OR04-6 Predictors of Clinical Outcome after Adrenalectomy for Unilateral Primary Aldosteronism

Abstract

Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT) with an estimated prevalence of 10% in referred populations and 15-20% in patients with resistant hypertension. The most common cause of unilateral PA is aldosterone-producing adenomas (APAs). HT and hypokalemia improve in nearly 100% of patients with unilateral PA after unilateral adrenalectomy. However, complete clinical success (defined as blood pressure ≤130x80 mmHg without anti-hypertensive drugs) has been reported in about 50% (range, 35-80%) of patients with unilateral PA after surgery. HT duration and severity have been associated with clinical outcome after adrenalectomy, but few reports with a limited number of cases evaluated the prognostic role of somatic KCNJ5 mutations. In this study, our aim was to determine clinical and molecular features associated with complete clinical success after unilateral adrenalectomy in unilateral PA patients. We retrospectively evaluated 103 PA patients (42 males; median age 49 yrs, 20-74) with a median follow-up of 25 months. Hypokalemia was present in 78% of the cases. Anatomopathological analysis revealed 94 APAs and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 mutations were identified in 27 out of 67 (40%) tumors: p.Gly151Arg (n= 13), p.Leu168Arg (n= 13) and p.Glu145Gln (n= 1). Complete clinical success was reported in 32 out of 103 (31%) patients. In univariate analysis, HT duration, body mass index (BMI kg/m2), female sex and somatic KCNJ5mutations were associated with HT resolution after adrenalectomy. Complete clinical success was reported in 50% of patients with HT duration ≤5 yrs (vs. 24% with HT duration >5 yrs; p= 0.011), in 40% of patients with BMI <25 (vs. 22% with BMI ≥25; p= 0.042), in 38% of women (vs. 21% of men; p= 0.079) and in 70% of the patients with tumors harboring KCNJ5 somatic mutations (vs. 30% with WT tumors; p= 0.003). According to a stepwise multivariate logistic regression analysis, only the presence of a somatic KCNJ5 mutation was an independent predictor of complete success after adrenalectomy (relative risk 4.8, 95% confidence interval 1.24 to 19.21; p= 0.023). In conclusion, the presence of a somatic KCNJ5 mutation was an independent predictor of complete clinical success after unilateral adrenalectomy in patients with unilateral PA.