al-Adsani H, Hoffer L J, Silva J E
Division of Endocrinology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
J Clin Endocrinol Metab. 1997 Apr;82(4):1118-25. doi: 10.1210/jcem.82.4.3873.
We have investigated the effects of modifying the dose of thyroxine on resting energy expenditure (REE) and on the thermic effect of glucose (TEG) in 9 randomly recruited patients on chronic treatment with this hormone. The initial dose was changed twice in each patient at 6-8 wk intervals, aiming to have a normal, a slightly reduced, and a slightly elevated serum TSH concentration. A total of 27 dose points for each measured variable (3 per patient) were gathered. Dose changes were monitored with serum free T4, T3, and TSH. At the end of each dose period, low density lipoprotein and high density lipoprotein cholesterol, triglycerides, angiotensin converting enzyme, and sex hormone binding globulin were also measured, along with a systematic assessment of symptoms and signs. The investigators involved in the measurements were blinded to the dose of T4. Serum free T4 and TSH significantly correlated to the dose in each patient and in the whole group, whereas serum T3 levels were minimally affected by the dose and did not correlate with it, with free T4 or with TSH. This latter was below normal on 9 occasions, normal in 12, and above normal in 6. Serum free T4 and T3 remained within the normal range on all except 2 occasions. REE and TEG were normalized to fat-free mass (FFM). In each patient there was a significant negative correlation between REE and TSH. This correlation was maintained when all data were pooled (r2 = 0.64; P < 0.001). Also, initial REE and its change between the highest and the lowest thyroxine dose were significantly correlated with, respectively, initial serum TSH (r2 = 0.85; P < 0.001) and the change in serum TSH between the highest and the lowest dose of T4 (r2 = 0.67; P < 0.0065). REE decreased approximately 15% when TSH increased between 0.1 and 10 mU/L. In 6 of the 9 patients, TEG increased with the reduction of the dose, and higher values were associated with higher TSH levels but without reaching statistical significance (F = 2.852, P = 0.077). None of the other indices were significantly affected by the changes in dose. These results indicate that, in patients on chronic treatment with thyroxine, REE is significantly influenced by the dose of this hormone in a dose range encompassing serum TSH concentrations that are considered acceptable in the management of hypothyroid patients. In the absence of physiological or behavioral compensations, these changes in REE may be clinically relevant.
我们研究了改变甲状腺素剂量对9例随机招募的长期接受该激素治疗患者静息能量消耗（REE）和葡萄糖热效应（TEG）的影响。每位患者的初始剂量每隔6 - 8周改变两次，目标是使血清促甲状腺激素（TSH）浓度达到正常、略降低和略升高。每个测量变量共收集了27个剂量点的数据（每位患者3个）。通过血清游离T4、T3和TSH监测剂量变化。在每个剂量期结束时，还测量了低密度脂蛋白和高密度脂蛋白胆固醇、甘油三酯、血管紧张素转换酶和性激素结合球蛋白，并对症状和体征进行了系统评估。参与测量的研究人员对T4剂量不知情。每位患者及整个研究组中，血清游离T4和TSH与剂量显著相关，而血清T3水平受剂量影响极小，与剂量、游离T4或TSH均无相关性。后者有9次低于正常，12次正常，6次高于正常。除2次外，血清游离T4和T3均保持在正常范围内。REE和TEG均根据去脂体重（FFM）进行了标准化。每位患者的REE与TSH之间均存在显著负相关。将所有数据汇总后，这种相关性依然存在（r2 = 0.64；P < 0.001）。此外，初始REE及其在最高和最低甲状腺素剂量之间的变化分别与初始血清TSH（r2 = 0.85；P < 0.001）以及T4最高和最低剂量之间血清TSH的变化（r2 = 0.67；P < 0.0065）显著相关。当TSH在0.1至10 mU/L之间升高时，REE下降约15%。9例患者中有6例，TEG随剂量降低而升高，较高的值与较高的TSH水平相关，但未达到统计学显著性（F = 2.852，P = 0.077）。剂量变化对其他指标均无显著影响。这些结果表明，在长期接受甲状腺素治疗的患者中，在一个包含甲状腺功能减退患者管理中认为可接受的血清TSH浓度的剂量范围内REE受该激素剂量的显著影响。在没有生理或行为代偿的情况下，REE的这些变化可能具有临床意义。
