Thyrotropin suppression by metformin

Context: Drug-drug interactions are common but often are discovered only long after initial drug release. Metformin has been available in the United States for 9 yr and elsewhere for many years, but as of yet there are no reports that the drug modifies thyroid hormone economy. Objective: The objective of the study was to describe the clinical and biochemical findings of four patients with chronic hypothyroidism, previously euthyroid on fixed doses of L-T(4) for several years, in whom the metformin was initiated. Design: This was a retrospective review. Setting: The study was conducted at a tertiary care military hospital providing care to active-duty soldiers, sailors, and marines, retirees of the armed forces, and their eligible dependents. Participants: Four patients with chronic hypothyroidism who were placed on metformin participated in the study. Intervention, Main Outcome Measure: Serum TSH, free T(4), and free T(3) levels were measured during metformin treatment. Results: Initiation of treatment with metformin ( three for diabetes mellitus and one for nonalcoholic steatohepatitis) caused suppression of TSH to subnormal levels without clinical symptoms of hyperthyroidism in any patients. There was no change in free T(4) or free T(3) in patient 1. Conclusions: No other potential causes of TSH suppression, including medication changes or interference in the TSH assay, could be identified. The mechanism of the fall in serum TSH in these four patients is unclear at this time. Should these findings be confirmed in larger prospective studies, metformin's ability to suppress TSH without causing clinical or chemical hyperthyroidism might render this drug a useful adjunct to the treatment of patients with thyroid cancer.