Endocrine Abstracts

Primary aldosteronism (PA) is considered the sole, often curable, cause of hypertension in 5–10% of patients. Yet there has been only one RCT, and practice has changed little since the advent of CT scanning. Adrenal vein sampling (AVS) and adrenalectomy remain the standard, invasive interventions, leading to a 50% reduction in pill count as the average clinical improvement.

Study Design

In MATCH (Is Metomidate PET-CT superior to Adrenal vein sampling in predicting ouTCome from adrenalectomy in patients with primary Hyperaldosteronism), 142 patients, mean age 52, 32% female, 32% of African ancestry, 46% hypokalemic, had both AVS and 11C-metomidate PET CT (MTO) in random order, and were referred for surgery if aldosterone/cortisol ratio differed >4-fold between adequately cannulated adrenal veins, and/or SUVmax on MTO was >1.25x higher, in a definite tumour, than the opposite adrenal. The primary outcome is the proportion of patients in whom adrenalectomy achieved complete or partial biochemical or clinical cure, analysed hierarchically using PASO criteria.¹ Anticipating ~50% incidence of unilateral PA, MATCH is powered to detect 25% superiority of MTO vs AVS, or non-inferiority at a lower-bound CI of -17%. Secondary outcomes include non-randomised comparison of outcomes between unilateral and bilateral PA; prediction of clinical outcome from home BP readings before and after starting spironolactone 100mg daily for 4 weeks; quality-of-life assessments; and analyses, by RNAseq, of genotype and transcriptomes of tumors, correlated with ethnicity and outcomes.

Results

The analysis set is 75 patients who, on 31st Dec 2020, had undergone adrenalectomy with >6 months follow-up. 67 patients (89%) had complete biochemical cure following PASO criteria, ¹ and 63 (84%) had complete or partial clinical cure. In 39/75 surgical patients, only one of MTO or AVS was scored as high-probability using criteria above. This score was confirmed at the multi-centre, MDT meeting which reviewed all MTO scans without knowledge of AVS. The primary analysis compared accuracy of MTO and AVS by McNemar test. The 39 discordant results were allocated as a win to the positive investigation if the patient was cured, or to the negative investigation, if not cured. 50/56 CYP11B2-positive tumors had a known mutation; the frequency was CACNA1D>KCNJ5>ATP1A1>ATP2B3>CTNNB1>GNAQ>CLCN2, differing between patients whose hypertension was completely or partially cured. Two other tumors had novel gene mutations. Several RNAseq transcripts varied with genotype and outcome, including some encoding measurable, secreted proteins.

Full primary and secondary outcomes will be presented.

Reference

1. Williams TA, et al. Lancet Diabetes Endocrinol. 2017; 5:689–699.