The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and amiodarone-induced hypothyroidism

• Metformin/amiodarone combination therapy is well tolerated.
• Metformin reduces elevated, but not normal, thyrotropin levels.
• This effect correlates weakly with an improvement in insulin sensitivity.
• Metformin may bring benefits to patients with amiodarone-induced hypothyroidism.

BackgroundChronic metformin treatment was found to reduce elevated thyrotropin levels. Amiodarone treatment is associated with a range of effects in thyroid function from mild derangements to overt thyroid dysfunction. No previous study has investigated the effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with amiodarone-induced hypothyroidism.MethodsThe study included three age-, sex- and weight-matched groups of amiodarone-treated patients with type 2 diabetes: patients with treated overt hypothyroidism (group I, n = 15), patients with untreated subclinical hypothyroidism (group II, n = 15), and subjects without thyroid disorders (group III, n = 18). The lipid profile, fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, the estimated glomerular filtration rate, as well as serum levels of thyrotropin, thyroid hormones, prolactin, insulin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 6 months of metformin treatment (2.55–3 g daily).ResultsIn all groups of patients, metformin reduced plasma glucose and triglycerides, serum insulin, glycated hemoglobin as well as HOMA1-IR. The estimated glomerular filtration rate, thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. In patients with untreated amiodarone-induced hypothyroidism, but not in the other groups of patients, metformin reduced serum levels of thyrotropin and this effect correlated weakly with its action on insulin sensitivity.ConclusionsThe obtained results indicate that the effect of metformin on hypothalamic-pituitary-thyroid axis activity is partially related to thyroid function. Metformin treatment may bring clinical benefits to patients with amiodarone-induced hypothyroidism and poor tolerance of exogenous l-thyroxine.