Heikinheimo O, Ranta S, Grunberg S, Lähteenmäki P, Spitz I M
Department of Medical Chemistry, University of Helsinki, Finland.
Metabolism. 1997 Mar;46(3):292-6. doi: 10.1016/s0026-0495(97)90256-0.
The effects of short-term administration of the antiprogestin and antiglucocorticoid, mifepristone, have been well characterized. However, little is known about the effects of prolonged administration of mifepristone. We analyzed hormonal parameters in four female and three male patients with unresectable meningioma who were treated with mifepristone (200 mg/d) for 20 to 40 months. Serum samples were collected at monthly intervals approximately 24 hours following mifepristone ingestion. Serum thyrotropin (TSH), thyroxine (T4), free T4 (fT4), 3,5,3-triiodothyronine (T3), prolactin, and cortisol were analyzed by fluoroimmunoassay, and androstenedione by radioimmunoassay (RIA). Levels of mifepristone and its three most proximal metabolites were measured by high-performance liquid chromatography. TSH values increased significantly (P < .005, one-way ANOVA), with the most pronounced increase evident during the first 3 months of mifepristone treatment. Despite these changes, concentrations of TSH remained within the normal range throughout the treatment period. There were no significant changes in serum T4, fT4, T3 or prolactin; however, a transient decrease in serum T4 was noted at 2 to 3 months. Cortisol and androstenedione values increased significantly and in parallel (P < .05), suggesting an adrenal origin also for androstenedione. As during short-term administration, levels of mifepristone and its metabolites remained stable in the micromolar range. Individual levels of mifepristone were significantly correlated with those of TSH and cortisol. This suggests that the alterations in the pituitary-thyroid and -adrenal axes occurred in a concentration-dependent manner. It is concluded that long-term mifepristone treatment results in resetting of the pituitary-thyroid balance. As in the case with cortisol and androstenedione, it is likely that the alterations in serum TSH are due to the antiglucocorticoid properties of mifepristone. The clinical significance of these biochemical alterations in thyroid homeostasis remains to be determined. However, monitoring thyroid function during long-term mifepristone treatment appears to be warranted.
抗孕激素和抗糖皮质激素米非司酮短期给药的效果已得到充分研究。然而，关于米非司酮长期给药的效果却知之甚少。我们分析了4名女性和3名男性不可切除脑膜瘤患者的激素参数，这些患者接受米非司酮（200mg/d）治疗20至40个月。在服用米非司酮后约24小时，每月采集一次血清样本。通过荧光免疫测定法分析血清促甲状腺激素（TSH）、甲状腺素（T4）、游离T4（fT4）、三碘甲状腺原氨酸（T3）、催乳素和皮质醇，通过放射免疫测定法（RIA）分析雄烯二酮。通过高效液相色谱法测定米非司酮及其三种最接近的代谢物的水平。TSH值显著升高（P <.005，单因素方差分析），在米非司酮治疗的前3个月升高最为明显。尽管有这些变化，但在整个治疗期间TSH浓度仍保持在正常范围内。血清T4、fT4、T3或催乳素无显著变化；然而，在2至3个月时观察到血清T4短暂下降。皮质醇和雄烯二酮值显著且平行升高（P <.05），表明雄烯二酮也来源于肾上腺。与短期给药期间一样，米非司酮及其代谢物的水平在微摩尔范围内保持稳定。米非司酮的个体水平与TSH和皮质醇的水平显著相关。这表明垂体-甲状腺和垂体-肾上腺轴的改变是以浓度依赖的方式发生的。结论是长期米非司酮治疗导致垂体-甲状腺平衡的重新设定。与皮质醇和雄烯二酮的情况一样，血清TSH的改变可能是由于米非司酮的抗糖皮质激素特性。这些甲状腺稳态生化改变的临床意义仍有待确定。然而，在长期米非司酮治疗期间监测甲状腺功能似乎是必要的。
