FP40-2 Clinical and histopathological manifestation of KCNJ5 mutations in primary aldosteronism

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP40-Renin-Angiotensin-Aldosterone System/Endocrine Hypertension
Basic/Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:50 AM
Room 135 (Moscone Center)

Poster Board MON-723
Kazutaka Nanba*1, Kuniko Sawai1, Mika Tsuiki1, Aya Tsumagari1, Kanako Nakao1, Takeshi Usui1, Tetsuya Tagami1, Hiroshi Okuno1, Tetsuro Yamamoto2, Kazuto Shigematsu3, Koshiro Nishimoto4, Kuniaki Mukai5, Akira Shimatsu1 and Mitsuhide Naruse1
1National Hospital Organization Kyoto Medical Center, Kyoto, Japan, 2National Hospital Organization Kyoto Medical Center, 3The Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan, 4University of Michigan, MI, 5School of Medicine, Keio University, Tokyo, Japan
Background: Although recent discovery of somatic KCNJ5 mutations in primary aldosteronism (PA) suggests genetic basis for the pathogenesis of the common endocrine hypertension, clinical and histopathological significance of the somatic mutation in PA is not fully established. The aim of the study was to investigate the clinical and histopathological manifestation of the somatic KCNJ5 mutations in various subtypes of PA. Patients and Methods: Forty-four patients with PA who underwent unilateral adrenalectomy were studied. The subtypes of PA diagnosed based on the clinical, histological, and immunohistochemical analyses with anti-CYP11B2 antibodies were as follows: APA (n=26), APA associated with subclinical Cushing’s syndrome (APA+SCS, n=2), aldosterone-producing adrenocortical carcinoma (APC, n=3) and non-APA PA (NAPA, n=13) including multiple aldosterone-producing cell clusters. Results: Somatic KCNJ5 mutation was identified in 35% (9/26) of APA (G151R, n=2; L167F, n=1; L168R, n=5; A172V, n=1), and 100% of APA+SCS (L168R, n=2). L167F and A172V were novel mutations of KCNJ5. In contrast, mutations were not demonstrated in all of the NAPA and APC. Overall prevalence of KCNJ5 mutation in PA was 25% (11/44) in the present study. Prevalence of female, prevalence of hypokalemia, plasma aldosterone concentration (PAC), aldosterone to renin ratio, PAC after cosyntropin stimulation, and tumor size were all significantly higher in PA patents with KCNJ5 mutation than those without mutation (P<0.05). There was no significant difference in age, number of anti-hypertensive drugs, body mass index, serum potassium, and plasma renin activity between patients with and without mutation. In APA, however, prevalence of female was the only difference between patients with and without mutation (78% vs. 18%, P<0.01). Conclusions: The present study clearly suggested that somatic KCNJ5 mutations were exclusively present in APA (+SCS) and significantly involved in the pathogenesis of hyperaldosteronism in the subtype, especially in female patients. Low overall prevalence of the mutation in PA however suggests diverse pathogenesis underlying development of hyperaldosteronism and waits further investigation.

Nothing to Disclose: KN, KS, MT, AT, KN, TU, TT, HO, TY, KS, KN, KM, AS, MN

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