Metformin and thyroid: an update.

BACKGROUND Metformin is one of the most widely prescribed antidiabetic medications with a favorable safety profile. In the last decade, several studies have reported a TSH-lowering effect of metformin in patients with diabetes mellitus. OBJECTIVE To review literature data on the role of metformin use on thyroid function tests and the course of thyroid cancer. METHODS WE PERFORMED A SEARCH IN THE PUBMED DATABASE USING THE TERMS: 'metformin', 'thyroid', 'TSH', 'diabetes', 'polycystic ovarian syndrome (PCOS)' and 'thyroid cancer'. RESULTS The majority of available evidence suggests that metformin therapy results in a modest reduction of TSH levels in diabetic and/or PCOS patients with thyroid disorder, while thyroid hormone levels remain unaltered. It appears that this effect is independent of thyroid autoimmunity and thyroxine treatment. However, metformin use in subjects with an intact thyroid axis is not associated with a significant change of TSH levels. Concerning thyroid cancer, there is experimental evidence showing antimitogenic properties of metformin in differentiated and medullary thyroid cancer cells. On the other hand, there is also data supporting that metformin administration inhibits iodine uptake by thyroid cells and thus may limit the effectiveness of radioactive iodine treatment. CONCLUSIONS Most studies suggest a TSH suppressive action of metformin in subjects with overt or subclinical thyroid dysfunction, while this is not apparent in euthyroid individuals. It appears that metformin has antimitogenic properties against various thyroid cancer types; however, experimental evidence of reduced efficacy of radioactive iodine treatment following metformin administration may limit its use in the management of differentiated thyroid cancer.