Abstract
Background
A pheochromocytoma is a rare cause of secondary hypertension. Its diagnosis is important as the hypertension is usually curable by resection of the tumor, whereas the condition is potentially lethal if undetected. Biochemical confirmation of excessive catecholamine production is a prerequisite to a definitive diagnosis. Various studies from other countries have indicated that measuring of the urinary metanephrine, using a specific procedure, is the single most reliable screening test for all patients suspected of having a pheochromocytoma. However, the diagnostic value of urinary metanephrine has never been reported in Korea. We investigated the diagnostic value of 24-hours urinary metanephrine in patients with a suspected pheochromocytoma.
Methods
This was a retrospective evaluation study, which included 95 patients with sustained hypertension and paroxysmal symptoms, and 38 patients with asymptomatic adrenal incidentaloma at Seoul National University Hospital, between July 2000 and October 2002. We performed the 24-hour urinary total metanephrine test on all patients. The diagnosis of a pheochromocytoma was applied only when confirmed by pathological analysis of a resected specimen. The possibility of a pheochromocytoma was ruled out when all biochemical tests were normal, which were performed at least in duplicate, or there was no evidence of a mass in abdominal radiological studies or histological verification. We determined the upper reference limit for urinary metanephrine as 1.3 mg/day and calculated the sensitivity and specificity of the 24-hour urinary metanephrine test.
Results
Seventeen patients were diagnosed with a pheochromocytoma. The total metanephrine measurement had sensitivities and specificities of 82.4 and 73.3% in all the patients, 90.9 and 66.7% in patients with hypertension and paroxysmal symptoms, and 66.7 and 90.6% in patients with adrenal incidentaloma, respectively.
Conclusion
The urinary total metanephrine measurement had relatively lower sensitivities and specificities than in other countries (sensitivity: 83~100%, specificity: 80~98%). The sensitivity of urinary metanephrine was relatively high in patients with hypertension and paroxysmal symptoms, and the specificity was high in patients with an adrenal incidentaloma. We suggest that normetanephrine and metanephrine should be separately measured, and a reasonable upper reference limit be used. It may also be necessary to measure urinary metanephrine together with urinary catecholamine or VMA to improve the diagnostic value of the urinary metanephrine test.
References
1. Mannelli M. Diagnostic problems in pheochromocytoma. J Endocrinol Invest. 1989. 12:739–757.
2. Sheops SG, Jiang NS, Klee GG. Diagnostic evaluation of pheochromocytoma. Endocrinol Metab Clin North Am. 1988. 17:397–414.
3. Eisenhofer G, Lenders JW, Linehan WM, Walther MM, Goldstein DS, Keiser HR. 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.
4. Gifford RW Jr. Management of hypertensive crises. JAMA. 1991. 266:829–835.
5. Louie AK, Louie EK, Lannon RA. Systemic hypertension associated with tricyclic antidepressant treatment in patients with panic disorder. Am J Cardiol. 1992. 70:1306–1309.
6. Pacak K, Linehan WM, Eisenhofer G, Walther MM, Goldstein DS. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med. 2001. 134:315–329.
7. James BY, Lewis L. Wilson JD, Foster DW, Kronenberg HM, Larsen PR, editors. Catecholamines and the Adrenal Medulla. Williams Textbook of Endocrinology. 1998. 9th ed. philadelphia: WB Saunders Co;705–728.
8. Pomares FJ, Canas R, Rodriguez JM, Hernandez AM, Parrilla P, Tebar FJ. Differences between sporadic and multiple endocrine neoplasia type 2A phaeochromocytoma. Clin Endocrinol (Oxf). 1998. 48:195–200.
9. Stein PP, Black HR. A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience. Medicine (Baltimore). 1991. 70:46–66.
10. Veil K, Pertti K, Kari M, Jouko P, Arja V, Ilkka K, Kerttu I. Reference Intervals for 24-h Urinary Normetanephrine, Metanephrine, and 3-Methoxy-4-hyderoxymandelic Acid in Hypertensive Patients. Clin Chem. 1992. 38:416–420.
11. Jones DH, Reid JL, Hamilton CA, Alllison DJ, Welbourn RB, Dollery CT. The biochemical diagnosis, localization and follow up of phechromocytoma: the role of plasma and urinary catecholamine measurments. Q J Med. 1980. 195:341–361.
12. Plouin PF, Duclos FM, Menard J, Comoy E, Bohoun C, Alexandre JM. Biochemical tests for diagnosis for pheochromocytoma:urinary versus plasma determinations. Br Med J. 1981. 282:853–854.
13. Bachmann AW, Hawkins PG, Gorrdon RD. Pheochromocytomas secreting adrenaline but not noradrenaline do not cause hypertension and require precise adrenaline measurement for diagnosis. Clin Exp Pharmacol Physiol. 1989. 16:275–279.
14. 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.
15. Manu P, Runge LA. Biochemical screening for pheochromocytoma: superiority of urinary metanephrine measurments. Am J Epidemiol. 1984. 120:788–790.
16. Hsiao RJ, Parmer RJ, Takiyyunddin MA, O'Connor D. Chromogram A storage and secretion; sensitivity and speificity for the diagnosis of pheochromcytoma. Medicine. 1991. 70:33–45.
17. Veil K, Pertti K, Kari M, Jouko P, Arja V, Ilkka K, Kerttu I. Reference Intervals for 24-h Urinary Normetanephrine, Metanephrine, and 3-Methoxy-4-hyderoxymandelic Acid in Hypertensive Patients. Clin Chem. 1992. 38:416–420.
18. Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G, Angeli A. Asurvey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab. 2000. 85:637–644.
19. Feldman JM. Falsely elevated urinary excretion of catecholamines and metanephrines in patients receiving labetalol therapy. J Clin Pharmacol. 1987. 27:288–292.
20. Cook FJ, Chandler DW, Snyder DK. Effect of buspirone on urinary catecholamine assays (letter). N Engl J Med. 1995. 332:401.
21. Page LB, Raker JW, Berberich FR. Pheochrom ocytoma with predominant epinephrine secretion. Am J Med. 1969. 46:648–652.
22. Jan T, Metzger BE, Baumann G. Epinephrineproducing pheochromocytoma with hypertensive crisis after corticotropin injection. Am J Med. 1990. 89:824–825.
23. St John Sutton MG, Sheps SG, Lie LJ. Prevalence of clinically unsuspected pheochromocytoma. Mayo Clin Proc. 1981. 56:354–360.
24. Bravo EL. Pheochromocytoma. Current concepts in diagnosis, localization, and management. Primary Care. 1983. 10:75–86.
25. Erik AM, Claude S. Uirnary and Plasma Catecholamine and Urinary Catecholamine Metabolites in Pheochromocytoma: Diagnostic Value in 19 Cases. Clin Chem. 1994. 40:250–256.
26. Thomas GR, Thomas AS, Lyle WH. Advances in Catecholamine and Metabolite Measurements for Diagnosis of Pheochromocytoma. Clin Chem. 1991. 37:1854–1867.
27. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW. Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. J Clin Endocrinol Metab. 1998. 83:2175–2185.