Mikosch P, Igerc I, Kudlacek S, Woloszczuk W, Gallowitsch H J, Kresnik E, Stettner H, Grimm G, Lind P, Pietschmann P
Department of Nuclear Medicine and Special Endocrinology, Klagenfurt State Hospital, Klagenfurt, Austria.
Eur J Clin Invest. 2006 Aug;36(8):566-73. doi: 10.1111/j.1365-2362.2006.01678.x.
Suppressive thyroid hormone therapy is generally a lifelong treatment for patients with differentiated thyroid cancer (DTC). However, long-standing thyrotropin (TSH) suppression is a risk factor for osteoporosis. Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are central regulators of bone turnover. The aim was to analyze the effects of a suppressive thyroid hormone therapy in males with DTC on the OPG/RANKL system and on bone metabolism.
The OPG and soluble RANKL (sRANKL) were determined in 40 men (mean age, 53.2 years) with DTC on suppressive thyroid hormone therapy (TSH; 0.053 +/- 0.037 mU L(-1), duration 5.7 +/- 4.4 years) and 120 healthy controls matched for age. The markers of bone metabolism were C-terminal telopeptide of type I collagen in serum (sCTx) and osteocalcin (OC).
The control group had OPG values (mean +/- SD) of 1.9 +/- 1.0 pmol L(-1) and sRANKL values of 0.40 +/- 0.62 pmol L(-1). In patients with DTC, results for OPG were 3.03 +/- 1.04 pmol L(-1) (P < 0.05) and for sRANKL were 0.13 +/- 0.16 pmol L(-1) (P < 0.05). The control group presented values for sCTx of 2669 +/- 1132 pmol L(-1) and for OC of 17.89 +/- 6.5 ng mL(-1). Patients with DTC on suppressive thyroid hormone therapy had increased sCTx values of 3810 +/- 2020 pmol L(-1) (P = 0.03) but comparable OC values of 19.21 +/- 7.67 ng mL(-1) (NS).
Suppressive thyroid hormone therapy in men with DTC increased bone degradation and induced significant changes in the OPG/RANKL system. These changes include, besides the risk of osteoporosis, possible negative effects on the vascular function and an increased risk of cardiovascular disease.
对于分化型甲状腺癌（DTC）患者，甲状腺激素抑制治疗通常是一种终身治疗方法。然而，长期促甲状腺激素（TSH）抑制是骨质疏松的一个危险因素。骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）是骨转换的核心调节因子。本研究旨在分析甲状腺激素抑制治疗对男性DTC患者OPG/RANKL系统及骨代谢的影响。
对40例接受甲状腺激素抑制治疗（TSH；0.053±0.037 mU/L，治疗时间5.7±4.4年）的男性DTC患者（平均年龄53.2岁）和120例年龄匹配的健康对照者测定OPG和可溶性RANKL（sRANKL）。骨代谢标志物为血清I型胶原C末端肽（sCTx）和骨钙素（OC）。
对照组OPG值（均值±标准差）为1.9±1.0 pmol/L，sRANKL值为0.40±0.62 pmol/L。DTC患者中，OPG结果为3.03±1.04 pmol/L（P<0.05），sRANKL结果为0.13±0.16 pmol/L（P<0.05）。对照组sCTx值为2669±1132 pmol/L，OC值为17.89±6.5 ng/mL。接受甲状腺激素抑制治疗的DTC患者sCTx值升高至3810±2020 pmol/L（P=0.03），但OC值相当，为19.21±7.67 ng/mL（无统计学差异）。
男性DTC患者接受甲状腺激素抑制治疗会增加骨降解，并引起OPG/RANKL系统的显著变化。除骨质疏松风险外，这些变化可能对血管功能产生负面影响，并增加心血管疾病风险。
