PERIPHERAL SERUM THYROXINE, TRIIODOTHYRONINE AND REVERSE TRIIODOTHYRONINE KINETICS IN THE LOW THYROXINE STATE OF ACUTE NONTHYROIDAL ILLNESSES - A NON-COMPARTMENTAL ANALYSIS
PERIPHERAL SERUM THYROXINE, TRIIODOTHYRONINE AND REVERSE TRIIODOTHYRONINE KINETICS IN THE LOW THYROXINE STATE OF ACUTE NONTHYROIDAL ILLNESSES - A NON-COMPARTMENTAL ANALYSIS
复制标题
DOI：
10.1172/jci110478
复制
发表时间：
1982-01-01
影响因子：
15.9
通讯作者：
NICOLOFF, JT
中科院分区：
文献类型：
--
作者：
KAPTEIN, EM;ROBINSON, WJ;NICOLOFF, JT
急性危重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（rT 3）值升高。为了更好地确定这些变化的机制，标记T4，T3或rT 3的血清动力学消失研究确定在16例低T4状态，并与27个甲状腺功能正常的控制和一个单一的主题与T4结合球蛋白几乎没有。T4的血清游离部分显著增加（0.070 ± 0.00000）。0.007%，正常值[NL] 0.0315 ±。0.0014，P < 0.001），T3（0.696 ±. 0.065%，nl 0.310 ±。0.034，P < 0.001）和rT 3（0.404 ± 0.001）。0.051%，nl 0.133 ±。0.007，P < 0.001），表明血清结合受损。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 ± 0.01）。0.22 l/天/m2，nl 0.73 . ±. 0.05，P < 0.001）和部分分解率（FCR）（32.8 ± 0.05）。2.6%，NL 12.0 ±。0.8，P < 0.001），类似于甲状腺功能正常的低T4结合球蛋白受试者。T4从血清中排出的速率（Kii）降低（15.2 ± 0.01）。4.6第-1天，NL 28.4 ±。3.9，P < 0.001）表明血管外T4结合的损害超过血清结合缺陷。这一缺陷并没有明显减少T4在处置地点的可用性，这一点可以从T4的处置率增加（0.101 ± 0.001）中反映出来。0.018 d-1，nl 0.021 ±. 0.003，P < 0.001）。血清T3结合的降低与MCR的预期增加相关（18.80 ± 0.01）。2.22 l/天/m2，nl 13.74 .+-. 1.30，P < 0.05）和总分布容积（26.55 ± 0.05）。4.80 l/m2，nl 13.10 . ±. 2.54，P < 0.01）。然而，未改变的Kii表明血管外结合损伤与血清中发现的相当。降低的T3产生速率（6.34 ±. 0.53μ g/天/m2，NL 23.47 ±。2.12，P < 0.005）似乎是由于5“-脱碘减少而导致外周T4向T3转化减少，而不是由于T4可用性减少。这一观点得到了rT 3生产率正态性的支持。正常的Kii值rT 3表明血清和血管外rT 3结合相当的缺陷。降低的MCR（25.05 ±. 6.03 l/天/m2，nl 59.96 .+-. 8.56，P < 0.005）和FCR（191.0 ±. 41.19%，nl 628.0。199.0，P < 0.02）与rT 3脱碘率受损一致。在急性非甲状腺疾病的低T4状态下，T4、T3和rT 3的甲状腺激素指数和动力学参数的这些改变可以通过以下方式来解释：T4、T3和rT 3与血管和血管外部位的结合减少，血管外T4结合的损害相应更大，以及影响T4和rT 3代谢的5“-脱碘活性受损。
The low thyroxine (T4) state of acute critical nonthyroidal illnesses is characterized by marked decreases in serum total T4 and triiodothyronine (T3) with elevated reverse T3 (rT3) values. To better define the mechanisms responsible for these alterations, serum kinetic disappearance studies of labeled T4, T3 or rT3 were determined in 16 patients with the low T4 state and compared with 27 euthyroid controls and a single subject with near absence of T4-binding globulin. Marked increases in the serum free fractions of T4 (0.070 .+-. 0.007%, normal [nl] 0.0315 .+-. 0.0014, P < 0.001), T3 (0.696 .+-. 0.065%, nl 0.310 .+-. 0.034, P < 0.001) and rT3 (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 T4 (1.69 .+-. 0.22 l/day per m2, 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 T4-binding globulin. The reduced rate of T4 exit from the serum (Kii) (15.2 .+-. 4.6 day-1, nl 28.4 .+-. 3.9, P < 0.001) indicated an impairment of extravascular T4 binding that exceeded the serum binding defect. This defect did not apparently reduce the availability of T4 to sites of disposal as reflected by the increased fractional disposal rate of T4 (0.101 .+-. 0.018 d-1, nl 0.021 .+-. 0.003, P < 0.001). The decreased serum T3 binding was asosociated with the expected increases in MCR (18.80 .+-. 2.22 l/day per m2, nl 13.74 .+-. 1.30, P < 0.05) and total volume of distribution (26.55 .+-. 4.80 l/m2, 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 T3 production rate (6.34 .+-. 0.53 .mu.g/day per m2, nl 23.47 .+-. 2.12, P < 0.005) appeared to result from reduced peripheral T4 to T3 conversion because of decreased 5''-deiodination rather than from a decreased T4 availability. This view was supported by the normality of the rT3 production rate. The normal Kii values for rT3 indicated a comparable defect in serum and extravascular rT3 binding. The reduced MCR (25.05 .+-. 6.03 l/day per m2, nl 59.96 .+-. 8.56, P < 0.005) and FCR (191.0 .+-. 41.19%, nl 628.0 .+-. 199.0, P < 0.02) for rT3 are compatible with an impairment of the rT3 deiodination rate. These alterations in thyroid hormones indices and kinetic parameters for T4, T3 and rT3 in the low T4 state of acute nonthyroidal illnesses can be accounted for by: decreased binding of T4, T3 and rT3 to vascular and extravascular sites with a proportionately greater impairment of extravascular T4 binding, and impaired 5''-deiodination activity affecting both T4 and rT3 metabolism.