It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.

中文翻译：

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治疗外源性糖皮质激素的副作用；我们能区分好与坏吗？

据估计，目前有 2% 至 3% 的人口接受全身或局部糖皮质激素治疗。糖皮质激素具有强大的抗炎作用，可以提供治疗效果，这是毫无疑问的。然而，与其使用相关的副作用，包括中心体重增加、高血压、胰岛素抵抗、2 型糖尿病 (T2D) 和骨质疏松症（通常统称为医源性库欣综合征），会带来重大的健康和经济负担。糖皮质激素产生所需和不良作用的差异作用的精确细胞机制尚不完全清楚。面对未满足的临床需求，即限制糖皮质激素引起的不良反应，同时确保保留抗炎作用，人们采取了多种策略。现有许可药物的联合处方治疗偶发不良反应可能是有效的，但检查不良反应预防的数据有限。新型选择性糖皮质激素受体激动剂和选择性糖皮质激素受体调节剂的设计目的是基于它们与糖皮质激素受体的相互作用，特异性地、选择性地激活抗炎反应。其中几种化合物目前正在进行临床试验以评估其功效。最近，尽管临床试验数据有限，但通过 11β-羟基类固醇脱氢酶亚型利用组织特异性糖皮质激素代谢的策略已显示出早期潜力。任何治疗的目的都是最大化益处，同时最小化风险，在本次综述中，我们定义了与糖皮质激素使用相关的不良反应概况，并评估了当前和正在开发的旨在限制副作用但保持理想治疗效果的策略。