Researchers from NIHR Cambridge BRC, University of Cambridge and Cambridge University Hospitals NHS Foundations Trust have developed a vital piece of technology that has dramatically advanced the ability to diagnose primary aldosteronism, a common cause of high blood pressure.
The UK-based study, which was a multi site collaboration between researchers at Cambridge BRC, Queen Mary University of London, Barts Health NHS Trust and University College London Hospitals NHS Foundation Trust has led to the development of a simple, minimally invasive Targeted Thermal Therapy (Triple T) that has the potential to transform treatment of this common cause of high blood pressure.
The vital molecular tracer and PET scanning method, that have dramatically advanced the ability to detect this common condition, was developed by researchers in Cambridge.
This breakthrough, published last Friday in The Lancet, could, after further testing, help millions of people worldwide, who currently go undiagnosed and untreated.
A hidden cause of high blood pressure
High blood pressure affects one in three adults in the UK. Around one in 20 of these are due to primary aldosteronism. However, fewer than one percent of those affected are ever diagnosed as the current diagnostic process includes an invasive, time-consuming procedure that can only be performed in the UK at fewer than a dozen specialist hospitals.
The condition occurs when tiny benign nodules in one or both adrenal glands produce excess aldosterone, a hormone that raises blood pressure by increasing salt levels in the body. Patients with primary aldosteronism often do not respond well to standard blood pressure medications and face higher risks of heart attacks, strokes, and kidney failure.
The new approach dramatically improves the outlook for people with primary aldosteronism by combining a diagnostic PET scan with Triple T.
First, a newly developed molecular tracer is injected into the blood which travels to the nodules in the adrenal gland, where it can be detected using a PET scanner– a high-tech piece of equipment that produces three-dimensional images inside the body. The PET scans take just 10 minutes and could become available at most large hospitals, meaning many more people can be diagnosed.
A game-changing alternative to surgery
Until now, primary aldosteronism has either been treated through life-long medication or via surgical removal of the entire adrenal gland, requiring general anaesthesia, a two- to three-day hospital stay, and weeks of recovery.
In future, once diagnosed, some patients could be offered Triple T which provides a faster, safer alternative to surgery, by selectively destroying the small adrenal nodules without removing the gland. This is currently only possible for nodules in the left adrenal gland which can be see via endoscopy into the stomach, from where they can be directly targeted.
Triple T is also known as endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA). It harnesses the energy of waves, adapting two well-established medical techniques: radiofrequency or microwaves generate heat in a small needle placed into the malfunctioning tissue, causing a controlled burn; ultrasound uses reflected sound waves to create a real-time video of the procedure.
In Triple T, as in routine endoscopy, a tiny internal camera—in this case using ultrasound as well as light—is passed by mouth into the stomach. The endoscopist visualises the adrenal gland and guides a fine needle from the stomach precisely into the nodule. Short bursts of heat destroy the nodule but leave the surrounding healthy tissues unharmed. This minimally invasive approach takes only 20 minutes and eliminates the need for internal or external incisions.
Successful trial shows promise
The study is called FABULAS, the name being an acronym for Feasibility study of radiofrequency endoscopic ABlation, with ULtrasound guidance, as a non-surgical, Adrenal Sparing treatment for aldosterone-producing adenomas.
FABULAS tested Triple T in 28 patients with primary aldosteronism, whose molecular scan had pinpointed a hormone-producing nodule in the left adrenal gland. The new procedure was found to be safe and effective, with most patients having normal hormone levels six months later. Many participants were able to stop all blood pressure medications, with no recurrence of the condition.
Professor Morris Brown, co-senior author of the FABULAS study and Professor of Endocrine Hypertension at Queen Mary University of London and Professor of Endocrinology at Barts Health NHS Trust, said: “It is 70 years since the discovery in London of the hormone aldosterone, and, a year later, of the first patient in USA with severe hypertension due to an aldosterone-producing tumour. This patient’s doctor, Jerome Conn, predicted, with perhaps only minor exaggeration, that 10-20% of all hypertensions might one day be traced to curable nodules in one or both glands. We are now able to realise this prospect, offering 21st-century breakthroughs in diagnosis and treatment.”
One of the trial participants, Michelina Alfieri, shared her experience:
“Before the study, I suffered from debilitating headaches for years despite multiple GP visits. As a full-time worker and single parent, my daily life was severely affected. This non-invasive treatment provided an immediate recovery—I was back to my normal routine straight away. I’m incredibly grateful to the team for giving me this choice.”
