Management of differentiated thyroid cancer with rising thyroglobulin and negative diagnostic radioiodine whole body scan.

Background: Differentiated thyroid carcinoma (DTC) with rising thyroglobulin (Tg) level and negative radioiodine whole body scan results has been observed in follow-up studies. The management of this condition remains controversial. Most studies support blind (131)I treatment while others oppose this approach.

Aims: To assess the effects of (131)I therapy for DTC with rising Tg and negative scan results.

Selection Criteria: Randomised controlled clinical trials, prospective controlled clinical trials and any trials using (131)I treatment or no treatment for Tg-positive and radioiodine-negative disease were included in this review.

Results: Due to the lack of any suitable randomised or prospective controlled trials in this area, it was not possible to undertake a meta-analysis. Eighteen trials were retrieved for further overall assessment. Of 438 patients from 16 studies who were treated empirically with (131)I for Tg-positive and radioiodine-negative disease, 267 (62%) displayed pathological uptake in the thyroid bed, lungs, bone, mediastinum and lymph nodes. In studies in which data were available for serum Tg levels during thyroid-stimulating hormone (TSH) suppression therapy or TSH withdrawal, 188 of 337 patients (56%) showed a decrease in serum Tg. Of 242 patients from five studies who received no specific treatment for Tg-positive and radioiodine-negative disease, 106 (44%) showed spontaneous normalisation and a significant decrease in serum Tg.

Conclusions: The currently available evidence is insufficient for reliable assessment of the potential of (131)I treatment for DTC with elevated Tg and negative scan results. A decrease in serum Tg in 62% of patients with DTC with elevated Tg and negative scan results suggests that (131)I therapy has a therapeutic effect for more than one-half of patients when the Tg level is considered an index of tumour burden. However, considering that 44% of patients with DTC with elevated Tg and negative scan results showed spontaneous normalisation and a significant reduction in serum Tg without any specific treatment, (131)I therapy should be individualised according to clinical characteristics. Other diagnostic techniques are strongly recommended for patients with Tg-positive and radioiodine-negative disease. If these diagnostic results are positive, treatment options such as surgery, external radiotherapy and tumour embolisation should be considered. If diagnostic results are negative, one course of (131)I treatment may be considered in high-risk patients with serum Tg >10 ng/mL after TSH withdrawal or >5 ng/mL under recombinant human TSH stimulation. No further (131)I therapy is indicated for patients with a negative post-therapy radioiodine scan.