Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy. (12th January 2015)

• Record Type: Journal Article
• Authors: Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M.; Hustad, Steinar; Kämpe, Olle; Hulting, Anna‐Lena; Husebye, Eystein S.; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie
• Is Part Of: Clinical endocrinology. Volume 83:Number 1(2015:Jul.)
• Page Start: 28
• Page End: 35
• Publication Date: 2015-01-12
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12670
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12670-abs-0001"> <title>Summary</title> <sec id="cen12670-sec-0001" sec-type="section"> <title>Context</title> <p>Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI).</p> </sec> <sec id="cen12670-sec-0002" sec-type="section"> <title>Objective</title> <p>The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice‐daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD.</p> </sec> <sec id="cen12670-sec-0003" sec-type="section"> <title>Design and setting</title> <p>An open, randomized, two‐period, 12‐week crossover multicentre trial in Norway and Sweden.</p> </sec> <sec id="cen12670-sec-0004" sec-type="section"> <title>Patients</title> <p>Ten Norwegian patients were admitted for 24‐h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic‐hyperinsulinaemic clamp.</p> </sec> <sec id="cen12670-sec-0005" sec-type="section"> <title>Intervention</title> <p>Thrice‐daily regimen of oral hydrocortisone (OHC) and CSHI treatment.</p> </sec> <sec id="cen12670-sec-0006" sec-type="section"> <title>Main outcome measure</title> <p>We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin‐like growth factor‐1, (IGF‐1), IGF‐binding protein‐3 (IGFBP‐3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic‐hyperinsulinaemic clamp was used to assess insulin sensitivity.</p> </sec> <sec id="cen12670-sec-0007" sec-type="section"> <title>Results</title> <p>Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late‐night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms.</p> </sec> <sec id="cen12670-sec-0008" sec-type="section"> <title>Conclusion</title> <p>Continuous subcutaneous hydrocortisone infusion replacement re‐established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night‐time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night‐time cortisol levels might be advantageous for patients with AD.</p> </sec> </abstract>