Change of Serum Antithyroglobulin Antibody Levels Is Useful for Prediction of Clinical Recurrence in Thyroglobulin-Negative Patients with Differentiated Thyroid Carcinoma

ORIGINAL ARTICLE E n d o c r i n e C a r e Change of Serum Antithyroglobulin Antibody Levels Is Useful for Prediction of Clinical Recurrence in Thyroglobulin-Negative Patients with Differentiated Thyroid Carcinoma Won Gu Kim,* Jong Ho Yoon,* Won Bae Kim, Tae Yong Kim, Eui Young Kim, Jung Min Kim, Jin-Sook Ryu, Gyungyub Gong, Suck Joon Hong, and Young Kee Shong Departments of Endocrinology and Metabolism (W.G.K., W.B.K., T.Y.K., E.Y.K., Y.K.S.), Nuclear Medicine (J.-S.R.), Pathology (G.G.), and Surgery (J.H.Y., S.J.H.), Asan Medical Center, University of Ulsan College of Medicine, Seoul 138 –736, Korea; and Thyroid Cancer Clinic (J.M.K.), National Cancer Center, Goyang 410-769; Korea Objectives: The aim of the study was to evaluate the usefulness of the antithyroglobulin autoantibody (TgAb) value at 6 –12 months after remnant ablation in predicting recurrence in differentiated thyroid carcinoma patients who had undetectable thyroglobulin (Tg) values. The change in TgAb concentration measured between the time of remnant ablation (TgAb1) and 6 –12 months thereafter (TgAb2) was also evaluated as a possible prognostic indicator. Patients and Methods: Patients with differentiated thyroid carcinoma who underwent total thyroidectomy followed by 131I remnant ablation between 1995 and 2003 at the Asan Medical Center (Seoul, Korea) were enrolled. Of these, 824 patients with undetectable Tg at 6 –12 months after remnant ablation during thyroid hormone withdrawal were the subjects of this study. Results: TgAb2 was positive in 56 patients. Ten of 56 patients (18%) with positive TgAb2 had recurrence, whereas only 10 of 768 patients (1%) with negative TgAb2 had recurrence during 73.6 months of follow-up (P ⬍ 0.001). The change between TgAb1 and TgAb2 levels was evaluated in patients with positive TgAb2. TgAb concentration decreased by more than 50% in 21 patients (group 1) and by less than 50% in 16 patients (group 2), and it increased in 19 patients (group 3). The recurrence rates in groups 1, 2, and 3 were 0, 19, and 37%, respectively (P ⫽ 0.016). Conclusions: Serum TgAb levels measured at 6 –12 months after remnant ablation could predict recurrence in patients with undetectable Tg values. In patients with undetectable Tg and positive TgAb values, a change in TgAb concentration during the early postoperative period may be a prognostic indicator of recurrence. (J Clin Endocrinol Metab 93: 4683– 4689, 2008) S erum thyroglobulin (Tg) measurement is important for follow-up after thyroid surgery in patients with differentiated thyroid carcinoma (DTC) and for detection of persistent or recurrent thyroid cancer because the only source of Tg is thyroid tissue. However, in the presence of antithyroglobulin autoantibody (TgAb) a “negative Tg” immunometric assay (IMA) result is most likely a false-negative owing to TgAb interference with currently available IMA methodology (1–3). Recent guidelines recommend assessing TgAb quantitatively, with simultaneous measurement of serum Tg, every 6 –12 months after surgery (4, 5), and Tg IMA methods should not be used when TgAb is detected (3). The previously reported prevalence of TgAb in patients with DTC is 10 –25%, which was higher than in the general population (6 –9). TgAb decreases and eventually disappears in patients who achieve complete remission, although the time lag between the disappearance of antigen and antibody may be up to 3 yr (10). 0021-972X/08/$15.00/0 Abbreviations: CI, Confidence interval; CT, computed tomography; DxWBS, diagnostic whole-body scan; HR, hazard ratio; IMA, immunometric assay; MIBI, technetium-99m methoxyisobutyl isonitrile; RxWBS, posttreatment whole-body scan; Tg, thyroglobulin; TgAb, antithyroglobulin autoantibody; THW, thyroid hormone withdrawal. Printed in U.S.A. Copyright © 2008 by The Endocrine Society doi: 10.1210/jc.2008-0962 Received May 2, 2008. Accepted September 15, 2008. First Published Online September 23, 2008 * W.G.K. and J.H.Y. should be considered joint first coauthors. J Clin Endocrinol Metab, December 2008, 93(12):4683– 4689 jcem.endojournals.org 4683 4684 Kim et al. Antithyroglobulin Antibody Level in Thyroid Cancer Although persistence or increase in the serum TgAb concentration may be regarded as a marker of persistent disease, there is no general acceptance of the use of TgAb levels in the prediction of prognosis. A few cross-sectional studies and a limited longitudinal series have reported higher frequencies of recurrent or persistent disease associated with persistent TgAb (11–13), but some investigators did not find such correlations (6, 8, 14, 15). Recent longitudinal studies have reported that TgAb levels did not influence disease progression and TgAb decreased continuously after surgery in most patients during 3 yr of follow-up (10, 15). We hypothesized that the changing pattern of TgAb level during early follow-up might differ between patients with recurrent or persistent disease and those who achieve complete remission and remain disease free when serum Tg is undetectable owing to the presence of TgAb. This study evaluated the clinical significance of TgAb levels measured at the time of the first diagnostic whole-body scan (DxWBS), 6 –12 months after remnant ablation, in patients with undetectable Tg values. The changing pattern in TgAb levels between the initial postoperative 131I ablation values and measurements 6 –12 months thereafter was also evaluated for possible use as a prognostic indicator of persistent or recurrent disease. Patients and Methods Patients This study included 1499 consecutive DTC patients who underwent total thyroidectomy followed by immediate 131I remnant ablation between 1995 and 2003, according to the protocol established by the Endocrinology Division of the Asan Medical Center (Seoul, Korea). Patients with anaplastic carcinoma, or with poorly differentiated papillary thyroid carcinoma (such as the insular, tall cell variant) were excluded. Sixty patients with preoperative clinical evidence of extracervical metastasis or with radioiodine uptake outside the thyroid bed on postablation wholebody scans (RxWBSs) were excluded. Patients with no available Tg or TgAb data from the time of ablation and/or 6 –12 months thereafter were excluded. Patients who had thyroid bed radioiodine uptake on initial DxWBS were also excluded. Finally, 824 patients with undetectable Tg values 6 –12 months after 131I remnant ablation were included in this study. Informed consent for future reviewing of medical records was obtained from all subjects at the time of surgery. The Local Ethics Committee approved the retrospective review protocol. Initial treatment and follow-up with DxWBS Five to 6 wk after surgery, during which time thyroid hormone was withheld, ablative doses of 131I (3.7–5.55 GBq, 100 –150 mCi) were administered to all patients, and serum Tg and TgAb were measured (these are the Tg1 and TgAb1 values). RxWBSs were obtained 5–7 d after the administr (...truncated)