KCNJ5 Somatic Mutation is a Predictor of Hypertension Remission after Adrenalectomy for Unilateral Primary Aldosteronism.

CONTEXT Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140x90 mmHg without anti-hypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear. OBJECTIVE To determine clinical and molecular features associated with HT remission after adrenalectomy in unilateral PA patients. METHODS We retrospectively evaluated 100 PA patients (60 women; median age at diagnosis 48 yr) with a median follow-up of 26 m. Anatomopathological analysis revealed 90 APAs, one carcinoma and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases. RESULTS KCNJ5 mutations were identified in 33 out of 76 (43.4%) tumors: p.Gly151Arg (n= 17), p.Leu168Arg (n= 15) and p.Glu145Gln (n= 1). HT remission was reported in 37 out of 100 (37%) patients. Among patients with HT remission, 73% were women (p= 0.04), 48.6% used <3 antihypertensive medications (p= 0.0001) and 64.9% had HT duration <10 yrs (p= 0.0015) when compared to those without HT remission. Somatic KCNJ5 mutations were associated with female gender (p= 0.004), larger nodules (p= 0.001) and HT remission (p= 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (p= 0.004). CONCLUSION The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.