Unstimulated high sensitive thyroglobulin measurement predicts outcome of differentiated thyroid carcinoma

Background: Thyroglobulin (Tg) measurement following thyrotropin (TSH) stimulation is used in the follow-up of patients with differentiated thyroid carcinoma (DTC). However, high-sensitive assays allow accurate measurement of serum Tg even without TSH stimulation. Here, we prospectively evaluated the impact of unstimulated high-sensitive Tg measurement in early and long-term outcome of patients with DTC. Methods: One hundred and ninety five patients affected with DTC were evaluated. Six months after thyroid ablation (i.e., thyroidectomy plus radioiodine) serum Tg was measured during TSH-suppressive thyroxine (T4) treatment (onT4-Tg). Patients with undetectable onT4-Tg and negative neck ultrasound (US) were considered disease free and onT4-Tg was measured every 12 months for a mean follow-up of 6.8 (4.7-8.9) years. Patients with an increase in onT4-Tg underwent specific diagnostic work-up and appropriate treatment if necessary. Results: Four patients showed recurrence at first follow-up visit with a corresponding increase in onT4-Tg concentrations (sensitivity 100%). Three patients had false positive onT4-Tg measurement (specificity 98%) with a spontaneous decrease within 3-6 months in all cases (specificity 100%). Three of 188 patients with undetectable serum onT4-Tg at first follow-up showed recurrence later with an increase in onT4-Tg as the first (n=2) or unique (n=1) sign of relapse (sensitivity 100%). Among 185 disease-free patients in a prolonged follow-up, 12 had a transient increase in onT4-Tg (specificity 91.6%). However, a spontaneous reduction within 3-6 months occurred in all cases (specificity 100%). Conclusions: Undetectable serum onT4-Tg using a high-sensitivity immunoradiometric assay 6 months after thyroid ablation predicts low-risk of DTC recurrence. When onT4-Tg became detectable during follow-up, the evaluation of Tg slope in a 3-6 months period accurately discriminated patients with DTC recurrence from those without recurrence. This helped avoid unnecessary diagnostic or therapeutic procedures.