OR02-02 Pre-operative Blood Pressure Response To Aldosterone Antagonists And Urinary Hybrid Steroid Ratios Predict Clinical Outcomes In Unilateral Primary Aldosteronism For At Least 2 Years Post-adrenalectomy

Abstract Disclosure: X. Wu: None. E. Goodchild: None. R. Senanayake: None. W. Bashari: None. J. Salsbury: None. C.P. Cabrera: None. G. Argentesi: None. S.M. O’Toole: None. J. McFarlane: None. M. Matson: None. L. Parvanta: None. N. Hilliard: None. V. Kosmoliaptsis: None. A. Marker: None. D.M. Berney: None. W. Tan: None. R. Foo: None. C.A. Mein: None. E. Wozniak: None. A. Sahdev: None. N. Bird: None. K. Laycock: None. E. Adeyeye: None. A. Dawnay: None. D. Gillett: None. A. Prete: None. A.E. Taylor: None. W. Arlt: None. A.N. Bhuva: None. C. Manisty: None. K.J. Cruickshank: None. H. Cheow: None. G. Mark: None. W. Drake: None. M.J. Brown: None. Introduction: A recent prospective, within-patient study (MATCH) demonstrated 11C-metomidate PET-CT is non-inferior to Adrenal Vein Sampling in accurately detecting unilateral Primary Aldosteronism (PA)1. At 6 months post-adrenalectomy 79.5% and 28.2% of patients achieved, respectively, partial/complete or complete clinical success (by PASO consensus). These outcomes reiterate the need for careful selection of patients for surgery, especially when a widely available non-invasive test could increase, by many-fold, the number of patients diagnosed with unilateral PA. In MATCH, age, sex, genotype of tumour and systolic blood pressure (SBP) response (reduction to <135 mmHg) after 4 weeks of Spironolactone therapy all predicted clinical success at 6 month-adrenalectomy. Aims and Methods: To determine whether these short-term clinical outcomes and the above predictors of success are sustained at 2-year follow-up; and establish whether baseline urinary hybrid steroid (18-OH cortisol/cortisol) ratio could assist clinical decision making by providing surrogate evidence of genotype and probability of clinical success. We report outcomes for all patients who had undergone adrenalectomy with ­­>2-year follow-up on 20th December 2022, including all 78/142 surgical patients in the original study, in addition to 18/40 in the study extension. Results: Partial/complete or complete clinical success were achieved in 78/96 (81%) and 24/96 (25%) of patients respectively. The mean defined daily dose of antihypertensives at 2 years was 1.32 (SD 1.76), comparable to 1.34 (1.90) at 6 months, and significantly lower than at baseline: 3.86 (2.47), t = 7.70, p = 0.0001. Younger age and female sex were associated with higher likelihood of complete clinical success (Fisher’s Exact test p = 0.0084 and p = 0.0001 respectively). Pre-operatively, SBP reduction to <135 mmHg after 4 weeks of spironolactone was seen in 10/23 patients and associated with higher likelihood of complete clinical success at 2 years (versus 6/39 complete clinical success in the SBP >135 mmHg group, Fisher’s exact test p = 0.0135). 13/18 (72%) of patients harbouring KCNJ5 mutations achieved complete clinical success at 2 years, compared to 1/20 (5%) with CACNA1D mutations. A baseline hybrid steroid ratio >2 was seen in 13/14 (93%) patients with KCNJ5 mutations. Absence of clinical success in the KCNJ5 cohort was seen in the only patient with a ratio <2. Conclusion: Favorable clinical outcomes seen at 6 months post-adrenalectomy were sustained at 2-year follow-up. SBP response to spironolactone and KCNJ5 genotype are both potential predictors of ongoing clinical success at 2 years. The presence of high urinary hybrid steroid ratios in patients with KCNJ5 mutations could highlight, pre-operatively, those likely to derive the most clinical benefit from surgery. 1. Nature Medicine, in press, https://doi.org/10.1038/s41591-022-02114-5 Presentation: Thursday, June 15, 2023