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

Carregando...
Imagem de Miniatura
Citações na Scopus
42
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
ENDOCRINE SOC
Citação
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.104, n.10, p.4695-4702, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
Referências
  1. Adolf C, 2018, J CLIN ENDOCR METAB, V103, P4543, DOI 10.1210/jc.2018-00617
  2. Arlt W, 2017, JCI INSIGHT, V2, DOI 10.1172/jci.insight.93136
  3. Arnesen T, 2013, LANGENBECK ARCH SURG, V398, P869, DOI 10.1007/s00423-013-1093-2
  4. Azizan EAB, 2013, NAT GENET, V45, P1055, DOI 10.1038/ng.2716
  5. Beuschlein F, 2013, NAT GENET, V45, P440, DOI 10.1038/ng.2550
  6. Celen O, 1996, ARCH SURG-CHICAGO, V131, P646
  7. Charmandari E, 2012, J CLIN ENDOCR METAB, V97, pE1532, DOI 10.1210/jc.2012-1334
  8. Choi M, 2011, SCIENCE, V331, P768, DOI 10.1126/science.1198785
  9. Fernandes-Rosa FL, 2014, HYPERTENSION, V64, P354, DOI 10.1161/HYPERTENSIONAHA.114.03419
  10. Funder JW, 2016, J CLIN ENDOCR METAB, V101, P1889, DOI 10.1210/jc.2015-4061
  11. Gerards J, 2019, J CLIN ENDOCR METAB, V104, P3192, DOI 10.1210/jc.2019-00299
  12. Heaton JH, 2012, AM J PATHOL, V181, P1017, DOI 10.1016/j.ajpath.2012.05.026
  13. Ip JCY, 2015, ANZ J SURG, V85, P279, DOI 10.1111/ans.12470
  14. Kitamoto T, 2018, J HYPERTENS, V36, P619, DOI 10.1097/HJH.0000000000001578
  15. Lenzini L, 2015, J CLIN ENDOCR METAB, V100, pE1089, DOI 10.1210/jc.2015-2149
  16. Lim V, 2014, J CLIN ENDOCR METAB, V99, P2712, DOI 10.1210/jc.2013-4146
  17. Malachias MVB, 2016, ARQ BRAS CARDIOL, V107, P1, DOI [10.5935/abc.20160162, 10.5935/abc.20160140]
  18. Meyer A, 2005, WORLD J SURG, V29, P155, DOI 10.1007/s00268-004-7496-z
  19. Milliez P, 2005, J AM COLL CARDIOL, V45, P1243, DOI 10.1016/j.jacc.2005.01.015
  20. Monticone S, 2018, LANCET DIABETES ENDO, V6, P41, DOI 10.1016/S2213-8587(17)30319-4
  21. Nanba K, 2019, HYPERTENSION, V73, P885, DOI 10.1161/HYPERTENSIONAHA.118.12070
  22. Nanba K, 2018, J CLIN ENDOCR METAB, V103, P3869, DOI 10.1210/jc.2018-01004
  23. Nanba K, 2012, J CLIN ENDOCR METAB, V97, P1688, DOI 10.1210/jc.2011-2504
  24. Okamura T, 2017, ENDOCR J, V64, P39, DOI 10.1507/endocrj.EJ16-0243
  25. Rossi GP, 2008, HYPERTENSION, V51, P1366, DOI 10.1161/HYPERTENSIONAHA.108.111369
  26. Rossi GP, 2006, J AM COLL CARDIOL, V48, P2293, DOI 10.1016/j.jacc.2006.07.059
  27. Rossi GP, 2013, HYPERTENSION, V62, P62, DOI 10.1161/HYPERTENSIONAHA.113.01316
  28. Savard S, 2013, HYPERTENSION, V62, P331, DOI 10.1161/HYPERTENSIONAHA.113.01060
  29. Sawka AM, 2001, ANN INTERN MED, V135, P258, DOI 10.7326/0003-4819-135-4-200108210-00010
  30. Scholl UI, 2013, NAT GENET, V45, P1050, DOI 10.1038/ng.2695
  31. STREETEN DHP, 1990, AM J HYPERTENS, V3, P360, DOI 10.1093/ajh/3.5.360
  32. Sukor N, 2010, J CLIN ENDOCR METAB, V95, P1360, DOI 10.1210/jc.2009-1763
  33. Tang L, 2018, INT J ENDOCRINOL, DOI 10.1155/2018/4920841
  34. Teo AED, 2015, NEW ENGL J MED, V373, P1429, DOI 10.1056/NEJMoa1504869
  35. Vilela LAP, 2017, ARCH ENDOCRIN METAB, V61, P305, DOI 10.1590/2359-3997000000274
  36. Williams B, 2018, EUR HEART J, V39, P3021, DOI 10.1093/eurheartj/ehy339
  37. Williams TA, 2017, LANCET DIABETES ENDO, V5, P689, DOI 10.1016/S2213-8587(17)30135-3
  38. Wu VC, 2017, SCI REP-UK, V7, DOI 10.1038/srep39121