Metanephrine In Patients Research Articles

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

PS-C22-5: PLASMA METANEPHRINES PROVIDE GREATER SPECIFICITY THAN URINARY METANEPHRINES IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA: A PROSPECTIVE TRIAL

Introduction: Pheochromocytoma and paraganglioma (PPGL), and obstructive sleep apnea (OSA) are important secondary causes of hypertension. Both plasma and urinary metanephrines have high diagnostic sensitivity and specificity for diagnosis of PPGL. Patients with OSA have increased nocturnal catecholamine release, which can lead to increased metanephrines production over 24 hours. We hypothesized that morning plasma metanephrines have a higher diagnostic accuracy than 24-hour urinary metanephrines in patients with OSA. Methods: We recruited patients undergoing polysomnography for suspected OSA. Plasma and 24-hour urinary metanephrines were measured. Patients with elevated metanephrines had repeated measurements of metanephrines, imaging and follow-up, to diagnose, or exclude, PPGL. Results: Seventy-six patients completed polysomnography and biochemical testing, of which 68 had OSA. One patient had a PPGL, while PPGL was excluded in the remaining patients. At baseline, OSA patients were more likely to have falsely-elevated urinary (17 of 67, 25.4%), than falsely-elevated plasma metanephrines (2 of 67, 2.9%) (P &lt; 0.01). Seven patients had normal metanephrines on repeat testing. Nine patients with persistently elevated metanephrines underwent abdominal imaging: six patients had no PPGL, one had lipid-rich adrenal adenomas, one had indeterminate adrenal adenoma, and one had bladder tumor. This final patient with biopsy-proven bladder PPGL had marginally-elevated urinary metanephrines, but false-negative plasma metanephrines, due to the small tumor size. Falsely-elevated urine metanephrines were more common in patients with severe OSA (13 of 3, 38.2%), compared to moderate OSA (1 of 13, 7.7%) and mild OSA (3 of 20, 15%), P &lt; 0.01. Falsely-elevated plasma and urine metanephrines were all due to elevation of normetanephrine, while metanephrine was normal in all patients. Declines in metanephrines were observed only in patients with OSA treated with continuous positive pressure ventilation, while those untreated had no improvements. Conclusion: In patients with OSA, metanephrines measured in plasma provide better specificity than those measured in urine for the diagnosis of PPGL. However, one patient with a small PPGL was missed by plasma metanephrines.

Comparison of plasma metanephrines in patients with cyanotic and acyanotic congenital heart disease.

The co-occurrence of cyanotic congenital heart disease (CCHD) and PHEO/PGL has been reported, but the role of the hypoxic environment in the pathogenesis of PHEO/PGL remains unclear. Our aim was to compare plasma metanephrine and normetanephrine levels between patients with CCHD and patients with acyanotic congenital heart disease (ACCHD). We performed a cross-sectional study in a prospective cohort of 44 patients with congenital heart disease (CHD) (31 (70.5%) females) with a median age of 37.5 (31.0-55.6) years at the time of evaluation. Thirty-two (73%) patients had CCHD and 12 (27%) patients had ACCHD. Morning blood samples for plasma determination of metanephrine and normetanephrine were collected. Plasma normetanephrine levels were significantly higher in patients with CCHD compared to ACCHD (p = 0.002). Ten (31.3%) patients with CCHD had plasma normetanephrine levels elevated above the reference range, while all ACCHD patients had normal levels. Patients with lower oxygen saturation and higher proBNP had significantly higher normetanephrine levels (ρ = -0.444, p = 0.003 and ρ = 0.449, p = 0.002, respectively). No chromaffin cell tumors were detected. Increased plasma normetanephrine levels in patients with CCHD can be explained by the effect of hypoxia. Future research is needed to better understand the impact of chronic hypoxia in CCHD on increased sympathetic outflow, hyperplastic response of chromaffin tissue, and the role of somatic mutations in CCHD-PHEO/PGL pathogenesis related to hypoxia.

Preanalytical Considerations and Outpatient Versus Inpatient Tests of Plasma Metanephrines to Diagnose Pheochromocytoma.

