Investigating the protective role of metformin on lithium‐induced hypothyroidism

Abstract

Induction of oxidative stress events has been shown to be associated with lithium (Li) hypothyroidism induction. Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used in polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li‐induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T3 and TSH levels (down to 2 ng/ml and 0.05 µU/ml, respectively) in coordination with an observable reduction in T4 level (up to 2.1 ng/ml). Also, a significant reduction in Li‐related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co‐administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.

Rosuvastatin potentiates the thyrotropin‐lowering effect of metformin in men with non‐autoimmune subclinical hypothyroidism and prediabetes

“…5 0 -adenosine monophosphate-activated protein kinase, hypothalamic-pituitary-thyroid axis, metformin, statins Overactive anterior pituitary thyrotropes are target cells for metformin, [1][2][3][4][5][6][7][8][9][10] a ubiquitously prescribed insulin sensitizer, useful in type 2 diabetes and related insulin resistance states. 11 Thyroid hormone deficiency with increased thyrotropin concentration is more commonly observed in patients with type 2 diabetes and other insulin resistance states than in the general population.…”

“…11 Thyroid hormone deficiency with increased thyrotropin concentration is more commonly observed in patients with type 2 diabetes and other insulin resistance states than in the general population. 12 Administered to individuals with elevated thyrotropin concentrations, metformin reduced thyrotropin levels and this effect was observed in subjects with thyroid hypofunction of autoimmune and non-autoimmune origin, [1][2][3][4][5][6] iatrogenic hypothyroidism [7][8][9] and resistance to thyroid hormone. 10 The thyrotropin-lowering effect of this agent was absent in euthyroid subjects.…”