糖皮质激素状态评估的当前挑战和未来方向。

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2024-05-25 DOI:10.1210/endrev/bnae016
Sophie A Clarke, Pei Chia Eng, Alexander N Comninos, Katharine Lazarus, Sirazum Choudhury, Christie Tsang, Karim Meeran, Tricia M Tan, Waljit S Dhillo, Ali Abbara
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引用次数: 0

摘要

糖皮质激素(GC)按昼夜节律和超昼夜节律分泌,在维持生理平衡方面起着至关重要的作用,GC 过多或不足都会对健康产生不利影响。目前对 GC 状态的评估主要是临床评估,通常与血清皮质醇值相结合,而血清皮质醇值可能会受到刺激或抑制,这取决于所评估的 GC 干扰。在皮质醇水平极端紊乱的情况下,即皮质醇水平明显过低或过高时,可能会出现明显的 GC 功能障碍症状和体征。然而,当皮质醇 GC 状态的干扰值不那么极端时,例如在评估 GC 替代方案的优化情况时,症状和体征可能会比较隐蔽或没有特异性。目前用于评估 GC 状态的工具最适合用于识别严重的紊乱,但对于确认最佳 GC 状态可能缺乏敏感性。此外,单一的皮质醇值并不一定能反映个体的 GC 状态,因为它们受个体间和个体内差异的影响,没有考虑到皮质醇分泌的搏动性、结合蛋白的变化、由 11β-eta- 羟基类固醇脱氢酶 (11β-HSD) 活性决定的局部组织浓度以及 GC 受体的敏感性。在本综述中,我们评估了评估 GC 状态的可能替代方法,这些方法并不完全依赖于循环皮质醇水平的测量。我们讨论了代谢组图谱、miRNA、基因表达、表观遗传学和其他新型生物标记物(如 GDF-15 和骨钙素)的潜在变化,这些变化将来可能有助于对 GC 状态进行客观分类。
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Current Challenges and Future Directions in the Assessment of Glucocorticoid Status.

Glucocorticoid hormones (GC) are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being assessed. In the setting of extreme perturbations in cortisol levels i.e. markedly low or high levels, symptoms and signs of GC dysfunction may be overt. However, when disturbances in cortisol GC status values are less extreme, such as when assessing optimization of a GC replacement regimen, signs and symptoms can be more subtle or non-specific. Current tools for assessing GC status, are best suited to identifying profound disturbances but may lack sensitivity for confirming optimal GC status. Moreover, single cortisol values do not necessarily reflect an individual's GC status, as they are subject to inter- and intra-individual variation, do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11βeta-hydroxysteroid dehydrogenase (11β-HSD) activity, as well as GC receptor sensitivity. In the present review, we evaluate possible alternative methods for the assessment of GC status that do not solely rely on measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, miRNA, gene expression, epigenetic, and other novel biomarkers such as GDF-15 and osteocalcin, that could in future aid in the objective classification of GC status.

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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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