CONTEXT: Somatic mutations in the selectivity filter of KCNJ5 K(+) channel were found to be associated with higher plasma aldosterone concentrations in the patients with an aldosterone-producing adenoma (APA). OBJECTIVE: We investigated whether plasma aldosterone levels and the lateralization index are higher from the side with the APA with the mutation, as compared with those without the mutation. DESIGN: From 170 consecutive APA patients with comprehensive clinical and KCNJ5 data and a conclusive diagnosis, we recruited 91 patients with adrenal vein sampling and follow-up data. We measured CYP11B1 and CYP11B2 mRNA in APA tissue and plasma aldosterone (PAC) and plasma cortisol concentrations (PCC) in adrenal vein blood. To determine whether KCNJ5 mutations affected aldosterone output from the APA, we calculated the lateralization index (defined as the ratio of PAC to PCC at the APA side over the PAC to PCC ratio at the contralateral side). We also calculated two indexes of the aldosterone production from the APA side and the contralateral suppression index. RESULTS: The mRNA content of CYP11B2, but not of CYP11B1, and, accordingly, the lateralization index was higher (29.9 ± 7.4 vs. 10.3 ± 3.6, P < 0.02) in the APA with the mutation than in the APA without the mutation. CONCLUSIONS: APA patients with the somatic KCNJ5 mutations showed a higher production of aldosterone than those without such mutations, which translates in a higher lateralization index. Thus, they are more likely to be identified at adrenal vein sampling and therefore to receive adrenalectomy.
CONTEXT: Somatic mutations in the selectivity filter of KCNJ5 K(+) channel were found to be associated with higher plasma aldosterone concentrations in the patients with an aldosterone-producing adenoma (APA). OBJECTIVE: We investigated whether plasma aldosterone levels and the lateralization index are higher from the side with the APA with the mutation, as compared with those without the mutation. DESIGN: From 170 consecutive APA patients with comprehensive clinical and KCNJ5 data and a conclusive diagnosis, we recruited 91 patients with adrenal vein sampling and follow-up data. We measured CYP11B1 and CYP11B2 mRNA in APA tissue and plasma aldosterone (PAC) and plasma cortisol concentrations (PCC) in adrenal vein blood. To determine whether KCNJ5 mutations affected aldosterone output from the APA, we calculated the lateralization index (defined as the ratio of PAC to PCC at the APA side over the PAC to PCC ratio at the contralateral side). We also calculated two indexes of the aldosterone production from the APA side and the contralateral suppression index. RESULTS: The mRNA content of CYP11B2, but not of CYP11B1, and, accordingly, the lateralization index was higher (29.9 ± 7.4 vs. 10.3 ± 3.6, P < 0.02) in the APA with the mutation than in the APA without the mutation. CONCLUSIONS: APA patients with the somatic KCNJ5 mutations showed a higher production of aldosterone than those without such mutations, which translates in a higher lateralization index. Thus, they are more likely to be identified at adrenal vein sampling and therefore to receive adrenalectomy.
Authors: A Ram Hong; Jung Hee Kim; Young Shin Song; Kyu Eun Lee; Soo Hyun Seo; Moon-Woo Seong; Chan Soo Shin; Sang Wan Kim; Seong Yeon Kim Journal: PLoS One Date: 2016-01-25 Impact factor: 3.240