Sampling of blood in the supine position for diagnosis of pheochromocytoma and paraganglioma (PPGL) results in lower rates of false positives for plasma normetanephrine than seated sampling. It is unclear how inpatient vs outpatient testing and other preanalytical factors impact false positives. We aimed to identify preanalytical precautions to minimize false-positive results for plasma metanephrines. Impacts of different blood sampling conditions on plasma metanephrines were evaluated, including outpatient vs inpatient testing, sampling of blood in semi- vs fully recumbent positions, use of cannulae vs direct venipuncture, and differences in outside temperature. A total of 3147 patients at 10 tertiary referral centers were tested for PPGL, including 278 with and 2869 without tumors. Rates of false-positive results were analyzed. Outpatient rather than inpatient sampling resulted in 44% higher plasma concentrations and a 3.4-fold increase in false-positive results for normetanephrine. Low temperature, a semi-recumbent position, and direct venipuncture also resulted in significantly higher plasma concentrations and rates of false-positive results for plasma normetanephrine than alternative sampling conditions, although with less impact than outpatient sampling. Higher concentrations and rates of false-positive results for plasma normetanephrine with low compared with warm temperatures were only apparent for outpatient sampling. Preanalytical factors were without impact on plasma metanephrines in patients with PPGL. Although inpatient blood sampling is largely impractical for screening patients with suspected PPGL, other preanalytical precautions (eg, cannulae, warm testing conditions) may be useful. Inpatient sampling may be reserved for follow-up of patients with difficult to distinguish true- from false-positive results.

Comparison of plasma metanephrines in patients with cyanotic and acyanotic congenital heart disease

Comparison of plasma metanephrines in patients with cyanotic and acyanotic congenital heart disease

Optimized procedures for testing plasma metanephrines in patients on hemodialysis

Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

Clinical factors affecting spot urine fractionated metanephrines in patients suspected pheochromocytoma/paraganglioma.

Urinary measurement of fractionated metanephrines is one of the best available biochemical tests for the diagnosis of pheochromocytoma and paraganglioma; however, false-positive results remain an issue. In addition, despite their convenience, there is no evidence to suggest that spot urine samples should replace the standard 24-h urine collection method. The objective of this study is to elucidate clinical variables that may influence the levels of spot urine fractionated metanephrines and to examine their instability. The study is a retrospective review of prospectively collected data from 949 patients whose spot urine fractionated metanephrines were measured under suspicion of pheochromocytoma or paraganglioma at our institution from January 2011 to June 2017. The effects of clinical factors such as age, sex, renal function, and medications on the level of spot urine fractionated metanephrines were evaluated. Urinary fractionated metanephrines were significantly higher in female subjects. They correlated with age but not with estimated glomerular filtration rate (eGFR). A multivariate regression model for urinary fractionated metanephrine levels revealed that age, female sex, eGFR, and the presence of α1-blocker medication were significantly positively correlated with urinary metanephrine (M) levels. Age, female sex, eGFR, and presence of α1-blockers and antidepressant and antipsychotic medications positively correlated with urinary normetanephrine (NM). In addition, age, female sex, eGFR, and presence of α1-blockers and antidepressant and antipsychotic medications were positively correlated with urinary M + NM. In conclusion, sex, age, eGFR, and treatment with α1-blockers, antidepressants, and antipsychotics may affect the levels of urinary fractionated metanephrines. When assessing urinary fractionated metanephrines in patients with suspected PPGLs, we must consider these factors.

MON-395 Takotsubo Cardiomyopathy And Metanephrines

Takotsubo (stress) cardiomyopathy, is defined by transient left ventricular systolic dysfunction without epicardial coronary disease. Case report A 50-year-old man presented with headache and visual disturbance with no past medical history of note. He had recently separated from his wife and children had moved out of the family home. He was very depressed and stressed due to this. His blood pressure was 180/110 mmHg and bloods showed creatinine of 442 umol/L; potassium 3.6 mmol/L; eGFR 13 mL/min/1.73m2. Renal Ultrasound and virology/immunology screen were normal. Echocardiogram showed severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 35% with LV hypertrophy. Plasma normetanephrine and metanephrine levels were elevated at 4805 pmol/L (120-1180) and 819 (80 - 510) respectively. Urine 24 hour metanephrines showed elevated urine normetanephrine output of 7.62 umol/24 h (0-3.3) and mildly elevated urine metanephrine output of 1.31 umol/24 h (0-1.2). CT Adrenals showed a low density 1 cm left adenoma with benign washout characteristics. He was started on alphablocker and amlodipine with good effect. 2 months later, repeat Echo normalised with LVEF of 55-60%. Repeat urine metanephrines were normal. Plasma normetanephrine dropped to 1253 pmol/L and plasma metanephrine to 338 pmol/L. I123 MIBG (meta-iodo-benzyl guanidine) SPECT-CT normal uptake. Overnight dexamethasone suppression test and aldosterone renin ratio were normal. Discussion: This 50-year-old gentleman under considerable emotional stress, presented with severe hypertension and severely impaired LV function. On follow-up, the LV impairment returned to normal and the initially elevated plasma and urine metanephrines normalised. The adrenal tumour was an incidental benign non-secretory tumour. There are several reports of phaeochromocytomas presenting with stress cardiomyopathy, however stress cardiomyopathy mimicking phaeochromocytoma is not well reported. A study by Wittstein et al reported significant elevations of metanephrines in patients with stress cardiomyopathy. However this has not been universally accepted and subsequent studies have not fully replicated this. As per a 2017 metanalysis by Darr et al the sensitivity and specificity of plasma metanephrines for phaeochromocytoma/paraganglioma is 94% and 93% and for urinary metanephrines, 91% and 93%. Critical illness can elevate plasma and urinary metanephrines. In this case, the patient did have severe hypertension, but was not critically ill. The current case report provides a cautionary example that the specificity of plasma and urinary metanephrines in the diagnosis of phaeochromocytoma and paraganglioma may be impaired in people presenting with stress related cardiomyopathy. This is especially true in this case given that this patient also had an incidental adrenal tumour.

