Scan to supersede catheterisation for aldosteronism diagnosis

A novel form of molecular imaging scan enables non-invasive diagnosis of unilateral primary aldosteronism and identifies patients whose hypertension can be cured, or greatly improved, by adrenal surgery.

UK researchers have shown that carbon-labelled metomidate PET CT scanning is as accurate as the current standard of an adrenal vein sampling (AVS) procedure in predicting the biochemical remission of primary aldosteronism and the resolution of hypertension after surgery.

The scan uses a very short-acting dose of [11C] metomidate, a radioactive dye that sticks only to the aldosterone-producing adrenal nodule.

Since molecular imaging is quick, safe and reliable compared to adrenal vein catheterisation, it may now be a preferred option to diagnose unilateral aldosterone-producing adrenal adenomas when AVS is either unavailable, unsuccessful or not desired by the patient, the researchers from Queen Mary University of London (QMUL), said.

Publishing their results in Nature Medicine (link here) the research team  say the new technique solves a 60-year problem of how to detect the tiny aldosterone- producing nodules without a difficult catheter study that is available in only a handful of hospitals, and often fails.

In their paper they explained that carbon-labelled metomidate can be used as a PET radiotracer in combination with high-resolution CT to accurately detect adrenocortical tumours expressing the CYP11B2 aldosterone synthase in patients who have been pretreated with three days of dexamethasone.

Their study compared AVS and metomidate scans in 128 adult patients recruited from endocrinology or hypertension clinics in in the UK, who were undergoing investigations for primary aldosteronism.

The results showed that metomidate and AVS graded 67/128 (52%) and 58/128 (45%) patients, respectively, as having a high probability of unilateral primary aldosteronism, indicating surgery).

The two techniques were concordant in the diagnosis of unilateral disease in 30% patients, whereas 37% were diagnosed by one of the techniques alone

At nine months of follow up, 78 patients (61%) were treated surgically and 50 (39%) managed medically

Of the patients receiving surgery, all but one achieved one or more surgical outcome criterion for success. The accuracies of metomidate at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%, respectively.

For AVS, the accuracies were 63.6 and 61.5%.

While metomidate scanning was not significantly superior to AVS, the differences were within the pre-specified −17% margin for non-inferiority.

Professor Morris Brown, co-senior author of the study and Professor of Endocrine Hypertension at QMUL, said it was noteworthy that the combination of a ‘hot nodule’ on the scan and urine steroid test detected 18 of the 24 patients who achieved a normal blood pressure off all their drugs.

“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.”

The researchers said the convenience of molecular imaging would increase further as a new fluoro-analogue is becoming available that is transportable to most hospitals with PET imaging facilities.

“The longer-term impact … may be a reassessment of who undergoes lateralisation and surgery, and a stimulus to decision-making by molecular, rather than anatomical, diagnosis,” they wrote.

“Our principal finding is that [metomidate scanning] following pre-treatment with dexamethasone enables non-invasive detection of unilateral ‘aldosterone-producing adrenal] nodules and is at least as accurate in the prediction of outcomes from adrenalectomy as the standard, invasive investigation, AVS,” they concluded.

“The high proportion (almost two-thirds) of patients in whom we found and cured unilateral primary aldosteronism highlights the underdiagnosis in usual practice of unilateral disease,” they added.

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