Cardiovascular events and biochemically negative paragangliomas: a systematic review

To study cardiovascular morbidity in patients with biochemically inactive pheochromocytomas/paragangliomas.

PubMed, Cochrane, and Scopus databases were searched by two independent reviewers to identify relevant studies. Twenty-four case reports ( n  = 24 patients) met the inclusion criteria providing data on the cardiovascular status of biochemically negative pheochromocytomas/paragangliomas patients. Methodological quality was assessed by the Grading of Recommendations, Assessment, Development and Evaluations system, and all included studies were assessed for the risk of bias. This systematic review was conducted in conformance with the PRISMA statement and registered to PROSPERO (ID: CRD42024530601).

Almost half of patients (46%) presented objective abnormal findings on noninvasive cardiovascular examination performed routinely before surgery, whereas 67% complained of pheochromocytoma/paraganglioma-related symptoms (angina, headache, diaphoresis, shortness of breath, palpitations) and exhibited relevant clinical signs (hypertension, tachycardia, tachypnea, pallor). Preoperatively, only 38% of patients with biochemically negative pheochromocytomas/paragangliomas were treated with alpha-blockers, 25% did not receive any pharmaceutical preparation whereas data were not available for the remaining 37% of patients. Following an uneventful surgery, 70% of patients exhibited resolution of the preoperatively detected cardiovascular symptoms and signs.

The high occurrence of cardiovascular abnormalities in patients with pheochromocytomas/paragangliomas characterized as "biochemically negative" based on routine biochemical analyses highlights the difficulty in the appropriate classification of these tumors regarding their secretory profile and thus the risk of missing cardiovascular system involvement with potentially deleterious effects.