The impact of combination therapy with metformin and exogenous vitamin D on hypothalamic-pituitary-thyroid axis activity in women with autoimmune thyroiditis and high-normal thyrotropin levels.

Abstract

Metformin was found to decrease thyrotropin levels in subjects with non-autoimmune but not with autoimmune hypothyroidism. Vitamin D reduced thyroid autoimmunity without affecting thyrotropin and thyroid hormone levels. The aim of the current study was to investigate whether exogenous vitamin D modulates the impact of metformin on hypothalamic-pituitary-thyroid axis activity in young women with autoimmune thyroiditis. This case-control study included 32 prediabetic women with Hashimoto's thyroiditis, high-normal thyrotropin levels (2.5-4.5mIU/L) and vitamin D insufficiency. Based on patient preference, these individuals received either metformin (3g daily) plus vitamin D (4000IU daily) (n=17) or were treated with only metformin (3g daily) (n=15). Plasma levels of glucose, serum levels of insulin, thyrotropin, total and free thyroid hormones and 25-hydroxyvitamin D, as well as serum titres of thyroid antibodies, were assessed at baseline and 6months later. Thirty-one women completed the study. At baseline, there were no differences between the treatment groups. In both study arms, metformin reduced plasma glucose levels and improved insulin sensitivity but this effect was stronger in subjects receiving vitamin D. Only metformin administered with vitamin D decreased thyrotropin levels, increased 25-hydroxyvitamin D levels and reduced thyroid antibody titres. The impact on thyrotropin and antibody titres correlated with the increase in 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. This study has shown for the first time that exogenous vitamin D potentiates the impact of metformin on thyrotropin levels in women with autoimmune thyroiditis.