Prognostic factors for cardiovascular complications induced by catecholamines in pheochromocytomas and...

Pheochromocytomas and paragangliomas (PPGLs) can trigger major cardiovascular events (MACEs) due to unpredictable release of catecholamines. The aim of this systematic review and meta-analysis was to determine prognostic factors associated with MACEs in PPGLs patients.

A literature search was conducted in PubMed and the Cochrane Library from January 1980 to March 2026. Assessment of clinical, laboratory, imaging, histological, and genetic parameters was performed on the pooled data.

Nine retrospective cohort studies involving 1566 patients with PPGL were included. MACEs were observed in 302 patients [pooled estimate of 21% (95% CI 14-29%)], 95 of those having Takotsubo syndrome [pooled estimate 39% (95% CI 23-54%)]. Tumor necrosis/hemorrhage and diabetes were associated with increased risk of MACEs [71% (95% CI 25-115%, p < 0.001) and 56% (95% CI 2-109%, p = 0.02), respectively]; additional predictors of MACES were dyspnea and chest pain [5-fold (95% CI 3.3-7.4, p < 0.001) and 2.7-fold (95% CI 1.5-4, p < 0.001) increased risk of MACEs]. Patients with MACEs had an average maximum diastolic blood pressure increase of 19.3 mmHg (95% CI 2.5-36mmHg, p = 0.02) and 9.4 mm larger tumor size (95% CI 1.2-17.56, p = 0.02) than those without. No significant associations between age, adrenergic-noradrenergic phenotype, metastatic disease, familial PPGLs, and MACEs were found.

This is, to the best of our knowledge, the first meta-analysis of cohort studies of catecholamine-induced MACEs in patients with PPGL. 21% of PPGL cases developed MACEs. Necrosis/hemorrhage, dyspnea, chest pain, and diabetes were associated with an increased likelihood of development of MACEs. However, these results should be interpreted with caution due to statistical and methodological heterogeneity.