チロトロピン抑制療法が分化型甲状腺癌患者の心拍変動およびQT分散に及ぼす影響

Effect of thyrotropin suppressive therapy on heart rate variability and QT dispersion in patients with differentiated thyroid cancer.

• Chunhua Liu
• Haihong Lv
• Qian Li
• Songbo Fu
• Jiaojiao Tan
• Chenyi Wang
• Xiaoqian Wang
• Yuping Ma

抄録

チロトロピン（TSH）抑制療法が分化型甲状腺癌（DTC）患者の自律神経調節および心室再分極に及ぼす影響は明らかにされていない。本研究の目的は、DTC患者におけるTSH抑制療法後の心拍変動（HRV）およびQT分散の変化を評価することであった。症例は、外因性レボチロキシン投与後1年以内のDTC患者271例と定義し、全患者を対象に、完全な病歴、標準的な12リード心電図（ECG）を含む身体検査、および24"Zs_200A"h外来心電図モニター（ホルター）を受け、レボチロキシンを用いて遊離チロキシン（FT4）を正常値、遊離トリヨードチロニン（FT3）を測定した。TSH抑制療法のHRVおよびQT分散に対する効果を評価するために、患者を異なるTSHレベルに応じて3群に分けた：TSH"Zs_200A"<"Zs_200A"0.1"Zs_200A"mIU/L群と、0.1"Zs_200A"≤"Zs_200A"TSH"Zs_200A"<"Zs_200A"0．5"Zs_200A"mIU/L群をTSH抑制群とし、0.5"Zs_200A"≤"Zs_200A"TSH"Zs_200A"<"Zs_200A"2．0"Zs_200A"mIU/L群では、TSH"Zs_200A"<"Zs_200A"0.1"Zs_200A"mIU/L群（P"Zs_200A"<"Zs_200A".001：SDNN、SDANN、HF、LF/HF、QTd、QTcd；P"Zs_200A"<"Zs_200A".05：rMSSD）と0"Zs_200A"<"Zs_200A".05: rMSSD)と0.1"Zs_200A"≤"Zs_200A"TSH"Zs_200A"<"Zs_200A"0.5"Zs_200A"mIU/L群(P"Zs_200A"<"Zs_200A".001：SDNN、HF、LF/HF、QTd、QTcd）、特にTSH"Zs_200A"<"Zs_200A"0.1"Zs_200A"mIU/L群で顕著であった。さらに、TSHレベルはSDNN（β"Zs_200A"="Zs_200A"15.829、P"Zs_200A"<"Zs_200A".001）に比例するが、LF/HF（β"Zs_200A"="Zs_200A"-0.671、P"Zs_200A"-0.1）には反比例することがわかった。671、P"Zs_200A"<"Zs_200A".001）、QTd（β"Zs_200A"="Zs_200A"-16.674、P"Zs_200A"<"Zs_200A".001）、およびQTcd（β"Zs_200A"="Zs_200A"-18.血清TSHが抑制されている患者では、優甲状腺状態と比較して迷走神経緊張が低下した状態で交感神経活動が亢進し、最終的には交感神経の不均衡を示し、心室回復時間の不均一性が増加していた。以上の結果から、TSH抑制療法は心血管系に大きな影響を与え、DTC患者の治療・管理において一定の指針となる役割を持っていることが明らかになった。

The effects of thyrotropin (TSH) suppressive therapy on autonomic regulation and ventricular repolarization in patients with differentiated thyroid cancer (DTC) have not been elucidated. The aim of present study was to evaluate variation in heart rate variability (HRV) and QT dispersion after TSH suppressive therapy in patients with DTC.Cases, defined as 271 patients with DTC within 1 year of exogenous levothyroxine, and all patients underwent a full history, physical examination, including standard 12 lead electrocardiogram (ECG), and 24 h ambulatory ECG monitoring (Holter) with normal free thyroxine (FT4) and free triiodothyronine (FT3) with levothyroxine. To evaluate effects of TSH suppressive therapy on HRV and QT dispersion, patients were divided into three groups according to different levels of TSH: TSH < 0.1 mIU/L group and 0.1 ≤ TSH < 0.5 mIU/L group were as TSH suppression groups, and 0.5 ≤ TSH < 2.0 mIU/L group was as TSH replacement group.Comparing with 0.5 ≤ TSH < 2.0 mIU/L group, significant changes in both time and frequency domain of HRV and QT dispersion were observed in TSH < 0.1 mIU/L group (P < .001: SDNN, SDANN, HF, LF/HF, QTd, and QTcd; P < .05: rMSSD) and 0.1 ≤ TSH < 0.5 mIU/L group (P < .001: SDNN, HF, LF/HF, QTd, and QTcd), and especially were more pronounced in TSH < 0.1 mIU/L group. Moreover, we found that TSH level was proportional to SDNN (β = 15.829, P < .001), but inversely proportional to LF/HF (β = -0.671, P < .001), QTd (β = -16.674, P < .001) and QTcd (β = -18.314, P < .001) in DTC patients with exogenous levothyroxine.Compared with euthyroid state, patients with suppressed serum TSH have increased sympathetic activity in the presence of diminished vagal tone, ultimately showed sympathovagal imbalance and with an increased inhomogeneity of ventricular recovery times. These findings revealed that TSH suppression therapy had a significant impact on cardiovascular system and had certain guiding role in the treatment and management of patients with DTC.