Does a highly sensitive thyroglobulin (Tg) assay change the clinical management of low‐risk patients with thyroid cancer with Tg on T4 < 1 ng/ml determined by traditional assays?

Summary Objective  To evaluate a highly sensitive thyroglobulin (Tg) assay [functional sensitivity (FS): 0·1 ng/ml] (Tg‐ICMA) in low‐risk patients with known Tg on T4 ≤ 1 ng/ml measured by a traditional assay (FS: 1 ng/ml) (Tg‐IRMA). Methods  Tg‐ICMA was measured in serum samples stored at –70 °C. Samples were obtained 6 months or more after total thyroidectomy and remnant ablation with 131 I, during L‐T4 therapy (TSH < 0·4 mIU/l). All patients had well‐differentiated and completely resected tumours, no ectopic uptake on post‐therapy whole‐body scans and were considered to be at low risk for recurrence. On the occasion of collection and retesting for this study, Tg‐IRMA was ≤ 1 ng/ml in all samples and no antibody interference was observed. Results  Tg‐ICMA ≤ 0·1 ng/ml was observed in 130/178 (73%) patients and recurrence was diagnosed in only 1/130 (0·8%). Tg‐IRMA measured after L‐T4 withdrawal was > 1 ng/ml in 5/130 (3·8%) patients. Forty‐eight (27%) patients had Tg‐ICMA > 0·1 ng/ml (0·12–1·6 ng/ml) and recurrence was diagnosed in 5/48 (10·5%). Tg‐IRMA measured after L‐T4 withdrawal was > 1 ng/ml in 20/48 (41·6%) patients. A negative predictive value of 100% was achieved with Tg‐ICMA on T4 ≤ 0·1 ng/ml combined with neck ultrasonography (US) or with stimulated Tg‐IRMA ≤ 1 ng/ml. Conclusions  Patients at low risk for recurrence with undetectable Tg on T4 measured by a highly sensitive assay (FS: 0·1 ng/ml) in the absence of antibody interference and with a negative sensitive neck US do not need to be submitted to Tg stimulation. Recurrence is rare in these cases and only a minority of patients convert to stimulated Tg > 1–2 ng/ml.