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One pitfall in 24-hour urine collection is the input of incorrect urinary volume by the reference laboratory. This may lead to an incorrect diagnosis of pheochromocytoma or paraganglioma. A 48-year-old African-American woman was seen in the clinic for an elevated 24-hour urine metanephrine screen during workup for secondary hypertension. Urine volume was found to be incorrectly inputted by the lab as 9750 mL rather than 975 mL. The urinary metanephrines were then recalculated and the 24-hour urinary metanephrines resulted within normal limits. This case highlights this unique and potentially under-recognised error in testing with 24-hour urine volume collection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although currently the primary strategy for the treatment of pheochromocytomas is surgery, it is associated with a high risk of intraoperative hemodynamic instability (IHD), even with adequate preoperative medical preparation, which may result in life-threatening situations. The aim of this study was to develop and validate a nomogram for preoperative prediction of IHD related to pheochromocytoma surgery. The development cohort consisted of 283 patients with pheochromocytoma who underwent unilateral laparoscopic or open adrenaletomy at our center between January 1, 2007 and December 31, 2016. The clinicopathological characteristics of each patient were recorded. The least absolute shrinkage and selection operator binary logistic regression model was used for data dimension reduction and feature selection, while multivariable logistic regression analysis was used to develop the prediction model. An independent cohort consisting of 119 consecutive patients from January 1, 2017 to December 31, 2018 was used for validation. The performance of the prediction model was assessed in regards to discrimination, calibration, and clinical usefulness. The predictors of this model included body mass index, coronary heart disease, tumor size, and preoperative use of crystal/colloid fluid. For the validation cohort, the model showed good discrimination with an area under the receiver operating characteristic of 0.767 (95% CI, 0.667-0.857) and good calibration (unreliability test, p = 0.852; Hosmer-Lemeshow test, p = 0.9309). Decision curve analysis demonstrated that the model was clinically useful. This nomogram to facilitate preoperative individualized prediction of IHD in patients with pheochromocytoma may help to improve the perioperative strategy and treatment outcome.

The diagnostic utility of different thresholds of elevated urinary fractionated metanephrine (UFM) for pheochromocytoma-paraganglioma (PPGL) was evaluated in 10 164 community-dwelling subjects (2012-2017). Levels were ≥1.5× the upper normal limit (UNL) in 276 subjects (2.7%) and ≥2×UNL in 138 (1.4%). PPGL was subsequently diagnosed in 59 (mean age 51.9 ± 14.3, 64% female); 58 (98.3%) with UFM ≥ 2×UNL. Positive predictive values (PPV) were 42% for UFM ≥ 2×UNL, 55% for UFM ≥ 2.5×UNL, and 69% for UFM ≥ 3×UNL. The main reason for PPGL screening (52.5%) was adrenal incidentaloma. Mean (median) metanephrine/normetanephrine levels were 6.7 ± 9×UNL (3 × UNL) and 6.1 ± 8.9×UNL (2.5 × UNL). Six patients (10.2%) had an extra-adrenal tumor (one malignant paraganglioma); one had bilateral pheochromocytoma. Only one patient presented with the "classic triad" (headache, palpitations, sweating). In conclusion, after excluding obvious reasons for false-positive results, thorough diagnostic assessment for PPGL is justified in all subjects with UFM ≥ ×2UNL. The PPV of milder UFM elevations is very low., (©2019 Wiley Periodicals, Inc.)

