Thyroid hormone regulates lipid metabolism. In particular, it has been reported to regulate plasma high-density lipoprotein cholesterol (HDL-C) levels and the activity of molecules involved in HDL metabolism. We investigated changes in the concentrations of lipids and apolipoproteins and in the function of HDL according to acute dynamic changes in thyroid function. Concentrations of plasma lipids and apolipoproteins, paraoxonase-1 activity, and cholesterol efflux were measured in 27 patients with differentiated thyroid carcinoma who underwent total thyroidectomy and radioactive iodine (RAI) treatment, at 3 distinct times: After surgery (baseline subclinical hyperthyroid state), on the day of undergoing RAI treatment (overt hypothyroid state), and 3 months post-RAI treatment (subclinical hyperthyroid state). The mean free T4 and thyroid-stimulating hormone concentrations were 0.24±0.06ng/dL and 91.2 (77.8-118.2) μIU/mL, respectively, on the day of RAI treatment. Total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apoB levels, and the apoA-I/II ratio were significantly increased in the overt hypothyroid state and recovered to baseline values with levothyroxine replacement. HDL-C and apoE levels were persistently elevated despite levothyroxine replacement. Paraoxonase-1 activity, corrected for apoA-I, decreased in the overt hypothyroid state but recovered with levothyroxine replacement (P=.009). Cholesterol efflux also decreased significantly in the overt hypothyroid state (21.5±5.1% vs 18.9±2.9%, P=.005), but remained low despite recovery of thyroid function. Changes in thyroid function are associated not only with changes in the concentrations of various plasma lipid components but also with changes in HDL function.