Tg2GIMA measurement is unreliable because of interference causing Tg2GIMA underestimation and the trend in TgAb concentrations (measured by the same method) becomes the primary (surrogate) tumor-marker.
Papers of particular interest, published within the annual period of review, have been highlighted as:
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