Objective: Some cases of pseudopheochromocytoma have been described among hypertensive patients with obstructive sleep apnea (OSA). This study examined whether a pathological rise of urinary metanephrines is a common feature in hypertensive OSA patients and, in such a case, whether the ventilation treatment during sleep (continuous or biphasic positive airway pressure) may normalize high metanephrines levels., Methods: Patients with endocrine diseases, drug abuse, therapy with TCA and cardiovascular events in the previous 6 months were excluded. Thirty-four hypertensive patients with OSA (BMI 40.6 ± 8.7 kg/m(2)) performed three 24-h urine collections for metanephrine assessment, before and after 1 month of ventilation therapy., Results: Urinary normetanephrine (uNMT) was above the normal limit in 21 of 34 of the patients. In the 16 to 21 patients with high uNMT who were compliant to ventilation treatment, uNMT decreased in 13 by 26% and normalized in six of 13. uNMT levels were associated with apnea hypopnea index (AHI) (r = 0.799, P < 0.0001) and minimal SaO2 (r = -0.700, P < 0.01). The ventilation therapy-induced changes in AHI were associated with those in uNMT (r = 0.689, P < 0.005). In the multivariate analysis with uNMT changes as dependent variable and changes in AHI, BMI, SBP as independent variables, only AHI changes were independently associated with uNMT changes (β = 0.738, P < 0.01)., Conclusion: Two-thirds of OSA hypertensive patients have uNMT values above the normal limit. The early identification of these patients is important as ventilation therapy can correct the pathological sympathoadrenal activation. Patients who do not normalize uNMT with ventilation therapy deserve a strict follow-up as this lack of normalization may indicate insufficient ventilation therapy or resistance of sympathetic hyperactivity to this treatment, not excluding an early stage of a chromaffin tumor.

Ambulatory blood pressure variability (ABPV) is a predictor of cardiovascular risk in hypertensives. Factors that contribute to ABPV are not well described. This pilot study aimed to investigate the relationship between ABPV and urine catecholamine metabolites in order to rationalise further therapeutic intervention in the management of hypertension. Twenty individuals (14 female), aged from 23 to 71 years, with primary hypertension were identified from referrals to a regional hypertension clinic. Individuals had a 24-h ambulatory blood pressure recording (Del Mar Reynolds), and a 24-h urine collection was analysed for metadrenaline and normetadrenaline by reverse-phase chromatography (Spherisorb ODS2) and electrochemical detection (Coulochem II). Normetadrenaline concentration correlated with systolic blood pressure (SBP) variability, r=0.493, P=0.02, and with SBP coefficient of variability, r=0.490, P=0.02. Metadrenaline concentration did not correlate with either SBP variability, r=0.177, P=0.43, or coefficient of variability, r=0.185, P=0.42. A correlation was observed between 24 h urinary normetadrenaline and measures of SBP variability but not 24 h urinary metadrenaline and blood pressure variability. It is hypothesised that sympathetic activity may influence SBP variability.

We report a patient who presented with two episodes of severe hypertension after intramuscular injection of betamethasone. The first attack was associated with pulmonary edema, while the second attack was associated with high anion gap metabolic acidosis, renal failure, hyperglycemia, and hypokalemia. The attacks led to the diagnosis of pheochromocytoma, which was confirmed by appropriate diagnostic tests. The tumor was excised successfully and the patient is presently asymptomatic.We believe that these episodes were initiated by glucocorticoid injection, an event reported in a few cases. We briefly review potential mechanisms resulted in hypertensive crisis in such patients.

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).

The patient is a 44-year-old man with a 4-year history of intermittently elevated blood pressure (BP) controlled by diet and exercise. Three months before evaluation he described daily "spikes" of BP with sharp unilateral headaches. He was seen in the emergency department with a BP of 212/106 mm Hg and was started on hydrochlorothiazide 25 mg daily. He denied palpitations, diaphoretic episodes, pallor, and tremor. The patient did not want to take medication and specifically requested an evaluation to rule out pheochromocytoma. Results from 24-hour urine tests for total metanephrines was 812 mg/24 h (normal, 130-520 mg/24 h), for total catecholamines was 53 mg/24 h (normal, 0-135 mg/24 h), and for vanillylmandelic acid was 4.7 mg/24 h (normal, <7 mg/24 h). Thyroid-stimulating hormone was 0.87 (normal, 0.4-4.0 IU/mL). Physical examination revealed normal optic fundi, negative cardiac examination results, and presence of peripheral pulses without bruits. His BP was now 136/74 mm Hg, with a heart rate of 76 beats per minute.

