Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.

An international survey of polypectomy training and assessment.

Background and study aims Colonic polypectomy is acknowledged to be a technically challenging part of colonoscopy. Training in polypectomy is recognized to be often inconsistent. This study aimed to ascertain worldwide practice in polypectomy training. Patients and methods An electronic survey was distributed to endoscopic trainees and trainers in 19 countries asking about their experiences of receiving and delivering training. Participants were also asked about whether formal polypectomy training guidance existed in their country. Results Data were obtained from 610 colonoscopists. Of these responses, 348 (57.0 %) were from trainers and 262 (43.0 %) from trainees; 6.6 % of trainers assessed competency once per year or less often. Just over half (53.1 %) of trainees had ever had their polypectomy technique formally assessed by any trainer. Approximately half the trainees surveyed (51.1 %) stated that the principles of polypectomy had only ever been taught to them intermittently. Of those trainees with the most colonoscopy experience, who had performed over 500 procedures, 48.2 % had had training on removing large polyps of over 10 mm; 46.2 % (121 respondents) of trainees surveyed held no record of the polypectomies they had performed. Only four of the 19 countries surveyed had specific guidelines on polypectomy training. Conclusions A significant number of competent colonoscopists have never been taught how to perform polypectomy. Training guidelines worldwide generally give little direction as to how trainees should acquire polypectomy skills. The learning curve for polypectomy needs to be defined to provide reliable guidance on how to train colonoscopists in this skill.

Genetic influence on blood pressure and lipid parameters in a sample of Polish twins.

We studied 76 healthy monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs (mean age 35 +/- 8 years, body mass index, BMI, 23.6 +/- 3.9 kg/m2) to determine genetic and environmental contributions to systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-chol), high-density lipoprotein cholesterol (HDL-chol) and triglycerides (TG)I. SBP, DBP and HR were measured clinically and by ambulatory blood pressure monitoring (ABPM). Parameters of the genetic models for age-, sex- and BMI-adjusted data were estimated by model fitting and path analysis technique using LISREL 8. We found significant genetic effect on SBP and DBP for both clinical and ABP measurements, ranging from 37% for night-time ambulatory DBP to 79% for daytime ambulatory SBP. Estimates of genetic effects were higher for daytime than night-time ABP values, and higher for ambulatory 24-h SBP than office SBP measurements, with the reverse true for DBP. Significant genetic effect on HR ranged from 59% for office measurements to 69% for 24-h mean values. In summary, we also found genetic effect on TC, LDL-chol and HDL-chol with estimates ranging from 36% to 64%, but not on TG. Furthermore, a shared environmental component for TG was found, estimated at 36%. We showed significant genetic effect on both office and ambulatory BP and HR, with stronger genetic effect on daytime than night-time BP. We also found genetic effect on TC and lipoprotein fractions, but no significant genetic effect on TG. Environmental factors influencing serum TG, such as alcohol consumption, may explain the apparent lack of genetic effect in this healthy, non-obese population.

Dopamine and dopa urinary excretion in patients with pheochromocytoma--diagnostic implications.

Pheochromocytoma, a potentially life-threatening disease, is a rare cause of hypertension. Most pheochromocytomas secrete excessive amounts of noradrenaline and adrenaline. It has been suggested by some authors that high circulating levels of dopamine and the catecholamine precursor dihydroxyphenylalanine (dopa) are more often associated with malignant rather than benign pheochromocytomas. Therefore the aim of this study was to evaluate urinary excretion of dopamine and dopa in patients with pheochromocytoma and to determine their role as a potential marker for malignancy of the tumour. We retrospectively analysed 120 consecutive patients (mean age 41 +/- 12 years) with histopathologically confirmed pheochromocytomas. All subjects were divided as follows: group 1 included patients with both elevated and normal dopamine urinary excretion; group 2 was characterized by increased and normal dopa urinary excretion. Dopamine urinary excretion was increased in all patients with malignant pheochromocytoma, but higher levels were also observed in some patients with a benign tumour included in group 1. Urinary excretion of dopa was in the normal range in all subjects with malignant pheochromocytoma. The results indicate that in some pheochromocytoma patients excessive dopamine excretion may point to malignant tumour, but is not a discriminating marker for malignancy in the whole studied group.

Immunomorphological studies and cytometric DNA ploidy in diagnostics of pheochromocytoma.

