Several Types of Somatic Mutations Induce Autonomous Production of Aldosterone in Primary Aldosteronism
نویسندگان
چکیده
We detected a low CYP17/HSD3B2 ratio in APA tissue, indicating that the cortisol pathway is suppressed in APA and also observed a high CYP11B2/CYP11B1 ratio in APA tissue, suggesting that the aldosterone pathway is accelerated in APA [8]. Furthermore, we reported that there were no KCNJ5 gene mutations in the normal tissue adhering to KCNJ5 gene mutationharboring APA, suggesting that somatic mutations of the KCNJ5 gene only occur in APA tissue [9]. On the other hand, we had clearly demonstrated that APA cells produce markedly less cortisol than normal adrenal cells, and it is suggested that KCNJ5 gene mutations dominantly induce the aldosterone production pathway as well as a concomitant decline in cortisol production, resulting in highly autonomous aldosterone production [9]. It is possible to consider that accelerated aldosterone production in APA is caused mainly by channelopathies, as reported by Gomez-Sanchez CE [4]. Those channelopathies may increase calcium entry inside adrenal cells, activating Ca-dependent intracellular signaling systems related to regulating aldosterone synthesis. Then we have questions how to treat the patients with PA possessing those channelopathies, to do surgery or not? We should perform adrenal vein sampling (AVS) before surgical treatment because of precise detection of unilateral adrenal lesions, while AVS cannot always be done for all patients with PA because of inadequate numbers of AVS-radiologists. Is it possible to use calcium channel blockade for medical treatment? Moreover, selective CYP11B2 inhibitors have recently been reported, which could be promising drug candidates for the treatment of aldosterone related diseases [10-12]. Then, new treatment, such as local injection of specific CYP11B2 inhibitors should also be considered for adrenal lesions that cause hyperaldosteronism. Moreover, we should precisely evaluate the long-term efficacy of MR antagonists for hyperaldosteronism[13].
منابع مشابه
Role for germline mutations and a rare coding single nucleotide polymorphism within the KCNJ5 potassium channel in a large cohort of sporadic cases of primary aldosteronism.
Primary aldosteronism (autonomous aldosterone production with suppressed renin) plays an important pathophysiological role in what has been previously labeled as essential hypertension. 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-prod...
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