Objectives: To report one case of adrenal incidentaloma and to review the sensitivity and specificity of urine methanephrines in the diagnosis of pheochromocytoma., Methods: We report the case of a patient with high blood pressure and a left adrenal incidentaloma. Surgical excision of the mass was indicated after elevated urine methanephrine., Results: Pathologic study of the nodule established the diagnosis of cortical adenoma., Conclusions: The elevation of urine normethanephrine is a non-specific parameter for the diagnosis of pheochromocytoma.

This Hypertension Grand Rounds shows how applying new clinical laboratory techniques helped to diagnose pheochromocytoma in a difficult case. In the setting of long-standing, sustained hypertension, the patient had a hypertensive paroxysm during anesthesia induction for surgery, leading to suspicion of a pheochromocytoma. Conventional testing, including CT scanning and fractionated urinary metanephrine test, was not diagnostic. The patient had another hypertensive paroxysm during subsequent anesthesia induction, requiring intensive care. Consistently elevated plasma levels of free normetanephrine provided the first and only biochemical evidence for a pheochromocytoma in this case. 6-[18F]Fluorodopamine positron emission tomography and 123I-metaiodobenzylguanidine scintigraphy subsequently agreed on the existence of a small left adrenal mass, which when removed surgically proved to be a pheochromocytoma. Postoperatively, plasma levels of normetanephrine normalized, and there were no further hypertensive paroxysms, although the patient remained hypertensive. This case illustrates the superiority of plasma levels of free (unconjugated) metanephrines, compared with other biochemical tests, to detect pheochromocytoma. It also confirms that functional imaging by 6-[18F]fluorodopamine or 123I-metaiodobenzylguanidine scanning can localize pheochromocytoma in difficult cases in which other imaging tests are not diagnostic.

A 44-year-old woman presented with sudden onset of chest pain, headache and nausea. Physical examination was remarkable for mild hypotension and tachycardia. ECG demonstrated sinus tachycardia with poor R wave progression in precordial leads and T wave inversion in leads V1-3. Cardiac enzymes were raised. Echocardiographic examination revealed normal cavity diameters with basal and mid left ventricular hypokinesia and an ejection fraction of 45%. A diagnosis of non-ST elevation myocardial infarction was made. A few orthostatic hypotensive attacks occurred at follow-up. A coronary angiogram showed normal coronary arteries. Within a few days, the echocardiographic findings, ECG and all cardiac markers had returned to normal. Two months later she presented with headache, palpitation, fever, neck swelling, flushing and hypertensive attacks. Phaeochromocytoma was diagnosed on the basis of increased metanephrine on urinalysis and a left suprarenal mass on CT scan.

This report describes a rare case of ACTH-independent macronodular adrenal hyperplasia (AIMAH) arisen with symptomatic severe hypertension and hypokaliemia. A 55-year-old man was admitted to hospital with a clinical picture characterized by several episodes of transient ischemic attacks (TIA) and right hemiplegia, related to severe arterial hypertension. Laboratory tests showed urinary levels of catecholamines, metanephrines and vanillylmandelic acid (VMA) in normal range; high urinary free cortisol excretion, elevated serum cortisol with loss of the circadian rhythm and low ACTH plasma levels. ACTH failed to respond to CRH administration. Serum cortisol levels were not modified after high doses of dexamethasone. MRI showed bilateral macronodular hyperplasia of adrenal glands, whereas pituitary-MRI did not show tumoral lesions. Therefore, ACTH-independent macronodular hyperplasia was suspected. Though obese, the patient had no typical Cushing habit, and symptomatic hypertension with hypokaliemia was the only clinical evidence for this rare kind of Cushing's syndrome. After obtaining a satisfactory control of blood pressure, the patient was successfully submitted to laparoscopic bilateral adrenalectomy and underwent complete clinical remission. The histology showed adrenal macronodular hyperplasia. During the twenty-four month follow-up, the patient had no further transient ischemic attacks or need of glucocorticoid replacement therapy and withdrew the antihypertensive drugs.

The association between neuroblastic tumours and congenital heart disease is widely confirmed in the literature references. The authors describe a case of a patient with congenital heart disease, high blood pressure, renal artery stenosis and high levels in 24 hours urine metanephrines. A MIBG-I-123 scintigraphy was essential for the diagnosis of neuroblastic tumour.

