Context: 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). Design: A total of 20 clinically stable patients with ischemic (n ϭ 12) or nonischemic (n ϭ 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66 -77; median, 25-75th percentile) who underwent 3-d synthetic

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... 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 g/m 2 body surface⅐d) or placebo infusion. Results: 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 ϭ 0.03) without side effects. Heart rate decreased significantly after T 3 infusion (63, 60 -66 vs. 69, 60 -76 beats per minute; P ϭ 0.008). Plasma noradrenaline (347; 270 -740 vs. 717, 413-808 pg/ml; P ϭ 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P ϭ 0.02), and aldosterone (175, 152-229 vs. 231, 154 -324 pg/ml; P ϭ 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 ϭ 0.02) and stroke volume (40, 34 -44 vs. 35, 28 -39 ml/m 2 body surface; P ϭ 0.01) increased, whereas external and intracardiac workload did not change. Conclusions: 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. (J Clin Endocrinol