Supplementary Material for: Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

Background: Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Methods: Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Results: Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. Conclusion: This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms.

背景：尽管甲状腺功能亢进症（hyperthyroidism）会增加心房颤动（atrial fibrillation）的发病风险，但既往研究提示血清三碘甲状腺原氨酸（triiodothyronine, T3）浓度降低与术后心房颤动（postoperative atrial fibrillation, POAF）存在关联。然而，使用甲状腺激素（thyroid hormones, TH）进行治疗并未降低POAF的发病风险。本研究重新评估了甲状腺激素状态、心房电机械功能与POAF之间的关联。
方法：本研究前瞻性纳入了39例维持窦性心律（sinus rhythm）、无房颤或甲状腺疾病病史且拟行心脏手术（cardiac surgery）的患者。术前采集血清样本，检测促甲状腺激素（thyrotropin）、游离甲状腺素（free thyroxine, FT4）、总甲状腺素（total thyroxine, TT4）、T3、反三碘甲状腺原氨酸（reverse T3, rT3）、3-碘甲状腺原胺（3-iodothyronamine, 3-T1AM）以及3,5-二碘甲状腺原氨酸（3,5-diiodothyronine, 3,5-T2）的浓度，并同步评估心脏功能的超声心动图与电生理参数。术后10天内，采用动态心电图（Holter-ECG）与遥测监护对POAF进行筛查。
结果：17例发生POAF的患者中，7例存在非甲状腺性病态综合征（nonthyroidal illness syndrome, NTIS，定义为T3降低和/或T4降低综合征）；而维持窦性心律的22例患者中仅2例存在NTIS（P<0.05）。在POAF患者中，血清FT3浓度显著降低，但仍处于参考范围内。3,5-T2浓度与rT3浓度呈正相关，与FT3浓度呈负相关。此外，NTIS患者以及最终发生POAF的受试者的3,5-T2浓度均显著升高。多变量logistic回归分析显示，FT3、3,5-T2、心房总传导时间、左心房容积指数以及Fas配体（Fas ligand）均为POAF的独立预测因子。
结论：本研究证实了POAF患者血清FT3浓度降低，且首次报道了心脏NTIS患者的3,5-T2浓度升高。由此可见，NTIS的发病机制可能涉及更为精细的稳态代偿调控机制（allostatic mechanisms）。