Objective  To investigate the clinical characteristics of biochemically negative pheochromocytoma and paraganglioma (PPGL) and to identify risk factors associated with intraoperative hemodynamics instability (IHI), providing guidance for diagnosis and perioperative management.

Methods  A retrospective analysis was conducted on 181 PPGL patients who underwent surgical resection and were pathologically confirmed at Henan University People’s Hospital between December 2016 and November 2023. Patients were divided into a biochemically negative group (n = 52) and a biochemically positive group (n = 129) based on plasma free metanephrine (MN) and normetanephrine (NMN) levels. Clinical features, laboratory data, imaging findings, preoperative preparation, and intraoperative hemodynamic changes were compared between groups. Logistic regression analysis was performed to identify risk factors for IHI among the biochemically negative subgroup.

Results  The weight, duration of onset and incidence of shock in the biochemical negative group were higher than those in the biochemical positive group, while the prevalence of diabetes, systolic blood pressure and heart rate were lower than those in the biochemical positive group (all P＜0.05). Biochemically negative patients exhibited lower serum calcium, renin activity, and cortisol levels, whereas the aldosterone-to-renin ratio was higher (all P＜0.05). Functional imaging positivity was significantly lower in the negative group (63.6% vs 100%, P = 0.008), and the maximal tumor diameter was smaller. Although the overall incidence of IHI was low in the biochemical negative group (23.4% vs 42.1%, χ² = 4.778, P = 0.029), there were still some patients with significant hemodynamic fluctuations. Univariate logistic regression analysis showed that fasting glucose (OR = 1.961, 95%CI: 1.128 to 3.410), elevated fasting glucose (OR = 6.125, 95%CI: 1.425 to 26.328), and tumor diameter ＞4 cm (OR = 7.071, 95%CI: 1.328 to 37.651) were significantly associated with IHI.

Conclusions  Biochemically negative PPGL presents with relatively subtle clinical and imaging features. These patients remain at risk for IHI. Tumor diameter ＞4 cm, elevated fasting blood glucose were associated with IHI. Therefore, enhanced risk assessment and management should be implemented during the perioperative period.