Objectives: Phaeochromocytoma may be either sporadic or part of a familial cancer syndrome. We have investigated whether there are differences between sporadic and MEN 2A phaeochromocytomas., Design: A retrospective study. We analysed age at presentation, sex, mode of presentation, clinical data, laboratory and imaging techniques, treatment, pathology and follow-up., Patients: Forty-six patients diagnosed with phaeochromocytoma between 1979 and 1995 (23 sporadic and 23 familial) at the Hospital Universitario Virgen de la Arrixaca (Murcia, Spain), a tertiary referral centre., Results: Mean age at presentation was 47 +/- 16 years for sporadic and 38 +/- 11 years for familial phaeochromocytoma (P < 0.05). The most common clinical feature and the presenting feature in cases of isolated phaeochromocytoma was hypertension. Of the MEN 2A patients, 52% were asymptomatic at diagnosis and only 35% presented with hypertension. Levels of adrenaline, noradrenaline, dopamine and metanephrines in a 24-hour urine connection confirmed the diagnosis in 95% of the isolated and 91% of the familial phaeochromocytomas. Computed tomography located 100% of the sporadic and 76% of the familial phaeochromocytomas (P < 0.02). All the MEN 2A phaeochromocytomas were bilateral compared with none of the sporadic phaeochromocytomas (P < 0.001). All the patients with familial phaeochromocytoma underwent bilateral adrenalectomy. The patients with sporadic phaeochromocytoma had the affected gland or the tumour, if extraadrenal, removed., Conclusions: In comparing sporadic and MEN 2A phaeochromocytoma we found differences in age at presentation, mode of presentation, clinical data, duration of clinical features, imaging findings bilaterality and type of surgical treatment required.

The dosage of urinary catecholamines and their metabolites is a main element of diagnosis in the research of a pheochromocytoma in patients with high blood pressure. The literature reports high values of these compounds in patients treated with labetalol (an alpha/beta-blocker). An analytical interference has been evoked to explain these misleading results, which have not been observed with other beta-blockers. The goal of this work was to look for this eventual analytical interference in the dosage of urinary metanephrine by reversed phase liquid chromatography coupled with electrochemical detection, in patients with high blood pressure. Eighteen hypertensive patients, 52 +/- 14 years old, were included in the study. In 8 patients, a dosage of metanephrine, normetanephrine and creatinine on a 24 hours urine sample was performed before (D1) and 24 hours after (D3) the prescription of labetalol (200 mg twice a day). In the other group, labetalol was not prescribed but dosage was made in the same conditions. Urinary excretion of these compounds (metanephrine+normetanephrine) divided by urinary creatinine was not modified in the treated group (0.16 +/- 0.08 vs 0.14 +/- 0.04), nor in the reference group (0.17 +/- 0.08 vs 0.17 +/- 0.08). This study shows that administration of labetalol in patients with essential hypertension does not interfere with urinary metanephrine and normetanephrine determination after 48 hours of treatment. This implies that research for a pheochromocytoma is possible in patients with hypertension and receiving labetalol, by using reversed phase liquid chromatography coupled with an electrochemical detector for the dosage of urinary metanephrine and normetanephrine.

The urinary excretion of normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid was quantified by HPLC in hypertensive patients who were being routinely investigated for the exclusion of pheochromocytoma. The data were used to calculate reference intervals for these analytes. Age- and sex-specific 95% reference intervals for 24-h urinary excretion were as follows (mumol/24 h): normetanephrine in men ages 16-35 years (n = 17) 0.7-3.4, in men older than 35 years (n = 121) 0.8-5.1, in women ages 16-35 years (n = 41) 0.5-2.1, and in women older than 35 years (n = 144) 0.6-3.3 mumol/24 h; metanephrine in men (n = 138) 0.3-2.0, and in women (n = 185) 0.2-1.3; and 3-methoxy-4-hydroxymandelic acid in men (n = 142) 10-54, and in women (n = 184) 9-38. Normetanephrine or metanephrine excretion rates or both exceeded the proposed reference intervals in seven of the eight patients with pheochromocytoma. Determination of 3-methoxy-4-hydroxymandelic acid excretion did not yield any additional diagnostic information.