What’s Next?
The success of FABULAS has led to a larger randomised trial called ‘WAVE’, which is comparing Triple T with traditional adrenal surgery. The results are expected in 2027.
Professor Stephen Pereira, Chief Investigator of FABULAS and Professor of Hepatology & Gastroenterology at UCL Institute for Liver and Digestive Health, added: “With appropriate training, this less invasive technique could be widely offered in endoscopy units across the UK and beyond.”
Clinical Endocrinology Lead at Addenbrooke’s Hospital and Professor of Clinical Endocrinology at the University of Cambridge, Professor Mark Gurnell, said: “This breakthrough was made possible thanks to the collaborative development of novel PET tracer molecules, which enable non-invasive diagnosis by allowing us to precisely locate and treat adrenal nodules for the first time.
“Thanks to this work, we may finally be able to diagnose and treat more people with primary aldosteronism, lowering their risk of developing cardiovascular diseases and other complications, and reducing the number of people dependent on long-term blood pressure medication,” he added.
A major step forward for hypertension treatment
For the millions of people suffering from undiagnosed primary aldosteronism, this research offers new hope. The potential to be freed from a life of struggling with high blood pressure via simple, non-invasive diagnosis, and safely targeted thermal therapy, allowing faster recovery and better outcomes.
With further studies underway, this breakthrough treatment could soon become a standard procedure worldwide, transforming care for patients with this curable form of hypertension.
Successful trial shows promise
The study is called FABULAS, the name being an acronym for Feasibility study of radiofrequency endoscopic ABlation, with ULtrasound guidance, as a non-surgical, Adrenal Sparing treatment for aldosterone-producing adenomas.
FABULAS tested Triple T in 28 patients with primary aldosteronism, whose molecular scan had pinpointed a hormone-producing nodule in the left adrenal gland. The new procedure was found to be safe and effective, with most patients having normal hormone levels six months later. Many participants were able to stop all blood pressure medications, with no recurrence of the condition.
Professor Morris Brown, co-senior author of the FABULAS study and Professor of Endocrine Hypertension at Queen Mary University of London and Professor of Endocrinology at Barts Health NHS Trust, said: “It is 70 years since the discovery in London of the hormone aldosterone, and, a year later, of the first patient in USA with severe hypertension due to an aldosterone-producing tumour. This patient’s doctor, Jerome Conn, predicted, with perhaps only minor exaggeration, that 10-20% of all hypertensions might one day be traced to curable nodules in one or both glands. We are now able to realise this prospect, offering 21st-century breakthroughs in diagnosis and treatment.”
One of the trial participants, Michelina Alfieri, shared her experience:
“Before the study, I suffered from debilitating headaches for years despite multiple GP visits. As a full-time worker and single parent, my daily life was severely affected. This non-invasive treatment provided an immediate recovery—I was back to my normal routine straight away. I’m incredibly grateful to the team for giving me this choice.”
What’s Next?
The success of FABULAS has led to a larger randomised trial called ‘WAVE’, which is comparing Triple T with traditional adrenal surgery. The results are expected in 2027.
Professor Stephen Pereira, Chief Investigator of FABULAS and Professor of Hepatology & Gastroenterology at UCL Institute for Liver and Digestive Health, added: “With appropriate training, this less invasive technique could be widely offered in endoscopy units across the UK and beyond.”
Clinical Endocrinology Lead at Addenbrooke’s Hospital and Professor of Clinical Endocrinology at the University of Cambridge, Professor Mark Gurnell, said: “This breakthrough was made possible thanks to the collaborative development of novel PET tracer molecules, which enable non-invasive diagnosis by allowing us to precisely locate and treat adrenal nodules for the first time.
“Thanks to this work, we may finally be able to diagnose and treat more people with primary aldosteronism, lowering their risk of developing cardiovascular diseases and other complications, and reducing the number of people dependent on long-term blood pressure medication,” he added.
A major step forward for hypertension treatment
For the millions of people suffering from undiagnosed primary aldosteronism, this research offers new hope. The potential to be freed from a life of struggling with high blood pressure via simple, non-invasive diagnosis, and safely targeted thermal therapy, allowing faster recovery and better outcomes.
With further studies underway, this breakthrough treatment could soon become a standard procedure worldwide, transforming care for patients with this curable form of hypertension.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02755-7/fulltext