Objective assessment of vascular dysfunction in pheochromocytoma and paraganglioma patients and reversal following curative surgery: Results from prospective PheoCard study.

Abstract

Background: Hypertension and cardiovascular changes are hallmarks of pheochromocytoma/paraganglioma. Endothelium-dependent flow-mediated vasodilatory response and endothelium-independent nitroglycerin-mediated vasodilatory response, which are linked to cardiovascular mortality, have not been studied in pheochromocytoma/paraganglioma. This study evaluated extent of vascular changes and impaired vasodilatory responses in patients with pheochromocytoma/paraganglioma and their reversal following curative surgery.

Methods: This prospective cohort study evaluated flow mediated vasodilatory response and nitroglycerin-mediated vasodilatory response in 40 patients with pheochromocytoma/paraganglioma (at diagnosis; after alpha blockade; 7 days, 3 months, and 6 months postsurgery) and in matched control subjects (at baseline), normalized for confounding factors affecting vasodilatory response. Patients underwent curative open/minimally invasive surgery. Significance of linear changes in vascular indices over time was calculated using appropriate statistical methods.

Results: Mean age of patients with pheochromocytoma/paraganglioma (10 normotensive, 6 paraganglioma, 25 male) was 35.4 ± 15.5 years. No patients had persistent hypercatecholaminism; 42.5% remained hypertensive postsurgery. Flow-mediated vasodilatory response and nitroglycerin-mediated vasodilatory response exhibited less vasodilation in study group compared with normotensive and essential hypertensive control subjects. Mean flow-mediated vasodilatory response (%) in pheochromocytoma/paraganglioma cohort increased from 3.4 ± 1.2 at baseline to 5.1 ± 1.8 after alpha blockade and 7.2 ± 1.8, 8.0 ± 2.7, and 9.4 ± 2.9 at 7 days, 3 months, and 6 months postsurgery, respectively, with 6-month values approaching those of healthy control subjects (9.1 ± 4.5, P < .001). Mean nitroglycerin-mediated vasodilatory response (%) improved from 8.0 ± 2.4 (baseline) to 10.7 ± 2.7 after alpha blockade and 13.6 ± 3.3, 16.1 ± 5.2, and 17.0 ± 4.5 (near-normal) at 7 days, 3 months, and 6 months postsurgery, respectively (P < .001).

Conclusions: In this first-of-its-kind study performed using objective noninvasive vascular assessment methodology, patients with pheochromocytoma/paraganglioma were found to have impaired endothelium-dependent and endothelium-independent vasodilatory responses. The stunted vasodilatory responses are reversed and normalized following curative resection of catecholamine-secreting tumors.