老年脓毒症病人的内分泌应激改变

doi:10.3969/j.issn.1003-9198.2025.04.005

摘要/Abstract

摘要： 随着全球老龄化的加速,老年人群的脓毒症发病率和病死率显著上升,已成为严重威胁公共健康的问题。老年病人面对脓毒症时,其内分泌应激反应呈现出明显的年龄相关特征,这些内分泌应激改变不仅影响脓毒症的疾病进程,也给病人的临床管理带来诸多挑战。本综述系统总结了老年脓毒症病人下丘脑-垂体-肾上腺(HPA)轴、下丘脑-垂体-甲状腺(HPT)轴、下丘脑-垂体-性腺(HPG)轴和肾素-血管紧张素-醛固酮系统(RAAS)的变化及其潜在机制,深入分析激素替代治疗所带来的风险与益处,为优化老年脓毒症病人治疗策略提供坚实的理论依据。

关键词: 老龄化, 脓毒症, 内分泌系统

Abstract: With the accelerating pace of global aging, the incidence rate and mortality rate of sepsis among the elderly have risen significantly, posing a serious threat to public health. The elderly patients with sepsis exhibit distinct age-related characteristics in their endocrine stress responses, which not only influence the progression of sepsis but also present challenges to clinical management.This review systematically summarizes the dysfunction and underlying mechanisms of hypothalamic-pituitary-adrenal (HPA) axis, hypothalamic-pituitary-thyroid (HPT) axis, hypothalamic-pituitary-gonadal (HPG) axis and renin angiotensin-aldosterone system (RAAS) in the elderly patients with sepsis, and comprehensively analyzes the risks and benefits of hormone replacement therapy, providing a theoretical foundation for optimizing treatment strategies in the elderly patients with sepsis.

Key words: aging, sepsis, endocrine system

中图分类号:

R 631

孙才智, 秦海东. 老年脓毒症病人的内分泌应激改变[J]. 实用老年医学, 2025, 39(4): 347-351.

SUN Caizhi, QIN Haidong. Endocrine stress changes in elderly patients with sepsis[J]. Practical Geriatrics, 2025, 39(4): 347-351.

