Patti Giuseppa, Zucconi Alice, Matarese Simona, Tedesco Caterina, Panciroli Marta, Napoli Flavia, Di Iorgi Natascia, Maghnie Mohamad
Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genoa 16100, Italy.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genoa 16100, Italy.
J Clin Endocrinol Metab. 2025 Feb 18;110(3):863-872. doi: 10.1210/clinem/dgae564.
The management of adrenal insufficiency (AI) is challenging, and the overall goals of treatment are to prevent life-threatening adrenal crises, to optimize linear growth, to control androgen levels without overdosing in patients with congenital adrenal hyperplasia (CAH), and to improve quality of life in affected individuals. Standard glucocorticoid formulations fail to replicate the circadian rhythm of cortisol and control the adrenal androgen production driven by adrenocorticotropin. To personalize and tailor glucocorticoid therapy and to improve patient outcomes, new pharmacological strategies have been developed that best mimic physiological cortisol secretion. Novel therapeutic approaches in the management of AI include new ways to deliver circadian cortisol replacement as well as various adjunctive therapies to reduce androgen production and/or androgen action/effects. Preclinical studies are exploring the role of restorative cell-based therapies, and a first recombinant adeno-associated virus-based gene therapy is also being developed in humans with CAH. In this article, we present 3 illustrative cases of AI with different underlying etiologies and times of presentation. Diagnostic and management processes are discussed with an emphasis on treatment and outcomes. We have also provided the most up-to-date evidence for the tailored management of children and adolescents with AI.
肾上腺功能不全（AI）的管理具有挑战性，治疗的总体目标是预防危及生命的肾上腺危象，优化线性生长，在先天性肾上腺皮质增生症（CAH）患者中控制雄激素水平而不过量，并改善受影响个体的生活质量。标准糖皮质激素制剂无法复制皮质醇的昼夜节律，也无法控制促肾上腺皮质激素驱动的肾上腺雄激素生成。为了使糖皮质激素治疗个性化并优化治疗效果，已开发出能最佳模拟生理性皮质醇分泌的新药理学策略。AI管理中的新型治疗方法包括昼夜皮质醇替代治疗的新方式以及各种减少雄激素生成和/或雄激素作用/效应的辅助治疗。临床前研究正在探索基于细胞的恢复性疗法的作用，并且也正在针对CAH患者开展首个基于重组腺相关病毒的基因治疗。在本文中，我们展示了3例具有不同潜在病因和发病时间的AI病例。讨论了诊断和管理过程，重点是治疗和治疗效果。我们还提供了针对AI儿童和青少年个体化管理的最新证据。
