The level of KCNJ5 mRNA in cortisol-producing adenomas was approximately 30% of that in APA, and almost no expression was observed in pheochromocytomas.
Besides the recently described germline mutations in the KCNJ5 potassium channel associated with familial primary aldosteronism, somatic mutations in the same channel have been identified within aldosterone-producing adenomas.
In conclusion, the KCNJ5 protein was strongly expressed in the zona glomerulosa of normal adrenal glands but showed variable expression in the aldosterone-producing adenomas with and without mutation.
VDR mRNA levels were positively correlated with those of CYP11B2, CYP17A1 and CYP11B1 in APA tumor tissues and significantly higher in KCNJ5 mutated APAs than wild type.
Important advances made in the past year have included identification of KCNJ5 potassium channel mutations in the pathogenesis of both aldosterone-producing adenomas and familial hyperaldosteronism type III; characterization of phosphodiesterase 11A as a modifier of phenotype in Carney complex caused by protein kinase, cAMP-dependent, regulatory subunit, type-I mutations; the finding of 11β-hydroxysteroid dehydrogenase type I mutations as a novel mechanism for cortisone reductase deficiency; and demonstration of potential mortality benefit in pursuing comprehensive presymptomatic screening for patients with Li-Fraumeni syndrome, including possible reduction in risks associated with adrenocortical carcinoma.
Both KCNJ5 and CACNA1D mutations in familial hyperaldosteronism were only discovered following identification of similar or identical somatic mutations in aldosterone-producing adenomas.
Mutations in the potassium channel gene KCNJ5 are a cause of familial and sporadic forms of primary aldosteronism with around 30-40% of aldosterone-producing adenomas being affected by somatic mutations.
The lateralization index (ratio of aldosterone:cortisol on the side of the adenoma to aldosterone to cortisol on the contralateral side) and the contralateral suppression index (ratio of aldosterone:cortisol on the contralateral side to aldosterone to cortisol in the periphery) were calculated for the KCNJ5-mutated, ATPase-mutated, and the KCNJ5/ATPase mutation-negative APA patients.
Since we recently reported higher prevalence of mutations of the KCNJ5 gene and associations with autonomous cortisol secretion in Japanese aldosterone-producing adenomas than in Western countries, there might be different features of CPAs between Japan and the West.
As a major cause of aldosterone producing adenomas, numerous gain-of-function mutations in the KCNJ5 gene (encoding the K(+) channel subunit GIRK4) have been identified.
Mutations in the KCNJ5 gene, which encodes the inward rectifier K(+) channel 4 (G protein-activated inward rectifier K(+) channel 4, Kir3.4), cause familial hyperaldosteronism type III (FH-III) and are involved in the pathogenesis of sporadic aldosterone-producing adenomas.
In conclusion, somatic KCNJ5 mutations are conspicuously more popular than mutations of other genes in aldosterone-producing adenomas of Chinese patients.
Seven families with familial hyperaldosteronism caused by KCNJ5 germline mutations have so far been described, and multicentre studies have reported KCNJ5 mutations in approximately 40% of sporadic aldosterone-producing adenomas.