Tg-Ab and differentiated thyroid cancer

TOPIC: Tg-Ab measurements for prediction of recurrence in thyroid cancer

Title: The prevalence of transient change of serum thyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma

Authors: Kim WG , Yoon JH, Kim WB , Kim TY , Kim EY , Kim JM , Ryu JS , Gong G , Hong SJ , & Shong YK .

Reference: Journal of Clinical Endocrinology & Metabolism93: 4683–4689, 2008

Purpose

Evaluate the usefulness of thyroglobulin autoantibody (Tg-Ab) measurements 6-12 months after remnant ablation for predicting recurrence in patients with differentiated thyroid carcinoma (DTC) with undetectable thyroglobulin (Tg) levels. The change in Tg-Ab titers measured between the time of remnant ablation (Tg-Ab1) and 6-12 months thereafter (Tg-Ab2) was also evaluated as a possible prognostic marker.

Patients & Methods

Patients with DTC who underwent total thyroidectomy (Tx) followed by 131I remnant ablation between 1995 & 2003 at the Asian Medical Center (Seoul, Korea) were enrolled. Of these, 824 patients with undetectable Tg levels at 6-12 months after remnant ablation during thyroid hormone withdrawal were the subjects of present study.

Results

Tg-Ab2 was positive in 56 patients. Ten of these 56 patients (18%) with positive Tg-Ab2 had a recurrence, whereas only 10 of 768 patients (1%) with negative Tg-Ab2 had a recurrence during 74 months of follow-up (P<0.001). Changes between Tg-Ab1 & Tg-Ab2 titers were evaluated in patients with positive Tg-Ab2. Tg-Ab titers decreased by more than 50% in 21 patients (group 1) and by less than 50% in 16 patients (group 2), and Tg-Ab titers increased in 19 patients (group 3). Recurrence rates in groups 1, 2, and 3 were respectively 0, 19, and 37% (P=0.016).

Conclusions

Serum Tg-Ab titers measured 6-12 months after remnant ablation were predictive of a recurrence in patients with undetectable Tg levels. In patients with undetectable Tg and positive Tg-Ab, a change in Tg-Ab concentration during the early postoperative period may constitute a valuable prognostic marker of recurrence.

Commentary

Serum Tg measurement is important for follow-up of patients with differentiated thyroid carcinoma (DTC) after surgery and detection of persistent/recurrent thyroid cancer, since thyroid tissue is the only source of Tg production. However, in the presence of thyroglobulin autoantibody (Tg-Ab) a ‘negative Tg’ immunometric assay (IMA) result is most likely a false-negative results, owing to Tg-Ab interference with currently available IMA methodology. Recent guidelines have recommended assessing Tg-Ab quantitatively, with simultaneous measurement of serum Tg (every 6-12 months after surgery), and also that IMA methods to measure Tg should not be employed when Tg-Ab is positive. Complete elimination of follicular cells by total thyroidectomy followed by remnant ablation should lead to cessation of the antigenic stimulus and, consequently, to progressive decline of Tg-Ab titers, resulting eventually in Tg-Ab disappearance. Thus, persistence of Tg-Ab for a long period after initial treatment or increasing Tg-Ab concentration indicates persistence of Tg-producing tissues which, in turn, reflects persistent/recurrent DTC because all normal follicular cells have already been destroyed. Indeed, previous studies have reported that Tg-Ab disappeared after ablation of thyroid tissue, with a median disappearance time of 3 years or less. There were some limitations to this study. First, the authors did not check whether Tg-Ab titers <100 U/ml would affect serum Tg measurements. Second, they did not distinguish cases where Tg-Ab2 levels were obtained at 6 months from those where Tg-Ab2 was measured at 12 months, although the majority of measurements were performed at 12 months. Third, Tg-Ab was not determined preoperatively in all patients. Despite these inherent limitations, this is the first study to indicate the prognostic value of changing patterns of Tg-Ab titers that used the same Tg-Ab assay methodology throughout the study. Summary and Commentary prepared by Takashi Akamizu (Related to Chapter 18 of TDM)