Coexisting Prolactinoma and Primary Aldosteronism: Is There a Pathophysiological Link?
Coexisting Prolactinoma and Primary Aldosteronism: Is There a Pathophysiological Link?
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DOI：
10.1210/jc.2015-2422
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发表时间：
2015-09-01
影响因子：
5.8
通讯作者：
Reincke, Martin
中科院分区：
文献类型：
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作者：
Williams, Tracy Ann;Dietz, Anna S.;Reincke, Martin
背景：催乳素瘤-原发性醛固酮增多症(PA)并存的报道很少见。目的：本研究的目的是确定PRL瘤-PA患者，并验证PRL浓度升高在PA发病中起作用的假设。背景和设计：来自两个转诊中心(德国慕尼黑和意大利都灵)的PA患者和来自一个中心(都灵)的原发性高血压(EH)患者被诊断为高催乳素血症/催乳素瘤。用基因芯片检测PRL受体(PRLR)基因在醛固酮腺瘤和正常肾上腺组织中的表达，并用实时荧光定量聚合酶链式反应(Real-Time-PCR)进行验证。H295R肾上腺细胞与100 nM催乳素孵育，用实时荧光定量聚合酶链式反应检测基因表达水平和醛固酮产量。结果：发现7例催乳素瘤-PA患者：分别来自慕尼黑和都灵PA队列的584例患者中的4例和442例患者中的3例。出现巨大催乳素瘤的人数不成比例(7人中有5人)。在14790例EH队列患者中，有5例有高催乳素血症，没有出现大催乳素瘤。在PA患者与EH患者1：3的病例对照中，270例PA患者中有2例出现高催乳素血症，而EH队列中未发现高催乳素血症(n=810)。与正常肾上腺相比，产生醛固酮的腺瘤中PRLR基因的表达显著上调(分别是基因芯片和实时定量PCR的1.7倍和1.5倍)。在H295R细胞中，PRL处理使细胞色素P11.82的表达和醛固酮的产生增加1.3倍。结论：系统性高催乳素血症引起的PRL升高可能是两者共存的PA的发生发展的原因之一。
Context: Coexisting prolactinoma-primary aldosteronism (PA) is infrequently reported.Objective: The objective of the study was to identify patients with prolactinoma-PA and test the hypothesis that elevated prolactin (PRL) concentrations play a role in PA pathogenesis.Setting and Design: Hyperprolactinemia/prolactinoma was diagnosed in PA patients from two referral centers (Munich, Germany, and Turin, Italy) and in essential hypertensive (EH) patients from one center (Turin). PRL receptor (PRLR) gene expression was determined by microarrays on aldosterone-producing adenomas and normal adrenals and validated by real-time PCR. H295R adrenal cells were incubated with 100 nM PRL, and gene expression levels were determined by real-time PCR and aldosterone production was quantified.Results: Seven patients with prolacti noma-PA were identified: four of 584 and three of 442 patients from the Munich and Turin PA cohorts, respectively. A disproportionate number presented with macroprolactinomas (five of seven). There were five cases of hyperprolactinemia with no cases of macroprolactinoma of 14 790 patients in a general EH cohort. In a population of PA patients case-control matched 1:3 with EH patients there were two cases of hyperprolactinemia of 270 PA patients and no cases in the EH cohort (n = 810). PRLR gene expression was significantly upregulated in the aldosterone-producing adenomas compared with normal adrenals (1.7-fold and 1.5-fold by microarray and real-time PCR, respectively). In H295R cells, PRL treatment resulted in 1.3-fold increases in CYP11.82 expression and aldosterone production.Conclusion: Elevated PRL caused by systemic hyperprolactinemia may contribute to the development of PA in those cases in which the two entities coexist.