Papillary thyroid carcinomas with biochemical incomplete or indeterminate responses to initial treatment: repeat stimulated thyroglobulin assay to identify disease-free patients

Papillary thyroid cancer (PTC) patients treated with thyroidectomy and radioiodine remnant ablation (RRA) often have detectable TSH-stimulated thyroglobulin (Tg) levels without localizable disease after primary treatment. To assess the value of repeat stimulated Tg assays in these patients' follow-up, we retrospectively analyzed 86 cases followed in 5 Italian thyroid-cancer referral centers. We enrolled 86 patients with PTCs treated with total/near-total thyroidectomy plus RRA between January 1,1990 and January 31, 2006. In all cases, the initial postoperative visit revealed stimulated serum Tg ≥1 ng/mL, negative Tg antibodies, and no structural evidence of disease. None received empiric radioiodine therapy. Follow-up (median: 9.6 years) included neck ultrasound and basal Tg assays (yearly) and at least 1 repeat stimulated Tg assay. Of the 86 patients analyzed (initial risk: low 63 %, intermediate 35 %, high 2 %), one (1 %) had ultrasound-detected lymph node disease and persistently elevated stimulated Tg levels at 3 years. In 17 (20 %), imaging findings were consistently negative, but the final stimulated Tg levels was still >1 ng/mL (median 2.07 ng/mL, range 1.02-4.7). The other 68 (80 %) appeared disease-free (persistently negative imaging findings with stimulated Tg levels ≤1 ng/mL). Mean intervals between first and final stimulated Tg assays were similar (5.2 and 4.8 years) in subgroups with versus without Tg normalization. Reclassification as disease-free was significantly more common when initial stimulated Tg levels were indeterminate (<10 ng/mL). In unselected PTC cohorts with incomplete/indeterminate biochemical responses to thyroidectomy and RRA, periodic remeasurement of stimulated Tg allows most patients to be classified as disease-free.