PSAT373 Metformin Decreases Serum Thyroglobulin Concentration in Non-Medullary Thyroid Carcinoma

BACKGROUND: The conventional treatment of non-medullary thyroid carcinoma (NMTC) includes surgical resection, TSH suppression and 131-iodine. Although highly successful, some patients develop persistent/recurrent NMTC requiring alternative therapies, including external radiation and multikinase inhibitors, which may have clinically significant adverse side effects. In vitro studies, in vivo studies in animals, and association studies in humans suggest that metformin, an inexpensive medication with a modest side effect profile, may help prevent or treat NMTC. No interventional metformin trials have been performed in humans. HYPOTHESIS: We performed a proof-of-concept intervention trial to test the hypothesis that metformin will decrease serum thyroglobulin concentration (Tg), a surrogate marker for NMTC, in humans with persistent/recurrent NMTC burden. METHODS: In this IRB approved study, we administered metformin to patients with persistent/recurrent NMTC and analyzed the change in Tg. When available and possible, tumor burden was evaluated by CT imaging. Ten patients with persistent/recurrent well-differentiated NMTC (6 classic papillary thyroid cancer, 1 tall cell variant of papillary thyroid cancer, 2 follicular thyroid cancer, and 1 hurthle cell thyroid cancer) were included. All had exhausted conventional therapies including total thyroidectomy and 131-iodine. All had biochemical evidence of NMTC with Tg > 2 ng/mL, and with non-detectable serum thyroglobulin antibody concentrations. Six had microscopic NMTC not detectable by conventional imaging, and four had NMTC detectable on CT imaging. Five patients elected to be treated with metformin (500 to 2000 mg/d) for two to five months. The remaining five served as untreated controls. Since the Tg variances in the two groups were not equal, the nonparametric Mann-Whitney test was used to determine if the change in Tg was different in the metformin treated and untreated groups. RESULTS: Tg decreased in all five patients receiving metformin and increased in all five controls. The mean Tg decrease with metformin therapy was 21.7 ± 8.4%, and the mean Tg increase in the control group was 16.6 ± 12.1%; p < 0.02. TSH was suppressed to < 0.1 mIU/L in both groups at baseline and did not change significantly during the study. Two of the five patients receiving metformin elected to continue the metformin for longer, and the CT imaging studies were evaluable by RECIST criteria. There was no decrease in tumor size in either patient. The progression-free survival was 6 months in one patient and 10 months in the other, which may be longer than that reported for similar historical controls that range from 3.6 to 5.8 months. SUMMARY: In summary, metformin caused a TSH-independent decrease of Tg in patients with persistent/recurrent NMTC, but no decrease in tumor size in two evaluable patients. More extensive studies are necessary to determine if metformin slows NMTC progression. CONCLUSION: Metformin decreases Tg in NMTC. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.