Diagnosing phaeochromocytoma/paraganglioma in a patient presenting with critical illness: biochemistry versus imaging.

Phaeochromocytomas and paragangliomas (PPGLs) are revealed by acute cardiovascular complications involving end-organ damage in up to 20% of cases, a presentation associated with particularly high risk for mortality. Among such cases, PPGLs should be considered in patients with unexplained left ventricular failure, multi-organ failure, hypertensive crises or shock. The diagnosis of PPGL commonly relies on measurements of metanephrines in plasma or urine. However, acute critical illness is usually associated with sympathoadrenal activation. Thus, levels of metanephrines in patients in an acute emergency or intensive care setting, whether treated or not with vasoactive drugs, usually cannot be used to reliably diagnose PPGL. Delays in provision of diagnostic test results, particularly when these require 24-h urine collections, may also be incompatible for any need for rapid decisions on patient management or therapeutic interventions. The acute emergency situation therefore represents one exception to the rule where imaging studies to search for a PPGL may be undertaken without biochemical evidence of a catecholamine-producing tumour.

Correlation between malondialdehyde and metanephrine in patients with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is one of the most common diseases , so in this study the serum level of malondialdehyde and its relationship with metanephrine was investigated in acute lymphoblastic leukemia patients over one month of treatment. Some biochemical parameters (serum glucose , total serum protein , malondialdehyde ,vitamin C, and metanephrine) changed as well as white blood cell count and blood hemoglobinlevelswere analyzed in sixty patients diagnosed with acute lymphoblastic leukemia over one month of treatment compared to healthy control group.Statistically significant increases (p

Correlation between malondialdehyde and metanephrine in patients with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is one of the most common diseases , so in this study the serum level of malondialdehyde and its relationship with metanephrine was investigated in acute lymphoblastic leukemia patients over one month of treatment. Some biochemical parameters (serum glucose , total serum protein , malondialdehyde ,vitamin C, and metanephrine) changed as well as white blood cell count and blood hemoglobinlevelswere analyzed in sixty patients diagnosed with acute lymphoblastic leukemia over one month of treatment compared to healthy control group.Statistically significant increases (p

Normotensive Incidentally Discovered Pheochromocytomas Display Specific Biochemical, Cellular, and Molecular Characteristics

A number of incidentally discovered pheochromocytomas are not associated with hypertension. The characteristics of normotensive incidentally discovered pheochromocytomas (NIPs) are poorly known. The purpose of this work was to assess the clinical, hormonal, histological, and molecular features of NIPs. This was a retrospective cohort recruited from 2001 to 2011 in 2 tertiary care medical departments. Clinical, biological, and radiological investigations performed in 96 consecutive patients with sporadic unilateral pheochromocytomas were examined; 47 patients had overt pheochromocytomas responsible for hypertension. Among the patients with incidental pheochromocytomas, 28 had hypertension and 21 were normotensive (NIPs). A total of 62 tumors were examined to determine the Pheochromocytoma of the Adrenal Gland Scale Score, and 29 were studied for the expression of 16 genes involved in chromaffin cell function. Tumor size and metaiodobenzylguanidine (MIBG) scintigraphy results were similar for hypertensive pheochromocytomas (HPs) and NIPs. Patients with NIPs displayed reduced summed levels of urinary catecholamines and metanephrines and, more specifically, reduced levels of adrenaline and metadrenaline compared with those of patients with HPs (P < .001). Urinary metanephrines had 98% diagnostic sensitivity in patients with HPs and only 75% in patients with NIPs (P < .01). Tumor diameter positively correlated with the total amount of urinary concentrations of metanephrines in patients with HPs (P < .001) but not in patients with NIPs. NIPs displayed global decreased chromaffin gene expression (reaching significance for 5 of them) and 2 corresponding proteins (phenylethanolamine N-methyltransferase and secretogranin II) and a significant increase in the cellularity, mitotic activity, and presence of atypical mitosis (P < .05). NIPs differ from pheochromocytomas responsible for hypertension and display features of altered chromaffin differentiation. These tumors may be misdiagnosed with the use of the usual biological diagnostic tools.

