High-resolution daily profiles of tissue adrenal steroids by portable automated collection

作者：Thomas J. Upton, Eder Zavala, Paal Methlie, Olle Kämpe, Stylianos Tsagarakis, Marianne Øksnes, Sophie Bensing, Dimitra Argyro Vassiliadi, Marianne A. Grytaas, Ileana Ruxandra Botusan, Grethe Åstrøm Ueland, Katarina Berinder, Kateřina Šimůnková, Maria Balomenaki, D Margaritopoulos, Nina Henne, Robin E. Crossley, Georgina M. Russell, Eystein Sverre Husebye, Stafford Louis Lightman · 发表于：Science Translational Medicine · 年份：2023 · DOI：10.1126/scitranslmed.adg8464 · 被引用次数：91 · 研究领域：Hormonal and reproductive studies、Hormonal Regulation and Hypertension、Stress Responses and Cortisol

Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of the disease. Because adrenal hormones are secreted with both circadian and ultradian periods, conventional single-time point measurements provide limited information about rhythmicity and, crucially, do not provide information during sleep, when many hormones fluctuate from nadir to peak concentrations. If blood sampling is attempted overnight, then this necessitates admission to a clinical research unit, can be stressful, and disturbs sleep. To overcome this problem and to measure free hormones within their target tissues, we used microdialysis, an ambulatory fraction collector, and liquid chromatography-tandem mass spectrometry to obtain high-resolution profiles of tissue adrenal steroids over 24 hours in 214 healthy volunteers. For validation, we compared tissue against plasma measurements in a further seven healthy volunteers. Sample collection from subcutaneous tissue was safe, well tolerated, and allowed most normal activities to continue. In addition to cortisol, we identified daily and ultradian variation in free cortisone, corticosterone, 18-hydroxycortisol, aldosterone, tetrahydrocortisol and allo-tetrahydrocortisol, and the presence of dehydroepiandrosterone sulfate. We used mathematical and computational methods to quantify the interindividual variability of hormones at different times of the day and develop "dynamic markers" of normality in heal...