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脑膜炎球菌败血症中的正常甲状腺病态综合征:外周甲状腺激素代谢及结合蛋白的影响

Euthyroid sick syndrome in meningococcal sepsis: the impact of peripheral thyroid hormone metabolism and binding proteins.

作者信息

den Brinker Marieke, Joosten Koen F M, Visser Theo J, Hop Wim C J, de Rijke Yolanda B, Hazelzet Jan A, Boonstra Venje H, Hokken-Koelega Anita C S

机构信息

Erasmus MC-Sophia Children's Hospital, Department of Pediatrics, Division of Endocrinology, Room SP-3435, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.

出版信息

J Clin Endocrinol Metab. 2005 Oct;90(10):5613-20. doi: 10.1210/jc.2005-0888. Epub 2005 Aug 2.

Abstract

CONTEXT AND OBJECTIVES

The objective of this study was to elucidate the influence of disease severity, deiodination, sulfation, thyroid hormone binding, and dopamine use on thyroid function in euthyroid sick syndrome.

SETTING

The study was performed at a university-affiliated pediatric intensive care unit (PICU).

DESIGN

This was an observational cohort study.

PATIENTS

Sixty-nine children with meningococcal sepsis were studied.

MAIN OUTCOME MEASURES

Differences in thyroid function among nonsurvivors, shock survivors, and sepsis survivors on PICU admission were the main outcome measures.

RESULTS

The main study group consisted of 45 non-dopamine-treated children. All children had decreased total T3 (TT3)/rT3 ratios without elevated TSH. T4 sulfate levels were decreased in 88%. Nonsurvivors had paradoxically higher TT3/rT3 ratios than shock survivors (0.71 vs. 0.30); this ratio also correlated with shorter duration of disease (r = -0.43). TT4 and T4-binding globulin (TBG) levels declined with increasing disease severity. TBG levels correlated inversely with elastase levels (r = -0.46). Only TSH levels were significantly lower in 24 dopamine-treated children compared with non-dopamine-treated children (0.65 vs. 0.84), whereas other thyroid hormones did not significantly differ. Both higher TT3/rT3 ratios and lower TT4 levels were predictive for mortality, but this disappeared when IL-6 was entered into the regression model.

CONCLUSIONS

All children with meningococcal sepsis showed signs of euthyroid sick syndrome. Alterations in peripheral thyroid hormone metabolism related inversely to the duration of disease and seemed to be enacted by profound induction of type 3 deiodinase rather than by down-regulation of type 1. Lower TT4 levels were related to increased turnover of TBG by elastase. Dopamine was found to suppress only TSH secretion, not other thyroid hormone levels, on PICU admission. Both the TT3/rT3 ratio and TT4 levels were predictive for mortality, but were not superior to IL-6.

摘要

背景与目的

本研究的目的是阐明疾病严重程度、脱碘作用、硫酸化作用、甲状腺激素结合以及多巴胺使用对正常甲状腺病态综合征患者甲状腺功能的影响。

设置

本研究在一所大学附属医院的儿科重症监护病房(PICU)进行。

设计

这是一项观察性队列研究。

患者

对69例患有脑膜炎球菌败血症的儿童进行了研究。

主要观察指标

入住PICU时,非存活者、休克存活者和败血症存活者之间甲状腺功能的差异是主要观察指标。

结果

主要研究组由45例未接受多巴胺治疗的儿童组成。所有儿童的总T3(TT3)/反式T3(rT3)比值均降低,促甲状腺激素(TSH)未升高。88%的儿童硫酸化T4水平降低。非存活者的TT3/rT3比值反常地高于休克存活者(0.71对0.30);该比值也与疾病持续时间缩短相关(r = -0.43)。TT4和甲状腺激素结合球蛋白(TBG)水平随疾病严重程度增加而下降。TBG水平与弹性蛋白酶水平呈负相关(r = -0.46)。与未接受多巴胺治疗的儿童相比,24例接受多巴胺治疗的儿童中只有TSH水平显著降低(0.65对0.84),而其他甲状腺激素无显著差异。较高的TT3/rT3比值和较低的TT4水平均为死亡的预测因素,但当将白细胞介素-6(IL-6)纳入回归模型时,这种情况消失。

结论

所有患有脑膜炎球菌败血症的儿童均表现出正常甲状腺病态综合征的体征。外周甲状腺激素代谢的改变与疾病持续时间呈负相关,似乎是由3型脱碘酶的深度诱导而非1型脱碘酶的下调所致。较低的TT4水平与弹性蛋白酶导致的TBG周转率增加有关。发现多巴胺在入住PICU时仅抑制TSH分泌,而不影响其他甲状腺激素水平。TT3/rT3比值和TT4水平均为死亡的预测因素,但并不优于IL-6。

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