Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial

Gagliardi, Lucia, Nenke, Marni A., Thynne, Tilenka R. J., von der Borch, Jenny, Rankin, Wayne A., Henley, David E., Sorbello, Jane, Inder, Warrick J. and Torpy, David J. (2014) Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial. Journal of Clinical Endocrinology and Metabolism, 99 11: 4149-4157. doi:10.1210/jc.2014-2433


Author Gagliardi, Lucia
Nenke, Marni A.
Thynne, Tilenka R. J.
von der Borch, Jenny
Rankin, Wayne A.
Henley, David E.
Sorbello, Jane
Inder, Warrick J.
Torpy, David J.
Title Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial
Journal name Journal of Clinical Endocrinology and Metabolism   Check publisher's open access policy
ISSN 1945-7197
0021-972X
Publication date 2014-11-01
Year available 2014
Sub-type Article (original research)
DOI 10.1210/jc.2014-2433
Open Access Status
Volume 99
Issue 11
Start page 4149
End page 4157
Total pages 9
Place of publication Chevy Chase MD, United States
Publisher Endocrine Society
Collection year 2015
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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