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

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). 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. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. 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. 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. 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.

Björnsdottir S ，Øksnes M ，Isaksson M ，Methlie P ，Nilsen RM ，Hustad S ，Kämpe O ，Hulting AL ，Husebye ES ，Løvås K ，Nyström T ，Bensing S ... -  《-》

Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of addison's disease: a randomized clinical trial.

Oksnes 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 ... -  《-》

Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial.

Gagliardi L ，Nenke MA ，Thynne TR ，von der Borch J ，Rankin WA ，Henley DE ，Sorbello J ，Inder WJ ，Torpy DJ ... -  《-》

Continuous subcutaneous hydrocortisone infusion in Addison's disease.

Løvås K ，Husebye ES 《-》

A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia.

Nella AA ，Mallappa A ，Perritt AF ，Gounden V ，Kumar P ，Sinaii N ，Daley LA ，Ling A ，Liu CY ，Soldin SJ ，Merke DP ... -  《-》