Plasma-freevsdeconjugated metanephrines for diagnosis of phaeochromocytoma

The diagnosis of phaeochromocytoma is commonly performed by the measurements of plasma-free normetanephrine and metanephrine. Plasma-deconjugated normetanephrine and metanephrine have been proposed as alternative, equivalent, but easier to measure biomarkers. The aim of this study was to compare the diagnostic performance of plasma-free vs deconjugated normetanephrine and metanephrine in patients tested for phaeochromocytoma. The study population included a reference group of 262 normotensive and hypertensive volunteers, 198 patients with phaeochromocytoma and 528 patients initially suspected of having the tumour, but with negative investigations after at least 2years of follow-up. Measurements were performed using liquid chromatography with electrochemical detection. Plasma concentrations of free normetanephrine were 17-fold higher in patients with phaeochromocytoma than in the reference population, a 72% larger (P<0·001) difference than that for the 10-fold higher levels of plasma-deconjugated normetanephrine. In contrast, relative increases in plasma concentrations of free and deconjugated metanephrine were similar. Using upper cut-offs established in the reference population, measurements of plasma-free metabolites provided superior diagnostic performance than deconjugated metabolites according to measures of both sensitivity (97% vs 92%, P=0·002) and specificity (93% vs 89%, P=0·012). The area under the receiver operating characteristic curve for the free metabolites was larger than that for the deconjugated metabolites (0·986 vs 0·965, P<0·001). Measurements of plasma-free normetanephrine and metanephrine are superior to the deconjugated metabolites for diagnosis of phaeochromocytoma.

The Effect of Exogenous Glucocorticoids on Plasma Catecholamines and Metanephrines in Patients Without Phaeochromocytomas

The aim of the study was to evaluate the effects of steroid administration under standardised conditions in a range of patients both normal and with adrenal pathologies and to review the impact on plasma catecholamines and metanephrines. Corticosteroid administration has been linked to the development of hypertensive crises in patients with phaeochromocytoma, however a mechanism for this is not fully understood. We aimed to add useful information about the effect of steroids on levels of these hormones under usual circumstances. A prospective, observational cohort study of 50 patients undergoing the low-dose dexamethasone suppression test (LDDST) was undertaken. Additional blood samples were taken at the start and end of the standard LDDST. Biochemical analysis was carried out for plasma catecholamines and plasma free metanephrines. Demographic and hormonal data were acquired from review of the notes or measured at baseline. No significant changes in plasma catecholamines or metanephrines were seen at the end of the LDDST compared to baseline. This was also true of subgroup analysis, divided by age, gender, or type of underlying pathology. Our results suggest that hypertensive reaction responses, rare as they are, are unlikely to be related to normal adrenal physiology. Thus LDDST is likely to be safe under most circumstances, however caution should be exercised in patients with adrenal masses with imaging characteristics compatible with phaeochromocytoma. It may be prudent to defer glucocorticoid administration until functioning phaeochromocytoma has been excluded biochemically.

The diagnostic efficacy of urinary fractionated metanephrines measured by tandem mass spectrometry in detection of pheochromocytoma

There are limitations to currently available biochemical tests for pheochromocytoma. Our objective was to evaluate the diagnostic efficacy of a novel tandem mass spectrometry assay for the measurement of fractionated urinary metanephrines in patients suspected to have a pheochromocytoma. We also developed clinically based cut-offs for positivity of this measurement. We examined the medical records of 506 patients (including 102 patients with a catecholamine-producing tumour) who underwent measurement of 24-h urinary fractionated metanephrines using tandem mass spectrometry as well as adrenal imaging at Mayo Clinic, Rochester. The cut-offs for positivity were defined as follows: total metanephrines (sum of the metanephrine fractions) 5163 nmol/day, normetanephrine fraction 4001 nmol/day, metanephrine fraction 1531 nmol/day. Receiver operating characteristic (ROC) curves were constructed. The diagnostic efficacy was as follows: normetanephrine fraction sensitivity 87.3% [(95% confidence interval (CI) 79.4-92.4%], specificity 95.0% (92.5-96.8); metanephrine fraction sensitivity 56.9% (47.2-66.1), specificity 95.0% (92.5-96.8); elevation of either normetanephrine or metanephrine fraction sensitivity 97.1% (91.7-99.0) and specificity 91.1% (87.9-93.5). Areas under the ROC curves (AUCs) were 0.972 (95% CI 0.955-0.990) for the normetanephrine fraction, 0.800 (0.741-0.858) for the metanephrine fraction, 0.991 (0.985-0.996) for total metanephrines, and 0.991 (0.985-0.996) for a regression-derived ROC curve incorporating both the metanephrine and normetanephrine fractions. Measurement of 24-h urinary fractionated metanephrines by a tandem mass spectrometry assay appears to be an effective biochemical technique in the investigation of pheochromocytoma.

