Endocrine Abstracts (2013) 32 P9 | DOI: 10.1530/endoabs.32.P9

Insulin sensitivity in patients with Addison's disease: a randomised cross-over trial comparing conventional glucocorticoid replacement therapy with continuous subcutaneous hydrocortisone infusion therapy.

Sigridur Björnsdottir1, Thomas Nyström2, Magnus Isaksson3, Marianne Øksnes4, Eystein Husebye4, Kristian Løvås4, Olle Kämpe3, Anna Lena Hulting1 & Sophie Bensing1,3


1Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; 2Karolinska Institutet, Södersjukhuset, Stockholm, Sweden; 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 4Institute of Medicine, Haukeland University Hospital, Bergen, Norway.


Background: Conventional glucocorticoid replacement therapies result in unphysiological variation in plasma cortisol levels; concern has been raised regarding long-term metabolic consequences. Glucocorticoid replacement is technically feasible by continuous subcutaneous hydrocortisone infusion (CSHI), which can mimic the normal diurnal cortisol rhythm. The aim of this study was to compare insulin sensitivity in patients with Addison’s disease (AD) on CSHI vs three daily doses (t.i.d.) of oral hydrocortisone.

Design, subjects, and measurements: This was an open randomised, cross-over trial, comparing 2 months of CSHI vs t.i.d. oral hydrocortisone with a minimum of 3 months wash-out period in patients with long duration of AD. Treatment A was oral hydrocortisone with weight-adjusted doses as suggested by Mah et al. (1). Treatment B was CSHI using Solu-Cortef® (50 mg/ml) with a body surface area adjusted dose (10 mg/m2 per 24 h). Insulin sensitivity (mg/kg per min) was determined after 2 month of each treatment using the euglycemic hyperinsulinemic clamp technique (40 mU/m2). Whole-body insulin sensitivity (M-value) was calculated from the amount of glucose infused during the last 30 min of the clamp divided by body weight (kg) and period (min) and expressed as mg/kg per min.

Results: Fifteen patients (11 women and 4 men) age (49.4±6.2 years) and AD duration (15.5±10.3 years), took part in the study. After 2 months treatment (cross-over) the mean dose of oral hydrocortisone was (17±2.5 mg) and Solu-Cortef® in CSHI was (19.6±2.5 mg) respectively. There were no absolute differences between treatment A vs B regarding; BMI (24.8±2.1 vs 25.0±2.1 kg/m2; P=0.74), waist–hip ratio (0.84±0.1 vs 0.85±0.1; P=0.65), systolic blood pressure (115.9±12.7 vs 114±12.0 mmHg; P=0.67), nor in insulin sensitivity (8.1±3.6 vs 7.5±2.7 mg/kg per min; P=0.59) but there was a significant difference in diastolic blood pressure (77.2±5.2 vs 72.4±5.5 mmHg; P=0.02).

Conclusion: This is the first study to compare insulin sensitivity in patients with AD on CSHI vs oral hydrocortisone. CSHI replacement was not superior in terms of insulin sensitivity compared to conventional oral glucocorticoid replacement.

Reference

1. Mah PM, Jenkins RC, Rostami-Hodjegan A, et al. Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clinical Endocrinology 2004 61 367–375.