Mikosch P, Obermayer-Pietsch B, Jost R, Jauk B, Gallowitsch H J, Kresnik E, Leb G, Lind P
Department of Nuclear Medicine and Special Endocrinology, Klagenfurt State Hospital, Austria.
Thyroid. 2003 Apr;13(4):347-56. doi: 10.1089/105072503321669839.
Patients with differentiated thyroid carcinoma (DTC) must receive suppressive levothyroxine (LT(4)) therapy for the rest of their lives. The literature, however, presents conflicting results on how this affects bone metabolism. The aim of this study was to assess the influence of the estrogen status and LT(4) therapy, in particular LT(4) dosage in micrograms per kilograms (microg/kg), on bone metabolism in female patients with DTC.
Three markers of bone metabolism (C-terminal telopeptide of type I collagen in serum [SCTx]; N-terminal telopeptide of type I collagen in urine [U-NTx]; and osteocalcin [OC]) were investigated in four groups: group REF (healthy premenopausal female controls), group DTC-ES (premenopausal women with DTC and normal estrogen levels), group DTC-ED (postmenopausal women with DTC and estrogen deficiency), and group DTC-HRT (postmenopausal women with DTC undergoing hormone replacement therapy [HRT]). All patients with DTC were on a well-adjusted suppressive LT(4) therapy with TSH levels 0.1 mU/L or less.
In group DTC-ES bone turnover was comparable to group REF, whereas in group DTC-ED, all three markers were significantly increased as compared to groups REF and DTC-ES. In group DTC-HRT, the HRT normalized U-NTx and OC. However, in this group S-CTx was not completely normalized by HRT in all patients, although also significantly lowered compared to group DTC-ED. The analysis of LT(4 )dosage per kilogram showed that premenopausal DTC-patients had increased markers of bone metabolism if LT(4) dosage exceeded 2.6 microg/kg. Estrogen-deficient patients with DTC, however, had a much lower critical LT(4) dosage, above which increased markers of bone metabolism were seen.
A well-adjusted suppressive LT(4) therapy of less than 2.6 microg/kg and normal estrogen levels do not seem to increase bone metabolism in estrogen-sufficient patients with DTC. The normalization of an estrogen deficiency by HRT or other antiresorptive therapies and minimal suppressive dosages of LT(4) are attempts to optimize the care of patients with DTC. In postmenopausal patients with DTC and patients with DTC who require LT(4) dosages in excess of 2.6 microg/kg, the information provided by markers of bone metabolism may help to prevent bone damage.
分化型甲状腺癌(DTC)患者必须终生接受左甲状腺素(LT4)抑制治疗。然而,关于这对骨代谢的影响,文献给出了相互矛盾的结果。本研究的目的是评估雌激素状态和LT4治疗,特别是每千克微克数(μg/kg)的LT4剂量,对女性DTC患者骨代谢的影响。
在四组中研究了三种骨代谢标志物(血清I型胶原C末端肽[SCTx];尿I型胶原N末端肽[U-NTx];骨钙素[OC]):REF组(健康绝经前女性对照),DTC-ES组(绝经前DTC且雌激素水平正常的女性),DTC-ED组(绝经后DTC且雌激素缺乏的女性),以及DTC-HRT组(绝经后DTC且接受激素替代疗法[HRT]的女性)。所有DTC患者均接受调整良好的LT4抑制治疗,促甲状腺激素(TSH)水平为0.1 mU/L或更低。
DTC-ES组的骨转换与REF组相当,而在DTC-ED组中,与REF组和DTC-ES组相比,所有三种标志物均显著升高。在DTC-HRT组中,HRT使U-NTx和OC恢复正常。然而,在该组中,尽管与DTC-ED组相比也显著降低,但并非所有患者的S-CTx都能通过HRT完全恢复正常。每千克LT4剂量的分析表明,如果LT4剂量超过2.6 μg/kg,绝经前DTC患者的骨代谢标志物会升高。然而,雌激素缺乏的DTC患者的临界LT4剂量要低得多,超过该剂量会出现骨代谢标志物升高。
对于雌激素充足的DTC患者,调整良好的LT4抑制治疗剂量低于2.6 μg/kg且雌激素水平正常似乎不会增加骨代谢。通过HRT或其他抗吸收疗法使雌激素缺乏恢复正常以及LT4的最小抑制剂量是优化DTC患者护理的尝试。对于绝经后DTC患者和需要LT4剂量超过2.6 μg/kg的DTC患者,骨代谢标志物提供的信息可能有助于预防骨损伤。