Kaptein E M, Robinson W J, Grieb D A, Nicoloff J T
J Clin Invest. 1982 Mar;69(3):526-35. doi: 10.1172/jci110478.
The low thyroxine (T(4)) state of acute critical nonthyroidal illnesses is characterized by marked decreases in serum total T(4) and triiodothyronine (T(3)) with elevated reverse T(3) (rT(3)) values. To better define the mechanisms responsible for these alterations, serum kinetic disappearance studies of labeled T(4), T(3), or rT(3) were determined in 16 patients with the low T(4) state and compared with 27 euthyroid controls and a single subject with near absence of thyroxine-binding globulin. Marked increases in the serum free fractions of T(4) (0.070+/-0.007%, normal [nl] 0.0315+/-0.0014, P < 0.001), T(3) (0.696+/-0.065%, nl 0.310+/-0.034, P < 0.001), and rT(3) (0.404+/-0.051%, nl 0.133+/-0.007, P < 0.001) by equilibrium dialysis were observed indicating impaired serum binding. Noncompartmental analysis of the kinetic data revealed an increased metabolic clearance rate (MCR) of T(4) (1.69+/-0.22 liter/d per m(2), nl 0.73+/-0.05, P < 0.001) and fractional catabolic rate (FCR) (32.8+/-2.6%, nl 12.0+/-0.8, P < 0.001), analogous to the euthyroid subject with low thyroxine-binding globulin. However, the reduced rate of T(4) exit from the serum (Kii) (15.2+/-4.6 d(-1), nl 28.4+/-3.9, P < 0.001) indicated an impairment of extravascular T(4) binding that exceeded the serum binding defect. This defect did not apparently reduce the availability of T(4) to sites of disposal as reflected by the increased fractional disposal rate of T(4) (0.101+/-0.018 d(-1), nl 0.021+/-0.003, P < 0.001). The decreased serum T(3) binding was associated with the expected increases in MCR (18.80+/-2.22 liter/d per m(2), nl 13.74+/-1.30, P < 0.05) and total volume of distribution (26.55+/-4.80 liter/m(2), nl 13.10+/-2.54, P < 0.01). However, the unaltered Kii suggested an extravascular binding impairment comparable to that found in serum. The decreased T(3) production rate (6.34+/-0.53 mug/d per m(2), nl 23.47+/-2.12, P < 0.005) appeared to result from reduced peripheral T(4) to T(3) conversion because of decreased 5'-deiodination rather than from a decreased T(4) availability. This view was supported by the normality of the rT(3) production rate. The normal Kii values for rT(3) indicated a comparable defect in serum and extravascular rT(3) binding. The reduced MCR (25.05+/-6.03 liter/d per m(2), nl 59.96+/-8.56, P < 0.005) and FCR (191.0+/-41.19%, nl 628.0+/-199.0, P < 0.02) for rT(3) are compatible with an impairment of the rT(3) deiodination rate. These alterations in thyroid hormones indices and kinetic parameters for T(4), T(3), and rT(3) in the low T(4) state of acute nonthyroidal illnesses can be accounted for by: (a) decreased binding of T(4), T(3), and rT(3) to vascular and extravascular sites with a proportionately greater impairment of extravascular T(4) binding, and (b) impaired 5'-deiodination activity affecting both T(4) and rT(3) metabolism.
急性危重症非甲状腺疾病的低甲状腺素（T4）状态的特征是血清总T4和三碘甲状腺原氨酸（T3）显著降低，而反T3（rT3）值升高。为了更好地确定导致这些改变的机制，对16例处于低T4状态的患者进行了标记T4、T3或rT3的血清动力学消失研究，并与27例甲状腺功能正常的对照者以及1例几乎没有甲状腺素结合球蛋白的个体进行了比较。通过平衡透析观察到T4（0.070±0.007%，正常[nl]0.0315±0.0014，P<0.001）、T3（0.696±0.065%，nl 0.310±0.034，P<0.001）和rT3（0.404±0.051%，nl 0.133±0.007，P<0.001）的血清游离分数显著增加，表明血清结合受损。对动力学数据的非房室分析显示，T4的代谢清除率（MCR）增加（1.69±0.22升/天·m²，nl 0.73±0.05，P<0.001）和分解代谢率（FCR）增加（32.8±2.6%，nl 12.0±0.8，P<0.001），类似于甲状腺素结合球蛋白低的甲状腺功能正常的个体。然而，T4从血清中流出的速率（Kii）降低（15.2±4.6天⁻¹，nl 28.4±3.9，P<0.001），表明血管外T4结合受损超过血清结合缺陷。这种缺陷显然没有降低T4向处置部位的可用性，这由T4的分数处置率增加（0.101±0.018天⁻¹，nl 0.021±0.003，P<0.001）反映出来。血清T3结合减少与MCR预期增加（18.80±2.22升/天·m²，nl 13.74±1.30，P<0.05）和分布总体积增加（26.55±4.80升/m²，nl 13.10±2.54，P<0.01）相关。然而，未改变的Kii表明血管外结合受损与血清中发现的相当。T3生成率降低（6.34±0.53μg/天·m²，nl 23.47±2.12，P<0.005）似乎是由于5'-脱碘作用降低导致外周T4向T3转化减少，而不是由于T4可用性降低。rT3生成率正常支持了这一观点。rT3的正常Kii值表明血清和血管外rT3结合存在类似缺陷。rT3的MCR降低（25.05±6.03升/天·m²，nl 59.96±8.56，P<0.005）和FCR降低（191.0±41.19%，nl 628.0±199.0，P<0.02）与rT3脱碘率受损一致。急性非甲状腺疾病低T4状态下甲状腺激素指标以及T4、T3和rT3动力学参数的这些改变可由以下原因解释：（a）T4、T3和rT3与血管和血管外部位的结合减少，血管外T4结合受损程度相对更大；（b）影响T4和rT3代谢的5'-脱碘活性受损。
