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


METHODS
An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden.


METHODS
Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp.


METHODS
Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment.


METHODS
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.


CONCLUSIONS
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.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Sigridur
S
Björnsdottir
Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Marianne
M
Øksnes
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Magnus
M
Isaksson
Department of Clinical Science, University of Bergen, Bergen, Norway.
Paal
P
Methlie
Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway.
Roy M
RM
Nilsen
Department of Clinical Science, University of Bergen, Bergen, Norway.
Steinar
S
Hustad
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Olle
O
Kämpe
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Anna-Lena
AL
Hulting
Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Eystein S
ES
Husebye
Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Kristian
K
Løvås
Division of Internal Medicine, Department of Clinical Science and Education, Södersjukhuset AB, Stockholm, Sweden.
Thomas
T
Nyström
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Sophie
S
Bensing
D000224:Addison Disease / Q000188:drug therapy*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D015309:Glucose Clamp Technique; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood; D055104:Infusions, Subcutaneous; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009664:Norway; D013548:Sweden; D055815:Young Adult
D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone