Single-dose rexinoid rapidly and specifically suppresses serum thyrotropin in normal subjects
Single-dose rexinoid rapidly and specifically suppresses serum thyrotropin in normal subjects
复制标题
DOI：
10.1210/jc.2006-0696
复制
发表时间：
2007-01-01
影响因子：
5.8
通讯作者：
Haugen, Bryan R.
中科院分区：
文献类型：
--
作者：
Golden, Wendy M.;Weber, Katie B.;Haugen, Bryan R.
内容：维甲酸X受体激动剂（rexinoids）已被证明对某些恶性肿瘤患者有益，但在某些晚期癌症患者中似乎会导致中枢性甲状腺功能减退。Rexinoids对健康受试者甲状腺功能的影响尚不清楚。目的：本研究的目的是确定单剂量贝沙罗汀对健康受试者TSH、T-4和T-3水平的影响。设计：本研究是一项随机、双盲、安慰剂对照、交叉试验。设置：本研究在综合临床研究中心进行（科罗拉多州奥罗拉市的科罗拉多大学健康科学中心）。干预措施：单剂量瑞昔诺在0、1、2、4、8、12、24和48小时测量TSH。主要结果测量：结果：单剂量贝沙罗汀随时间推移抑制血清TSH（P < 0.001）。与安慰剂组相比，12 h时TSH水平显著降低（P = 0.043）; 24 h时最低值为0.32 +/- 0.02 mU/L（P < 0.001）。随着时间的推移（48小时），游离T-4指数和游离T-3指数也显着低于安慰剂（分别为P = 0.029; P = 0.004）。血清催乳素、皮质醇和甘油三酯未受影响（均P > 0.05）。单剂量贝沙罗汀对24 h的rT（3）或T-3/rT（3）比值无显著影响。结论：单剂量瑞昔诺丁可快速特异性抑制健康受试者的血清TSH水平。这些数据提供了对rexinoids引起中枢性甲状腺功能减退的机制的深入了解，以及这种作用可用于治疗甲状腺激素抵抗和分泌TSH的垂体瘤等疾病的潜在方法。
Context: Retinoid X receptor agonists (rexinoids) have demonstrated benefit in patients with certain malignancies but appear to cause central hypothyroidism in some patients with advanced cancer. The influence of rexinoids on thyroid function in healthy subjects is not clear.Objective: The objective of this study was to determine the effect of a single dose of bexarotene on levels of TSH, T-4, and T-3 in healthy subjects.Design: This study was a randomized, double-blind, placebo-controlled, crossover trial.Setting: This study was conducted at the General Clinical Research Center (University of Colorado Health Sciences Center, Aurora, CO).Subjects: Six healthy adults (> 18 yr old) were studied.Intervention: Single-dose rexinoid (bexarotene, 400 mg/m(2)) or placebo, with TSH measurements at 0, 1, 2, 4, 8, 12, 24, and 48 h, were used.Main Outcome Measure: The main outcome was the serum TSH level at 24 h.Results: Single-dose bexarotene suppressed serum TSH (P < 0.001) over time. Compared with placebo, levels of TSH were significantly lower by 12 h (P = 0.043); the nadir of 0.32 +/- 0.02 mU/liter (P < 0.001) was seen at 24 h. Free T-4 index and free T-3 index were also significantly lower than placebo over time (48 h) (P = 0.029; P = 0.004, respectively). Serum prolactin, cortisol, and triglycerides were not affected (P > 0.05 for all). There was no significant effect of single-dose bexarotene on rT(3) or T-3/rT(3) ratio at 24 h.Conclusion: A single dose of a rexinoid can rapidly and specifically suppress serum TSH levels in healthy subjects. These data provide insight into the mechanisms by which rexinoids cause central hypothyroidism and potential ways this effect can be used for treatment of disorders such as thyroid hormone resistance and TSH-secreting pituitary tumors.