Nagamine Tomoko, Tanimura-Inagaki Kyoko, Nagao Mototsugu, Kobayashi Shunsuke, Shuto Yuki, Tamura Hideki, Okazaki-Hada Mikiko, Fukuda Izumi, Sugihara Hitoshi, Oikawa Shinichi, Iwabu Masato
Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Ther Adv Endocrinol Metab. 2025 Sep 9;16:20420188251372381. doi: 10.1177/20420188251372381. eCollection 2025.
The impact of Graves' hyperthyroidism treatment on lipid metabolism remains unclear. This prospective observational study aimed to clarify the changes in lipid profiles and associated metabolic pathways, including cholesterol synthesis, absorption, and low-density lipoprotein (LDL) receptor regulation, following treatment.
Seventeen patients newly diagnosed with Graves' hyperthyroidism were enrolled and followed for 6 months after achieving euthyroid status. Serum lipids (total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides), apolipoproteins, non-cholesterol sterols (markers of cholesterol synthesis and absorption), proprotein convertase subtilisin/kexin type 9 (PCSK9), and lipoprotein lipase (LPL) levels were measured at baseline, at euthyroid status (Eu-0M), and 6 months after euthyroid status (Eu-6M).
After treatment, serum total cholesterol, LDL-C, and HDL-C levels increased rapidly compared to baseline, while triglyceride levels showed a delayed but significant increase at Eu-6M. Levels of apolipoprotein (apo) AI, AII, B, and CIII increased significantly after treatment, whereas apo B-48 increased only at Eu-6M, and apo CII and apo E remained unchanged. Markers of cholesterol synthesis (lathosterol) and absorption (sitosterol, campesterol, and cholestanol) increased significantly after treatment, indicating enhanced cholesterol metabolism. Circulating PCSK9 levels increased significantly and remained elevated, while LPL levels did not change significantly.
Treatment of Graves' hyperthyroidism rapidly increases cholesterol levels through enhanced cholesterol synthesis and absorption, possibly mediated by increased circulating PCSK9.
格雷夫斯病甲亢治疗对脂质代谢的影响尚不清楚。这项前瞻性观察性研究旨在明确治疗后脂质谱以及相关代谢途径（包括胆固醇合成、吸收和低密度脂蛋白（LDL）受体调节）的变化。
纳入17例新诊断的格雷夫斯病甲亢患者，在达到甲状腺功能正常状态后随访6个月。在基线、甲状腺功能正常状态时（Eu-0M）以及甲状腺功能正常状态6个月后（Eu-6M）测量血清脂质（总胆固醇、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯）、载脂蛋白、非胆固醇固醇（胆固醇合成和吸收的标志物）、前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）和脂蛋白脂肪酶（LPL）水平。
治疗后，与基线相比，血清总胆固醇、LDL-C和HDL-C水平迅速升高，而甘油三酯水平在Eu-6M时出现延迟但显著的升高。治疗后载脂蛋白（apo）AI、AII、B和CIII水平显著升高，而apo B-48仅在Eu-6M时升高，apo CII和apo E保持不变。治疗后胆固醇合成标志物（羊毛甾醇）和吸收标志物（谷甾醇、菜油甾醇和胆甾烷醇）显著增加，表明胆固醇代谢增强。循环PCSK9水平显著升高并维持在高位，而LPL水平无显著变化。
格雷夫斯病甲亢的治疗通过增强胆固醇合成和吸收迅速升高胆固醇水平，这可能由循环PCSK9增加介导。
