Background: Thyroid carcinoma patients with high thyroglobulin (Tg) level but negative total body scan (TBS) are difficult to treat with radioiodine (RAI). The objective of this study was to determine if treatment with rosiglitazone (RZ), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, was associated with an increase in RAI uptake in thyroid carcinoma patients with high serum Tg and negative TBSs. We also determined if there was a correspondence between the effect of RZ and the degree of staining for PPAR-gamma within thyroid cancer tissues.
Methods: We prescribed 8 mg of RZ daily for 6 weeks in 23 patients with epithelial cell thyroid carcinoma who previously had negative posttherapeutic I-131 total body scans (post Rx TBSs) with high serum Tg concentrations. Diagnostic total body scans (Dx TBSs) before and 6 weeks after RZ treatment were compared. An ablative dose of I-131 was then given to all patients, and post Rx TBS was performed to evaluate RAI uptake. Immunohistochemical staining of PPAR-gamma expression in thyroid cancer biopsies was done to correlate this with possible effects of RZ on RAI uptake.
Results: Seven patients had strong PPAR-gamma-positive staining in thyroid biopsies, nine patients had weakly positive staining, and seven patients had negative staining. Five of seven patients with strong staining had either positive post Rx TBS, or both Dx TBS and post Rx TBS. One of nine patients with weak staining had positive Dx TBS and post Rx TBS. In contrast, none of the seven patients with negative staining had positive TBS.
Conclusions: RZ can increase RAI uptake in thyroid tissue in the majority of patients with epithelial cell thyroid carcinoma whose previous posttherapeutic I-131 scans were negative provided they have high intensity and extent of PPAR-gamma expression in thyroid tissue. Few, if any, patients with weak or no PPAR-gamma expression in thyroid cancer tissue increase RAI uptake after RZ treatment.