A newly developed 10-minute scan could improve the diagnosis and treatment of patients with suspected primary aldosteronism, a UK pilot trial suggests.

A substantial proportion of patients with hypertension have dysregulated aldosterone production, with primary aldosteronism the most extreme phenotype, researchers from the University of College London (UCL) wrote in a letter to the New England Journal of Medicine.

Diagnosis involves multiple steps, with the complicated process compounded by the need for invasive adrenal-vein sampling to best guide treatment approach.

Lifelong medical therapy to block aldosterone production is recommended for bilateral disease, while adrenalectomy is the standard treatment for unilateral disease.

To improve and simplify treatment decisions, the research team developed a new radioactive tracer compound that binds to the enzyme aldosterone synthase (CYP11B2-specific radioligand) and can be used in Positron Emission Tomography-Computer Tomography (PET-CT) imaging.

To test the technology, the team scanned 17 consecutive patients with confirmed primary aldosteronism who were scheduled for adrenalectomy following lateralised findings on adrenal-vein sampling.

Identifying adrenal lesions in primary aldosteronism

PET-CT showed avid uptake in adrenal lesions, with rapid clearance from adjacent and contralateral adrenal tissue and most other organs, with no reported adverse effects from the radioligand.

Imaging using the newly developed tracer found one or more lesions in all 17 adrenal glands that were predicted to be dominant by adrenal-vein sampling, the researchers reported.

In five cases, microlesions (<1cm³ as measured with PET) were also detected in the contralateral adrenal glands.

CYP11B2 PET-CT imaging showed standard uptake values that were several times as high in the adrenal glands that were identified as dominant as those in the contralateral adrenal glands.

‘Moreover, when lesion volume was accounted for, the side of the dominant adrenal identified by our method was consistent with results of adrenal-vein sampling in all 17 cases,’ the researchers wrote.

CYP11B2 PET-CT not only detected macroscopic adrenal lesions but also revealed pathological features of primary aldosteronism in two patients with multiple aldosterone-producing micronodules.

In addition, almost half (12 of 27) of the adrenal lesions detected with PET were not seen on CT or magnetic resonance imaging (MRI) results reported independently by an experienced adrenal radiologist.

Potential to alter treatment stratification

A phase 2 clinical trial is now underway to assess the performance of the technology in a broader population of patients with primary aldosteronism, the researchers added.

‘We speculate that this method may have the potential to alter treatment stratification for patients across the wide spectrum of aldosterone dysfunction, including classical primary aldosteronism as currently defined,’ they concluded.

Study clinical lead Professor Bryan Williams, chair of medicine at UCL and consultant physician at University College London Hospitals NHS Foundation Trust (UCLH), said clinicians had been waiting for this kind of test for many decades.

‘It offers huge potential to completely change the way we make this diagnosis and enable us to provide better targeted treatment for our patients,” he said.

Importantly, the technique allowed clinicians to visualise primary aldosteronism for the first time.

‘We can see it light up on the scan. The intensity of the signal reflects the level of aldosterone over-production,’ Professor Williams said.

‘This might allow us, in future, to more precisely target these over-producing areas.’

Further hypertension research

The study was conducted at UCL and UCLH and was funded by the Medical Research Council and the National Institute for Health and Care Research UCLH Biomedical Research Centre.

Earlier this year, Professor Williams and fellow researchers reported results from a phase 3 clinical trial of the investigational, highly selective aldosterone synthase inhibitor baxdrostat, which showed significant reductions in blood pressure compared with placebo at 12 weeks in patients with uncontrolled or treatment-resistant hypertension.

He said the findings suggested aldosterone was playing an important role in causing difficult-to-control blood pressure in millions of patients.

It is estimated that as many as half a billion people could benefit from the therapy globally, including 10 million people in the UK.