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.

Purpose No conclusion exists for the optimum duration of preoperative administration of doxazosin (DOX) before adrenalectomy for pheochromocytoma. The purpose of this study is to investigate whether perioperative hemodynamics and postoperative outcomes are related to the duration of DOX administration. Methods In total, 132 patients managed preoperatively with single α-receptor blocker DOX were enrolled. All patients underwent adrenalectomy for pheochromocytoma in the Department of Urology, Peking University First Hospital, between January 2001 and July 2019. Patients were divided into three groups based on the duration of preoperative administration of DOX: group A (≤14 days), group B (15–30 days), and group C (>30 days). Patient and tumor characteristics, intraoperative hemodynamics, and postoperative outcomes were recorded and compared. Results These patients included 57 men and 75 women, with an average age of 48 years. Clinical characteristics, preoperative hemodynamics, medicine management and surgical approaches were comparable between the three groups. Among the three groups, we found that group C (>30 days) had the lowest intraoperative minimum heart rate [group A vs. group B vs. group C = 60 (52–67) vs. 59 (50–61) vs. 51.5 (50–58.75), p = 0.024] and highest risk of postoperative hypotension requiring vasopressor support [group A vs. group B vs. group C = 14 (20.3%) vs. 12 (27.9%) vs. 10 (50.0%), p = 0.032]. Conclusion The current study indicated that preoperative management of pheochromocytoma with single α-receptor blocker DOX for more than 30 days after final dose adjustment might lead to intraoperative bradycardia and more postoperative hypotension requiring vasopressor support. Thus, our study does not support long-term (over 30 days) preoperative administration of pheochromocytoma with single α-receptor blocker DOX in the final dose.