To summarize how thyroid hormones exert their effects on lipid metabolism through specific interaction with their nuclear receptors, to review studies of the effects of new and selective thyromimetic drugs in animals and humans and to identify important questions for future research. RECENT FINDINGS: Thyroid hormones exert their effects by stimulation of thyroid hormone receptors that have different tissue distribution and metabolic targets. TRß is predominant in liver and mainly responsible for effects on cholesterol and lipoprotein metabolism, whereas TR? is most important in fat, muscle, and heart. Thyroid hormone analogs (thyromimetics, tiromes) have been developed that activate TRß and are selectively taken up and/or activated by the liver. Such compounds stimulate hepatic LDL receptors, cholesterol elimination as bile acids and cholesterol, and presumably promote reverse cholesterol transport. In animals, they retard atherosclerosis progression. In humans, eprotirome exerts favorable lipid-modulating effects while lacking thyroid hormone-related side-effects and maintaining normal hypothalamic-pituitary-thyroid feedback. When added to statins, it reduces LDL and non-HDL cholesterol, apolipoprotein B, and triglycerides as well as lipoprotein (a). SUMMARY: Liver-specific and ß-selective thyroid hormone analogs activate a spectrum of favorable thyroid hormone actions that optimize lipid metabolism and promote cholesterol elimination. Further studies should establish long-term safety and potential clinical usefulness of thyromimetics.

Metabolism Unit Department of Endocrinology Karolinska Institutet at Karolinska University Hospital Huddinge Stockholm Sweden

Lipid lowering with thyroid hormone and thyromimetics

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