Insulin sensitivity in patients with Addison

Sigridur Bjornsdottir; Thomas Nystrom; Magnus Isaksson; Marianne Oksnes; Eystein Husebye; Kristian Lovas; Olle Kampe; Anna Lena Hulting; Sophie Bensing

doi:10.1530/endoabs.32.P9

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

ECE2013 Poster Presentations Adrenal cortex (64 abstracts)

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 Björnsdottir ¹ , Thomas Nyström ² , Magnus Isaksson ³ , Marianne Øksnes ⁴ , Eystein Husebye ⁴ , Kristian Løvås ⁴ , Olle Kämpe ³ , Anna Lena Hulting ¹ & Sophie Bensing ^1,

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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.