参考文献

[1] MEYER N J, PRESCOTT H C. Sepsis and septic shock[J].N Engl J Med, 2024, 391(22): 2133-2146.
[2] RUDD K E, JOHNSON S C, AGESA K M, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study[J].Lancet, 2020, 395(10219): 200-211.
[3] GOODACRE S, FULLER G, CONROY S, et al. Diagnosis and management of sepsis in the older adult[J].BMJ, 2023, 382: e075585.
[4] FOWLER C, RAOOF N, PASTORES S M. Sepsis and adrenal insufficiency[J].J Intensive Care Med, 2023, 38(11): 987-996.
[5] KÖHALMI E, BAKÓ G. Endocrine changes, endocrine diseases in the elderly[J].Orv Hetil, 2024, 165(2): 51-58.
[6] RAFF H, BIRU N, REISINGER N, et al. Dissociation of ACTH and cortisol in septic and non-septic ICU patients[J].Endocrine, 2017, 55(1): 307-310.
[7] WEPLER M, PREUSS J M, MERZ T, et al. Impact of downstream effects of glucocorticoid receptor dysfunction on organ function in critical illness-associated systemic inflammation[J].Intensive Care Med Exp, 2020, 8(Suppl 1): 37.
[8] NIXON M, UPRETI R, ANDREW R. 5α-Reduced glucocorticoids: a story of natural selection[J].J Endocrinol, 2012, 212(2): 111-127.
[9] CHAN E D, CHAN M M, CHAN M M, et al. Use of glucocorticoids in the critical care setting: science and clinical evidence[J].Pharmacol Ther, 2020, 206: 107428.
[10]RYGÅRD S L, BUTLER E, GRANHOLM A, et al. Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis[J].Intensive Care Med, 2018, 44(7): 1003-1016.
[11]ROCHWERG B, OCZKOWSKI S J, SIEMIENIUK R A C, et al. Corticosteroids in sepsis: an updated systematic review and meta-analysis[J].Crit Care Med, 2018, 46(9): 1411-1420.
[12]MUHAMMAD A, HAQ I U, KHAN M A, et al. Thyroid functions and cognitive decline in the elderly[J].Cureus, 2024, 16(11): e74484.
[13]VANH D. The ageing thyroid: implications for longevity and patient care[J].Nat Rev Endocrinol, 2024, 20(1): 5-15.
[14]LEE J, JANG H, PEARCE E N, et al. Exposome-wide association study of thyroid function using U.S. National Health and Nutrition Examination Survey data[J].Environ Res, 2025, 269: 120884.
[15]WASYLUK W, WASYLUK M, ZWOLAK A. Sepsis as a pan-endocrine illness-endocrine disorders in septic patients[J].J Clin Med, 2021, 10(10): 2075.
[16]SIAMPA V N, ABADI S, AMAN A M, et al. Association between severity of sepsis and thyroid function profile[J].Acta Biomed, 2023, 94(6): e2023239.
[17]VIDART J, AXELRUD L, BRAUN A C, et al. Relationship among low T3 levels, type 3 deiodinase, oxidative stress, and mortality in sepsis and septic shock: defining patient outcomes[J].Int J Mol Sci, 2023, 24(4): 3935.
[18]SUN C, BAO L, GUO L, et al. Prognostic significance of thyroid hormone T3 in patients with septic shock: a retrospective cohort study[J].PeerJ, 2023, 11: e15335.
[19]KIM R B, KIM M, CHO Y Y, et al. Thyroid function tests in patients at the emergency department compared to a prior healthy setting[J].PLoS One, 2018, 13(8): e0202422.
[20]HONG J, ZHANG L, LAI Y, et al. Causal association between thyroid dysfunction and sepsis: a two-sample mendelian randomization study[J].Front Endocrinol, 2024, 15: 1348248.
[21]DE SILVAN L, PAPANIKOLAOU N, GROSSMANN M, et al. Male hypogonadism: pathogenesis, diagnosis, and management[J].Lancet Diabetes Endocrinol, 2024, 12(10): 761-774.
[22]WASYLUK W, WASYLUK M, ZWOLAK A. Sepsis as a pan-endocrine illness-endocrine disorders in septic patients[J].J Clin Med, 2021, 10(10): 2075.
[23]MCCOSHR B, O’BRYNEK T, KARSCHF J, et al. Regulation of the gonadotropin-releasing hormone neuron during stress[J].J Neuroendocrinol, 2022, 34(5): e13098.
[24]DARDEND B, MOOREF A, BRAKENRIDGES C, et al. The effect of aging physiology on critical care[J].Crit Care Clin, 2021, 37(1): 135-150.
[25]FERRUCCI L, MAGGIO M, BANDINELLI S, et al. Low testosterone levels and the risk of Anemia in older men and women[J].Arch Intern Med, 2006, 166(13): 1380-1388.
[26]XU J, TONG L, YAO J, et al. Association of sex with clinical outcome in critically ill sepsis patients: a retrospective analysis of the large clinical database MIMIC-III[J].Shock, 2019, 52(2): 146-151.
[27]MEHDI S F, QURESHI M H, PERVAIZ S, et al. Endocrine and metabolic alterations in response to systemic inflammation and sepsis: a review article[J].Mol Med, 2025, 31(1): 16.
[28]CONTI S, CASSIS P, BENIGNI A. Aging and the renin-angiotensin system[J].Hypertension, 2012, 60(4): 878-883.
[29]LEGRAND M, KHANNAA K, OSTERMANN M, et al. The renin-angiotensin-aldosterone-system in sepsis and its clinical modulation with exogenous angiotensin II[J].Crit Care, 2024, 28(1): 389.
[30]MONTEZANOA C, TOUYZR M. Oxidative stress, noxs, and hypertension: experimental evidence and clinical controversies[J].Ann Med, 2012, 44(Suppl 1): S2-S16.
[31]LEISMAND E, HANDISIDESD R, BUSSEL W, et al. ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock[J].Crit Care, 2024, 28(1): 130.
[32]LIJ X, XIAO X, TENG F, et al. Myeloid ACE2 protects against septic hypotension and vascular dysfunction through Ang-(1-7)-Mas-mediated macrophage polarization[J].Redox Biol, 2024, 69: 103004.
[33]ZHANG L, ZHANG Y, QIN X, et al. Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein[J].Crit Care, 2022, 26(1): 171.
[34]GARCIA B, ZARBOCK A, BELLOMO R, et al. The role of renin-angiotensin system in sepsis-associated acute kidney injury: mechanisms and therapeutic implications[J].Curr Opin Crit Care, 2023, 29(6): 607-613.
[35]PATEL V B,MORI J,MCLEAN B A, et al. ACE2 deficiency worsens epicardial adipose tissue inflammation and cardiac dysfunction in response to diet-induced obesity[J].Diabetes, 2016, 65(1): 85-95.