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HORIZON 2020 | MEDICINE

Solving genetic riddles and finding hormone rhythms

The EU-supported ULTRADIAN project aims to improve and simplify the diagnosis and treatment of hormone diseases for both patients and the national health service.

Professor Eystein Husebye
Professor Eystein Husebye
Photo:
Ingvild Festervoll Melien

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The project came about because accurately analysing and measuring hormone variations during a 24-hour period has proved very difficult. The current procedures are also time-consuming for both patients and the national health service.

“Hormones are rhythmically secreted into the body, which causes large variations in hormone levels depending on the time of day, meals and stress. These hour-to-hour fluctuations are called ultradian variations. These are difficult to capture with ordinary diagnostics,” explains Professor Eystein Husebye, who heads the ULTRADIAN project. He works at the Department of Clinical Science at the University of Bergen (UiB).

 

Unique register

He and his team have discovered that hereditary autoimmune diseases may be more common than previously thought. This is in large part thanks to the pioneering work they did when they established the Register for Organ-specific Autoimmune Diseases (ROAS) in 1996.

The register is unique. No other register in the world contains as much information about patients with Addison’s disease. The researchers’ general strategy involves studying all aspects of adrenal cortex failure, everything from occurrence to causal mechanisms at a cellular level. The goal is to achieve better diagnostics, treatment and follow-up of patients.

 

Stress and salt

Addison’s disease is also known as primary adrenal insufficiency or hypoadrenalism. The destruction of the adrenal cortex reduces the production of essential hormones. The adrenal cortex normally produces the hormones cortisol and aldosterone.

“Cortisol is important when it comes to being able to cope with stress. Aldosterone is important when it comes to regulating the salt and water balance in the body,” explains Husebye.

Discovering whether your adrenal cortex is malfunctioning can be difficult. Often the only symptoms are diffuse such as feeling lethargic, light-headed and tired, and lacking energy. On the other hand, if you have extremely low levels of cortisol and aldosterone you can experience what is called an Addison crisis.

“In these circumstances your heart can stop. Sometimes the diagnosis is not discovered until the person is autopsied,” says Husebye.

 

Developed new patient card

Husebye has, together with Swedish colleagues, developed a special business card-sized card that patients with Addison’s disease carry on them. The card provides information about the disease, both in their first language and English. This makes it easier for health professionals to give the necessary fluids and hormone treatment.

“Unfortunately, patients find that they are not taken seriously even if they tell a doctor what treatment they need,” says Husebye.

 

New knowledge about gene pairs

The researchers have discovered that genes act in pairs. Previously, it was believed that both genes in the same pair had to be damaged in order for autoimmunity to occur in the disease they are studying.

“We have now discovered that the disease can occur even if only one of the genes is damaged. Some gene changes code for a protein that binds itself to the healthy gene product such that it does not work normally, which we call a dominant negative effect,” explains Husebye. The study was published in 2015 in the world’s most cited immunology journal, Immunity, and was conducted in partnership with Israeli, Finnish and British researchers.

“This knowledge may be transferable to other hereditary diseases. By conducting research into sick genes and malfunctioning hormone production, we are also learning a lot about how this works in healthy people,” says Husebye, who has long worked with researchers in Norway (University of Oslo) and internationally (including the Weizmann Institute of Science in Israel and Karolinska Institutet in Sweden).

 

New measuring methods are attracting attention

Researchers from UiB and a number of international partners are currently in the process of revolutionising the way hormones are measured.

Until now the normal procedure has been to measure hormones in a blood sample at a specific time of day, often in office hours. This tells you the hormone status of the body at exactly this point in time, but not very much about how hormone levels change during the day.

With the new method a simple way has been found to measure hormone levels throughout the day in the same way as patients with diabetes can measure their blood sugar.

“We are going to do the same thing for measuring other hormones. We know that these hormones are secreted in pulses that form rhythms and not evenly over the day. If you contract a disease, it is not only the levels that can change, but also the hormone rhythms. That is why it is important to have accurate measurements over an entire day,” says Eystein Husebye.