Twenty-four men, mean age 63 +/- 1.7 years, with systemic systolic hypertension were studied before and after 1 month of therapy with oral hydrochlorothiazide, 50 mg/day. The control mean plasma volume was 2,664 +/- 96 ml, cardiac index 3.9 +/- 0.2 liters/min/m2, stroke volume index 52 +/- 2 ml/beat/m2, systemic vascular resistance 1,351 +/- 80 dynes s cm-5, plasma aldosterone 8.6 +/- 1.0 ng/dl and 24-hour urinary excretion of metanephrines 0.371 +/- 0.044 mg. On renin-sodium profiling in 23 patients, 12 were classified into a normal group and 11 into a low-renin group; none had high renin values. Based on multiple regression analysis, the 24-hour urinary excretion of total metanephrines appeared to be the single most important factor explaining 28% of the variability in systolic blood pressure (BP). After therapy with oral hydrochlorothiazide, the elevated systolic BP decreased (p less than 0.0001) and diastolic BP decreased (p less than 0.005), with concomitant reduction in systemic vascular resistance (p less than 0.03). Patients in both the normal- and low-renin groups had normal plasma volume and responded similarly to thiazide diuretic therapy, without symptomatic side effects.

1. The 24 h urinary excretion of adrenaline, noradrenaline, normetadrenaline, metadrenaline and vanilloylmandelic acid has been compared in 17 male normotensive subjects and 25 age-matched male hypertensive patients studied under similar in-patient conditions. 2. 24 h urinary metadrenaline was significantly lower in the hypertensive patients. With this exception, no significant differences were found between the two groups when the total 24 h excretion of free catecholamines and their metabolites was analysed. 3. Diurnal variation in free catecholamine excretion was found in both normotensive and hypertensive subjects. There was no corresponding variation in metabolite excretion. 4. No correlation could be established between systolic or diastolic blood pressure and the amounts of the catecholamines or their metabolites in the urine of either group. 5. The results are considered in the light of recent work demonstrating high plasma catecholamine concentrations in hypertension. They lend no support to the concept that excessive circulating catecholamines are responsible for the elevated blood pressure in essential hypertension.

The circadian rhythms of sodium (Na+), potassium (K+), aldosterone (ALDO), 11-deoxycorticosterone (DOC), 18-hydroxy-DOC (18-OH-DOC), cortisol (F), corticosterone (B), adrenaline (A), noradrenaline (NA), dopamine (DA), metanephrine (MN), normetanephrine (NMN), homovanillic acid (HVA), kallikrein (KE) and prostaglandins E (PGE) and F2 alpha (PGF2 alpha) excretion were studied in eight young borderline hypertensive men (BHT) and in six healthy age-matched normotensive subjects (NT) during hospitalization, after adaptation to the hospital regimen and a diet containing 135 mmol Na+ and 90 nmol K+. Urine samples were collected in 4 h periods for 24 h: 1. at normal daily activity, 2. during a 24 h bed rest. The results were evaluated by means of cosinor analysis. The circadian rhythms of ALDO, F, B, 18-OH-DOC and PGF2 alpha excretion were similar in both groups, with the exception of higher mesors of urinary ACTH-dependent corticosteroids in BHT at normal daily activity. Differences were observed in the rhythms of Na+, A, NA, DA, HVA and PGE excretion, this, however, above all during the normal daily regimen. The curve of urinary Na+ was flat in BHT due to a higher portion of Na+ excreted during the night. In the rhythms of A, NA and PGE excretion, the acrophases were shifted to the later hours in BHT, and the mesors of A and NA were also significantly higher. In contrast, DA and HVA excretion curves were flat with a lower mesor. These changes normalized, or at least mitigated, during a 24 h bed rest. The results of the study show that the circadian rhythm of Na+ excretion are disturbed already in the initial stage of hypertension. The likely cause is the exaggerated rise in adrenergic activity in the kidney during the day, induced by orthostasis and the concomitant physical (and mental?) activity, which is inadequately compensated for by the activation of natriuretic mechanisms.

