Thyroid Diseases, Metformin and the AMP Kinase Pathway

ABSTRACT

An increase in the adenosine monophosphate (AMP)/adenosine triphosphate ratio activates AMP-activated protein kinase (AMPK), leading to inhibition of the mammalian target of rapamycin signaling pathway that is associated with autophagy, mitochondriogenesis, glucose uptake, mRNA stabilization, and cell cycle regulation. Metformin activates AMPK and inhibits mitochondrial oxidative phosphorylation. Currently, there is an increasing interest in investigating the effects of metformin on thyroid diseases. Recent data show an association between metformin treatment and lower incidence of thyroid cancer, better survival of patients with thyroid cancer, and lower thyroid volume and nodule size. Insulin-like growth factor receptor and AKT pathways are the AMPK-independent mechanisms through which metformin acts on thyroid diseases. Although metformin has a promising role in adjuvant therapy for thyroid cancers, welldesigned prospective trials are required before reaching a final decision.