Inaba Masaaki, Mori Katsuhito, Tsujimoto Yoshihiro, Yamada Shinsuke, Yamazaki Yuko, Emoto Masanori, Shoji Tetsuo
Renal Center, Ohno Memorial Hospital, 1-26-10, Minami-Horie Nishi-ku, Osaka 550-0015, Japan.
Department of Nephrology, Osaka City University School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Nutrients. 2021 Dec 17;13(12):4537. doi: 10.3390/nu13124537.
Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients.
This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study.
The serum FT4 and TSH of HD patients ( = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9 μIU/mL, which were within the respective normal range, while serum FT3 was 2.2 ± 0.3 pg/mL. As many as 101 out of 332 (30.4%) HD patients exhibited a serum FT3 less than the normal lower limit of 2.2 pg/mL. The serum FT3/FT4 ratio correlated significantly positively with serum creatinine, and inversely with serum log CRP and total cholesterol, while it exhibited a tendency towards positive correlation with serum albumin. Multiple regression analysis, which included serum creatinine, albumin, and log CRP, simultaneously, in addition to sex, age, diabetic kidney disease or not, log HD duration, body mass index, systolic blood pressure, and Kt/V, as independent variables, revealed an independent and significant positive association of serum creatinine, but not serum albumin or CRP, with the serum FT3/FT4 ratio.
The present study demonstrated an independent and positive correlation of serum creatinine with the serum FT3/FT4 ratio in HD patients. The lack of association of the serum FT3/FT4 ratio with serum albumin and CRP suggested the presence of a creatinine-specific mechanism to associate with serum FT3/FT4 ratio. Because of the local activation of T4 to T3 at muscle tissue, a lower muscle mass may be causatively associated with low T3 syndrome.
低T3综合征的定义是尽管血清促甲状腺激素（TSH）正常且游离甲状腺素（FT4）通常也正常，但游离三碘甲状腺原氨酸（FT3）水平下降。低FT3/FT4比值是低T3综合征的一个相关标志物，已知它是血液透析（HD）患者的死亡风险因素，在普通人群中也是低肌肉量的风险因素。由于肌肉组织中T4会局部激活转化为FT3，我们研究了FT3/FT4比值与血清肌酐之间的关联，血清肌酐是HD患者肌肉量和力量的一个标志物，以此来探究肌肉组织在HD患者低T3综合征发生发展中的意义。
这是一项横断面研究，源自我们对日本HD患者进行的前瞻性队列研究DREAM。在排除了患有已治疗和未治疗的甲状腺功能障碍的患者后，对332例患者进行了研究分析。
HD患者（n = 332）的血清FT4和TSH分别为0.9±0.1 ng/dL和2.0±0.9 μIU/mL，均在各自的正常范围内，而血清FT3为2.2±0.3 pg/mL。332例HD患者中有多达101例（30.4%）的血清FT3低于2.2 pg/mL的正常下限。血清FT3/FT4比值与血清肌酐显著正相关，与血清log CRP和总胆固醇呈负相关，而与血清白蛋白呈正相关趋势。多元回归分析同时纳入血清肌酐、白蛋白、log CRP，以及性别、年龄、是否患有糖尿病肾病、log HD时长、体重指数、收缩压和Kt/V作为自变量，结果显示血清肌酐与血清FT3/FT4比值存在独立且显著的正相关，而血清白蛋白或CRP与血清FT3/FT4比值无此关联。
本研究表明HD患者血清肌酐与血清FT3/FT4比值存在独立的正相关。血清FT3/FT4比值与血清白蛋白和CRP缺乏关联，提示存在一种与血清FT3/FT4比值相关的肌酐特异性机制。由于肌肉组织中T4向T3的局部激活，较低的肌肉量可能与低T3综合征存在因果关系。
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