目的: 分析散发嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PPGL)患者中血浆游离型甲氧基肾上腺素类物质(metanephrines,MNs)正常者的临床特点,MNs已作为PPGL的首选检测方法在临床中广泛应用,MNs正常的PPGL较少见。方法: 选择2015年3月—2020年1月于北京大学第一医院行泌尿外科手术,病理确诊为PPGL的散发患者共104例,所有患者均有术前血浆游离型MNs检测结果,其中8例(7.69%)MNs正常。回顾MNs正常患者的就诊原因,临床表现,术前检测血浆游离型MNs、3-甲氧基酪胺(3-methoxytyramine, 3-MT)、血儿茶酚胺和嗜铬粒蛋白A(chromograninA, CgA)的结果,影像学表现,术前诊断,术前用药准备,术中血压波动情况及肿瘤组织病理学特点,并与同期MNs升高的PPGL患者相比较。对MNs正常患者进行术后随访。结果: MNs正常的8例PPGL患者中,最常见的临床症状为多汗(3/8)、腰腹痛(3/8)、头痛(2/8)、心悸(2/8)和疲乏(2/8)。对比MNs正常组和升高组患者的其他生化检验结果,血3-MT、儿茶酚胺诊断阳性率组间差异无统计学意义,血浆CgA诊断阳性率在MNs正常组显著下降(2/5 vs.41/43,P=0.005)。两组患者增强CT出现典型表现的比例差异无统计学意义。在8例MNs正常患者中,6例因明确的PPGL既往史,或典型的症状及CT表现,3-MT、CgA升高,PET-CT阳性等原因诊断为PPGL,2例误诊为无功能腺瘤或原发性醛固酮增多症。全部MNs正常患者均应用α受体阻滞剂术前准备,其中1例出现术中平均动脉压<60 mmHg。8例术后随访的中位时间为1.5(0.5~4.5)年,增强CT检查均未见新发肿瘤证据。2例MNs正常患者术后复查3-MT和(或)CgA降至正常。结论: 对于出现PPGL典型症状的肾上腺或腹膜后肿瘤患者及有PPGL既往史患者,MNs检测正常不能作为排除PPGL的充分依据。血3-MT、儿茶酚胺、CgA及影像学检查或对PPGL的诊断有帮助。怀疑MNs正常的PPGL患者推荐应用α受体阻滞剂术前准备,但应避免过量。MNs正常患者的术后随访应重点监测术前阳性的生化指标。

Objective: Plasma free metanephrines (MNs) have been widely used as an initial test for pheochromocytoma and paraganglioma (PPGL). PPGL without MNs elevation has been reported on rare occasions. The objective of this study was to analyze the clinical profile of sporadic PPGL patients with normal MNs. Methods: In the study, 104 patients with sporadic PPGL diagnosed by histopathology in Peking University First Hospital from March 2015 to January 2020 were enrolled. All the patients had plasma MNs result, of whom, eight (7.69%) were with normal MNs. The reasons for their medical visits, clinical manifestations, the levels of plasma free MNs, 3-methoxytyramine (3-MT), catecholamines and chromogranin A (CgA), and the imaging findings were documented. Their preoperative diagnosis, perioperative medical management, and intraoperative blood pressure were analyzed. All the data mentioned above were compared with the MNs elevated group. The postoperative follow-up for MNs normal patients were applied. Results: For the eight PPGL patients with normal plasma MNs, the most common clinical symptoms were sweating (3/8), abdominal and back pain (3/8), headache (2/8), palpitations (2/8), and fatigue (2/8). There were no significant differences in plasma free 3-MT and catecholamines’ diagnostic positive rate between the MNs normal group and MNs elevated group, but the rate for plasma CgA was significantly decreased in the MNs normal group (2/5 vs. 41/43, P=0.005). No significant difference was found for the incidence of typical findings by enhanced CT between the two groups. In these eight MNs normal patients, six were diagnosed with PPGL by the previous history of PPGL, typical symptoms and CT findings, or elevation of 3-MT, CgA levels or positive results of PET-CT; two patients were misdiagnosed as nonfunctioning adenoma or primary aldosteronism. All these MNs normal patients underwent preoperative management with alpha adrenergic receptor blockers, of whom, one had an average intraoperative arterial pressure <60 mmHg during surgery. The median follow-up time for the eight patients was 1.5 (0.5-4.5) years. No evidence of new tumors was found on the enhanced CT scans. Two MNs normal patients’ plasma 3-MT and (or) CgA decreased to normal. Conclusion: For patients with adrenal or retroperitoneal tumors, typical symptoms or a previous history of PPGL, normal plasma MNs is not a sufficient exclusion for PPGL. Plasma 3-MT, catecholamine, CgA results and the imaging findings are helpful for the diagnosis of PPGL. We recommend patients with suspected MNs normal PPGL take alpha adrenergic receptor blockers as preoperative blockade, but should avoid overdose. Postoperative follow-up for patients with normal MNs should focus on the positive biochemical markers before surgery.