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

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 26-40-Glucocorticoid Actions & Disease
Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-34
Sigridur Bjornsdottir*1, Marianne Oksnes2, Magnus Isaksson3, Roy Miodini Nilsen4, Eystein Sverre Husebye5, Kristian Lovas6, Olle Kampe7, Anna-Lena Hulting8, Thomas Nystrom9 and Sophie Bensing10
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Sweden, 2Institute of Medicine, Haukeland University Hospital, Bergen, Norway, 3Uppsala University, 4Haukeland University hospital, Bergen, Norway, 5Haukeland Univ Hosp, Bergen, Norway, 6University of Bergen, Bergen, Norway, 7Uppsala University, Uppsala, Sweden, 8Karolinska Univ Hosp, Stockholm, Sweden, 9Karolinska Institutet, Department of Clinical Science and Education, Division of Internal Medicine, Södersjukhuset AB, Stockholm, Sweden., 10Karolinska Institutet, Stockholm, Sweden
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 of oral hydrocortisone (OHC).

 

Design, Subjects, Measurements

This was an open randomised, cross-over trial, comparing 3 months of weight adjusted OHC with 3 months on CSHI in 33 AD patients. Treatment A was OHC with weight-adjusted doses as suggested by Mah et al (1). Treatment B was CSHI using Solu-Cortef® (50mg/ml) with a body surface area adjusted dose (10mg/m2/24hrs). Patients were examined at baseline and after 2 and 3 months of each treatment. Insulin sensitivity was determined after 2 month of each treatment in 15 Swedish patients using the euglycemic hyperinsulinemic clamp technique (40mU/m2). Whole-body insulin sensitivity (glucose disposal), 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/min. We also assessed fasting insulin sensitivity, in all 33 patients, using HOMA and the insulin resistance index (HOMA-IR) calculated as ((fasting plasma glucose [mmol/L] x fasting serum insulin [μU/mL]) /22.5). Statistical analyses were performed with linear mixed effects models with random intercepts.

 

Results

Twenty-five women and 8 men mean±SD, age 48±12 and AD duration 12±10 years participated in the study. The median dose of OHC was 0.23 mg/kg/day, (range; 0.2-0.5) and 0.28 mg/kg/24h, (0.24-0.5) in CSHI.

Body Mass index (BMI) and log HOMA index slightly increased during CSHI (p for trend 0.037 and 0.011), but compared with OHC no significant difference was found (p for interaction 0.085 and 0.19). No difference was found in insulin sensitivity, M-value (p= 0.59). There were no treatment differences over time in waist-hip ratio, (p for interaction 0.24) systolic or diastolic blood pressure (p for interaction 0.73 and 0.94).

Conclusion

CSHI replacement over a three-month period does not influence antropometric measures, blood pressure, or insulin sensitivity, compared with OHC. More randomized trials on long-term effects of CSHI replacement on cardiovascular parameters are needed.

(1)  Mah PM. et al. Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 2004;61(3):367-75.

Nothing to Disclose: SB, MO, MI, RMN, ESH, KL, OK, ALH, TN, SB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm