Hormonal disorders can affect people's immune systems, metabolism and even bones, and unravelling the mystery around something called ultradian rhythms could help improve diagnosis and lead to better treatments, according to Professor Eystein Sverre Husebye, who works at the Department of Clinical Science at the University of Bergen (UiB) in Norway.
What exactly are ultradian rhythms?
‘Hormones have different rhythms, so they are secreted in pulses (by glands around the body). We know a lot about circadian rhythms, which are daily variations, but ultradian rhythms are periods which are shorter than 24 hours where the pulsed secretion of hormones has a frequency of (for example) once an hour or once every 30 minutes. These are important to understand how hormones function.’
What happens if the ultradian rhythms of hormones are out-of-sync?
‘The consequences could be obesity, hypertension, heart disease, cardiovascular disease, osteoporosis or ulcers – hormone diseases can have a lot of bad consequences.
‘Many people go for several years before they get a diagnosis for a hormone disease. One of the reasons is these changes (in hormonal rhythms) develop very slowly, sometimes over several years, and can be misdiagnosed for other diseases – just as plain obesity, hypertension or osteoporosis.
‘Many people go for several years before they get a diagnosis for a hormone disease.’
Professor Eystein Sverre Husebye, University of Bergen, Norway
‘For example, primary hyperaldosteronism, which can cause a severe type of hypertension (high blood pressure), is vastly under-diagnosed today. An early and correct diagnosis is important because sometimes this type of hypertension can be cured by surgery, otherwise with specific anti-hypertensive drugs. If we can develop an easier way to diagnose these disorders – which is currently quite elaborate and takes a lot of resources as people have to come to hospital several times – we could make a big cost saving.
‘It would be better to measure hormone cycles at all possible times of the day, not just when the laboratory is open or when the doctor is working.’
You are the project coordinator of the EU-funded ULTRADIAN project, which has developed a new diagnostic tool for hormone disorders. How does it work?
‘Normally doctors take a blood sample in the morning at a laboratory, but the result gives you only the level the moment the blood is drawn, not the dynamic over the 24 hour cycle.
‘We want to revolutionise diagnostics in endocrinology by not providing single point measurements, but instead a dynamic picture of hormonal variations in patients over a 24-hour cycle to find the subtle changes in the rhythm – earlier and more easily than we do today.
‘Our 24-hour profiles are created through a device connected to a thread (catheter) inserted under the skin. The sampler collects tissue fluid continuously and divides the fluid into portions. The person wearing the device can go about daily activities while the fluid is collected.’
How will this technique help those with hormone disorders?
‘The other aim of the project is the assay (testing) of these hormones. We use liquid chromatography–mass spectrometry where we are able to measure 10 to 15 different steroid hormones in just 10 microlitres of tissue fluid. It’s a very sensitive technique. We collect 72 samples in 24-hour cycles and measure these hormone profiles in each sample.
‘We hope this will help more people get diagnosed earlier and provide something that is cost-effective. Instead of putting people in a hospital bed for a few days and doing lots of tests, doctors can do the investigation in an outpatient clinic.
‘We also hope the sampler can be used in other areas, such as (to) measure (the) concentration of drugs in the tissue and perhaps help to monitor premature babies. In general, it could provide techniques to measure out what’s going on in the body in very small volumes.’
What stage is the project at now?
‘We are doing clinical studies (tests in humans) including sampling a lot of healthy patients to define the normal ranges of different hormones. At the same time we are doing several clinical studies on patients with endocrine diseases. One of the disorders we are studying is called Cushing’s syndrome, caused by too much cortisol being produced in the body. Another is Addison’s disease, a condition where there is lack of cortisol and another crucial hormone called aldosterone. We are also studying an endocrine disease called congenital adrenal hyperplasia, an inborn error of steroid metabolism, as well as primary hyperaldosteronism – all to improve diagnostics.’
When could we hope to see your diagnostic tool on the market?
‘I think by the end of the project (August 2019) we will have a prototype that will be ready to be mass-produced. We are also trying to develop a diagnostic package that contains the sampler and the interpretation of the assays because treating hormone disorders is not only looking at a single value measure, you must interrupt the variations of the rhythm and determine what that means.’
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