Continuous Subcutaneous Hydrocortisone Infusion Therapy in Addison's Disease: A
Randomized, Placebo-Controlled Clinical Trial.
Author(s): Gagliardi L(1), Nenke MA, Thynne TR, von der Borch J, Rankin WA, Henley DE,
Sorbello J, Inder WJ, Torpy DJ.
Affiliation(s): Author information:
(1)Endocrine and Metabolic Unit (L.G., M.A.N., T.R.J.T., D.J.T.), Royal Adelaide
Hospital, Adelaide 5000, Australia; School of Medicine (L.G., M.A.N., D.J.T.),
University of Adelaide 5000, Australia; Diabetes Centre (J.v.d.B.), Royal
Adelaide Hospital, Adelaide 5000, Australia; Department of Chemical Pathology
(W.A.R.), SA Pathology, Adelaide 5000, Australia; Department of Endocrinology and
Diabetes (D.E.H.), Sir Charles Gairdner Hospital, Perth 6009, Australia; School
of Medicine and Pharmacology (D.E.H.), University of Western Australia, Perth
6009, Australia; Department of Diabetes and Endocrinology (J.S., W.J.I.),
Princess Alexandra Hospital, Brisbane 4102, Australia; and School of Medicine
(W.J.I.), University of Queensland, Brisbane 4072, Australia.
Publication date & source: 2014, J Clin Endocrinol Metab. , 99(11):4149-57
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.
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