KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism

Author(s):Show less -

Vilela, Leticia A. P. ^[1] ; Rassi-Cruz, Marcela ^[1] ; Guimaraes, Augusto G. ^[1] ; Moises, Caio C. S. ^[1] ; Freitas, Thais C. ^[1] ; Alencar, Natalia P. ^[1] ; Petenuci, Janaina ^[1] ; Goldbaum, Tatiana S. ^[1] ; Maciel, Ana Alice W. ^[1] ; Pereira, Maria Adelaide A. ^[1] ; Silva, V, Giovanio ; Pio-Abreu, Andrea ^[2] ; Zerbini, Maria Claudia N. ^[3] ; Cavalcante, Aline C. B. S. ^[4] ; Carnevale, Francisco C. ^[4] ; Pilan, Bruna ^[4] ; Yamauchi, Fernando ^[4] ; Srougi, Vitor ^[5] ; Tanno, Fabio Y. ^[5] ; Chambo, Jose L. ^[5] ; Latronico, Ana Claudia ^[1] ; Mendonca, Berenice B. ^[1] ; Fragoso, V, Maria Candida B. ; Bortolotto, Luiz A. ^[6] ; Drager, Luciano F. ^{[6, 2]} ; Almeida, Madson Q. ^{[7, 8]}

Affiliation

^[1] Univ Sao Paulo, Serv Endocrinol & Metabol, Lab Hormonios & Genet Mol LIM 42, Unidade Suprarrenal, Hosp Clin, Fac Med, BR-05403900 Sao Paulo - Brazil

^[2] Silva, Giovanio, V, Univ Sao Paulo, Hosp Clin, Unidade Hipertensao Disciplina Nefrol, Fac Med, BR-01246000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Div Anat Patol, BR-05403900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Hosp Clin, Inst Radiol InRad, Fac Med, BR-05402000 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Hosp Clin, Fac Med, Servi Urol, BR-05402000 Sao Paulo - Brazil

^[6] Univ Sao Paulo, Inst Cora InCor, Fac Med, Unidade Hipertensao, BR-05402000 Sao Paulo - Brazil

^[7] Fragoso, Maria Candida B., V, Univ Sao Paulo, Serv Endocrinol & Metabol, Lab Hormonios & Genet Mol LIM 42, Unidade Suprarrenal, Hosp Clin, Fac Med, BR-05403900 Sao Paulo - Brazil

^[8] Fragoso, Maria Candida B., V, Univ Sao Paulo, ICESP, Serv Endocrinol, Fac Med, BR-05403010 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 104, n. 10, p. 4695-4702, OCT 2019.
• Web of Science Citations: 0

Abstract

Context: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive 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 patients with unilateral PA. Methods: We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 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 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.GIu145GIn (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P= 0.0001), and 64.9% had HT duration <10 years (P= 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (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. (AU)

• FAPESP's process: 15/17049-8 - Genetic investigation of aldosterone-producing adrenocortical tumors by next generation sequencing
• Grantee: Madson Queiroz Almeida
• Support type: Regular Research Grants