Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Curr Opin Nephrol Hypertens. 2019 Mar;28(2):105-112. doi: 10.1097/MNH.0000000000000487.
Immunohistochemistry for aldosterone synthase (CYP11B2) has markedly provided a comprehensive picture of the adrenocortical diseases, particularly primary aldosteronism. The findings from CYP11B2-immunohistochemistry are consistent with the clinical courses of most patients with primary aldosteronism. We herein review the updated pathophysiology and usefulness of the method for understanding individual patients with different subtypes of primary aldosteronism.
After our discovery of aldosterone-producing cell clusters (APCCs) using the immunohistochemistry for CYP11B2, we found possible APCC-to-APA transitional lesions (pAATLs) in a few cases that had been hitherto classified as unilateral hyperplasia or multiple nodules. On the basis of morphological and functional features of pAATLs as well as distributions of somatic mutations within the lesions, we have made a hypothesis that APCC grows to APA via pAATL for one of developmental courses of APA. Recently, we successfully performed in-situ detection of aldosterone on adrenal tissue sections using a state-of-the-art technique, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-imaging). This method revealed in-situ synthesis of aldosterone in APCCs and APAs in addition to several other steroids.
CYP11B2 immunohistochemistry revealed the pathophysiology of aldosterone production in the past decade, especially formation of APCC in normal adrenals and pAATL that is a possible lesion developing from APCC to APA. The term 'idiopathic hyperaldosteronism' may soon become obsolete.
醛固酮合酶(CYP11B2)的免疫组织化学分析显著地提供了一个全面的肾上腺皮质疾病的图片,特别是原发性醛固酮增多症。CYP11B2-免疫组织化学的研究结果与大多数原发性醛固酮增多症患者的临床过程一致。本文综述了该方法在理解不同亚型原发性醛固酮增多症患者方面的更新病理生理学和用途。
在用 CYP11B2 免疫组织化学方法发现醛固酮产生细胞簇(APCCs)后,我们在一些先前被归类为单侧增生或多发结节的病例中发现了可能的 APCC 到 APA 的过渡性病变(pAATLs)。基于 pAATLs 的形态和功能特征以及病变内体细胞突变的分布,我们提出了一个假设,即 APCC 通过 pAATL 向 APA 生长,这是 APA 发育过程之一。最近,我们成功地使用一种最先进的技术,基质辅助激光解吸电离成像质谱(MALDI-imaging),对肾上腺组织切片中的醛固酮进行了原位检测。该方法除了几种其他类固醇外,还揭示了 APCCs 和 APAs 中醛固酮的原位合成。
CYP11B2 免疫组织化学在过去十年中揭示了醛固酮产生的病理生理学,特别是在正常肾上腺中形成 APCC 和 pAATL,这可能是 APCC 向 APA 发展的病变。“特发性醛固酮增多症”这个术语可能很快就会过时。