Bolk Nienke, Visser Theo J, Kalsbeek Andries, van Domburg Ron T, Berghout Arie
Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
Clin Endocrinol (Oxf). 2007 Jan;66(1):43-8. doi: 10.1111/j.1365-2265.2006.02681.x.
Standard drug information resources recommend that l-thyroxine be taken half an hour before breakfast on an empty stomach, to prevent interference of its intestinal uptake by food or medication. We observed cases in which TSH levels improved markedly after changing the administration time of l-thyroxine to the late evening. We therefore conducted a pilot-study to investigate whether l-thyroxine administration at bedtime improves TSH and thyroid hormones, and whether the circadian rhythm of TSH remains intact. DESIGN Patients were studied on two occasions: on a stable regimen of morning thyroxine administration and two months after switching to night-time thyroxine using the same dose. On each occasion patients were admitted for 24 h and serial blood samples were obtained.
We investigated 12 women treated with l-thyroxine because of primary hypothyroidism, who used no medication known to interfere with l-thyroxine uptake.
Patients were admitted to hospital and blood samples were obtained at hourly intervals for 24 h via an indwelling catheter. Following this first hospital admission, all women were asked to switch the administration time from morning to bedtime or vice versa. After 2 months they were readmitted for a 24-h period of hourly blood sampling. Blood samples were analysed for serum TSH (immunometric assay), FT4 and T3 (competitive immunoassay), T4 and rT3 (radioimmunoassay), serum TBG (immunometric assay) and total protein and albumin (colourimetric methods).
A significant difference in TSH and thyroid hormones was found after switching to bedtime administration of l-thyroxine. Twenty-four-hour average serum values amounted to (mean +/- SD, morning vs bedtime ingestion): TSH, 5.1 +/- 0.9 vs 1.2 +/- 0.3 mU/l (P < 0.01); FT4, 16.7 +/- 1.0 vs 19.3 +/- 0.7 pmol/l (P < 0.01); T3, 1.5 +/- 0.05 vs 1.6 +/- 0.1 nmol/l (P < 0.01). There was no significant change in T4, rT3, albumin and TBG serum levels, nor in the T3/rT3 ratio. The relative amplitude and time of the nocturnal TSH surge remained intact.
l-thyroxine taken at bedtime by patients with primary hypothyroidism is associated with higher thyroid hormone concentrations and lower TSH concentrations compared to the same l-thyroxine dose taken in the morning. At the same time, the circadian TSH rhythm stays intact. Our findings are best explained by a better gastrointestinal uptake of l-thyroxine during the night.
标准药物信息资源建议左甲状腺素应在早餐前半小时空腹服用，以防止食物或药物干扰其肠道吸收。我们观察到将左甲状腺素的给药时间改为深夜后促甲状腺激素（TSH）水平显著改善的病例。因此，我们进行了一项初步研究，以调查睡前服用左甲状腺素是否能改善TSH和甲状腺激素水平，以及TSH的昼夜节律是否保持完整。
对患者进行了两次研究：一次是在稳定的早晨服用甲状腺素方案下，另一次是在改用相同剂量的夜间甲状腺素两个月后。每次研究时，患者均住院24小时，并采集系列血样。
我们调查了12名因原发性甲状腺功能减退而接受左甲状腺素治疗的女性，她们未使用已知会干扰左甲状腺素吸收的药物。
患者入院，通过留置导管每小时采集一次血样，共采集24小时。第一次住院后，要求所有女性将给药时间从早晨改为睡前，反之亦然。2个月后，她们再次入院进行24小时的每小时一次的血样采集。对血样进行血清TSH（免疫测定法）、游离甲状腺素（FT4）和三碘甲状腺原氨酸（T3）（竞争性免疫测定法）、甲状腺素（T4）和反三碘甲状腺原氨酸（rT3）（放射免疫测定法）、血清甲状腺素结合球蛋白（TBG）（免疫测定法）以及总蛋白和白蛋白（比色法）分析。
改为睡前服用左甲状腺素后，TSH和甲状腺激素水平出现显著差异。24小时平均血清值为（均值±标准差，早晨服用与睡前服用）：TSH，5.1±0.9 vs 1.2±0.3 mU/L（P<0.01）；FT4，16.7±1.0 vs 19.3±0.7 pmol/L（P<0.01）；T3，1.5±0.05 vs 1.6±0.1 nmol/L（P<0.01）。T4、rT3、白蛋白和TBG血清水平以及T3/rT3比值均无显著变化。夜间TSH高峰的相对幅度和时间保持完整。
与早晨服用相同剂量的左甲状腺素相比，原发性甲状腺功能减退患者睡前服用左甲状腺素与更高的甲状腺激素浓度和更低的TSH浓度相关。同时，TSH的昼夜节律保持完整。我们的研究结果最好的解释是夜间左甲状腺素的胃肠道吸收更好。
