Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, CRC, Room 6-3940, 10 Center Drive, MSC 1613, Bethesda, Maryland 20892-1613, USA.
J Clin Endocrinol Metab. 2011 Nov;96(11):3466-74. doi: 10.1210/jc.2011-1329. Epub 2011 Aug 24.
Levothyroxine (L-T(4)) therapy is based on the assumption that the conversion of T(4) into T(3) provides adequate amounts of active hormone at target tissues. However, in rodents, L-T(4) alone does not restore a euthyroid state in all tissues. Previous combination L-T(4)/liothyronine (L-T(3)) therapy trials focused on quality-of-life endpoints, and limited information is available on the effects on other measures of thyroid hormone action.
Our objective was to evaluate the efficacy of thyroid hormone replacement with L-T(4) or L-T(3) at doses producing equivalent normalization of TSH.
PARTICIPANTS, DESIGN, AND SETTING: Fourteen hypothyroid patients participated in this randomized, double-blind, crossover intervention at the National Institutes of Health Clinical Center.
L-T(3) or L-T(4) were administered thrice daily to achieve a target TSH from 0.5-1.5 mU/liter. Volunteers were studied as inpatients after 6 wk on a stable dose and at the target TSH.
Serum thyroid hormones, lipid parameters, and indices of glucose metabolism were evaluated.
No difference was observed in TSH between L-T(3) and L-T(4) treatments. L-T(3) resulted in significant weight loss [L-T(4), 70.6 ± 12.5, vs. L-T(3), 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). No significant differences were observed in high-density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance, or insulin sensitivity.
The substitution of L-T(3) for L-T(4) at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.
左甲状腺素（L-T4）治疗基于这样一种假设，即 T4 转化为 T3 可在靶组织中提供足够量的活性激素。然而，在啮齿动物中，单独使用 L-T4 并不能使所有组织恢复到甲状腺功能正常状态。以前的 L-T4/三碘甲状腺原氨酸（L-T3）联合治疗试验侧重于生活质量终点，而关于甲状腺激素作用的其他措施的信息有限。
我们的目的是评估 L-T4 或 L-T3 替代甲状腺激素治疗，剂量使 TSH 正常化。
参与者、设计和环境：14 名甲状腺功能减退患者在国立卫生研究院临床中心参加了这项随机、双盲、交叉干预研究。
L-T3 或 L-T4 每天三次给药，以达到 TSH 目标为 0.5-1.5 mU/L。志愿者在稳定剂量下住院治疗 6 周后，在 TSH 目标下进行研究。
评估血清甲状腺激素、脂质参数和葡萄糖代谢指数。
L-T3 和 L-T4 治疗之间 TSH 无差异。L-T3 导致显著的体重减轻[L-T4，70.6±12.5，vs. L-T3，68.5±11.9kg（P=0.009）]和总胆固醇降低 10.9±10.0%（P=0.002）、低密度脂蛋白胆固醇降低 13.3±12.1%（P=0.002）和载脂蛋白 B 降低 18.3±28.6%（P=0.018）。高密度脂蛋白胆固醇、心率、血压、运动耐量或胰岛素敏感性无显著差异。
用 L-T3 替代 L-T4 等量替代（相对于垂体）可降低体重，并导致甲状腺激素对脂质代谢的作用更大，而未检测到心血管功能或胰岛素敏感性的差异。
