背景:已观察到体细胞突变可诱导产生醛固酮的腺瘤(APAs)。这些可能在怀孕期间加速。体细胞PRKACA突变在产生皮质醇的腺瘤(CPAs)中很常见。然而,他们在APA中的作用,特别是醛固酮和皮质醇产生腺瘤(A/CPAs),不是很了解。本研究旨在探讨PRKACA突变与妊娠期间A/CPA加速发育之间的关系。
方法:一名原发性醛固酮增多症(PA)合并严重库欣综合征(CS)的患者在分娩后一年接受肾上腺肿瘤手术切除。病理检查显示,肾上腺皮质腺瘤的特征主要是肾小球带增生。体细胞突变分析显示存在体细胞PRKACA突变,它被各种计算数据库验证为有害突变。免疫组织化学结果显示细胞色素P450家族11亚家族B成员1(CYP11B1)染色呈阳性,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)。我们的研究包括20例先前记录的醛固酮和皮质醇产生腺瘤(A/CPAs)病例的回顾,其中2例CYP11B1和CYP11B2同时呈阳性,与我们的发现一致.
结论:PRKACA的体细胞突变可能与LHCGR的上调有关,协同驱动共同分泌肿瘤在怀孕期间加速生长,从而加剧疾病进展。
BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.