ECE2024 Poster Presentations Adrenal and Cardiovascular Endocrinology (95 abstracts)
Different metabolic pathways associated with total cortisol exposure and the cortisol time profile: A randomized cross-over clinical trial
Johanna McQueen 1,2 , Terence Garner 3 , Dimitrios Chantzichristos 1,2 , Hans Lennernäs 4 , Stéphanie Espiard 5 , Oskar Ragnarsson 1,2,6 , Ragnhildur Bergthorsdottir 1,2 , Stanko Skrtic 1 , Adam Stevens 3 & Gudmundur Johannsson 1,2
1Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden; 2Sahlgrenska University Hospital, Gothenburg, Endocrinology, Diabetology, and Metabolism,, Gothenburg, Sweden; 3Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 4Uppsala University, Department of Pharmaceutical Biosciences, Uppsala, Sweden; 5Lille University Hospital, Department of Endocrinology, Diabetology and Metabolism, Huriez Hospital, Lille, France; 6Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
Context: Excess cortisol exposure and disruption of the circadian cortisol profile are both associated with adverse clinical outcome.
Objective: The aim of this study was to identify unique metabolites and metabolic pathways associated with total cortisol exposure and the cortisol time profile.
Design: A randomized, 12-week, two period, cross-over clinical trial.
Patients and interventions: Eighteen adults with primary adrenal insufficiency received the same daily dose of dual-release hydrocortisone (HC) tablets once-daily (OD) and conventional immediate-release HC tablets 3 times daily (TID) during 12 weeks each.
Main outcome measures: Total cortisol exposure was calculated by the area under the concentration-time curve from pharmacokinetic sampling over 24 h (AUC0-24). The variability of the serum cortisol time profile was quantified by calculating the lag–1 autocorrelation (AUTO) from serum cortisol concentrations over 24-hours. Metabolomic analysis in serum and urine were performed using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography-mass spectrometry (LC–MS), respectively. The relationship between total cortisol exposure, the variability of the cortisol time profile and metabolite expressions were assessed using a Bayesian generalized linear model.
Results: During TID, cortisol exposure was 20% higher and the variability of the cortisol time profile was larger, compared to OD. In total, 2406 metabolites were detected. 109 metabolites in serum and 21 in urine were uniquely correlated with total cortisol exposure. These metabolites were involved in arginine biosynthesis and alanine–aspartate–glutamate and tryptophan metabolism. Further, 40 metabolites in serum and 2 in urine were uniquely correlated with the cortisol profile variability. These metabolites were involved in primary bile acid biosynthesis and cysteine–methionine metabolism.
Conclusion: We identified different groups of metabolites and metabolic pathways that specifically correlated with total exposure of cortisol and cortisol profile variability, respectively. These findings suggest that total exposure and the time profile of serum cortisol have independent metabolic and regulatory effects in the human body.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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