Glucocorticoid Treatment and Quality of Life in Addison’s disease
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Addison’s disease (AD) is rare and result in lack of the adrenal hormones cortisol, aldosterone and adrenal androgens. Despite conventional oral replacement therapy, mortality is increased and Health-Related Quality-of-life (HRQoL) is reduced. Currently, the non-physiological circadian cortisol profile is suspected to be a major cause, although evidence has been lacking. Here, we aimed to develop a better tool for evaluating HRQoL in AD, and to investigate whether a more physiological circadian cortisol profile would result in benefit for AD patients.
An AD-specific HRQoL questionnaire (AddiQoL) was developed through a multistep approach. After testing the original AddiQoL in 86 patients in UK, the AddiQoL was translated to five European languages and tested in further 615 AD patients in respective countries. Applying Rasch analysis, a valid and reliable 30 item AddiQoL was produced.
In a randomized controlled multicenter trial with cross-over design, we compared the effects of three months treatment with continuous subcutaneous hydrocortisone infusion (CSHI) to the effects of three months treatment with conventional oral hydrocortisone (OHC) in 33 AD patients. The primary endpoint was the effect on ACTH levels. Secondary endpoints were effects on metabolism, HRQoL and sleep. CSHI produced a more physiological circadian cortisol biorhythm than conventional therapy and induced normalization of morning ACTH and cortisol levels, restoration of nighttime cortisol levels and changes in glucocorticoid metabolism resembling healthy individuals. The late night decrease in glucose seen with OHC was counteracted, without decreasing overall insulin sensitivity. CSHI did not significantly affect sleep but might have positive HRQoL effects.
The AddiQoL development provided a valid and reliable new tool for HRQoL evaluation in AD. Mimicking the physiological cortisol rhythm with CSHI proved safe and provides a means for further improving replacement therapy in AD.