SOMATIC MUTATIONS IN THE KCNJ5 GENE AFFECT CARDIAC REMODELING AND REGRESSION OF LEFT VENTRICULAR HYPERTROPHY INPRIMARY ALDOSTERONISM DUE TO ALDOSTERONE-PRODUCING ADENOMA

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 53-73-Primary Aldosteronism & Mineralocorticoid Excess
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-55
Gian Paolo Rossi*1, Teresa M. Seccia1, Claudio Letizia2, Maria Verena Cicala1, Laura Zinnamosca2, Maniselvan Kuppusamy1, Maurizio Cesari1, Susanna Sciomer3, Maurizio Iacobone1, Franco Mantero1 and Achille C. Pessina1
1University of Padova, Padova, Italy, 2University 'La Sapienza', Rome, Italy, 3University 'La Sapienza', Italy
Context. Considering the detrimental cardiovascular (CV) effects of aldosterone, APA patients carrying somatic mutations in the  selectivity filter of KCNJ5 K+ channel, which were found to be associated with higher plasma aldosterone secretion from aldosterone producing adenomas (APA), might develop a more prominent CV damage than those without such mutations.

Objective. To test this hypothesis we compared the echocardiographic changes between APA patients with(mutAPA) and without (wtAPA) the G151R, G151E, L168R, and T158A mutations.

Design. From a cohort of 250 consecutive PA patients, we identified 170 patients who had an unequivocal diagnosis of APA by the four corners criteria, and high-quality echocardiographic data.  Of them 106 who had comprehensive clinical and KCNJ5 sequencing information and outcome data at long-term follow-up, were analyzed using the rest as controls.

Results. The KCNJ5 mutations were about two-fold more prevalent in women than in men and overall involved 18.8% of the APA.  At baseline the mutAPA patients were similar to the wtAPA patients for systolic and diastolic blood pressure and need for antihypertensive medications, in spite of higher plasma aldosterone (PAC,70.0 (41.9 -98.1) ng/dl vs 44.5 (38.2 - 50.7), p< 0.0001), aldosterone-renin-ratio (ARR, 513 (381 - 1571)ng/dl/ng/ml/h vs 169 (72 - 266), p< 0.0001), and left ventricular mass index (LVMI, 60±7.4 mg/h2.7vs 49±3.6, p=0.004).

At long-term follow-up after adrenalectomy the mutAPA showed a greater fall of LVMI than the wtAPA (14.9±3.9 mg/m2vs 6.4±1.2, p=0.007), despite a similar fall of BP and a similar  normalization of PAC and ARR.

Conclusions. In APA patients the occurrence of the somatic KCNJ5 mutations implies higher PAC, ARR, and LVMI, and a greater decrease of LVMI after adrenalectomy than in the wild type APA patients. However, the presence of these mutations did not compromise the chances of being cured from the hyperaldosteronism and the high blood pressure.

Nothing to Disclose: GPR, TMS, CL, MVC, LZ, MK, MC, SS, MI, FM, ACP

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm