Glucocorticoid (GC) hormones 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 ie, 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 nonspecific. 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 intraindividual variation and do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11beta-hydroxysteroid dehydrogenase 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 the measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, micro RNA, gene expression, and epigenetic and other novel biomarkers such as growth differentiating factor 15 and osteocalcin, which could in the future aid in the objective classification of GC status.

中文翻译：

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糖皮质激素状态评估的当前挑战和未来方向。


糖皮质激素 （GC） 激素以昼夜节律和超节律分泌，在维持生理稳态方面起关键作用，GC 过量和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的，通常与血清皮质醇值相结合，根据所评估的 GC 紊乱，血清皮质醇值可能会受到刺激或抑制。在皮质醇水平极度扰动的情况下，即明显低或高水平，GC 功能障碍的症状和体征可能是明显的。然而，当皮质醇 GC 状态值的紊乱不那么严重时，例如在评估 GC 替代方案的优化时，体征和症状可能更轻微或非特异性。当前评估 GC 状态的工具最适合识别严重干扰，但可能缺乏确认最佳 GC 状态的敏感性。此外，单个皮质醇值并不一定反映个体的 GC 状态，因为它们受个体间和个体内差异的影响，并且没有考虑皮质醇分泌的搏动性、结合蛋白的变化或由 11β-羟基类固醇脱氢酶活性决定的局部组织浓度，以及 GC 受体敏感性。在本综述中，我们评估了评估 GC 状态的可能替代方法，这些方法不仅仅依赖于循环皮质醇水平的测量。我们讨论了代谢组学谱、微 RNA、基因表达、表观遗传学和其他新生物标志物（如生长分化因子 15 和骨钙素）变化的潜力，这在未来可能有助于 GC 状态的客观分类。