Continuous subcutaneous hydrocortisone infusion failed to improve subjective health status in patients with Addison disease, results from a randomized, placebo-controlled trial suggest.
“Patients with Addison disease report impaired subjective health status. Since cortisol exhibits a robust circadian cycle which entrains other biological clocks, impaired [subjective health status] may be due to non-circadian cortisol profile achieved with conventional glucocorticoid replacement,” researchers wrote in the Journal of Clinical Endocrinology & Metabolism.
Continuous subcutaneous hydrocortisone infusion (CSHI) is designed to mimic a circadian cortisol profile, although whether it affects subjective health status remains unclear, according to background information in the article.
To shed light on this question, Lucia Gagliardi, MBBS, FRACP, PhD, of the Royal Adelaide Hospital in Australia, and colleagues conducted a multicenter, double blind, placebo-controlled trial comparing CSHI with oral glucocorticoid therapy.
In random order, they administered 4 weeks of CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone separated by a 2-week washout period.
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) were used to assess subjective health status. After treatment, the researchers polled participants on their treatment preference.
The researchers also compared cortisol exposure during each treatment using 24-hour urine free cortisol and diurnal salivary cortisol.
Among the 10 participants who completed the study, baseline subjective health status scores indicated mild impairment. Scores were 48.4 for SF-36 physical component summary and 53.3 for mental component summary; 18.1 for the GH-28; 3.7 for the GSRS; and 94.7 for the AddiQoL.
At 13.5, FS score was comparable to others with Addison disease.
During CSHI, salivary cortisol at 0800 hours was higher (P=.03), but it was not at any other time points. Urinary free cortisol was not different between treatments (P=.87).
Subjective health assessments did not differ between treatments. Five participants preferred CSHI, four preferred oral hydrocortisone and one was uncertain, the researchers reported.
Although the study had limitations, the data suggest that, despite establishing a more circadian cortisol pattern during treatment, the beneficial effects of CSHI on subjective health status were questionable.
“This is the first randomized, double-blind, placebo-controlled trial of CSHI compared with standard oral intermittent glucocorticoid replacement in patients with [Addison disease]. Our data indicate that in patients with good baseline [subjective health status], CSHI does not provide further improvement,” they concluded.