An analysis of the biochemical diagnosis of 66 pheochromocytomas

Abstract

Objectives: The aims of this study were to determine the performance of each variable, to define the optimal diagnostic thresholds and to determine the relative value of assaying chromogranin A (CgA). Design: Prospective study. Methods: Two groups of patients were studied: a control group of 71 patients and a group of 63 patients with a histologically-proven pheochromocytoma (52 pheochromocytomas and 14 paragangliomas). Fourteen of the patients had a family history of the disease. Eleven variables were assayed in each patient, i.e. the plasma and urinary concentrations of amines and their derivatives, and the CgA serum concentration.Results: The study of the control group showed that all the serum assays gave false positive results (from 6 to 23%), as did four of the six urinary assays (from 2.9 to 12.3%). The areas under the receiver operating characteristic curves varied from 0.689 to 0.992. The variables relating to the epinephrine pathway were significantly less expressed in the hereditary diseases than in the sporadic cases. The diagnostic thresholds of the three most efficient variables have been raised. Conclusions: Plasma determinations of metanephrines are now an easy and convenient tool for the diagnosis of pheochromocytoma. However, in our study the best specificity was obtained with the urinary tests rather than with the plasma assays while the highest sensitivities were for the normetanephrine assays. The assay of CgA was highly efficient in diagnosing pheochromocytomas in the absence of renal insufficiency. By combining it with fractionated metanephrine assays, the sensitivities of the latter were increased.European Journal of Endocrinology 156 569-575

Evaluation of an enzyme immunoassay for plasma-free metanephrines in the diagnosis of catecholamine-secreting tumors

“…The assay characteristics of metanephrines were always better than those of the catecholamines from which they were derived. Urinary metanephrines yielded the highest specificity and plasma metanephrines the highest sensitivity, in concordance with the conclusions of Sawka et al (9,11). In a retrospective study from Scotland, urinary free metanephrines had a sensitivity of 100% (specificity of 94%) compared with the sensitivity of 84% for urinary catecholamines, but plasma metanephrines were not evaluated in that study (12).…”

“…Testing of plasma metanephrines with an EIA may represent an alternative for centres that do not have access to the most accurate tandem mass spectrometry for plasma metanephrines, particularly in smaller units. A more recent study from a single French centre, also using HPLC, has compared the test characteristics of fractionated metanephrine measurements (urinary and plasma) to catecholamine measurements (urinary and plasma) (11). The assay characteristics of metanephrines were always better than those of the catecholamines from which they were derived.…”

Enzyme and acid deconjugation of plasma sulfated metanephrines

“…Our upper reference limits based on a 97.5 percentile for total metanephrines in hypertensive patients referred for biochemical measurements because of the presence of clinical signs suggestive of a pheochromocytoma that was finally excluded is 29.92 nmol/L for NMN and 11.26 nmol/L for MN and 9.31 nmol/L for NMN and 5.35 nmol/L for MN in healthy subjects [1]. These concentrations are similar to those reported by D'herbonez et al [12] that used the same protocol that we used to deconjugate metanephrines. Since adequate sulfatase treatment should increase these concentrations by 30%-40%, we would expect that these reference ranges should be reset to 40 nmol/L for NMN and 15 nmol/l for MN.…”

Adrenal incidentaloma: a diagnostic challenge

“…23 Assessment of plasma free metanephines seems to display better sensitivity than urinary total metanephrines and catecholamines, although it is inferior with respect to its specificity. [64][65][66] The demonstration of urinary norepinephrine >170 μg/24h, urinary epinephrine >35 μg/24h and urinary total metanephrines at least 1.8 mg/24h and vanillyl-mandelic acid (VMA) at least 11 mg/24h makes the diagnosis of PHEO highly probable (Table 2). 23,24 In a large cross-sectional multicentre study including 1,260 subjects, the combined assay of plasma free metanephrines exhibited a sensitivity of 100% and a specificity of 96.7%, yielding a negative predictive value of 100%.…”