Prognostic Impact of Serum Thyroglobulin Doubling-time Under Thyrotropin Suppression in Patients with Papillary Thyroid Carcinoma Who Underwent Total Thyroidectomy

Background: Detectable serum thyroglobulin (Tg) in patients with papillary thyroid carcinoma (PTC) after total thyroidectomy implies unsuccessful surgery, indicating a high risk of recurrence. Serum Tg kinetics in such patients have not been extensively studied. We studied serum Tg kinetics in patients with suppressed serum thyrotropin levels and undetectable anti-Tg antibody to minimize the effects of these factors on Tg values, and evaluated the relationship of prognosis to the serum Tg doubling-time.

Methods: Between January 1998 and December 2004, 1515 patients with PTC underwent total thyroidectomy in Kuma Hospital. After excluding patients with other thyroid cancers and those positive tests for anti-Tg antibody, there were 426 patients with 4 or more serum Tg measurements at a time that serum thyrotropin concentrations were <0.1 mIU/L. These patients were selected for the present retrospective study. Tg doubling-time was computed using Tg values measured during routine follow-up. Patients were followed for a mean of 88.1 months and a median of 86.7 months.

Results: Of the 426 patients, 137 patients had 4 or more measurements that revealed detectable Tg in serum Tg. The Tg doubling-time (DT), calculated using all available data, varied widely, and were grouped into those that were <1 year (17 patients), those that were 1-3 years (21 patients), and those that were ≥ 3 years (30 patients), as well as those with a negative value due to decrease in serum Tg (69 patients). There were also 88 patients who had three or fewer serum Tg measurements that showed detectable Tg levels, as well as 201 patients in whom serum Tg measurements were below the lower limit of detection. In the group of patients with a Tg-DT of <1 year the cause specific survival at 10 years was 50%, and in the group with a Tg-DT of 1-3 years it was 95%. In all other groups it was 100%. Many classical prognostic factors (TNM stage, age, and gender) as well as the Tg-DT were significant indicators of survival by univariate analysis, but Tg-DT remained the only independent predictor by multivariate analysis. Tg-DT was also the only independent predictor of distant metastases and loco-regional recurrence on multivariate analysis. Tg-DT calculated using only the first four data [Tg-DT (first four data)] was also the only independent predictor of survival, distant metastases, and loco-regional recurrence on multivariate analysis.

Conclusions: Tg-DT (all data or first four data) is a very strong prognostic predictor superior to the classical prognostic factors in patients with PTC.