Thyroid hormones: a potential ally to LDL-cholesterol-lowering agents

L-thyroxine (LT4) treatment of hypothyroidism, particularly in patients with thyroid-stimulating hormone (TSH) > 10mU/L, results in improved lipid profile, as LT4 stimulates low-density lipoprotein cholesterol (LDL-C) degradation and the conversion of cholesterol in bile acids by inducing LDL-receptor and 7 alpha hydroxylase expression, respectively. Statins decrease total cholesterol (TC) and LDL-C mainly by suppressing 3-hydroxy-3-methylglutaryl coenzyme A activity. Therefore, the addition of statins to LT4 treatment, following the reversal of hypothyroidism, acts synergistically and forms a powerful treatment modality in patients with this condition whose serum lipids have not achieved the target. Statin add-on therapies, such as ezetimibe (EZE) and the recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, in conjunction with LT4 therapy, produce an even more favorable profile. Ezetimibe blocks the intestinal absorption of cholesterol, while in patients with heterozygous familiar hyperlipidemia, PCSK9 inhibitors suppress PCSK9, thereby promoting LDL-C degradation. The synergy of these drugs results in a far better lipidemic profile than when each drug is administered alone, with LT4 treatment clearly enhancing, in many respects, the efficacy of therapy.