Treating the patient with differentiated thyroid cancer with thyroglobulin-positive iodine-131 diagnostic scan-negative metastases: Including comments on the role of serum thyroglobulin monitoring in tumor surveillance

Differentiated thyroid cancer (DTC) patients, especially the 10% to 15% at high risk of cancer-related death, should have long-term monitoring for detection of recurrence or metastasis. Conventional radiologic and ultrasonographic imaging is useful for localization of recurrent or persistent disease. For patients who have had ablation of residual thyroid tissue, measurement of serum thyroglobulin (Tg) levels and radioactive iodine (RAI) imaging provide highly sensitive tools for early detection. Serum Tg is reliable only in the absence of Tg autoantibodies. Sensitivity increases with TSH stimulation, either by withdrawal of thyroxine (T4) therapy, or administration of recombinant TSH (rTSH). In some patients, serum Tg levels are positive but the RAI whole body scan (WBS) is negative. In these patients, either the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between Tg synthesis and the iodine-trapping mechanism. Recent literature suggests that empiric high-dose RAI therapy of Tgpositive diagnostic scan-negative patients may result in a high rate of visualization of uptake in posttherapy scans (PTS). Evidence for subsequent improvement of parameters of disease activity has also been presented. Almost all such reported cases had micrometastases that were not visualized by conventional imaging. In our experience, aggressive macrometastases with negative diagnostic WBS do not show significant uptake after therapeutic doses of RAI. The small size of micrometastases in the first group of patients and a possible defect of the iodine-trapping mechanism in the second group may explain this apparent discrepancy. Based on presently available information, a generalized recommendation for RAI therapy of Tg-positive, diagnostic scan-negative patients should await further studies. Meanwhile, in some high-risk patients, in the absence of alternative therapies, empiric RAI therapy is justified.