Bolk Nienke, Visser Theo J, Nijman Judy, Jongste Ineke J, Tijssen Jan G P, Berghout Arie
Department of Internal Medicine, Maasstad Hospital Rotterdam, Rotterdam, The Netherlands.
Arch Intern Med. 2010 Dec 13;170(22):1996-2003. doi: 10.1001/archinternmed.2010.436.
Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed.
To ascertain if levothyroxine intake at bedtime instead of in the morning improves thyroid hormone levels, a randomized double-blind crossover trial was performed between April 1, 2007, and November 30, 2008, among 105 consecutive patients with primary hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. Patients were instructed during 6 months to take 1 capsule in the morning and 1 capsule at bedtime (one containing levothyroxine and the other a placebo), with a switch after 3 months. Primary outcome measures were thyroid hormone levels; secondary outcome measures were creatinine and lipid levels, body mass index, heart rate, and quality of life.
Ninety patients completed the trial and were available for analysis. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L (95% confidence interval [CI], 0.60-1.89 mIU/L; P < .001), an increase in free thyroxine level of 0.07 ng/dL (0.02-0.13 ng/dL; P = .01), and an increase in total triiodothyronine level of 6.5 ng/dL (0.9-12.1 ng/dL; P = .02) (to convert thyrotropin level to micrograms per liter, multiply by 1.0; free thyroxine level to picomoles per liter, multiply by 12.871; and total triiodothyronine level to nanomoles per liter, multiply by 0.0154). Secondary outcomes, including quality-of-life questionnaires (36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale, 20-Item Multidimensional Fatigue Inventory, and a symptoms questionnaire), showed no significant changes between morning vs bedtime intake of levothyroxine.
Levothyroxine taken at bedtime significantly improved thyroid hormone levels. Quality-of-life variables and plasma lipid levels showed no significant changes with bedtime vs morning intake. Clinicians should consider prescribing levothyroxine intake at bedtime.
isrctn.org Identifier: ISRCTN17436693 (NTR959).
左甲状腺素钠被广泛用于治疗原发性甲状腺功能减退症。目前已达成共识，左甲状腺素应在早晨空腹服用。一项初步研究表明，睡前服用左甲状腺素可显著降低促甲状腺激素水平，并提高游离甲状腺素和总三碘甲状腺原氨酸水平。迄今为止，尚未进行过大规模随机试验来研究左甲状腺素的最佳服用时间，包括生活质量评估。
为确定睡前而非早晨服用左甲状腺素是否能改善甲状腺激素水平，于2007年4月1日至2008年11月30日在荷兰鹿特丹马斯塔德医院对105例连续的原发性甲状腺功能减退症患者进行了一项随机双盲交叉试验。患者在6个月内被指导在早晨服用1粒胶囊，在睡前服用1粒胶囊（其中1粒含左甲状腺素，另1粒为安慰剂），3个月后进行换药。主要观察指标为甲状腺激素水平；次要观察指标为肌酐和血脂水平、体重指数、心率和生活质量。
90例患者完成试验并可进行分析。与早晨服用相比，睡前服用左甲状腺素的直接治疗效果为促甲状腺激素水平降低1.25 mIU/L（95%置信区间[CI]，0.60 - 1.89 mIU/L；P <.001），游离甲状腺素水平升高0.07 ng/dL（0.02 - 0.13 ng/dL；P =.01），总三碘甲状腺原氨酸水平升高6.5 ng/dL（0.9 - 12.1 ng/dL；P =.02）（将促甲状腺激素水平换算为微克/升，乘以1.0；游离甲状腺素水平换算为皮摩尔/升，乘以12.871；总三碘甲状腺原氨酸水平换算为纳摩尔/升，乘以0.0154）。次要观察指标，包括生活质量问卷（36项简短健康调查、医院焦虑抑郁量表、20项多维疲劳量表和症状问卷）显示，早晨与睡前服用左甲状腺素之间无显著变化。
睡前服用左甲状腺素可显著改善甲状腺激素水平。生活质量变量和血浆脂质水平在睡前与早晨服用之间无显著变化。临床医生应考虑开具睡前服用左甲状腺素的处方。
isrctn.org标识符：ISRCTN17436693（NTR959）
