Åkerström Tobias, Klimàcek Branislav, Annebäck Matilda, Norlén Olov, Stålberg Peter
Endocr Connect. 2025 Jun 26;14(6). doi: 10.1530/EC-25-0070. Print 2025 Jun 1.
Primary aldosteronism is the most common endocrine cause of hypertension, affecting 5-10% of hypertensive patients. Determining the source of aldosteronism is necessary for correct diagnosis and further molecular analysis. To investigate the relationship between aldosterone synthase (CYP11B2) expression and aldosterone synthesis, we analysed tissue aldosterone and CYP11B2 expression in different genotypes of unilateral PA disease (uPA). Forty-eight tumour samples from patients with confirmed uPA were included. Intratumoural aldosterone was detectable in most uPA cases and correlated with CYP11B2 protein expression (r 2 = 0.48, P < 0.0001). Aldosterone concentrations were significantly higher in tumours with ATP1A1, ATP2B3 and CACNA1D mutations compared to those with KCNJ5 mutations (P = 0.0001). Using CYP11B2 expression and tissue aldosterone, five tumours were reclassified as non-functional nodules. Furthermore, a second active nodule responsible for the aldosteronism, also carrying a driver mutation, was identified in these patients. These findings show that CYP11B2 expression relates to cell concentrations of aldosterone and may be used to clarify the source of aldosterone secretion. Furthermore, the results corroborate genotype differences between uPA patients.
原发性醛固酮增多症是高血压最常见的内分泌病因，影响5% - 10%的高血压患者。确定醛固酮增多症的病因对于正确诊断和进一步的分子分析至关重要。为了研究醛固酮合酶（CYP11B2）表达与醛固酮合成之间的关系，我们分析了单侧原发性醛固酮增多症（uPA）不同基因型患者组织中的醛固酮和CYP11B2表达。纳入了48例确诊为uPA患者的肿瘤样本。大多数uPA病例的肿瘤内可检测到醛固酮，且与CYP11B2蛋白表达相关（r² = 0.48，P < 0.0001）。与携带KCNJ5突变的肿瘤相比，携带ATP1A1、ATP2B3和CACNA1D突变的肿瘤中醛固酮浓度显著更高（P = 0.0001）。利用CYP11B2表达和组织醛固酮，5个肿瘤被重新分类为无功能结节。此外，在这些患者中还发现了另一个导致醛固酮增多症的活性结节，该结节也携带驱动突变。这些发现表明，CYP11B2表达与醛固酮的细胞浓度相关，可用于明确醛固酮分泌的来源。此外，结果证实了uPA患者之间的基因型差异。
