AI Article Synopsis

  • Rhythms in endocrine systems are vital, and hormonal disruptions can occur early in diseases, highlighting the need for better measurement techniques beyond traditional single-time blood tests.
  • To address this, researchers employed microdialysis and advanced chromatography methods to analyze adrenal hormones over a 24-hour period, involving 214 healthy volunteers and ensuring minimal disruption to their daily lives.
  • The study revealed various fluctuations in adrenal steroids like cortisol and aldosterone, and established "dynamic markers" of normalcy based on sex, age, and BMI, which could help identify endocrine disorders.

Article 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).

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http://dx.doi.org/10.1126/scitranslmed.adg8464DOI Listing

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