In a recent article published in Nature Medicine, researchers performed a prospective within-patient clinical trial, Is Metomidate superior to AVS in predicting ouTComes from adrenalectomy in primary Hyperaldosteronism (MATCH) in the United Kingdom (UK) in primary aldosteronism (PA) patients. These patients suffered from high blood pressure caused by a steroid hormone, aldosterone.

The primary objective of the trial was to assess the accuracy of a new type of computed tomography (CT) scan called [¹¹C]metomidate positron emission tomography (MTO) in detecting the aldosterone-producing nodules (or unilateral PA) for its biochemical remission and the resolution of hypertension with the help of surgery later. The MTO scan used a short-acting dose of metomidate, a radioactive dye binding the aldosterone-producing nodule only.

Additionally, the researchers compared the accuracy of this scan with adrenal vein sampling (AVS), the standard, invasive catheter test used for predicting outcomes from adrenalectomy.

Background

PA due to a unilateral aldosterone-producing adenoma frequently causes hypertension. Though curable by adrenal surgery, the invasive nature of the standard catheter test and its limited availability fails to detect unilateral PA in 99% of cases. Even when the catheter test detected the issue, doctors could offer a surgical cure to less than 1% of patients.

About the study

In the present study, researchers recruited PA patients through tertiary endocrinology clinics of St Bartholomew’s, Addenbrooke’s, Guy’s, and St Thomas’ hospitals in the UK. The study population comprised all patients aged 18 years or older who met the Endocrinology Society criteria for PA diagnosis.

The researchers randomly assigned all patients with confirmed PA to undergo AVS and MTO. All patients received 0.5 milligrams of dexamethasone four times orally every day for three days before MTO scanning, followed by positron emission tomography (PET) scanning. Three interventional radiologists performed all AVS procedures for the study. However, only one radiologist, blinded to the AVS result, analyzed all MTO scans and determined the probability of unilateral PA based on a pre-specified criterion.

The researchers reviewed all patients at a baseline visit, following which they put them on 50 mg spironolactone, up-titrated to 100 mg after two weeks. They recorded blood pressure response to spironolactone at two and four weeks from the initiation. Notably, the researchers concomitantly reviewed the results of both scans at multidisciplinary team (MDT) meetings. The study protocol mandated reviewing MTO results first, followed by AVS. After each review, they assigned a score of low, intermediary, or high probability of unilateral PA. A high score implied that doctors would recommend unilateral adrenalectomy for the patient. Likewise, the intermediary score prompted them to recommend surgery, for instance, due to uncontrolled blood pressure.

In patients referred for surgery, doctors continued spironolactone therapy until the day of surgery. They assessed outcomes from surgery biochemically and clinically at three and six months after surgery. The primary study outcomes reflected the normalization of biochemical and clinical parameters following adrenalectomy.

The secondary study outcomes of MATCH covered serial measurements made up to two years post-intervention. They considered MTO and AVS accurate if they recommended surgery that resulted in a cure or if the test did not indicate surgery.

Results

The study enrolled 128 patients who reached six- to nine-month follow-ups, of which 61% and 39% were surgically treated and managed medically, respectively. These patients attained a primary outcome six months post-unilateral adrenalectomy, and the medically managed patients reached the same nine to 12 months after their baseline visit.

Of the 78 patients who underwent surgery, 77 attained a successful PA surgical outcome. Following surgery, the MTO accuracy at successfully predicting biochemical and clinical parameters was 72.7 and 65.4%, respectively. On the contrary, AVS accuracy in predicting the same outcomes was 63.6 and 61.5%, respectively.

MTO accuracy was not markedly superior, but with the differences of 9.1% and 3.8%, with a 95% confidence interval, laid within the −17% non-inferiority margin. The researchers recorded no serious adverse events related to MTO or AVS investigation. Moreover, 22 of 24 serious adverse events were resolved.

Furthermore, the MTO scan found elevated aldosterone secretion, from a benign nodule in one of the adrenal glands, in two-thirds of patients. It yielded results as accurate as the AVS test but was non-invasive, painless, and technically feasible for every PA patient. Moreover, the MTO scan, in combination with the urine steroid test, detected 18/24 patients who were not on any drugs and yet attained normal blood pressure.

These aldosterone-producing nodules are very small and easily overlooked on a regular CT scan. When they glow for a few minutes after our injection, they are revealed as the obvious cause of Hypertension, which can often then be cured. Until now, 99% are never diagnosed because of the difficulty and unavailability of tests. Hopefully this is about to change.”

Professor Morris Brown, Professor of Endocrine Hypertension at Queen Mary University of London

"This study was the result of years of hard work and collaboration between centres across the UK. Much of the ‘on the ground’ energy and drive came from the talented research fellows who, in addition to doing this innovative work, gave selflessly of their time and energy during the national pandemic emergency. The future of research in this area is in very safe hands.”

Professor William Drake, Professor of Clinical Endocrinology at Queen Mary University of London

Conclusions

To conclude, MATCH validated MTO as an aldosterone synthase (CYP11B2)-selective investigation for lateralizing PA. Unlike AVS, MTO was quick, safe, and reliable. It could help diagnose unilateral PAs when AVS would be unavailable, technically infeasible, or failed for a patient. The MTO would attract more clinicians and patients to seek a PA diagnosis, especially in hospitals with PET imaging facilities.