Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy
Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy
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DOI：
10.1111/cen.12670
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发表时间：
2015-07-01
影响因子：
3.2
通讯作者：
Bensing, Sophie
中科院分区：
文献类型：
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作者：
Bjornsdottir, Sigridur;Oksnes, Marianne;Bensing, Sophie
阿迪森病(AD)患者的常规糖皮质激素替代治疗是非生理性的，可能会对死亡率、发病率和生活质量产生不良影响。目的比较常规每日三次糖皮质激素替代疗法和CSHI疗法对ADS患者的昼夜激素节律和胰岛素敏感性的影响。设计和建立一项在挪威和瑞典进行的开放、随机、两期、12周的交叉多中心试验。15例瑞典患者接受正血糖-高胰岛素钳夹治疗。干预：每日三次口服氢化可的松(OHC)和CSHI治疗。主要观察指标在OHC和CSHI治疗期间皮质醇、促肾上腺皮质激素(ACTH)、生长激素(GH)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)、血糖、胰岛素和甘油三酯的昼夜节律。结果持续皮下注射氢化可的松可提供更具生理性的皮质醇昼夜曲线，包括深夜皮质醇激增。对于CSHI，ACTH水平显示出接近正常的昼夜变化。CSHI阻止了夜间血糖的持续下降。两组患者的胰岛素敏感性无明显差异。结论持续皮下注射氢化可的松替代治疗可重建皮质醇昼夜节律，并使ACTH水平正常化。与OHC相比，接受CSHI替代治疗的患者夜间血糖水平更稳定，且不会影响胰岛素敏感性。因此，恢复夜间皮质醇水平可能对AD患者有利。
ContextConventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI).ObjectiveThe aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD.Design and settingAn open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden.PatientsTen Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp.InterventionThrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment.Main outcome measureWe measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity.ResultsContinuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms.ConclusionContinuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD.