Skip to main content
Log in

Choice of biochemical test for diagnosis of pheochromocytoma: Validation of plasma metanephrines

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Pheochromocytomas, although a rare cause of hypertension, are dangerous tumors that require consideration among large numbers of patients. The subsequent low prevalence of the tumor among those tested and inadequacies of commonly used biochemical tests make excluding or confirming the tumor an often difficult and time consuming task. Recognition that catecholamines are metabolized to free metanephrines within pheochromocytoma tumor cells, and that this process is independent of catecholamine release, provides a rationale for use of these metabolites in the biochemical diagnosis of pheochromocytoma. Measurements of plasma concentrations of free metanephrines thereby promise more reliable and efficient diagnosis of pheochromocytoma than offered by conventional biochemical tests.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Lo CY, Lam KY, Wat MS, Lam KS: Adrenal pheochromocytoma remains a frequently overlooked diagnosis. Am J Surg 2001, 179:212–215.

    Article  Google Scholar 

  2. Eisenhofer G, Huynh T-T, Hiroi M, Pacak K: Understanding catecholamine metabolism as a guide to the biochemical diagnosis of pheochromocytoma. Rev Endocrinol Metab Dis 2001, 2:297–311.

    Article  CAS  Google Scholar 

  3. Lenders JWM, Eisenhofer G, Armando I, et al.: Determination of plasma metanephrines by liquid chromatography with electrochemical detection. Clin Chem 1993, 39:97–103.

    PubMed  CAS  Google Scholar 

  4. Roden M, Raffesberg W, Raber W, et al.: Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen. Clin Chem 2001, 47:1061–1067. An HPLC assay for measurement of plasma free metanephrines is described that includes improvements over that first described by Lenders et al. [3].

    PubMed  CAS  Google Scholar 

  5. Pallant A, Mathian B, Prost L, et al.: Determination of plasma methoxyamines. Clin Chem Lab Med 2001, 38:513–517.

    Article  Google Scholar 

  6. Grouzmann E, Fathi M, Gillet M, et al.: Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma. Clin Chem 2001, 47:1075–1082.

    PubMed  CAS  Google Scholar 

  7. Bravo EL, Tarazi RC, Gifford RW, Stewart BH: Circulating and urinary catecholamines in pheochromocytoma. Diagnostic and pathophysiologic implications. N Engl J Med 1979, 301:682–686.

    Article  PubMed  CAS  Google Scholar 

  8. Peaston RT, Lai LC: Biochemical detection of phaechromocytoma: Should we still be measuring urinary HMMA? J Clin Pathol 1993, 46:734–737.

    PubMed  CAS  Google Scholar 

  9. Gerlo EA, Sevens C: Urinary and plasma catecholamines and urinary catecholamine metabolites in pheochromocytoma: diagnostic value in 19 cases. Clin Chem 1994, 40:250–256.

    PubMed  CAS  Google Scholar 

  10. Gardet V, Gatta B, Simonnet G, et al.: Lessons from an unpleasant surprise: a biochemical strategy for the diagnosis of pheochromocytoma. J Hypertens 2001, 19:1029–1035. A retrospective study of urinary biochemical test performance in 2003 patients tested for pheochromocytoma, 24 of whom were found to have pheochromocytoma. Analysis of receiver-operating characteristic curves established that measurements of urinary fractionated metanephrines offers a superior test for diagnosis of pheochromocytoma than measurements of urinary catecholamines, urinary total metanephrines, and urinary VMA.

    Article  PubMed  CAS  Google Scholar 

  11. Mannelli M, Ianni L, Cilotti A, Conti A: Pheochromocytoma in Italy: a multicentric retrospective study. Eur J Endocrinol 1999, 141:619–624. This epidemiologic study involving retrospective analysis of 284 patients with pheochromocytoma illustrates the diverse and aspecific clinical presentation of pheochromocytoma and findings of normal blood pressure in significant numbers of patients with the tumor. Measurements of urinary VMA were shown to be a relatively insensitive test for diagnosis of pheochromocytoma.