The aim of the study was to define features indicating malignancy in pheochromocytoma through analysis of clinical data, immunomorphological and nuclear DNA ploidy patterns with flow cytometry. The studied group consisted of 33 patients with hypertension and adrenal gland tumor. In all patients 24 hr measurements of adrenaline, noradrenaline, dopamine and their metabolites were taken and the content of these substances in the tumor tissue was measured. Morphologically most pheochromocytomas displayed alveolar pattern with polyhedral cells with clear cytoplasm. Nuclear pleomorphism was infrequent and mitotic figures were rare. In 5 tumors areas of ganglioneuromatous differentiation were present with neurofilament expression. Morphological features indicating malignancy were noted--vascular emboli of tumor cells, capsular infiltration and foci of necrosis. However, in the patient with metastases evident during operation, none of those features was found in the tumor sample. All pheochromocytomas expressed neuroendocrine markers (chromogranin A, synaptophysin and NSE) and most also vimentin. Reactivity of other markers was negligible. In DNA ploidy studies in 22/33 cases there was DNA diploid (normal) pattern. The patient with metastases belonged to this group. In 3 cases there were aneuploid tumor cells on histograms and in 8 increased number of tetraploid cells. The follow-up period of our patients was 1-43 months.

Incidence and clinical relevance of RET proto-oncogene germline mutations in pheochromocytoma patients.

BACKGROUND: Autosomal dominant cancer syndrome--multiple endocrine neoplasia type 2 (MEN 2), may exist more often than expected in patients with pheochromocytoma. Germline mutations identified recently in MEN 2 can be revealed by genetic screening. OBJECTIVE: To evaluate the frequency of RET (rearranged during transfection) mutations in patients with pheochromocytoma. DESIGN AND METHODS: We genetically screened germline mutations in the RET proto-oncogene and clinically re-evaluated patients with pheochromocytoma. A pentagastrin test and other biochemical studies were performed in all patients. SETTING: Department of Internal Medicine and Hypertension, The Medical University of Warsaw, Warsaw, Poland and the Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany. PARTICIPANTS: Seventy seven unselected patients with pheochromocytoma (19 men, 58 women, mean age: 51.55 +/- 1.5 years; pheochromocytoma confirmed histopathologically) out of 162 diagnosed and treated in the years 1957-1998 in the Department of Internal Medicine and Hypertension in Warsaw, Poland. The other 85 patients did not respond to the written invitation. MAIN OUTCOME MEASURES: The finding of RET mutations and diagnosis of MEN 2 in patients with pheochromocytoma. RESULTS: Genetic testing revealed germline mutations in the RET proto-oncogene in six patients (7.8%). All carriers had mutation of exon 11, codon 634: TGC to CGC. In four patients with this mutation, medullary thyroid carcinoma (MIC) was diagnosed and in three cases, surgically treated. Biochemical parameters: parathormone 31.88 +/- 2.87 pg/ml, calcitonin: 0 min 0.23 +/- 0.14 ng/ml; 2 min 0.49 +/- 0.21 ng/ml; 5 min 0.48 +/- 0.21 ng/ml, metoxycatecholamines: 601.62 +/- 42.71 microg/24h, epinephrine: 1.94 +/- 0.17 microg/24h, norepinephrine 13.96 +/- 1.3 microg/24h, carcinoembryonic antigen (CEA) 9.94 +/- 4.3 ng/ml. Ambulatory blood pressure monitoring (ABPM): systolic blood pressure (SBP): 116 +/- 1.9 mmHg, diastolic blood pressure (DBP): 73.7 +/- 0.9 mmHg. Clinical, biochemical and imaging procedures did not reveal any recurrence of pheochromocytoma in the 77 patients studied. CONCLUSIONS: Patients with pheochromocytoma should be genetically screened for mutations of the RET proto-oncogene. These patients should undergo clinical screening for MEN 2. In addition, genetic studies can be useful for the screening of the families of the carriers.

Effects of the correction of renal artery stenosis on blood pressure, renal function and left ventricular morphology.

The aim of this study was to evaluate the effect of renal artery stenosis (RAS) correction in hypertensive patients on 24 h SBP, 24 h DBP, creatinine clearance (GFR), urinary albumin excretion (UAE) and LV morphology and mass (LVMI). A total of 61 hypertensive patients with RAS undergoing PTRA and/or surgical treatment entered the prospective study. The final analysis was done in 44 patients (age range 45.8 +/- 16.2 years) with RAS (atherosclerosis (ASC) 31 patients, fibromuscular dysplasia (FMD) 12 patients, arteritis 1 patient) who underwent PTRA (34 patients) or surgical treatment (10 patients) and presented no Doppler signs of restenosis (or a new stenosis) during 1-year observation. The pre-interventional assessment repeated after 6 and 12 months included ABPM, GFR, UAE and echocardiography. The results were analysed in the combined group (CG) and in according aetiology. 24 h SBP and 24 h DBP decreased in all groups 6 months post-intervention and did not change further. Cure of HT was observed in 35% and 29% of ASC patients at 6 and 12 months respectively; and in 58% of FMD patients. Failure rate at 12 months was 48% in ASC against 25% in FMD. The mean GFR in CG was higher 12 months after intervention. The increase in GFR was noted in 45% of patients, the decrease in 25% of patients at 12 months. Normal values of UAE were found in 71% of patients, pre- and post-intervention alike. Mean LVMI and number of patients with LVH in CG decreased already during the initial 6 months post-intervention and did not change further. In conclusion, correction of RAS leads to cure of or improved control of hypertension in the majority of the patients with FMD, but in the ASC group in about half of cases no BP cure or improvement was seen. The renal function was improved or stable in two-thirds of patients after revascularization. Successful renal revascularization was followed by regression of LVH, which was evident within 6 months post-intervention.

Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy?

The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic < or =90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment.

Plasma fibrinogen as a risk factor for restenosis after percutaneous transluminal renal angioplasty in patients with atherosclerotic renal artery stenosis.

BACKGROUND: In contrast to those for coronary restenosis, the data regarding the risk factors for renal restenosis are limited. OBJECTIVE: To evaluate potential humoral risk factors for restenosis after percutaneous transluminal renal angioplasty (PTRA). METHODS: We studied 27 patients aged 54+/-10 years with atherosclerotic renal artery stenosis in a 1-year prospective follow-up. Restenosis (confirmed by angiography) occurred in eight patients 1-6 months after PTRA. We detected no Doppler ultrasound evidence of restenosis in 19 patients throughout 1 year. Blood studies were done before PTRA for all patients, at the time of diagnosis of restenosis and, for those without restenosis, after 1 year. including determinations of fibrinogen, lipids, platelets and leukocytes. RESULTS: The mean level of fibrinogen in patients who experienced restenosis was higher than that in those who did not (450+/-150 mg% versus 337+/-57 mg%, P < 0.01) and remained unchanged for both groups during follow-up. The other parameters did not differ between the groups before PTRA and did not change over time, with the exception of platelet count in patients who did not experience restenosis, which had decreased from 253+/-93G/l to 200+/-63G/l (P < 0.01) 1 year after PTRA. The logistic multiple regression analysis disclosed that an increment of fibrinogen level by 100 mg% was linked with an odds ratio for restenosis of 3.2 (95% confidence interval 1.1-9.8). CONCLUSIONS: Restenosis was associated with higher than normal levels of fibrinogen before PTRA. A high plasma fibrinogen level might play a role in the development of restenosis after PTRA.

Blood pressure, plasma NPY and catecholamines during physical exercise in relation to menstrual cycle, ovariectomy, and estrogen replacement.

Some evidences indicate that the female sex hormones protect against the development of cardiovascular diseases. Modulation of sympathetic activity may be one of the possibilities. We investigated the influence of treadmill stress on blood pressure (BP) and plasma neuropeptide Y (NPY), norepinephrine (NE) and epinephrine (E) concentrations in 11 normotensive, menstruating women in the follicular (HWf) and luteal (HWl) phases and in eight ovariectomized women, before (OVX) and after estrogen supplementation (OVXe). Both at rest and during exercise there were no differences in BP between HWf and HWl and between OVX and OVXe. During stress BP was significantly lower in HWf and HWl than in OVX but not in OVXe. NPY did not differ significantly between the groups of women either at rest or during activity. We did not observe differences in resting and stimulated NE and E between HWf and HWl and between OVX and OVXe. Neither resting nor activated NE and E differed between the groups, except higher stimulated NE in OVX than in HWf. These results suggest that the female sex hormones may modulate the BP response to dynamic exercise. Our data support evidence that this influence may be exerted by circulating catecholamines and not by NPY.

Alterations in plasma neuropeptide Y immunoreactivity and catecholamine levels during surgical removal of pheochromocytoma.

BACKGROUND: Neuropeptide Y, an abundant neurohormone present with catecholamines in the adrenal medulla, is a potent non-adrenergic vasoconstrictor and a vascular growth factor. OBJECTIVE: To determine the mechanism of the release from, and possible role of neuropeptide Y in, pheochromocytomas, compared with those of catecholamines. METHODS: Plasma and tumour levels of neuropeptide Y-immunoreactivity (by, radioimmunoassay) and of noradrenaline and adrenaline (by a radioenzymatic method) in 29 patients (19 women and 10 men, aged 22-68 years) were measured during surgical removal of the tumour, during alpha-adrenergic and beta-adrenergic blockade. Arterial systemic blood samples were withdrawn before the ligation of the vessels supplying the tumour, during its surgical manipulations and after its removal, while haemodynamics was monitored. RESULTS: Plasma neuropeptide Y levels in 17 patients (58.6%, group I) significantly increased during manipulations of the pheochromocytoma and returned completely to normal after its removal. This response was independent of the plasma neuropeptide Y immunoreactivity manipulation and was correlated to increases in plasma noradrenaline (r = 0.638, P < 0.02) but not adrenaline levels. Manipulation-induced increases in plasma neuropeptide Y-immunoreactivity were associated with greater neuropeptide Y content in tumours (r = 0.508, P < 0.05) but neither plasma nor tumour levels of neuropeptide Y immunoreactivity were correlated to tumour mass. Plasma levels of neuropeptide Y immunoreactivity in the remaining 12 patients (41.4%, group II) remained unchanged throughout the experimental period, while levels of circulating catecholamine rose. In all, in spite of our attempt at complete adrenergic blockade, tumour manipulation elevated arterial blood pressure and these changes were significantly correlated to increases in levels of catecholamines in patients in both groups but also to plasma neuropeptide Y immunoreactivity in patients in group I. CONCLUSION: Pheochromocytomas exhibit different patterns of secretion. For about half of the patients either the secretion of neuropeptide Y is uncoupled from that of catecholamines or its secretion could be obscured by an increase in degradation of neuropeptide Y to inactive fragments undetectable by radioimmunoassay.

