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Small adrenal tumours cause high blood pressure

In collaboration with a Cambridge research group, Danish researchers from the PUMPkin research centre at Aarhus University have revealed why up to 10 per cent of the population has high blood pressure.

In collaboration with a Cambridge research group, the Danish researchers, Poul Nissen and Hanne Poulsen, from Aarhus University have revealed why up to 10 percent of the population have high blood pressure. Photo: Lisbeth Heilesen
All animal cells depend on the sodium/potassium ion pump, which ensures plenty of extracellular sodium and intracellular potassium. The big difference thus created in the ion concentrations can be utilised for a variety of vital processes, such as communication with other cells and the exchange of substances. A normal pump pumps three sodium ions out and two potassium ions in per cycle (left). In adrenal tumours, however, mutations modify the basic mechanism so that the pump allows ions (protons or sodium ions) to flow into the cell (right). This upsets both the ion balance and the gradients across the membrane in the adrenal cortex cell, which it perceives as a signal to produce aldosterone. The overproduction of aldosterone leads to hypertension. Up to 10% of patients with hypertension have such tumours, but these can be removed by surgery, which can cure the patient. Figure: Hanne Poulsen

High blood pressure is a major health problem, as it increases the risk of cardiovascular diseases markedly. Almost one million Danes are believed to have high blood pressure, many without knowing it. For most patients, their high blood pressure is due to an unhealthy lifestyle – smoking, obesity and excessive salt in the diet. However, for about 10% of the patients, the cause might be found in the adrenal gland, a small hormone-producing gland located on top of the kidney.

Discovery of new tumours in the adrenal glands
If the body’s blood pressure is too low, the adrenal cortex releases the hormone aldosterone, which causes the kidney to take up more salt, thus elevating the blood pressure. However, this regulation may go wrong if tumours start to grow in the adrenal cortex, as high levels of aldosterone are then released all the time.

If the doctor discovers that a patient with high blood pressure has adrenal tumours, these can be removed by surgery, and the patient can be cured. But this assumes that the doctor is looking for tumours, and that they are sufficiently large to be seen. The British researchers used a very sensitive PET scanning method, where even very small tumours could be detected, and the tumours were then removed by surgery. A study of the tumours at the DNA level revealed that nine out of ten patients had a mutation in one of two proteins – the sodium/potassium ion pump or a calcium channel.

Mutated pumps overstimulate hormone production

To understand why these mutations lead to disease, the Danish scientists led by Senior Researcher Hanne Poulsen, Aarhus University, studied the behaviour of the mutated ion pumps. Ions are charged particles, which means that when a pump moves the ions around, it also creates a current. This current is quite small, but if there are enough pumps, the current can be measured with sensitive electrodes. The researchers therefore used a really large cell, i.e. a frog egg, and got it to make a considerable number of mutated pumps for their studies.

These studies revealed not only that the pump no longer worked as it should, but also that it even acquired a new role, as it now worked as an ion channel and therefore as a short circuit. The short circuit means that the tumour – consisting of adrenal cortex cells – continuously receives a signal to produce aldosterone, and this overproduction leads to hypertension.

The new research suggests that small tumours of the adrenal cortex may well be an underdiagnosed cause of high blood pressure. As the cure is known and simple – surgical removal of tumours – a better and earlier diagnosis will hopefully be able to help a large group of patients.

The results have just been published in the international journal Nature Genetics.

The Danish research group is affiliated with the Danish National Research Foundation’s PUMPkin Centre, and Hanne Poulsen is supported financially by the Lundbeck Foundation, the Carlsberg Foundation and L’Oréal/UNESCO.

More information

Senior Researcher Hanne Poulsen – hp@mb.au.dk - 30254065
Professor Poul Nissen – pn@mb.au.dk – 2899 2295

Department of Molecular Biology and Genetics
Aarhus University, Denmark