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

Abstract

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.

Thyroid hormones and diabetic nephropathy: An essential relationship to recognize

“…23,24 However, previous studies have shown that hyperlipidaemia and hyperglycaemia are strong independent risk factors for the prognosis of DN, and high-TSH patients in this study had more severe hyperlipidaemia and hyperglycaemia, which might also have contributed to more severe clinical and pathologic changes. Some studies have suggested that thyroid function is significantly associated with alterations in the lipid profile, [25][26][27][28][29] and have proposed SCH as a cause of dyslipidaemia, 30 possibly connected with TSH receptors. 31 In addition, serious SCH might influence glycaemic control in patients with T2DM, 32 while thyroid dysfunction might affect the expression of several glycaemic receptor proteins, 33 suggesting that abnormal levels of thyroid hormones might affect insulin sensitivity in DN patients with deviant blood glucose levels.…”

Long-term outcomes and risk factors of thyroid dysfunction during pegylated interferon and ribavirin treatment in patients with chronic hepatitis C infection in Taiwan

“…This biological relationship may explain the impact of hypothyroidism, which is often linked to excess TC and low-density lipoprotein cholesterol (LDL-C) [50]. It should be noted that endocrine disorders, including hypothyroidism and type 2 diabetes mellitus, may induce or exacerbate existing dyslipidemia and impede the achievement of optimal results through hypolipidemic drugs [51]. Therefore, CHC patients with dyslipidemia should be regularly checked for thyroid dysfunction, and both cholesterol and its subfractions should be monitored in CHC patients undergoing PEG-IFN/RBV treatment with thyroid failure [49, 51].…”

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

“…Both currently available PCSK9 inhibitors, alirocumab and evolocumab, bind to PCSK9 preventing its binding to the LDLR: this results in continuous LDLR recycling at the hepatic cell surface and clearing of LDL-C particles, causing a decrease in plasma LDL-C concentration ( 95 ). It has been proposed that TH, by stimulating LDLR activity and clearance of LDL-C via PCSK9, may support this mechanism ( 13 ). Also of interest is the fact that the correlation of circulating PCSK9 levels with thyroid function, even in the normal range, may be blunted by obesity ( 96 ).…”

“…Therefore, by thus lowering circulating 5α-stanols while increasing FT3/FT4, presumably by enhancing conversion of T4 to T3, it has the potential to improve thyroid hormone status ( 100 ). It is accordingly suggested that ezetimibe, together with statins, be combined with thyroxine, thereby both ameliorating thyroid function and reducing TC and LDL-C by actively inhibiting the synthesis and intestinal absorption of TC ( 13 ).…”

“…The development of powerful hypolipidemic drugs, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), which may be optimally combined with L-thyroxine (L-T4) to treat severe forms of familial hypercholesterolemia and hypothyroidism has opened up a new field of research investigating the underlying mechanisms connecting thyroid function to lipids ( 13 ).…”