    Article  PubMed  CAS  Google Scholar 

  12. Lenders JWM, Pacak K, Walther MM, et al.: Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 2002, 287:1427–1434. A large, multicenter cohort study comparing the diagnostic utility of six biochemical tests used for testing pheochromocytoma. Measurements of plasma free metanephrines and urinary fractionated metanephrines were found to provide the highest sensitivity out of all tests, but the latter test suffered from poor specificity.

    Article  PubMed  CAS  Google Scholar 

  13. Duncan MW, Compton P, Lazarus L, Smythe GA: Measurement of norepinephrine and 3,4-dihydroxyphenylglycol in urine and plasma for the diagnosis of pheochromocytoma. N Engl J Med 1988, 319:136–142.

    Article  PubMed  CAS  Google Scholar 

  14. Chan EC, Ho PC: High-performance liquid chromatography/ atmospheric pressure chemical ionization mass spectrometric method for the analysis of catecholamines and metanephrines in human urine. Rapid Commun Mass Spectrom 2001, 14:1959–1964. Methods employing GC-MS or LC-MS for measurement of urinary catecholamines and metanephrines, such as the method desribed in this article, promise potential for more accurate and analytically specific test results than offered by other methodologies such as spectrophotometry, radioenzymatic assays, immunoassays, and conventional HPLC methods.

    Article  Google Scholar 

  15. Eisenhofer G: Free or total metanephrines for diagnosis of pheochromocytoma: what is the difference? Clin Chem 2001, 47:988–989.

    PubMed  CAS  Google Scholar 

  16. Goldstein DS, Swoboda KJ, Miles JM, et al.: Sources and physiological significance of plasma dopamine sulfate. J Clin Endocrinol Metab 1999, 84:2523–2531.

    Article  PubMed  CAS  Google Scholar 

  17. Eisenhofer G, Lenders JW, Linehan WM, et al.: Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. N Engl J Med 1999, 340:1872–1879. s report establishes the advantages of the high diagnostic sensitivity offered by measurements of plasma free metanephrines for detection of pheochromocytoma during periodic screening for the tumor in patients with MEN 2 and VHL syndrome.

    Article  PubMed  CAS  Google Scholar 

  18. Raber W, Raffesberg W, Bischof M, et al.: Diagnostic efficacy of unconjugated plasma metanephrines for the detection of pheochromocytoma. Arch Intern Med 2000, 160:2957–2963. study supports the conclusions of an earlier study by Lenders by showing that measurements of plasma free metanephrines offered 100% sensitivity for diagnosis of pheochromocytoma compared with only 82% sensitivity for plasma or urinary catecholamines. Plasma concentrations of metanephrines were also shown to be less responsive than catecholamines to change of posture and intraoperative stress.

    Article  PubMed  CAS  Google Scholar 

  19. Lenders JW, Keiser HR, Goldstein DS, et al.: Plasma metanephrines in the diagnosis of pheochromocytoma. Ann Intern Med 1995, 123:101–109.

    PubMed  CAS  Google Scholar 

  20. Eisenhofer G, Friberg P, Pacak K, et al.: Plasma metadrenalines: do they provide useful information about sympatho-adrenal function and catecholamine metabolism? Clin Sci 1995, 88:533–542.

    PubMed  CAS  Google Scholar 

  21. Pacak K, Linehan WM, Eisenhofer G, et al.: Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 2001, 134:315–329.

    PubMed  CAS  Google Scholar 

  22. Bravo EL, Gifford RWJr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 1984, 311:1298–1303.

    Article  PubMed  CAS  Google Scholar 

  23. Grossman E, Goldstein DS, Hoffman A, Keiser HR: Glucagon and clonidine testing in the diagnosis of pheochromocytoma. Hypertension 1991, 17:733–741.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eisenhofer, G., Lenders, J.W.M. & Pacak, K. Choice of biochemical test for diagnosis of pheochromocytoma: Validation of plasma metanephrines. Current Science Inc 4, 250–255 (2002). https://doi.org/10.1007/s11906-002-0015-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-002-0015-4

Keywords

Navigation