KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas [Rapid Communication]

Yamada, Masanobu; Nakajima, Yasuyo; Taguchi, Ryo; Okamura, Takashi; Ishii, Sumiyasu; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Yoshino, Satoshi; Toki, Akiko; Ishida, Emi; Hashimoto, Kazuhito; Satoh, Tetsurou; Mori, Masataka

doi:10.1507/endocrj.ej12-0247

Cited by 40 publications

(32 citation statements)

References 26 publications

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“…Boulkroun et al, who examined the large number of APA cases to date, 380, found that 129 patients (34%) had mutations in Europe [9]. We found a higher frequency, 24 out of 33 (approximately 73%) APAs, in Japan [7,[11][12][13]. Several differences of clinical features have been reported between Japanese and Western APA patients.…”

Section: Immunohistochemistrysupporting

confidence: 56%

“…Several investigators including us have since confirmed these mutations in different countries [8,9,[11][12][13]22 [32]. Therefore, the overall prevalence of KCNJ5 mutations in APAs in Western countries is approximately 35~45%.…”

Section: Discussionmentioning

confidence: 84%

“…Thirty-three patients had been included in our previous study [7,[11][12][13]. Each subject was given written informed consent, and the study was approved by the Ethics Committee on human research of Gunma University.…”

Section: Subjectsmentioning

confidence: 99%

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Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

et al. 2017

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PRIMARY ALDOSTERONISM (PA) has been reported to affect at least 6~10% of patients with essential hypertension [1][2][3][4][5] and is caused mostly by an adrenal adenoma (aldosterone-producing adenoma, APA) or by adrenal hyperplasia (idiopathic hyperaldosteronism, IHA). Although the tumorigenesis of APA remained unclear, somatic mutations of the potassium Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations Abstract. Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e. they had a high frequency of KCNJ5 mutations and exhibited a frequent association with cortisol cosecretion. Therefore, APAs among Japanese patients may have different features from those in Western countries. We added recent cases, examined 47 cases (43% male) of APAs, including clinicopathological features, KCNJ5 mutations, and the mRNA levels of several steroidogenic enzymes, and compared the results obtained to those reported in other countries. While the prevalence of KCNJ5 mutations is approximately 40% in Western countries, 37 APA cases (78.7%) showed mutations: 26 with p.G151R and 11 with p.L168R. Although a significant gender difference has been reported in the frequency of KCNJ5 mutations in Europe, we did not find any gender difference. However, the phenotypes of Japanese patients with mutations were similar to those of patients in Western countries; patients were younger and had higher plasma aldosterone levels, lower potassium levels, and higher diastolic blood pressure. Reflecting these phenotypes, APAs with mutations had higher CYP11B2 mRNA levels. However, in contrast to APAs in Western countries, Japanese APAs with mutations showed lower CYP11B1, CYP17A1, and CYP11A1 mRNA levels. These findings demonstrated that Japanese APA patients may have distinct features including a higher prevalence of KCNJ5 mutations, no gender difference in the frequency of these mutations, and characteristics similar to the zona glomerulosa.

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Section: Immunohistochemistrysupporting

confidence: 56%

Section: Discussionmentioning

confidence: 84%

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Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

et al. 2017

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“…As seen in tumors showing subclinical Cushing's syndrome, urine cortisol levels of these 11 patients were within the normal range or slightly high, but below 150 µg/day. We examined the mutation of the PRKACA gene in all of the 33 APAs, but there were no such mutations in tumors showing We previously reported that some APAs showing clear autonomous cortisol secretion had mutation of the KCNJ5 gene, suggesting that these tumors had the same features as APAs not co-secreting cortisol [13]. In a previous study, we defined the patients with all of the following criteria as having "clear cortisol secretion": 1) low ACTH level <10 pg/mL, 2) suppressed accumulation of adosterol in scintigraphy on the intact side of the adrenal gland, and 3) post-adrenal insufficiency [13].…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported high prevalence of somatic mutation in a potassium channel gene, KCNJ5, of approximately 70%, in Japanese patients with adrenal aldosterone-producing adenomas (APAs) and some APAs co-secreting cortisol [12,13]. In contrast, in Western countries, the prevalence of the mutations has been reported to be approximately 35-40% of APAs, and cases of APAs co-secreting cortisol have rarely been reported [14].…”

Section: Pcr-rflp Assaymentioning

confidence: 99%

Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (<i>PRKACA</i>) gene in Japanese patients with several adrenal adenomas secreting cortisol [Rapid Communication]

et al. 2014

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Primary Aldosteronism: Molecular Mechanisms and Diagnosis

Rossi

Lenzini

2014

Primary Aldosteronism

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Primary aldosteronism (PA) is the most common endocrine form of high blood pressure (BP) and causes excessive organ damage to the heart, vessels, and kidneys, which translates into an excess of cardiovascular events.When the diagnosis is made early on and an appropriate therapy is timely instituted, the hyperaldosteronism and the hypokalemia can be cured in practically all the cases, while the arterial hypertension is cured in about 40 % of the cases and BP control markedly ameliorated in the rest. Thus, an aggressive diagnostic approach in hypertensive patients is justifi ed.The recent discoveries with molecular biology techniques have led to the identifi cation of some mechanisms that can explain the persistent hyperaldosteronism in spite of the high BP, the hypokalemia, and the suppression of renin, all factors that would be expected to shut down aldosterone secretion.The purpose of this chapter is to provide updated information on molecular genetics of PA and the diagnostic strategy for case detection and subtype differentiation of PA. While a cost effective strategy for the screening of patients with PA can be exploited at most centers, the identifi cation of its subtypes involves adrenal vein sampling, which is a procedure technically diffi cult to perform and interpret. Therefore, it should be undertaken at tertiary referral centers with experience in performing and interpreting this test.

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KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas [Rapid Communication]

Cited by 40 publications

References 26 publications

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (<i>PRKACA</i>) gene in Japanese patients with several adrenal adenomas secreting cortisol [Rapid Communication]

Primary Aldosteronism: Molecular Mechanisms and Diagnosis

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