RESEARCH HIGHLIGHTS Nature Reviews Endocrinology 10, 250 (2014); published online 4 March 2014; doi:10.1038/nrendo.2014.25

THERAPY

CORTISOL RHYTHMS IN ADDISON DISEASE Continuous subcutaneous hydrocortisone infusion (CSHI) may provide a safe alternative treatment for patients with Addison disease who do not respond favourably to oral hydrocortisone therapy, show the results of a new clinical trial. Oral hydrocortisone therapy is the most widely used treatment strategy for patients with Addison disease undergoing glucocorticoid replacement. Some patients, however, respond adversely to this treatment. “Health-related quality of life is reduced in patients with Addison disease, and some studies indicate increased mortality in these patients,” adds Marianne Øksnes, lead author of the study. “Oral replacement therapy could possibly predispose patients to long-term adverse metabolic disorders such as osteoporosis and cardiovascular disease.” Endogenous cortisol level fluctuations in healthy individuals follow a circadian rhythm. Recognising that current therapies do not result in oscillations of cortisol levels that adequately reflect these natural biorhythms, Øksnes and colleagues postulated that an imbalanced cortisol profile could contribute to the adverse effects associated with this therapy. The study researchers had previously demonstrated that CSHI therapy restores natural cortisol biorhythms in patients with Addison disease. In this new study, they compared the effectiveness of conventional oral glucocorticoid replacement with that of CSHI therapy in a prospective openlabel randomized crossover trial involving 33 patients with Addison disease from Norway and Sweden. The study lasted 10 months, with each treatment period being three months. Assessment of morning serum levels of adrenocorticotropic hormone and cortisol, and 24 h salivary cortisol levels showed restoration of the circadian rhythms of these hormones in patients undergoing CSHI therapy, but not in those receiving oral hydrocortisone. Furthermore, quality of life was improved in the CSHI group. “CSHI is a safe treatment option for patients who do not function well on oral replacement therapy,” concludes Øksnes. The researchers are now exploring the potential for CSHI to treat other adrenal insufficiency disorders, such as congenital adrenal hyperplasia. Jennifer Sargent Original article Øksnes, M. et al. Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of Addison’s disease: a randomized clinical trial. J. Clin. Endocrinol. Metab. doi:10.1210/jc.2013-4253

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Therapy. Cortisol rhythms in Addison disease.

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