Diagnostic Value of 24-hours Urinary Total Metanephrine As a Screening Test of Patients with Suspected Pheochromocytoma

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 1.3mg/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. Conclusions: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.

Plasma Metanephrines Are Markers of Pheochromocytoma Produced by Catechol-O-Methyltransferase Within Tumors

This study examined whether the high sensitivity of plasma free metanephrines for diagnosis of pheochromocytoma may result from production of free metanephrines within tumors. Presence in pheochromocytomas of catechol-O-methyltransferase (COMT), the enzyme responsible for conversion of catecholamines to metanephrines, was confirmed by Western blot analysis, enzyme assay, and immunohistochemistry. Western blot analysis and enzyme assay indicated that membrane-bound and not soluble COMT was the predominant form of the enzyme in pheochromocytoma. Immunohistochemistry revealed colocalization of COMT in the same chromaffin cells where catecholamines are translocated into storage vesicles by the vesicular monoamine transporter. Levels of free metanephrines in pheochromocytoma over 10,000 times higher than plasma concentrations in the same patients before removal of tumors indicated production of metanephrines within tumors. Comparisons of the production of metanephrines in patients with pheochromocytoma with production from catecholamines released or infused into the circulation indicated that more than 93% of the consistently elevated levels of circulating free metanephrines in patients with pheochromocytoma are derived from metabolism before and not after release of catecholamines into the circulation. The data indicate that the elevated plasma levels of free metanephrines in patients with pheochromocytoma are derived from catecholamines produced and metabolized within tumors. Some tumors do not secrete catecholamines, but all appear to metabolize catecholamines to free metanephrines, thus explaining the better sensitivity of plasma free metanephrines over other tests for diagnosis of pheochromocytoma.

Surgical Treatment of Pheochromocytomas

Pheochromocytomas are tumors that develop from chromaffin tissue of the embryonic sympathoadrenal system. These tumors may occur anywhere chromaffin tissue exists but most often develop in the adrenal medulla. Less than 50% of patients are diagnosed with pheochromocytomas while alive, and most of these tumors are found on autopsy. The classic signs and symptoms of pheochromocytomas are headache, perspiration, palpitations, pallor, and paroxysmal hypertension. Elevated levels of vanillylmandelic acid and metanephrines in patients' 24-hour urine collections are the most reliable diagnostic indicators of pheochromocytomas. Most patients with pheochromocytomas can be cured if diagnoses and surgical resections of tumors occur before irreversible cardiovascular disease and end-organ damage from hypertension develop.

Falsely elevated urinary excretion of catecholamines and metanephrines in patients receiving labetalol therapy.

Five patients with essential hypertension who were receiving treatment with the beta- and alpha-adrenoreceptor-blocking drug labetalol had elevated urinary excretion of catecholamines. When measured with a radioenzymatic assay, all five subjects had elevated urinary excretion of norepinephrine and normal urinary excretion of epinephrine; when measured with a fluorometric assay, four subjects had elevated urinary excretion of epinephrine with normal urinary excretion of norepinephrine, and one subject had elevated urinary norepinephrine excretion with normal urinary excretion of epinephrine. In three subjects who could be reevaluated three days to two months after labetalol therapy was discontinued, the urinary catecholamine levels had returned toward normal. Our studies indicate that labetalol produced a false elevation of urinary catecholamine levels. Although labetalol also interfered with the measurement of urinary excretion of metanephrine, it did not interfere with the measurement of urinary excretion of vanillylmandelic acid, homovanillic acid, 5-hydroxyindoleacetic acid, and serotonin, and it probably did not interfere with the measurement of plasma concentrations of dopamine, norepinephrine, and epinephrine. We conclude that labetalol therapy should be discontinued, and another beta-blocking drug, such as propranolol, that does not interfere with these tests should be temporarily substituted at least three days before a patient collects a 24-hour urine for measurement of the urinary excretion of catecholamines and metanephrine.