Following the results from the ULTRADIAN clinical study, Dr Thomas Upton updates us on U-RHYTHM, a wearable device to measure hormones, including cortisol levels, in the body over 24 hours, as people go about their daily activities. U-RHYTHM has been described as a "world first" and "revolution in hormone understanding".

Currently hormone levels (including cortisol) are usually only measured using blood samples in a research unit or in a hospital. This is a huge frustration for our community, as the samples are not representative of our daily lives. Therefore many continue to feel unwell on their current treatment, with no way to tell what their hormone levels are over the day and at night - until now. 

U-RHYTHM has the ability to perform continuous hormone sampling - whether at work, with friends and family, even during sleep. This means that we can get a better understanding of what normal hormone physiology is and use this information to inform hormone replacement in the future or to diagnose endocrine disease.

Read on to hear more from Dr Thomas Upton about the device, and watch their video to see U-RHYTHM in action!

Research Facts:

• Disease: Addison’s disease and other diseases affecting the adrenal gland including Cushing’s syndrome and primary aldosteronism.
• Research Team: Our research has been conducted as part of a Horizon 2020 EU project called ULTRADIAN. This project brings together multiple centres including experts in Addison’s disease in Bristol and the Karolinska Institute in Stockholm.
• Organisations: University of Bristol, Karolinska Institute, University of Bergen, Evangelismos Hospital Athens, DesignWorks Windsor.
• Timeline: 2016 - ongoing
• Research link: High-resolution daily profiles of tissue adrenal steroids by portable automated collection – Science Translational Medicine Volume 15 Issue 701 - 21 June 2023

What are the aims of this research?

U-RHYTHM is part of a system which allows hormones to be measured in tissue, without the need for blood. We use a technique called microdialysis, which works by allowing hormones to diffuse across a small membrane placed just below the surface of the skin. The fluid containing the hormones is stored in the U-RHYTHM portable device which is later sent off for analysis. During the sampling process, participants can continue most normal activities at home – the device samples automatically requiring no input from the wearer. We explain more in our video linked at the end of this article.

Why is this research important?

Hormone systems work dynamically – that is concentrations of hormones change throughout the day. This is due to multiple factors including intrinsic or internal rhythms (the circadian rhythm is a good example) and also responsiveness to the environment and the consequences of behaviour. Traditional measurements of hormone systems typically rely on single time points or integrated measures which cannot give much or any information about dynamics. Furthermore, really important changes occur during the night – a time that is almost inaccessible to measure except during hospitalization. Our research is important because it reveals insights about the importance of rhythms and dynamics, including reasons for variability that occurs between people.

How will findings benefit people with Addison’s disease and adrenal insufficiency?

The management of adrenal insufficiency has not really changed for decades and relies on more or less generic dosing that, in our opinion, does a poor job at replicating the normal rhythmicity of adrenal steroids that exists in health. Another critical issue is that our understanding of how to dose in response to ‘stressful’ situations (known as Sick Day Rules) is at best very crude.

Additionally, many patients with adrenal insufficiency feel that their quality of life is poor, or at least not as good as prior to the diagnosis.

"We think our research will benefit people with adrenal insufficiency by providing vital information about how to improve glucocorticoid replacement by making it more personalised and physiological. Additionally, such understanding could lead to the development of technologies for potential real time feedback about cortisol dosing."

Where did the name U-RHYTHM come from?

The name emerged during discussions amongst the ULTRADIAN partners. It sounds a bit like ‘your rhythm’, alluding to the personal kind of information that it provides.

What are the next steps for this research?

Right now we are collating and preparing data on our Addison’s, Cushing’s and primary aldosteronism patients. We hope to be able to do more follow-up studies in people with adrenal insufficiency in the near future.

The U-RHYTHM devices are now being sold to the rest of the research community by the University of Bristol spin-out company Dynamic-Therapeutics. We want this research and device to help other conditions, so please get in touch.

Does this mean cortisol sensors could be available in the future, similar to at home glucose monitors for diabetes?

That could definitely be possible – although still requires a lot of work! The CGM analogy is a good one, and has revolutionized how people manage diabetes. Hopefully we will have similar kind of technology for managing adrenal insufficiency in the not too distant future.

We saw you on the BBC, congratulations! Tell us more about public interest in the project. Does this help the development of the research?

Our work has generated a lot of interest both from research and patient communities. It's really important that we share our work and get feedback from patient advocacy groups such as the ADSHG who provide vital context for our research – and who we hope ultimately will be the beneficiaries of our findings.

You can read the BBC article online: 'Device developed in Bristol offers 'revolution' in hormone understanding'.

How can we support this research?

Please follow our social media threads, and contact us if you have any questions or suggestions! While we don’t have any active studies recruiting adrenal insufficient patients right now, we hope to do some in the future and it would be great to see you involved.

If you're a researcher or scientist and think this research may help your work, please get in touch with us via Dynamic-Therapeutics. 

What is your greatest wish for this research and the Addison's and adrenal insufficiency community? 

Ultimately we want our work to be meaningful and helpful to society, including patients with adrenal insufficiency. We hope that by increasing the understanding of how hormone systems work will eventually lead to a significant change in the way endocrinology and endocrine diseases are thought about and managed.

Watch Professor Stafford Lightman and Dr Thomas Upton, explain how U-RHYTHM works

	Author: Dr Thomas Upton, Post-doctoral Clinical Research Fellow, University of Bristol.  X / Twitter: @HotmasUpton
	'High-resolution daily profiles of tissue adrenal steroids by portable automated collection' by Thomas J. Upton, Eder Zavala, Stafford L. Lightman et al. in Science Translational Medicine [open access]
	U-RHYTHM Website The U-RHYTHM devices are now being sold to the rest of the research community by the University of Bristol spin-out company Dynamic-Therapeutics. We want this research and device to help other conditions, so please get in touch.
	X / Twitter: @Ultradian2020  Website: www.ultradian.eu
	ADSHG member Suzanne shares her experience of participating in the research trial in 2021 for the ULTRADIAN study testing U-RHYTHM. Read her story on our blog,

Thank you Thomas and the whole team at U-RHYTHM! We look forward to hearing more about this fantastic research, to provide both our patient community and the doctors looking after us with important information about cortisol levels, and improvements in steroid replacement regimens.

To learn more about wearable technology for Addison's and adrenal insufficiency, such as hydrocortisone infusion pumps, please visit our A-Z of Addison's Resources page, for links to previous articles and research.

Want to stay updated on research progress and hear the latest ADSHG news? Join our charity to become a member to hear direct.

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