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Pheochromocytoma is a rare tumor of chromaffin tissues most commonly arising from the adrenal medulla. We retrospectively reviewed the records of 38 patients with pheochromocytoma who underwent surgical treatment between 1977 and 2004 at our Yokohama City University Medical Center and Yokohama City University Hospital. Twenty two patients (57.9%) were females and 16 (42.1%) were males. The most frequent symptoms were headache (58%). One patient had bilateral adrenal tumors and pathological examination revealed malignant pheochromocytoma. Six patients had an extra-adrenal tumor and in 2 patients the tumor occurred in the urinary bladder. Twelve patients (31.6%) had sustained hypertension, 21 patients (55.3%) had paroxysmal hypertension and 5 patients (13.1%) remained normotensive. The 24-h urinary total metanephrines and vanillylmandelic acid (VMA) were the most sensitive biochemical tests for the diagnosis of pheochromocytoma. The sensitivity of urinary total metanephrines was 92.0% for all the patients and was 92.3% for the patients without paroxysmal hypertension. Fifteen patients had intraoperative hypertensive reactions in the surgical manipulation or hypotension after tumor resection. This group had more urinary excretion of VMA before surgery, compared with that with stable intraoperative blood pressure (p < 0.005).

A simple, direct and specific radioimmunoassay for serum and urinary metanephrine was developed, in which we used 125I-Synephrine and specific antiserum generated in rabbits by injecting with metanephrine conjugated with bovine serum albumin as described by Grota and Brown. The sensitivity of the assay was 2 pg/tube. Intra- and inter-assay coefficients of variation were 2.6 approximately 7.8% and 5.0 approximately 9.6%, respectively. The recoveries of metanephrine added at two levels of 250 pg/ml and 500 pg/ml to ten serum samples and ten urine samples (hydrolyzed and diluted) were 96.7 and 108% in serum, and 94.8 and 103% in urine, respectively. Normal values of serum metanephrine were 40.3 +/- 25.8 pg/ml (mean +/- SD) from 20 normal subjects. Normal values of 24 hour urinary metanephrine excretion were 12.5 +/- 6.7 ug/day from 24 normal subjects. Serum metanephrine values for 7 patients with pheochromocytoma were 210 approximately 628 pg/ml. Urinary metanephrine values for 9 patients with pheochromocytoma 8.7 approximately 302 ug/day.

Diagnosis of pheochromocytoma has been made by the determination of urinary noradrenaline and adrenaline excretion for 24 hours. The assay procedure and the collection of urine for 24 hrs. are intricate. In the present study, we have ascertained the clinical significance of urinary normetanephrine (NM) and metanephrine (M), chemically stable metabolites of catecholamines, in single voided urine for a diagnosis of pheochromocytoma. Urine and plasma samples were collected from 361 normal subjects, 59 patients with essential hypertension, 22 patients with chronic renal failure and 22 patients with pheochromocytoma. Urinary NM and M concentrations were determined by radioimmunoassay with prior hydrolysis by acidification with 1N HCl. Plasma NM and M concentrations in normal subjects were 71.8 +/- 30.7 pg/ml and 41.5 +/- 8.61 pg/ml, respectively. Plasma NM was increased in 8 and plasma M was increased in 20 of 21 patients with pheochromocytoma, although many of these overlapped with those patients with chronic renal failure (NM, 285.9 +/- 175.1 pg/ml; M, 206.3 +/- 186.7 pg/ml) and essential hypertension (NM, 107.7 +/- 90.7 pg/ml; M, 46.7 +/- 20.2 pg/ml). Urinary NM and M concentrations did not show specific diurnal variation and there was significant correlations between the values in single voided urine and those in the 24 hour urine. Urinary NM and M concentrations in normal controls were 197.5 +/- 46.7 ng/mg Cr. and 125.3 +/- 37.1 ng/mg Cr., respectively. Urinary NM concentration was increased in 14 and urinary M concentration was increased in all of 17 patients with pheochromocytoma. In addition, urinary M concentration was higher in most of the 17 patients with pheochromocytoma than that in the patients with chronic renal failure and essential hypertension. However, the values in three patients with Sipple's syndrome with a small adrenal tumor or recurrent cases overlapped with those in other diseases. Relationships between urinary concentrations of NM and/or M and tumor size showed positive correlations. Urinary NM and M concentrations showed significant decreases after surgical removal of the tumors. These results suggest that NM and/or M concentrations in single voided urine could be a sensitive and specific diagnostic tool for pheochromocytoma.