Pathogenesis of acute adrenal crisis in children: current concepts and emerging mechanisms
https://doi.org/10.23946/2500-0764-2025-10-4-22-31
Abstract
Aim. The aim of this article is to provide a comprehensive review of the pathogenetic mechanisms underlying the development of acute adrenal crisis (AAC) in children, with an emphasis on recent experimental and clinical findings. Materials and Methods. A comprehensive literature search was conducted using MEDLINE, Embase, Scopus, Cochrane, PubMed, Google Scholar and Elibrary databases, as well as through citation tracking of studies published between 2019 and June 2025. A total of 40 national and international publications were analyzed, including clinical, experimental, and genomic studies, as well as systematic reviews and meta-analyses focused on the pathogenesis of adrenal insufficiency and adrenal crisis in pediatric populations. Results. The classical pathogenesis of AAC is associated with cortisol and aldosterone deficiency, leading to severe metabolic and hemodynamic disturbances. However, in recent years, a new concept of the multifactorial nature of this syndrome has emerged, encompassing systemic, molecular, immune, and microbiota-related components. Key etiological forms have been analyzed, including congenital adrenal hyperplasia, glucocorticoid-induced adrenal insufficiency, and autoimmune adrenalitis. Data are presented on the involvement of pro-inflammatory cytokines (IL-6, TNF-α), mitochondrial dysfunction, altered expression of ACTH receptors (MC2R, MRAP), and epigenetic modifications (NR0B1, CYP21A2). Particular attention is given to sepsis-induced adrenal dysfunction, endothelial impairment, and the influence of the gut–adrenal axis on crisis development. Conclusion. The current understanding of AAC pathogenesis extends beyond the classical hormonal deficiency model and includes complex interactions among inflammatory, mitochondrial, immune, genetic, and microbiota-related mechanisms. The importance of early diagnosis, molecular stratification, and personalized treatment strategies is emphasized. These findings highlight the need to revise current approaches to prevention and management in pediatric practice, with a focus on targeted and multidisciplinary therapeutic interventions.
About the Author
Yu. V. Bykov
Stavropol State Medical University
Russian Federation
Russian Federation
Dr. Yuri V. Bykov, MD, Cand. Sci. (Medicine), Associate Professor of the Department of Anesthesiology and Intensive Care Medicine with a Course of Additional Professional Education
Mira Street, 310, Stavropol, 355020, Russia
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For citations:
Bykov Yu.V. Pathogenesis of acute adrenal crisis in children: current concepts and emerging mechanisms. Fundamental and Clinical Medicine. 2025;10(4):22-31. (In Russ.) https://doi.org/10.23946/2500-0764-2025-10-4-22-31
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