Patients with essential hypertension were treated for four weeks with the alpha- and beta-adreno-receptor blocking agent labetalol. Urinary excretion of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid was measured with various methods before and during treatment. An unidentified substance interfering with the fluorimetric method for catecholamines and the photometric assay for metanephrines caused falsely high values of those substances. Using appropriate methodology no changes of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid excretion were found after labetalol therapy. Our findings are important in preventing errors in the diagnosis of pheochromocytoma as well as in the evaluation of the effects of labetalol on the sympathetic nervous system in man.

The dipping of snuff provoked paroxysmal hypertension that induced myocardial ischemia in a 69-year-old woman with pheochromocytoma. The diagnosis of her tumor was delayed by a report of a falsely low urine metanephrine level, resulting from interference with the metanephrine assay by meglumine present in the urine because of contrast coronary angiography performed on the day of urine collection.

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.

A case is reported of a patient with a cerebral aneurysm in whom it was difficult to induce hypotension. The hyperadrenergic state mimicked, in some respects, that seen in patients with neural crest lesions. Possible mechanisms are discussed and the anaesthetic management described.

In a series of 53 pheochromocytoma patients operated on at Sahlgren's Hospital during 1956-82, a positive linear correlation is established between the 24-hour urinary excretion of vanilmandelic acid (mumol/24 h) and tumour mass (g). A similar correlation was found between the excretion of metanephrines and tumour mass in 33 subjects. The patients were subgrouped according to their type of hypertension. A statistically significant correlation between vanilmandelic acid excretion and tumour mass persisted in groups IA (sustained hypertension without attacks), IB (sustained hypertension with attacks), and II (paroxysmal hypertension) but not in group III (miscellaneous patients). There was also a correlation between metanephrine excretion and tumour mass in groups IB (n = 8) and II (n = 12). In 10 patients with the syndrome of multiple endocrine neoplasia, a positive correlation was found between tumour mass and the excretion of vanilmandelic acid, metanephrines and adrenaline.

Objective: To determine the optimal clinical strategy utilizing either 1) serum catecholamines, 2) urinary metanephrines, or 3) urinary vanillylmandelic acid measurements in the evaluation of hypertensive patients with suspected pheochromocytoma., Design: Prospective clinical determination of test-operating characteristics., Setting: Tertiary care university medical center., Patients/participants: 415 patients referred for evaluation of suspected pheochromocytoma., Interventions: All subjects had measurements of the three above-mentioned biochemical tests with the diagnosis of pheochromocytoma established by tissue confirmation., Results: All three biochemical tests were similar in sensitivity (0.70-0.75), specificity (0.90-0.95), and receiver operating characteristics. With an estimated disease prevalence of 5.9% in symptomatic hypertensive patients, the predictive value of any single negative test would be 98% in ruling out disease., Conclusions: All three biochemical tests have similar performance characteristics and only a single test need be performed to exclude pheochromocytoma in most symptomatic hypertensive patients in a primary care population.

1. Plasma noradrenaline concentrations were similar in normotensive and hypertensive outpatients, but were significantly lower in laboratory control subjects. 2. Standing plasma noradrenaline concentrations were similar in all three groups. 3. Urinary vanillyl mandelic acid, catecholamines and metanephrines were also similar in the normotensive and hypertensive groups. 4. Laboratory controls, possibly because of familiarity with the techniques of sphygmomanometry and blood sampling, may attain a 'basal' resting level of sympathetic nervous discharge more readily and rapidly than subjects who are unfamiliar with such procedures. 5. After orthostatic stimulation by standing for 2 min, the activity of the sympathetic nervous system, as determined by pulse rate and plasma noradrenaline concentrations, was similar in the three groups, despite the lower starting values in the laboratory staff. 6. The absence of differences in plasma noradrenaline or urinary catecholamine and metabolite concentrations does not support the hypothesis of excessive sympathetic nervous activity in essential hypertension.