Elsevier

Clinical Biochemistry

Volume 33, Issue 8, November 2000, Pages 649-655
Clinical Biochemistry

A Five-Year Report on Experience in the Detection of Pheochromocytoma

https://doi.org/10.1016/S0009-9120(00)00172-7Get rights and content

Abstract

Objective: The purpose of the study is to identify biochemical tests that are good predictors for the diagnosis of pheochromocytoma in patients at hypertension.

Setting: Review of data from of 3826 patients studied over a 5-year period, between 1994 and 1998, at the University Hospital “Virgen de la Arrixaca” Murcia, Spain.

Design and Methods: A retrospective study for the diagnosis of pheochromocytoma of 24-h urinary free catecholamines (norepinephrine, epinephrine, and dopamine) measured by high-performance liquid chromatography (HPLC)-electrochemical detector (ECD), total metanephrines (MNt), and vanillylmandelic acid measured by spectrophotometric methods.

Results: During this period, 57 patients were found to have pheochromocytoma, being 47 sporadic, 9 with multiple endocrine neoplasia type 2A, and 1 with neurofibromatosis. In all patients multiple endocrine neoplasia type 2A the tumor were bilateral but only in four of the sporadic tumor group (p < 0.0001, Fisher’s exact test). MNt was determined to be the best discriminator of hypertension and pheochromocytoma. It scored a sensitivity of 94.7% (95% confidence interval, 88.3–99.9%), a specificity of 95.3% (89.5–99.9%), and thus had the best negative predictive value of 99.9% (99.8–99.9%), and this biochemical test also had the best positive predictive value of 23.3% (10.8–59.9%). When combining both MNt and norephinephrine, the positive predictive value to increases to 85.6% (65.3–95.6%).

Conclusion: Urinary 24-h MNt excretion level is the best single biochemical test for screening and, in combination with norephinephrine, is diagnostic of the presence of pheochromocytoma.

Introduction

Pheochromocytoma is a catecholamine secreting tumor that arises from the chromaffin cells of the sympathoadrenal system and is a rare cause of secondary hypertension. Its diagnosis is important because the hypertension is usually curable by resection of the tumor, whereas the condition is potentially lethal if untreated. It occurs in 0.1% to 0.5% of patients with hypertension, with an incidence in the general population of 1 in 200,000 (1).

In a 50-yr autopsy series of 40078 patients at the Mayo Clinic, the prevalence of pheochromocytoma was 0.13% (2) and the prevalence of this disorder in the population of patients with an incidentally discovered adrenal mass was estimated to be 50 times higher or 6.5%.

Diagnosis or exclusion of potential pheochromocytoma is important before any surgical procedure because appropriate preparation is vital and intraoperative management is different for pheochromocytoma from that of other adrenal lesions 3, 4.

The clinical suspicion of a pheochromocytoma may be suggested by certain clinical signs and symptoms, especially hypertension with a characteristic triad: headache, diaphoresis, and palpitations. Perhaps, the most important confirmation study is the biochemical finding of excessive catecholamine production by the tumor, and radiologic studies for the localization of a suspected mass.

The biochemical tests for pheochromocytoma are based on detecting abnormally increased levels of several different free catecholamines or metabolites in urine or blood 3, 5, 6 and are routinely used in the evaluation of hypertension patients. They are: the measurement of the 24-h urinary excretion of free catecholamines [norepinephrine (NE), epinephrine (E), dopamine (DA)], and the metabolites such as total metanephrines (MNt) (free plus conjugated), and 3-methoxy-4-hydroxymandelic acid (VMA) 3, 5.

Recently, there has been much controversy regarding the methods of diagnosis 5, 6, 7, 8, 9. The aim of this retrospective study is to review our experience with 57 patients with pheochromocytoma in a large population of patients with hypertension suspected of having a pheochromocytoma and to identify specific tests that have good sensitivity, specificity, and positive and negative predictive values (PPV and NPV).

Section snippets

Patients

The patients’ database for this report includes 3826 patients who were examined at several community centers in Murcia and referred to the University Hospital “Virgen de la Arrixaca” (Murcia, Spain) by their physicians because hypertension was severe, resistant, or associated with diabetes or paroxysmal symptoms (1), between January 1994 and December of 1998.

All patients were evaluated by clinical history assessment and 24-h urinary collections for measurement of free catecholamines and

Results

We retrospectively evaluated our experience with pheochromocytoma from January 1994 to December 1998. Fifty-seven patients with surgically and histologically proven pheochromocytomas were found over 5 years from 3826 patients referred for tumor screen for suggested hypertension.

The patients were divided into the following groups: familial (MEN 2A), 9 patients (15.9%), sporadic tumor, 47 patients (82.5%), and neurofibromatosis type I (1.6%), 1 patient. The prevalence rate was 1.49% (range,

Discussion

The prevalence rate of 1.49%, is nearly 4- to 5-fold more than the suggested prevalence of the tumor in the literature for the hypertension population at large (1).

This study of 57 patients with histologically documented pheochromocytoma showed that at the time of diagnosis, the familial patients were younger than the sporadic patients. This was due to the high suspicion level and the screening of family members, which permitted diagnosis before clinical manifestations were seen (14). As in

Acknowledgements

The enthusiasm of the technicians of hormones laboratory and excellent suggestions made by Dr. Juan Rosique, are gratefully acknowledged.

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