Endocrine Abstracts

Context: Hypocortisolism has been associated with increased cardiovascular risk (CVR) and mortality. Higher levels of certain inflammatory markers such as Interleukin-6 (IL6) in patients with adrenal insufficiency (AI) may partly explain the increase in CVR. Recent studies demonstrate an increased prevalence of cardiovascular disease (CVD) in patients with elevated IL-6 levels. Hypocortisolism is generally treated with glucocorticoid replacement therapy (GRT). Current GRT regiments fail to adequately mimic the physiological rhythm of endogenous cortisol leading to temporary supra- and infraphysiological levels of cortisol.

Objective: This study aims to evaluate serum levels of Interleukin-6 in patients with primary or secondary AI receiving hydrocortisone replacement therapy (HRT) in a clinical setting.

Material and methods: Ten patients (8 female, 2 male, mean age in years: 53,4, range 28–67) with either primary or secondary AI on HRT were analyzed for cortisol and interleukin-6 levels over the course of two days. Blood samples were drawn in 3-hour intervals. A cardiopulmonary exercise test was performed during the second day to induce stress. The results were compared to 5 healthy individuals. One female control patient was excluded because of tendinitis (Data not shown). Hydrocortisone was taken orally twice a day, once in the morning and once midday (mean dose: 28.75 mg, range 15–42.5). Exclusion criteria were coronary heart disease, inflammatory diseases, valvular heart disease and heart arrhythmia.

Results: A total of 10 AI patients and 4 healthy controls were included in this study. Both groups were comparable with respect to sex and age. Compared to healthy controls, patients with primary or secondary AI showed higher levels of IL-6 over the course of two days (mean IL-6 AI group: 8.1 μg/dl (range: 4.25–14.15) vs healthy controls 5.1 μg/dl (range: 2.54–8.8); P=0.0970). At midnight of the first day AI patients showed significantly higher levels of IL-6 compared to healthy controls (mean IL-6 at 2400 h: 7.56 μg/dl vs 3.15 μg, P=0.0375) while midnight serum cortisol levels were higher in healthy controls (mean cortisol at 2400 h: 2.65 μg/dl vs 1.37 μg; P=0.25).

Conclusion: Our study indicates that hypocortisolism in AI may lead to a compensatory secretion of IL-6, therefore increasing the risk of cardiovascular disease and ultimately mortality. Retarded hydrocortisone preparations with a dual-release may deliver a new therapy option in avoiding increased levels of IL-6 in AI patients.