HDCN Article Review/Hyperlink

Heron E, Chatellier G, Billaud E, Foos E, Plouin P-F

The urinary metanephrine-to-creatinine ratio for the diagnosis of pheochromocytoma

Ann Int Med (Aug) 125:300-303 1996

Pheochromocytoma is distinctly rare, being less common than renovascular hypertension, primary hyperaldosteronism and Cushing's syndrome. Despite this, it is potentially fatal. The most common symptoms attributable to pheochromocytoma are headache, excess sweating and palpitations. Hypertension, either persistent or intermittent is usually present, and multiple endocrine neoplasia (types 2a and 2b) must be considered in all cases.

To make the diagnosis, it is necessary to perform assays of catecholamines or their metabolites, possibly perform provocative testing and do imaging studies. Traditionally, the use of urinary metanephrines and plasma catecholamines have been used to screen for the disease because they have high sensitivity and specificity. Urinary VMA is much less sensitive and hardly used today. The authors of this paper tried to improve the value of using urinary metanephrines in the diagnosis of pheochromocytoma by indexing urinary metanephrine excretion to that of creatinine. This tends to account for errors in timing of collection and authors hypothesized that it would improve the ability of the test to screen for pheochromocytoma.

The study was done in a hypertension referral practice in France over a one year period. Of a total of 1831 patients, they performed screening on 1031 (56%) patients whom they considered at risk for pheochromocytoma (a large proportion by any criteria). They measured urinary metanephrine and creatinine levels. They subsequently did imaging studies on subjects with elevated levels and followed up on slightly elevated levels.

Of the 1031 patients screened, 20 (2%) had a pheochromocytoma. Of these 20 patients, one had a normal urinary metanephrine level but had a high metanephrine to creatinine ratio. Of the 993 patients without pheochromocytoma, 38 had positive urinary findings. Fifteen had high metanephrine levels, 16 had high metanepgrine to creatinine ratios while 7 had both elevated. Pheochromocytoma was excluded in this group of 38 patients by repeat biochemical studies and in some, imaging studies. Their overall results are shown below. 

                        Urinary met     Urinary met/creat

sensitivity (%)               95               100
specificity (%)               98                98
positive pred value (%)       46                47
negative pred value (%)      100               100


Hence the negative predictive value and sensitivity of the test is excellent. Such a performance would be expected for any test used to screen for a potential fatal disease (i.e., false negative tests should be minimal while false positive tests are not as criticial).

As discussed by Emmanuel Bravo in the accompanying editorial, these tests are useful but the clinician must be aware of their limitations. Furthermore, the ability of these tests to screen patients with other diseases which mimic pheochromocytoma is unknown. The use of the urinary metanephrine to creatinine ratio appears to perform similarly to urinary metanephrine in screening for this rare disorder. Another recent paper by Lenders et al (Ann Intern Med 1995;123:101-109) proposed that plasma metanephrine levels are more sensitive than measuring plasma catecholamines or urinary metanephrines. In that paper, however urinary metanephrine was measured by a colorimetric assay while in the present paper liquid chromotography was used. For the practitioner who suspects the diagnosis, the measurement of urinary metanephrines on a 24 hour sample or plasma catecholamine levels remain the tests of choice. When the normal values for the urinary metanephrine to creatinine ratio are better defined in the United States, then this test may also become useful. (George Mansoor, M.D., University of Connecticut)