A speedy new scan could improve how millions of people with high blood pressure are treated, suggests a new study led by UCL (University College London) researchers.
About a quarter of people with high blood pressure have been estimated to have a problem with their adrenal glands producing too much of the hormone aldosterone, which regulates levels of salt in the body.
This problem is often missed, as the path to diagnosis is complex, involving multiple tests and, to guide treatment, an invasive procedure that is not always reliable.
The new 10-minute scan, developed at UCL and described in a research letter in the New England Journal of Medicine (NEJM), reveals overactivity in adrenal glands that was invisible with conventional tests, showing exactly where too much aldosterone is being made.
This, the researchers say, will make it easier to decide on the best treatment approach - either removal of an adrenal gland that is producing too much aldosterone, or the use of new medications that block aldosterone production, targeting the cause of high blood pressure in many patients.
Professor Bryan Williams, Chair of Medicine at UCL and clinical lead for the study, said: "We have been waiting for a test like this for many decades. This British innovation is going to transform the diagnosis of aldosterone excess as an important and previously hidden cause of hypertension in many of our patients. If offers huge potential to completely change the way we make this diagnosis and enable us to provide better targeted treatment for our patients."
The over-production of aldosterone, which raises high blood pressure by causing the body to retain too much salt, can result in a condition called primary aldosteronism, which increases the risk of heart disease, stroke and kidney disease. However, many people who do not meet the threshold for this condition are thought to have excess aldosterone raising their blood pressure.
Currently the condition is screened with a blood test and confirmed with a second test*. To decide on treatment, two catheters are inserted in veins on either side of the groin to measure levels of aldosterone on each side of the body. This helps clinicians determine if the problem is only located in one adrenal gland or both - but the test is not always accurate and not often offered as few hospitals have the expertise to perform this complex procedure.
To better detect the condition, researchers at UCL used a PET-CT scan, which creates detailed 3D images (computed tomography, or CT) of parts of the inside of the body and maps the accumulation of a tiny amount of radioactive tracer injected into a person's vein (position emission tomography or PET).
They built a new tracer compound designed to bind to the aldosterone-producing enzyme, aldosterone synthase. The tracer was highly selectively taken up by the parts of the adrenal gland that were over-producing aldosterone, lighting up these areas on the scan.
In their NEJM research letter, the researchers described how 17 patients were scanned in the world's first use of this technique at UCLH. The team found the source of over-production of aldosterone in every patient and did not see any side effects.
Professor Williams added: "This is the first time we have been able to visualise this disease. We can see it light up on the scan. The intensity of the signal reflects the level of aldosterone over-production. This might allow us, in future, to more precisely target these over-producing areas."
The achievement builds on more than a decade's work by Professor Erik Arstad (UCL Division of Medicine and UCL Chemistry) and colleagues, who pioneered and patented a new method to make radioactive tracers.
Using this method, they were able to repurpose a drug-like molecule that bound to the aldosterone-producing enzyme for use as a tracer, replacing a single atom with a radioactive version of that atom – meaning this molecule would light up on a PET-CT scan.
Professor Arstad said: "It is very rewarding to be able to bring laboratory innovation into the clinic for the benefit of patients with hard-to-treat hypertension."
The study was conducted at UCL and UCLH and was funded by the MRC and the NIHR University College London Hospitals Biomedical Research Centre.
The team is now embarking on a phase 2 clinical trial to gather sufficient data for the test to be approved for routine clinical use in the NHS.
In the UK, more than 14 million people are estimated to have high blood pressure (about one in three adults).
*For instance, a salt loading test, where a person increases their intake of salt (sodium), which would be expected to suppress aldosterone levels. If aldosterone levels are still high despite this increase, that confirms a primary hyperaldosteronism diagnosis.
