Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, No.6, Shuangyong Road, Nanning, 530021, P.R. China.
Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, P. R. China.
BMC Endocr Disord. 2024 Jul 16;24(1):116. doi: 10.1186/s12902-024-01645-x.
Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy.
A patient with primary aldosteronism (PA) associated with severe Cushing's syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings.
Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.
体细胞突变已被观察到可诱导醛固酮产生腺瘤（APA）。这些变化可能在怀孕期间加速。皮质醇产生腺瘤（CPA）中常见体细胞 PRKACA 突变。然而，其在 APA 中的作用，特别是在醛固酮和皮质醇产生腺瘤（A/CPA）中的作用尚不清楚。本研究旨在探讨 PRKACA 突变与怀孕期间 A/CPA 加速发展之间的关系。
一名患有原发性醛固酮增多症（PA）合并严重库欣综合征（CS）的患者在分娩一年后接受了肾上腺肿瘤切除术。病理检查显示肾上腺皮质腺瘤，主要表现为球状带增生。体细胞突变分析显示存在体细胞 PRKACA 突变，各种计算数据库验证为有害突变。免疫组化结果显示细胞色素 P450 家族 11 亚家族 B 成员 1（CYP11B1）、细胞色素 P450 家族 11 亚家族 B 成员 2（CYP11B2）和黄体生成素/绒毛膜促性腺激素受体（LHCGR）阳性染色。我们的研究包括对 20 例先前记录的醛固酮和皮质醇产生腺瘤（A/CPA）的病例进行了回顾，其中 2 例同时对 CYP11B1 和 CYP11B2 呈阳性，与我们的发现一致。
PRKACA 中的体细胞突变可能与 LHCGR 的上调相关，这协同驱动了怀孕期间共分泌肿瘤的加速生长，从而加剧了疾病的进展。
