Pingitore Alessandro, Galli Elena, Barison Andrea, Iervasi Annalisa, Scarlattini Maria, Nucci Daniele, L'abbate Antonio, Mariotti Rita, Iervasi Giorgio
Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Via Moruzzi 1 Località la Fontina, 56124 Pisa, Italy.
J Clin Endocrinol Metab. 2008 Apr;93(4):1351-8. doi: 10.1210/jc.2007-2210. Epub 2008 Jan 2.
Low-T(3) syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T(3) replacement therapy in patients with low-T(3) syndrome and ischemic or nonischemic dilated cardiomyopathy (DC).
A total of 20 clinically stable patients with ischemic (n = 12) or nonischemic (n = 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66-77; median, 25-75th percentile) who underwent 3-d synthetic L-T(3) infusion (study group); the other 10 patients (average age 68 yr, range 64-71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T(3) (initial dose: 20 microg/m(2) body surface.d) or placebo infusion.
After T(3) administration, free T(3) concentrations increased until reaching a plateau at 24-48 h (3.43, 3.20-3.84 vs. 1.74, 1.62-1.93 pg/ml; P = 0.03) without side effects. Heart rate decreased significantly after T(3) infusion (63, 60-66 vs. 69, 60-76 beats per minute; P = 0.008). Plasma noradrenaline (347; 270-740 vs. 717, 413-808 pg/ml; P = 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P = 0.02), and aldosterone (175, 152-229 vs. 231, 154-324 pg/ml; P = 0.047) significantly decreased after T(3) administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T(3) administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114-158 ml/m(2) body surface; P = 0.02) and stroke volume (40, 34-44 vs. 35, 28-39 ml/m(2) body surface; P = 0.01) increased, whereas external and intracardiac workload did not change.
In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T(3) administration.
低T₃综合征是心功能不全患者预后不良的一个预测指标。本研究旨在评估合成L-T₃替代疗法对低T₃综合征合并缺血性或非缺血性扩张型心肌病（DC）患者的短期影响。
共纳入20例临床稳定的缺血性DC患者（n = 12）或非缺血性DC患者（n = 8）。10例患者（平均年龄72岁，范围66 - 77岁；中位数，第25 - 75百分位数）接受了为期3天的合成L-T₃输注（研究组）；另外10例患者（平均年龄68岁，范围64 - 71岁）接受了安慰剂输注（对照组）。在基线以及3天合成L-T₃（初始剂量：20μg/m²体表面积·天）或安慰剂输注后，进行临床检查、心电图、心脏磁共振以及生物体液指标（游离甲状腺激素、促甲状腺激素、血浆肾素活性、醛固酮、去甲肾上腺素、N末端B型利钠肽原和白细胞介素-6）的评估。
给予T₃后，游离T₃浓度升高，直至在24 - 48小时达到平台期（3.43，3.20 - 3.84 vs. 1.74，1.62 - 1.93 pg/ml；P = 0.03），且无副作用。T₃输注后心率显著降低（63，60 - 66 vs. 69，60 - 76次/分钟；P = 0.008）。血浆去甲肾上腺素（347；270 - 740 vs. 717，413 - 808 pg/ml；P = 0.009）、N末端B型利钠肽原（3000，438 - 4005 vs. 3940，528 - 5628 pg/ml；P = 0.02）和醛固酮（175，152 - 229 vs. 231，154 - 324 pg/ml；P = 0.047）在给予T₃后显著降低。对照组在安慰剂输注后神经激素指标未改变。给予合成L-T₃后，左心室舒张末期容积（142，132 - 161 vs. 133，114 - 158 ml/m²体表面积；P = 0.02）和每搏输出量（40，34 - 44 vs. 35，28 - 39 ml/m²体表面积；P = 0.01）增加，而心脏外部和内部工作负荷未改变。
在DC患者中，短期合成L-T₃替代疗法显著改善了神经内分泌指标和心室功能。这些数据鼓励开展更多患者参与、更长时间给予合成L-T₃的进一步对照试验。
