Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Continuous subcutaneous hydrocortisone infusion therapy in Addison’s disease: a randomised, placebo-controlled clinical trial (#66)

Lucy Gagliardi 1 2 , Marni A Nenke 1 2 , Tilenka RJ Thynne 1 , Jenny von der Borch 3 , Wayne A Rankin 4 , David E Henley 5 6 , Jane Sorbello 7 , Warrick J Inder 7 8 , David J Torpy 1 2
  1. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
  2. School of Medicine, University of Adelaide, Adelaide, SA, Australia
  3. Diabetes Centre, Royal Adelaide Hospital, Adelaide, SA, Australia
  4. Department of Chemical Pathology, SA Pathology, Adelaide, SA, Australia
  5. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, WA, Australia
  6. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
  7. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Qld, Australia
  8. School of Medicine, University of Queensland, Brisbane, Qld, Australia

Patients with Addison’s disease (AD) report impaired subjective health status (SHS).1,2 Since cortisol exhibits a robust circadian cycle which entrains other biological clocks, impaired SHS may be due to the non-circadian 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.3,4
To determine the effect of CSHI on SHS in AD.
This was a multicentre, double-blind, placebo-controlled trial of CSHI versus oral glucocorticoid therapy. Participants received in random order four weeks of: CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone, separated by a two 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.
Ten participants completed the study. Baseline SHS scores (mean ± standard error) 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 0800h salivary cortisol 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.
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.

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