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Significance of the Study
This study compared the thyroid function and morphology of hyperlipidemic patients who received atorvastatin or rosuvastatin with those of a control group of non-statin-treated hyperlipidemic patients. There was an association between rosuvastatin treatment and reduction in thyroid volume and maximum nodule diameter. This could be a new treatment alternative for benign and malignant proliferative thyroid diseases.
Introduction
Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme, the rate-limiting step in cholesterol synthesis, and thus prevent cholesterol synthesis through mevalonate [1]. The effects of statins apart from lipid reduction are known as pleiotropic effects and are believed to be attributable to the inhibition of mevalonate and isoprenoid compound synthesis via the inhibition of HMG-CoA reductase [2, 3]. The mevalonate pathway provides the bioactive molecules essential for numerous cellular processes. The by-products of the mevalonate pathway, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, enable G proteins to be transported from within cells to the cell membranes and activated by posttranslational modification.
The resultant activated proteins of the Ras super-family participate in controlling processes such as cell proliferation and differentiation, and the regulation of the actin cytoskeleton, membrane traffic, and nuclear transport. Many studies have shown that the mechanism responsible for statin pleiotropy is the inhibition of the Ras super-family guanosine triphosphate (GTP)ases, which act as regulators in guanosine diphosphate/GTP transformation, and whose membrane localizations and functions depend on posttranslational protein isoprenylation [4-6]. When the pleiotropic effects of statins were first recognized, various studies investigated their antitumor, antiproliferative, and apoptotic effects [7-10].
Abnormal epithelial cell proliferation, which is common in thyroid tissue, may present as nodular or nonnodular thyroid growth or neoplasia [11]. However, little is known about the pleiotropic effects of statins on thyroid cells. A possible thyroid-statin association was first reported in 1999, when Vitale et al. [12] showed in vitro that statins induce apoptosis in “multiplying thyroid cells” independently of p53, through protein synthesis and a mechanism based on caspase enzymes. Rat thyroid cells with Ras-transformation were found to be more sensitive to HMG-CoA reductase inhibitors than normal cells. Ras mutation activation and other oncogenes are common in thyroid tumors; ras mutations may also be present in nodular hyperplasia of the thyroid [13, 14]. In a 2006 study performed on rats, Laezza et al. [15]...