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Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy
Author(s) -
Björnsdottir Sigridur,
Øksnes Marianne,
Isaksson Magnus,
Methlie Paal,
Nilsen Roy M.,
Hustad Steinar,
Kämpe Olle,
Hulting AnnaLena,
Husebye Eystein S.,
Løvås Kristian,
Nyström Thomas,
Bensing Sophie
Publication year - 2015
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12670
Subject(s) - medicine , endocrinology , circadian rhythm , hydrocortisone , glucocorticoid , insulin , adrenocorticotropic hormone , hormone replacement therapy (female to male) , crossover study , hormone , placebo , testosterone (patch) , alternative medicine , pathology
Summary Context 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 ). Objective 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 . Design and setting An open, randomized, two‐period, 12‐week crossover multicentre trial in Norway and Sweden. Patients Ten Norwegian patients were admitted for 24‐h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic‐hyperinsulinaemic clamp. Intervention Thrice‐daily regimen of oral hydrocortisone ( OHC ) and CSHI treatment. Main outcome measure 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. Results 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. Conclusion 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 .