Continuous Subcutaneous Hydrocortisone Infusion Therapy in Addison's Disease: A Randomized, Placebo-Controlled Clinical Trial
Continuous Subcutaneous Hydrocortisone Infusion Therapy in Addison's Disease: A Randomized, Placebo-Controlled Clinical Trial
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DOI：
10.1210/jc.2014-2433
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发表时间：
2014-11-01
影响因子：
5.8
通讯作者：
Torpy, David J.
中科院分区：
文献类型：
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作者：
Gagliardi, Lucia;Nenke, Marni A.;Torpy, David J.
背景：艾迪生病（AD）患者报告主观健康状况（SHS）受损。由于皮质醇表现出强大的昼夜节律周期，包含了其他生物钟，因此SHS受损可能是由于常规糖皮质激素替代所获得的非昼夜节律皮质醇谱所致。持续皮下氢化可的松输注（CSHI）再现了昼夜皮质醇谱，但其对SHS的影响尚未得到客观评估。目的：本研究的目的是确定CSHI对AD患者SHS的影响。背景和设计：这是一项多中心、双盲、安慰剂对照的CSHI与口服糖皮质激素治疗试验。参与者随机接受4周：CSHI和口服安慰剂，皮下安慰剂和口服氢化可的松，间隔2周洗脱期。采用简易36量表（SF-36）、一般健康问卷（GHQ-28）、疲劳量表（FS）、胃肠症状评定量表（GSRS）对SHS进行评估；Addison生活质量问卷（addqol）。参与者被问及他们的（盲法）治疗偏好。24小时尿液游离皮质醇（UFC）和每日唾液皮质醇收集量比较了每个治疗期间的皮质醇暴露情况。结果：10名参与者完成了研究。基线SHS评分（平均+/- SE）与轻度损害一致：SF-36身体成分总结48.4(+/- 2.4)，精神成分总结53.3 (+/- 3.0)；Ghq-28 18.1 (+/- 3.3)；GSRS 3.7 (+/- 1.6), AddiQoL 94.7（+/- 3.7）。FS与其他AD队列相似，为13.5 (+/- 1.0)（P = 0.82）。两组间UFC差异无统计学意义（P = 0.87）。CSHI期间，0800 h唾液皮质醇升高（P = 0.03），其他时间点均无显著差异。两组间SHS评分无差异。5名参与者首选CSHI， 4名口服氢化可的松，1名不确定。结论：生化测量表明在每个治疗期间皮质醇暴露相似，尽管在CSHI期间更明显的昼夜节律模式。CSHI不能改善基线SHS良好的AD患者的SHS。这使人们对AD患者SHS的昼夜皮质醇递送的潜在益处产生了一些怀疑。
Context: Patients with Addison's disease (AD) report impaired subjective health status (SHS). Since cortisol exhibits a robust circadian cycle that entrains other biological clocks, impaired SHS may be due to the noncircadian cortisol profile achieved with conventional glucocorticoid replacement. Continuous subcutaneous hydrocortisone infusion (CSHI) reproduces a circadian cortisol profile, but its effects on SHS have not been objectively evaluated.Objective: The aim of this study was to determine the effect of CSHI on SHS in AD.Setting and Design: This was a multicentre, double-blind, placebo-controlled trial of CSHI vs oral glucocorticoid therapy. Participants received in random order 4 weeks of: CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone, separated by a 2-week washout period. SHS was assessed using the Short-Form 36 (SF-36), General Health Questionnaire (GHQ-28), Fatigue Scale (FS), Gastrointestinal Symptom Rating Scale (GSRS); and Addison's Quality of Life Questionnaire (AddiQoL). Participants were asked their (blinded) treatment preference. Twenty-four hour urine free cortisol (UFC) and diurnal salivary cortisol collections compared cortisol exposure during each treatment.Results: Ten participants completed the study. Baseline SHS scores (mean +/- SE) were consistent with mild impairment: SF-36 physical component summary 48.4 (+/- 2.4), mental component summary 53.3 (+/- 3.0); GHQ-28 18.1 (+/- 3.3); GSRS 3.7 (+/- 1.6), and AddiQoL 94.7 (+/- 3.7). FS was similar to other AD cohorts 13.5 (+/- 1.0) (P = 0.82). UFC between treatments was not different (P = 0.87). The salivary cortisol at 0800 h was higher during CSHI (P = 0.03), but not at any other time points measured. There was no difference between the treatments in the SHS assessments. Five participants preferred CSHI, four oral hydrocortisone, and one was uncertain.Conclusions: Biochemical measurements indicate similar cortisol exposure during each treatment period, although a more circadian pattern was evident during CSHI. CSHI does not improve SHS in AD with good baseline SHS. This casts some doubt on the potential benefit of circadian cortisol delivery on SHS in AD.