Format

Send to

Choose Destination
Clin Endocrinol (Oxf). 2015 Jul;83(1):28-35. doi: 10.1111/cen.12670. Epub 2015 Jan 12.

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 information

1
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
2
Department of Clinical Science, University of Bergen, Bergen, Norway.
3
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
4
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
5
Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway.
6
Division of Internal Medicine, Department of Clinical Science and Education, Södersjukhuset AB, Stockholm, Sweden.

Abstract

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.

PMID:
25400085
DOI:
10.1111/cen.12670
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center