KCNJ5 gene somatic mutations affect cardiac remodelling but do not preclude cure of high blood pressure and regression of left ventricular hypertrophy in primary aldosteronism.
OBJECTIVE
Aldosterone exerts detrimental cardiovascular effects, and patients with an aldosterone-producing adenoma (APA) carrying somatic mutations in the KCNJ5 K(+) channel (mutAPA) have higher plasma aldosterone concentration than wild-type APA (wtAPA) patients. We therefore investigated whether mutAPA patients develop a more prominent cardiovascular damage than wtAPA patients.


RESULTS
From 257 consecutive primary aldosteronism patients, we identified 176 who had both a diagnosis of APA by the 'four corners' criteria and high-quality echocardiographic data. Of them, 129 with KCNJ5 sequencing information and long-term follow-up data were compared for echocardiographic changes according to presence (mutAPA, 26%) or absence (wtAPA, 74%) of the KCNJ5 mutations. At baseline, the mutAPA were similar to the wtAPA for blood pressure (BP) and need for antihypertensive medications. However, they had higher left ventricular mass index (59 ± 19 vs. 51 ± 13 g/h(2.7); P < 0.05) and plasma aldosterone concentration [49 (32-68) vs. 36 (25-52) ng/dl); P = 0.048] than the wtAPA patients. In spite of their more prominent cardiac involvement, the mutAPA patients exhibited a fall of BP and plasma aldosterone similar to wtAPA, and a regression of left ventricular mass index.


CONCLUSIONS
Compared to the wild-type APA patients those with KCNJ5 mutations showed more prominent cardiovascular damage. Notwithstanding this, their chances of being cured from the hyperaldosteronism and the high BP, and of regression of left ventricular hypertrophy after adrenalectomy, were not compromised by the presence of these mutations.
aDepartment of Medicine-DIMED, Internal Medicine 4, University of Padua, Padua bInternal Medicine and Medical Specialities, 'La Sapienza' University, Rome cDepartment of Medicine-DIMED, Endocrinology, University of Padua, Padua dDepartment of Cardiovascular and Respiratory Sciences, 'La Sapienza' University, Rome eMinimally Invasive Endocrine Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Gian Paolo
GP
Rossi
Maurizio
M
Cesari
Claudio
C
Letizia
Teresa M
TM
Seccia
Maria Verena
MV
Cicala
Laura
L
Zinnamosca
Maniselvan
M
Kuppusamy
Sara
S
Mareso
Susanna
S
Sciomer
Maurizio
M
Iacobone
Franco
F
Mantero
Achille C
AC
Pessina
D000236:Adenoma / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D000306:Adrenal Cortex Neoplasms / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D000315:Adrenalectomy; D000450:Aldosterone / Q000096:biosynthesis; D005260:Female; D005500:Follow-Up Studies; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics* / Q000502:physiology; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D020257:Ventricular Remodeling / Q000235:genetics* / Q000502:physiology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone