SAT-456 Reduced Cholesterol Absorption and Synthesis Markers in Patients with Hyperthyroidism Due to Graves’ Disease

Abstract

Background:Thyroid hormones have been reported to promote cell-surface expression of low-density lipoprotein receptor (LDL-R), and also increase mRNA expression of HMG-CoA reductase at the same time. Since LDL cholesterol (LDL-C) uptake via LDL-R is relatively superior to cholesterol synthesis in hyperthyroidism, plasma LDL-C levels can be lower as compared to euthyroid state. Conversely, hypothyroidism can increase plasma LDL-C levels because cholesterol absorption via Niemann-Pick C1-like 1 has been suggested to increase in hypothyroidism. However, there have been no reports about changes of cholesterol absorption and synthesis markers by the treatment of hyperthyroidism in patients with Graves’ disease. Patients and method: We collected plasma samples from patients with hyperthyroidism, who were diagnosed as Graves’ disease (n=17, M/F: 4/13, age: 24-70 years old). Thyroid hormones, general lipid profiles (Total cholesterol: TC, LDL-C, high-density lipoprotein cholesterol: HDL-C and triglyceride: TG), apolipoproteins, markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, cholestanol), lipoprotein lipase (LPL), and proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed before treatment, and at euthyroid state (eu), 3 and 6 months after attaining euthyroid state (eu-3M and eu-6M). Result: It took 159.2±108.6 days to attain euthyroid state by the thiamazole treatment. TC, LDL-C and HDL-C levels were increased at eu (TC, 144.5±26.7 to 225.0±61.6; LDL-C, 77.8±20.9 to 138.9±43.9; HDL-C, 49.7±12.6 to 67.9±20.0 mg/dL: P<0.0001 vs before treatment, respectively). Such changes remained at eu-3M and eu-6M. TG was not changed at eu, but significantly increased at eu-6M (85.0±49.1 to 113.7±60.8 mg/dL, P=0.02). Cholesterol absorption markers were increased at eu, eu-3M and eu-6M (e.g. campesterol, 2.6±1.2 to 4.9±2.3; sitosterol, 1.5±0.6 to 2.9±1.4; cholestanol, 1.9±0.6 to 3.2±1.1 μg/mL: P<0.0001, eu vs before treatment, respectively). Cholesterol synthesis marker was increased at eu, eu-3M and eu-6M (e.g. lathosterol, 1.8±0.7 to 2.3±0.9 μg/mL: P=0.005, eu vs before treatment). Both LPL and PCSK9 were also increased at eu, eu-3M and eu-6M. Conclusion: These data suggest that both cholesterol absorption and synthesis are downregulated in patients with hyperthyroidism due to Graves’ disease and can be restored by attaining euthyroid state. In turn, LDL-C and TG levels should be carefully monitored during the treatment of Graves’ disease because hyperlipidemia could emerge in euthyroid state.