Disappearance Rate of Catecholamines, Total Metanephrines, and Neuropeptide Y from the Plasma of Patients after Resection of Pheochromocytoma

Abstract

Background: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value. Methods: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration–time curve over 120 min. Results: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 ± 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated. Conclusions: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.

Systemic levels of neuropeptide Y and dipeptidyl peptidase activity in patients with Ewing sarcoma—Associations with tumor phenotype and survival

“…This was proposed previously for patients with neuroblastoma and pheochromocytoma. 23,24 Moreover, high systemic levels of NPY may identify a subset of potential candidates for anti-NPY therapies among a population of patients with ES once the role of the endogenous peptide in these tumors is fully elucidated. Finally, the universal, fusion typeindependent tissue expression of NPY may serve as a marker in differential diagnosis between ES and other small blue round cell tumors.…”

Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

“…Because timing and degree of glucose response differ according to dose and varying sensitivity among animals, adrenaline and noradrenaline measurements may suffer from problems of sample timing because of their very short plasma half‐lives [21]. The more stable plasma metanephrine and normetanephrine, metabolites of adrenaline and noradrenaline, respectively, are preferred in the biochemical diagnosis of pheochormocytomas, reflecting intermittent catecholamine secretion better [22]. Given that nephrines also increase in concentrations related to their parent amines after brief, intermittent exercise and with only a couple of minutes delay compared to A and NA [23], we considered nephrine analysis more appropriate for our purpose.…”

Circulating EM66 is a highly sensitive marker for the diagnosis and follow‐up of pheochromocytoma

“…have shown that major stress associated with catecholamine secretion also increased CgA serum level. Preoperative treatment of patients with pheochromocytoma is based on the use of α‐ and β‐blockers, and it is usually observed that the cessation of this treatment is responsible for a flare‐up of the sympathetic nerve system, which in turn leads to an elevation of catecholamine levels that return to normal range only within 1 week 21. Therefore, Cgs that are costored and coreleased with catecholamines may present recurrent elevated levels soon after surgical resection.…”

“…In 2 patients (cases no. 10 and 11, Table I), blood samples were collected at the clamping of the afferent vessels of the tumor by the surgeon (T 0 ) as described previously,21 and then at 1, 2, 5, 10, 20, 30, 60 and 120 min after clamping during resection. For these patients, late samples were obtained 24 hr or 7 days after the operation.…”