Basal Serum Thyroglobulin Measured by a Second-Generation Assay Is Equivalent to Stimulated Thyroglobulin in Identifying Metastases in Patients with Differentiated Thyroid Cancer with Low or Intermediate Risk of Recurrence

Abstract

Background: Guidelines for the follow-up of differentiated thyroid cancer (DTC) recommend the measurement of TSH-stimulated thyroglobulin (s-Tg) instead of basal Tg on T₄ therapy (b-Tg). However, these guidelines were established using first-generation Tg assays with a functional sensitivity (FS) of 0.5-1.0 ng/ml. Current more sensitive second-generation Tg assays (Tg2G; FS 0.05-0.10 ng/ml) have shown that low-risk DTC patients with undetectable b-Tg rarely have recurrences. Objectives: This study was undertaken to compare b-Tg using a chemiluminescent Tg2G assay (Tg2GICMA; FS 0.1 ng/ml) with s-Tg in DTC patients with an intermediate risk of recurrence. Methods: We evaluated 168 DTC patients with a low (n = 101) and intermediate (n = 67) risk of recurrence treated by total thyroidectomy (147 also treated with radioiodine), with a mean follow-up of 5 years. Results: b-Tg was undetectable with the Tg2GICMA in 142 of 168 patients. s-Tg was <2 ng/ml in 138 of these 142 patients, and only 3 of these 138 (2%) presented metastases on cervical ultrasound (US). Of the 4 of 142 patients with s-Tg >2 ng/ml, 1 had cervical metastases seen after radioiodine. Furthermore, 26 of 168 patients presented detectable b-Tg with the Tg2GICMA; 17 of these 26 patients also presented s-Tg >2 ng/ml. In 10 of these 17 patients, metastases were detected. Cervical US or b-Tg were positive in 14 of 15 patients with recurrent disease. Globally, the sensitivity and negative predictive value of the Tg2GICMA plus US were 93 and 99%, respectively. Conclusion: b-Tg measured with a Tg2GICMA and cervical US, used together, are equivalent to s-Tg in identifying metastases in patients with DTC with a low or intermediate risk of recurrence.

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy

“…showed that even patients with indeterminate response to therapy had a good prognosis, with no evidence of structural disease during follow-up, and could be observed conservatively (4,9,11,29). Current second generation Tg assays (0.05-0.1 ng/mL) have shown that patients with lowrisk DTC with undetectable baseline Tg rarely recur (5). In this sense, study published in 2016 by Janovsky (1) concluded that an excellent response to treatment can be confirmed by the trend of Tg and US, these being the best follow-up approaches, showing that the use of RRA only to achieve negative levels of Tg for surveillance is not necessary because it is not an isolated value, but the tendency of Tg during follow-up, the determining factor for both (1).…”

“…O ver the last decades, the incidence of DTC has increased significantly, especially of tumors smaller than 2 cm (1)(2)(3). Despite this, most of these patients have an excellent prognosis and a long followup during their lifetime (4,5). Nevertheless, rarely small tumors can metastasize and have an increased recurrence risk (6)(7)(8).…”

A Prospective Study Showing an Excellent Response of Patients with Low-Risk Differentiated Thyroid Cancer Who Did Not Undergo Radioiodine Remnant Ablation after Total Thyroidectomy

“…For low-risk thyroid cancer, studies suggest using 30 mCi for RRA, with the aim of achieving negative Tg levels for accurate surveillance [11,31,32] . Our study shows that the use of RRA just to turn Tg into an accurate marker is not necessary, because it is not a single Tg value that most matters, but rather the Tg trend during the follow-up, as others have also demonstrated [33,34] .…”

The Cut-Off Level of Recombinant Human TSH-Stimulated Thyroglobulin in the Follow-Up of Patients with Differentiated Thyroid Cancer

“…David A et al demonstrated that every rhTSH/Tg concentration increase over 1.0 ng/ml may indicate a relapse or a persistent disease. The increase in the rhTSH/Tg level to 1.0–5.0 ng/ml in the study group analyzed by the authors was linked to the presence of metastases in 30% of the patients and an increase in the value to over 5.0 ng/ml up to 81% [ 24 ]. The increase of the rhTSH/Tg level to over 1.0 ng/ml in our material was observed in all patients with the diagnosed persistent disease and in 4 out of 49 patients with ineffective ablation without any other disease foci in the image tests.…”