Van den Berghe Greet
Department of Intensive Care Medicine, University Hospital Gasthuisberg Catholic University of Leuven, B-3000 Leuven, Belgium.
Endocrinol Metab Clin North Am. 2003 Jun;32(2):385-410. doi: 10.1016/s0889-8529(03)00005-7.
Prolonged critical illness has a high morbidity and mortality. The acute and chronic phases of critical illness are associated with distinct endocrine alterations. The acute neuroendocrine response to critical illness involves an activated anterior pituitary function. In prolonged critical illness, however, a reduced pulsatile secretion of anterior pituitary hormones and the so-called "wasting syndrome" occur. The impaired pulsatile secretion of GH, thyrotropin and gonadotropin can be re-amplified by relevant combinations of releasing factors, which also substantially increase circulating levels of IGF-1, GH-dependent IGFBPs, thyroxin, tri-iodothyronine and testosterone. Anabolism is clearly re-initiated at the time GH secretagogues, thyrotropin-releasing hormone and gonadotropin-releasing hormone are coadministered but the effect on survival remains unknown. A lethal outcome of critical illness is predicted by a high serum concentration of IGFBP-1, pointing to impaired insulin effect rather than pituitary function, and survival was recently shown to be dramatically improved by strict normalization of glycemia with exogenous insulin. In addition to the illness-induced endocrine alterations, patients may have pre-existing central or peripheral endocrine diseases, either previously diagnosed or unknown. Hence, endocrine function testing in a critically ill patient represents a major challenge and the issue of treatment remains controversial. The recent progress in knowledge of the neuroendocrine response to critical illness and its interrelation with peripheral hormonal and metabolic alterations during stress, allows for potential new therapeutic perspectives to safely reverse the wasting syndrome and improve survival.
危重病的持续时间延长会导致高发病率和死亡率。危重病的急性期和慢性期与不同的内分泌改变有关。对危重病的急性神经内分泌反应涉及垂体前叶功能的激活。然而,在危重病持续时间延长时,会出现垂体前叶激素脉冲式分泌减少以及所谓的“消耗综合征”。生长激素(GH)、促甲状腺激素和促性腺激素的脉冲式分泌受损可通过释放因子的相关组合重新增强,这也会大幅提高胰岛素样生长因子-1(IGF-1)、GH依赖的胰岛素样生长因子结合蛋白(IGFBPs)、甲状腺素、三碘甲状腺原氨酸和睾酮的循环水平。当同时给予GH促分泌剂、促甲状腺激素释放激素和促性腺激素释放激素时,合成代谢明显重新启动,但对生存率的影响尚不清楚。高血清浓度的IGFBP-1预示着危重病的致命结局,这表明胰岛素作用受损而非垂体功能受损,最近研究表明,通过外源性胰岛素严格控制血糖正常化可显著提高生存率。除了疾病引起的内分泌改变外,患者可能既往存在已诊断或未知的中枢或外周内分泌疾病。因此,对危重病患者进行内分泌功能测试是一项重大挑战,治疗问题仍存在争议。最近在危重病神经内分泌反应及其与应激期间外周激素和代谢改变的相互关系方面的知识进展,为安全逆转消耗综合征和提高生存率提供了潜在的新治疗前景。