Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by 
transcriptional stimulation of LDL receptors in the liver. Here, we investigated 
whether thyroid hormone (TH) actions involve other mechanisms that may also 
account for the reduction in LDL-cholesterol, including effects on proprotein 
convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty 
hyperthyroid patients were studied before and after clinical normalization, and 
the responses to hyperthyroidism were compared with those in 14 healthy 
individuals after 14 days of treatment with the liver-selective TH analog 
eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating 
PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while 
cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, 
markedly increased bile acid synthesis and reduced fibroblast growth factor 
(FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not 
hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor 
eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces 
circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol 
in hyperthyroidism. TH also stimulates bile acid synthesis, although this 
response is not critical for its LDL-lowering effect.