Abstract：
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.
摘要：
糖皮质激素（GC）在昼夜节律和超节律中分泌，在维持生理稳态中起关键作用。GC过量和不足均对健康产生不利影响。目前对GC状态的评估主要是临床，通常与血清皮质醇值结合，根据所评估的GC干扰，可以刺激或抑制。在皮质醇水平极端扰动的情况下，即明显的低水平或高水平，GC功能障碍的症状和体征可能是明显的。然而,当皮质醇GC状态值的干扰不那么极端时，例如在评估GC替代方案的优化时，体征和症状可能更微妙或非特异性。当前用于评估GC状态的工具，最适合识别深度干扰，但可能缺乏确认最佳GC状态的敏感性。此外，单个皮质醇值不一定反映一个人的GC状态，因为它们受到个体间和个体内变化的影响，不要考虑皮质醇分泌的脉动性质，结合蛋白的变异，或由11β-羟基类固醇脱氢酶（11β-HSD）活性决定的局部组织浓度，以及GC受体敏感性。在本次审查中，我们评估了评估GC状态的可能替代方法，这些方法不仅依赖于测量循环皮质醇水平。我们讨论了代谢组学变化的潜力，miRNA,基因表达，表观遗传,和其他新的生物标志物，如GDF-15和骨钙蛋白，这在将来可能有助于GC状态的客观分类。
