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

Abstract

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 healthy individuals stratified by sex, age, and body mass index. Our results provide insight into the dynamics of adrenal steroids in tissue in real-world settings and may serve as a normative reference for biomarkers of endocrine disorders (ULTRADIAN, NCT02934399).

Abstract

A wearable microdialysis device allows LC-MS/MS analysis to quantify adrenal steroid hormone variability over 24 hours in healthy ambulatory adults.

Editor’s summary

Adrenal hormones are highly dynamic but commonly measured only at limited time points. Upton et al . present a flexible waist belt for minimally invasive, dense monitoring of diurnal variability in adrenal steroid hormones in humans. The well-tolerated belt includes a catheter that is inserted into subcutaneous fat, with microdialysis samples collected every 20 minutes for later analysis by LC-MS/MS. Profiling in mainly healthy individuals revealed inter-individual variation in adrenal steroid hormones over 24 hours and coordinated aspects of the hypothalamus-pituitary-adrenal (HPA) axis. Such high-resolution monitoring has the potential to advance the study of hormones in disease and chronobiology more generally. —Catherine Charneski