Glucocorticoid Treatment and Quality of Life in Addison’s disease
MetadataShow full item record
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.
Has partsPaper 1: Løvås K, Curran S, Øksnes M, Husebye ES, Huppert FA, Chatterjee VK 2010 Development of a Disease specific Quality of Life Questionnaire in Addison’s Disease. J Clin Endocrinol Metab 95(2):545-551. The article is available at: http://hdl.handle.net/1956/8312
Paper 2: Øksnes M, Bensing S, Hulting AL, Kämpe O, Hackemann A, Meyer G, Badenhoop K, Betterle C, Parolo A, Giordano R, Falorni A, Papierska L, Jeske W, Kasperlik-Zaluska AA, Chatterjee VKK, Husebye ES, Løvås K 2012 Quality of life in European patients with Addison’s disease; Validity of the disease-specific questionnaire AddiQoL. J Clin Endocrinol Metab 97(2):568-576. The article is available at: http://hdl.handle.net/1956/8317
Paper 3: Øksnes M, Björnsdottir S, Isaksson M, Methlie P, Carlsen S, Nilsen RM, Broman JE, Triebner K, Kämpe O, Hulting AL, Bensing S, Husebye ES, Løvås K 2014 Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of Addison’s disease: A randomized clinical trial; J Clin Endocrinol Metab 99(5):1665–1674. The article is available at: http://hdl.handle.net/1956/9578
Paper 4: Björnsdottir S, Øksnes M, Isaksson M, Methlie P, Nilsen RM, Kämpe O, Hulting AL, Husebye ES, Løvås K, Nyström T, Bensing S 2014 Circadian hormone profiles and insulin sensitivity in patients with Addison’s disease: A comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy. The article is not available in BORA.