OR34-07 Prospective Multicentre Study Comparing 11C-metomidate PET CT with Adrenal Vein Sampling (AVS) in the Detection of Unilateral Aldosterone-Producing Adenomas (APAs)
Authors: Wu Xilin , Goodchild Emily , Senanayake Russell , Bashari Waiel , Salsbury Jackie , Argentesi Giulia , O’Toole Samuel Matthew , Matson Matthew , Parvanta Laila , Marker Alison , Berney Daniel , Sadhev Anju , Bird Nicholas , McConnachie Alexander , Cruickshank Kennedy , Cheow Heok K , Gurnell Mark , Drake William , Brown Morris Jonathan 
Published: May 2020

Approximately 50% of Primary Aldosteronism (PA) cases are unilateral, potentially curable by adrenalectomy. However far fewer patients progress to surgery, partly due to difficulties in identifying unilateral disease. AVS is the current criterion standard method for lateralisation. However it is an invasive procedure, technically difficult to perform, and only available in few specialist centres. MATCH is a prospective, multicentre study comparing the diagnostic accuracy of AVS with 11C-metomidate PET-CT, a non-invasive functional scan (ClinicalTrials.gov Identifier NCT02945904).

Patients fulfilling Endocrine Society criteria for PA undergo both investigations in random order. At a multidisciplinary meeting PET-CT results are scored first, followed by AVS. Patients are offered surgery if one or both investigations indicate unilateral disease. Each investigation will be re-scored by an independent, blinded endpoints committee, without knowledge of other investigations or outcomes in the same patient. Hierarchical primary outcomes are the change in aldosterone renin ratio (ARR) and average home SBP readings. If no superiority is observed for either investigation, non-inferiority of PET-CT will be tested. MATCH is powered to detect 25% superiority, or non-inferiority within a margin of 18%. Factors predicting cure will be assessed as secondary outcomes. These include BP response to aldosterone antagonists, correlation of standardised uptake value (SUV) max ratio of adenoma to adjacent normal adrenal, and phenotyping / genotyping of tumours.

Target recruitment of 140 patients has been achieved. Interesting observations to date include a high prevalence of hypokalaemia (73%), reflective of our referral base and inclusion criteria. The surgery rate is also high at 66%, consistent with finding frequent patients in whom only one investigation yields a positive result. The following case illustrates such a patient. A slim 45-year-old lady with PA and failed ONDST had inconclusive AVS (selectivity index in right adrenal vein 2.6). PET-CT revealed a 29mm metomidate-avid left adrenal nodule (SUVmax ratio 1.52, &gt;1.25 suggestive of unilateral disease). Left adrenalectomy was recommended based on PET-CT, and achieved biochemical and clinical cure. However she required hydrocortisone replacement for 14 months. Her relatively low right adrenal vein cortisol, despite successful cannulation, was attributed to contralateral suppression by co-secretion of cortisol from her adenoma. This was confirmed by finding high CYP11B1 and CYP11B2 mRNA expression in her tumour, typical of a KCNJ5 mutation, confirmed as L168R on Sanger sequencing.

PA is a high risk subset of hypertension. Under-treatment has serious public health consequences. 11C-Metomidate PET CT has the potential to simplify the investigation pathway and allow more patients to receive potentially curable treatment.