New technology offers blood-free sensor readings of adrenal steroid levels enabled tracking at high resolution and across a full 24-hour day, according to researchers from the Universities of Bristol and Birmingham in the UK and the University of Bergen in Norway. Their study showed the device could detect early signs of endocrine diseases more accurately than existing tests taken at single time points.
The team noted that this is the first time that it has been possible to measure hormone changes as people go about normal daily activities, across both day and night. They said that the device had "the potential to revolutionise how diseases of the stress hormone system are diagnosed and treated".
The wearable device, called U-RHYTHM, is worn around the waist and automatically collects subcutaneous samples every 20 minutes, painlessly and without the need to take blood. It allows sampling for up to 72 hours in a single session irrespective of sleep, work, or other daily life activities.
Wellcome, which funded part of the early research, described the device, designed by the company Designworks, and available through University of Bristol spin out company Dynamic Therapeutics, as "a powerful research tool for studies on human rhythms in health and disease".
In the new study, published in Science Translational Medicine, the researchers analysed samples from 214 healthy volunteers wearing the U-RHYTHM device. Using data across multiple timepoints in 24 hours, they were able to create circadian adrenal hormone profiles of healthy people in real life conditions.
In addition to cortisol, they identified daily and ultradian variation in free cortisone, corticosterone, 18-hydroxycortisol, aldosterone, tetrahydrocortisol, and allo-tetrahydrocortisol, as well as the presence of dehydroepiandrosterone sulfate.
Mathematicians from the University of Birmingham's Centre for Systems Modelling and Quantitative Biomedicine then used these data to develop what they described as a new class of 'dynamic markers' to show what a healthy hormonal profile should look like, depending on an individual’s sex, age, body mass index, and other characteristics. These "may serve as a normative reference for biomarkers of endocrine disorders", the authors said.
Looking at Healthy Hormonal Rhythms in Real World Settings
"Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of the disease," the authors said. Disturbance of hormonal rhythms could be related to diseases like depression, heart disease, obesity, diabetes, and even critical illness.
Yet, because adrenal hormones are secreted with both circadian and ultradian periods, conventional single-time point measurements provide limited information about rhythmicity. Understanding the meaning of a hormone test is "very difficult or impossible" if only a single time point is taken, as this fails to consider hormonal rhythms. This in turn can lead to diagnostic delay and missed opportunities for treatment intervention.
Crucially, single measures do not provide information during sleep, when many hormones fluctuate from nadir to peak concentrations. However previously the only way to build an accurate picture was to take multiple blood samples during admission to a hospital or research unit, which is not only time consuming and inconvenient, but also stressful for the patient.
Circadian monitoring could therefore enable early warning signs of diseases caused by dysfunctional hormone levels to be spotted more easily. This could form "a baseline for new, better ways to diagnose endocrine conditions at a much earlier stage", they said. They added that their findings showed what healthy hormonal rhythms look like in the population, in real world settings, whereas until now scientists hadn’t been able to define what normal healthy rhythmicity looked like.
'Paradigm Shift in Understanding'
Lead endocrinologist for the study Dr Thomas Upton, clinical research fellow in automated sampling at the University of Bristol, said: "Our results represent a paradigm shift in the understanding of how the stress hormone system works in healthy people. The information we have gathered forms an entirely new reference range which has the potential to revolutionise how diseases of the stress hormone system are diagnosed and treated.”
Commenting for the Addison's Disease Self-Help Group, some of whose members participated in studies of U-RHYTHM, Dr Upton said: "The device has the potential to provide both our patient community and the doctors looking after us with important information about cortisol levels over the day, and how our replacement therapy can be improved by changes in both dose and timing of treatment."
Diagnostic Procedure Possible in Primary Care
Co-author Stafford Lightman, professor of medicine at Bristol Medical School, said: "Our results provide significant new insights into how the stress hormone system works in healthy people, and emphasises the importance of measuring change, not just sampling at single points. It also highlights the importance of measuring hormones during sleep, which has previously been impossible outside a hospital.
"The ability to measure the dynamics of hormone secretion across the day and night in patients in their own home will not only improve our ability to accurately diagnose any abnormality in hormone secretion without the need for complex inpatient investigations, but the whole diagnostic procedure can be performed from primary care and linked to newly available diagnostic algorithms.
"This will not only provide good, personalised medicine, but will also allow the patient to follow their own hormone profiles during diagnosis and therapy and empower better patient-doctor discussions."
The technology was funded by an EU Horizon 2020 project grant, and early research funded by a Wellcome technology development grant in 2021. Funding was also received by the Trond Mohn Foundation and Regional Health Authorities of Western Norway, Biotechnology and Biological Sciences Research Council, the Medical Research Council, Above and Beyond, University Hospitals Bristol and Weston NHS Foundation Trust, the Swedish Medical Research Council, and the Knut and Alice Wallenberg Foundation. OK is a board member of Navinci Diagnostics AB; SLL is listed as an inventor on the University of Bristol–owned patents related to the U-RHYTHM sampling technology "sampling apparatus providing a series of discrete fluid samples in a tube" granted in the UK, Europe, and US. The other authors declare that they have no competing interests.