Garden J M, Freinkel R K
Arch Dermatol. 1986 Sep;122(9):1007-10.
This study was undertaken to determine whether the commonly used treatment of psoriasis with potent topical glucocorticoids results in hypercortisolism and whether metabolic changes might provide a means for monitoring pharmacologic effects of excessive systemic absorption of glucocorticoids. Plasma cortisol, glucose, and insulin and circulating polymorphonuclear leukocytes were assessed under controlled conditions in five otherwise healthy patients with psoriasis (40% to 85% involvement) treated with topical desoximetasone, without occlusion. In all patients, there were rapid and sustained suppression of endogenous cortisol production, twofold to threefold increases in fasting insulin levels indicating insulin resistance, and elevated levels of polymorphonuclear leukocytes. Two patients also experienced reduced glucose tolerance. These findings suggest that application of potent corticosteroids to large areas of diseased skin results in sufficient systemic absorption to cause not only adrenal suppression but some degree of hypercortisolism with greater frequency and rapidity than has been suggested. Prospective monitoring of insulin-glucose relationships as a sensitive index of the metabolic effects of glucocorticoids may provide a means of assessing excess systemic absorption that is not predictable on the basis of adrenal suppression or circulating levels of the drug. Such prediction could have particular relevance in anticipating adverse clinical effects in the treatment of chronic skin disorders with potent topical glucocorticoids.
本研究旨在确定银屑病常用的强效外用糖皮质激素治疗是否会导致皮质醇增多症,以及代谢变化是否可能为监测糖皮质激素全身过量吸收的药理作用提供一种方法。在无封包的情况下,对5名其他方面健康的银屑病患者(皮损累及40%至85%)外用去氧米松进行治疗,并在对照条件下评估血浆皮质醇、葡萄糖、胰岛素水平以及循环中的多形核白细胞。所有患者内源性皮质醇分泌均迅速且持续受到抑制,空腹胰岛素水平升高两倍至三倍,提示胰岛素抵抗,多形核白细胞水平也升高。两名患者还出现了糖耐量降低。这些发现表明,在大面积患病皮肤上应用强效糖皮质激素会导致足够的全身吸收,不仅会引起肾上腺抑制,还会导致一定程度的皮质醇增多症,其发生频率和速度比之前认为的更高更快。将胰岛素 - 葡萄糖关系作为糖皮质激素代谢效应的敏感指标进行前瞻性监测,可能为评估全身过量吸收提供一种方法,而这种过量吸收无法根据肾上腺抑制或药物的循环水平来预测。这种预测对于预期强效外用糖皮质激素治疗慢性皮肤疾病时的不良临床效应可能具有特殊意义。