PROGNOSTIC VALUE OF SERUM THYROGLOBULIN KINETICS FOR PREDICTING RECURRENCE IN DIFFERENTIATED THYROID CANCER

Abstract

Background: Although absolute serum thyroglobulin (Tg) levels are routinely used to monitor differentiated thyroid cancer (DTC), a single measurement may not accurately predict disease progression in patients who have already achieved remission. While Tg kinetics have shown prognostic value, the optimal thresholds for detecting early recurrence in this specific excellent-response population remain poorly defined.

Objectives: The study aimed to evaluate the usefulness of serum thyroglobulin doubling time (Tg-DT) and thyroglobulin velocity (TgV) during thyroid-stimulating hormone (TSH) suppression for predicting tumor recurrence among patients with DTC who achieved remission.

Methods: This retrospective study analyzed 270 patients with DTC who underwent total/near-total thyroidectomy followed by radioactive iodine (RAI) ablation at Siriraj Hospital between January 2007 and December 2011. Eligible patients had achieved remission (Tg < 1 ng/mL with negative imaging) and had ≥ 4 Tg measurements obtained during TSH suppression. Tg-DT and TgV was calculated using non-linear regression and linear formulas, respectively.

Results: During the follow-up period, three patients (1.1%) experienced disease recurrence. Receiver operating characteristic analysis tentatively identified optimal exploratory cutoffs as Tg-DT ≤ 1 year and TgV ≥ 0.1 ng/mL/year. At these specific thresholds, both markers predicted recurrence with a sensitivity of 66.7% (95% CI: 9.4% -99.2%), a specificity of 100% (95% CI: 98.6% - 100%), and an overall accuracy of 99.6% (95% CI: 97.9% -99.9%). These high estimates should be interpreted with caution, given the wide confidence intervals resulting from the low event rate. Nominally shorter mean recurrence-free survival was observed among patients exceeding these thresholds compared to those below (2.8 years [95% CI: 2.6 -2.9] vs. 9.9 years [95% CI: 9.9 -10.0]; p < 0.0005).

Conclusion: Within this cohort, a Tg-DT ≤ 1 year and a TgV ≥ 0.1 ng/mL/year were associated with disease recurrence and may serve as highly specific preliminary indicators during remission. However, given the low number of recurrence events inherently observed in excellent-response patients, these kinetic markers should be interpreted as preliminary tools that complement, rather than replace, comprehensive clinical surveillance. Larger-scale studies are required to validate their routine clinical applicability.