Thyroglobulin-guided (131)I ablation in low-risk differentiated thyroid carcinoma: is the yardstick accurate enough?

To the Editor: Vaisman and colleagues recently suggested to rule out I ablation in patients with low-risk differentiated thyroid carcinoma (DTC) having negative neck ultrasound, negative thyroglobulin (Tg) antibodies (TgAb), and serum rhTSH-stimulated Tg levels from <1 to 5 ng/mL, measured 3 months after thyroidectomy and selective central compartment neck dissection. In our opinion, however, some critical points concerning Tg measurement need to be further elucidated. In fact, even if measurement of serum Tg levels at the time of I remnant ablation proved to be useful to predict early and long-term outcome of patients, discrepancies between undetectable Tg levels and residual I uptake on a posttreatment whole body scan (PT-WBS) have been reported. In particular, recurrences and metastases on the I PT-WBS scan were proved in 6.3% to 8.5% of patients with an undetectable preablative Tg value. Serum Tg levels that are measured by different methods vary by as much as a factor of 4, even after methods calibration against CRM 457 reference material. Another major problem that hampers accurate Tg measurement is the interference in the Tg assay by TgAb and heterophile antibodies (HAb), resulting in either an underestimation or overestimation of the serum Tg concentration. Immunometric Tg assays may also be subject to a high-dose hook effect, leading to inappropriately normal or low serum Tg values in sera with very high Tg concentrations, which require dilution for accurate measurement. Finally, undetectable serum Tg became detectable in a significant percentage of DTC patients by changing assays, suggesting that in many patients a decrease in immunological reactivity or structural changes of the Tg molecule caused the undetectable Tg levels. Recently, we proved that problems of various kinds may occur with Tg measurement at the time of ablation in up to 1 in 6 patients. Despite extensive laboratory work-up (ie, retesting using different Tg and TgAb immunoassays, recovery test, HAb screening) Tg still was undetectable in about 1 of 5 patients in our series. Considering the sensitivity of both serum Tg and I, an undetectable Tg in the presence of any residual I uptake is highly suspicious for having to deal with pitfalls in Tg measurement. Consequently, the non-negligible risk of a positive PT-WBS in patients with an undetectable Tg level should be considered if Tg is used as a yardstick to rule out I ablation in DTC patients. A single rhTSH-aided I administration (1.1–3.7 GBq) effectively ablates thyroid remnants in most DTC patients, without relevant shortand long-term side effects. The highly sensitive PT-WBS proved to be useful in prognostic stratification of DTC patients and validation of serum Tg as a tumor marker in the long-term DTC follow-up. Additionally, the need for further rhTSH stimulations is becoming virtually absent in low-risk patients treated by thyroid ablation if a second-generation Tg assay is used. Based on these considerations, the reason to perform an rhTSH stimulation every year in 90.4% of low-risk DTC patients to avoid I ablation, as proposed by Vaisman and colleagues, remains at least debatable in our opinion.