The new scan reliably detects primary aldosteronism, the most common cause of high blood pressure


In a recently published article in Nature medicineResearchers conducted a potential in-patient clinical trial, Is Metomidate is superior to aVS in expect ouTComes of primary adrenalectomy hhyperaldosteronism (MATCH) in the United Kingdom (UK) in patients with primary aldosteronism (PA). These patients suffered from aldosterone-induced hypertension.

Stady: [11C]metomidate PET-CT versus adrenal vein sampling for the diagnosis of surgically reversible primary aldosteronism: a prospective in-patient experience.  Image credit: Jaron Ontakray/Shutterstock
Stady: [11C]Positron emission tomography metomidate versus adrenal vein sampling for the diagnosis of surgically reversible primary aldosteronism: a prospective in-patient experience.. Image credit: Jaron Ontakray/Shutterstock

The primary goal of the trial was to evaluate the accuracy of a new type of CT scan called CT [11C]Positron emission tomography (MTO) in the detection of aldosterone-producing nodules (or unilateral PA) for biochemical remission and subsequent surgical-assisted treatment of hypertension. The MTO scan used a short-acting dose of metomidate, a radioactive dye that binds only aldosterone-producing nodules.

In addition, the researchers compared the accuracy of this assay to adrenal vein sampling (AVS), the standard invasive catheter test used to predict outcome of adrenalectomy.

background

PA due to monoaldosterone-producing adenoma often causes hypertension. Although treatable with adrenal surgery, the invasive nature of standard catheter testing and its limited availability fail to detect unilateral PA in 99% of cases. Even when catheter testing detected the problem, doctors could offer surgical treatment in less than 1% of patients.

about studying

In this study, the researchers recruited PA patients through tertiary endocrinology clinics at St Bartholomew, Addenbrooke, Guy’s and St Thomas Hospitals in the United Kingdom. The study population consisted of all patients 18 years of age or older who met the Endocrine Society criteria for a diagnosis of RA.

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

The researchers reviewed all the patients at a baseline visit, then put them on 50 mg of spironolactone, and titrated them to 100 mg after two weeks. They recorded the blood pressure response to spironolactone at two and four weeks after initiation. Notably, the researchers concurrently reviewed the results of both surveys at the MDT meetings. The study protocol mandated reviewing the results of MTO first, followed by AVS. After each review, they assigned a low, medium, or high likelihood score of unilateral PA. A high score means that doctors will recommend a unilateral adrenalectomy to the patient. Likewise, an intermediate outcome prompted them to recommend surgery, for example, because of uncontrolled blood pressure.

In patients referred for surgery, physicians continued treatment with spironolactone until the day of surgery. They evaluated the results of the surgery biochemically and clinically at three and six months after surgery. The results of the primary study reflected normalization of biochemical and clinical parameters after adrenalectomy.

The results of the MATCH secondary study covered serial measurements taken up to two years after the intervention. They considered MTO and AVS accurate if they recommended surgery that resulted in a cure or if testing did not indicate surgery.

results

The study included 128 patients who had access to a six- to nine-month follow-up, of whom 61% and 39% were treated surgically and medically, respectively. These patients achieved an initial outcome six months after 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 had a successful PA surgical outcome. After surgery, the accuracy of MTO in successfully predicting biochemical and clinical parameters was 72.7 and 65.4%, respectively. On the contrary, the accuracy of AVS in predicting the same outcomes was 63.6 and 61.5%, respectively.

The accuracy of MTO was not significantly superior, but with differences of 9.1% and 3.8%, with a 95% confidence interval, it was placed within a margin of not less than 17%. The investigators did not record any serious adverse events related to the investigation of MTO or AVS. Furthermore, 22 of the 24 severe 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 the patients. It yielded results as accurate as an AVS test but was non-invasive, painless, and technically feasible for every PA patient. Furthermore, MTO screening, in combination with urine steroid testing, detected 18/24 patients who did not take any medications and yet reached normal blood pressure.

These aldosterone-producing nodules are very small and can be easily missed on a regular CT scan. When it flares up for a few minutes after the injection, it is revealed as an obvious cause of high blood pressure, which can then often be treated. Even now, 99% are never diagnosed due to the difficulty and unavailability of tests. We hope this changes.”

Professor Maurice Brown, Professor of Hypertension Endocrinology at Queen Mary University of London

“This study was the result of years of hard work and collaboration between centers across the UK. Much of the energy and ‘down to earth’ motivation came from talented research colleagues who, in addition to doing this innovative work, selflessly gave their time and energy during the national epidemiological emergency The future of research in this field is in good hands.”

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

conclusions

In conclusion, MATCH validated MTO as a selective probe of aldosterone synthase (CYP11B2) to determine the side profile of PA. Unlike AVS, MTO was fast, safe and reliable. It can help diagnose unilateral PAs when AVS is not available, technically not feasible, or fails for the patient. MTO will attract more clinicians and patients to seek diagnosis of PA, especially in hospitals with PET imaging facilities.



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