Secondary hypertension in the elderly.

This paper discusses the most significant aspects of secondary hypertension in older patients against the background of a rising proportion of elderly in the hypertensive population. Renal artery stenosis and pheochromocytoma are singled out as those causes of secondary hypertension which appear to be related to older age. The available data relevant to epidemiology of these conditions and age-dependent clinical characteristics are reviewed. Preservation of renal function in the elderly with renal artery stenosis is underlined as an important goal of therapy with revascularising techniques. It is proposed that screening for renal artery stenosis and pheochromocytoma may be equally important in the elderly as in the younger hypertensive patient.

Regression of left ventricular hypertrophy in hypertensive patients after 1 year of treatment with rilmenidine: a double-blind, randomized, controlled (versus nifedipine) study.

OBJECTIVE: To assess the effect of 1-year treatment with rilmenidine, an oxazoline compound that exerts its antihypertensive effects through binding to imidazoline receptors in the brainstem, on left ventricular hypertrophy (LVH) secondary to essential, mild-to-moderate hypertension [supine diastolic blood pressure (DBP)95-115 mmHg]. METHODS: We performed a double-blind, randomized, controlled (versus slow-release nifedipine) trial. Adjustment of treatment took place every month (M) between inclusion (MO) and an evaluation after 6 months (M6), then during M9 and after 1 year (M12) to achieve supine DBP values < or = 90 mmHg. Patients were dropped from our study if they had DBP> 95mmHg during two consecutive visits or DBP>115 mmHg on one occasion. The daily dosage of rilmenidine was 1 mg, and could be increased to 2 mg/day. The daily dosage of slow-release nifedipine was started from the beginning at the maximum dosage of 40 mg/day, so that there was no true adjustment of treatment despite the allocation of patients to a different unit in the case of DBP> 95 mmHg. The primary criterion was the change in left ventricular mass index (LVMI, g/m2), assessed by echocardiography, between MO and M12 for patients who completed the trial. RESULTS: After a 1-month placebo run-in period, 76 patients were selected and 73 were included (35 treated with rilmenidine and 38 treated with nifedipine). Fifteen patients withdrew from the study and two completed the study with a major deviation from protocol, leaving 56 patients (24 treated with rilmenidine and 32 treated with nifedipine) for a per-protocol analysis. Baseline demographic characteristics and history of arterial hypertension for the rilmenidine and nifedipine groups were similar, for included patients and for those taken into account for the per-protocol analysis. Between MO and M12, DBP in members of the per-protocol population was adequately controlled for those in the rilmenidine group (102.7+/-4.6 versus 88.5+/-7.1 mmHg, respectively) and for those in the nifedipine group (102.7+/-5.1 versus 85.6+/-79 mmHg, respectively). During MO, LVMI of patients in the rilmenidine group (176.9+/-41.3 g/m2) was slightly higher than that of patients in the nifedipine group (172.6+/-35.1 g/m2). During M12, LVMI was observed to have decreased both for patients in the rilmenidine group (to 154.8+/-40.2 g/m2, a decrease of 22.1+/-23.3 g/m2, P< 0.001) and for those in the nifedipine group (to 145.6+/-36.4 g/m2, a decrease of 26.9+/-29.5 g/m2, P< 0.001) but the difference between these two groups was not significant (P= 0.5). CONCLUSION: One-year treatment with a daily dosage of 1 or 2 mg rilmenidine achieves a significant reduction of left ventricular mass, which is not statistically different than that occurring with a daily dosage of 40 mg of slow-release nifedipine.

Hemorrheological indices, catecholamines, neuropeptide Y and serotonin in patients with essential hypertension.

Hemorrheological and humoral abnormalities and excessive platelet activity can predict the development of cardiovascular complications in patients with essential hypertension. A study was conducted to assess the influence of gender on these factors and the interrelations between changes in hemorrheology and the sympatho-adrenal system in 54 patients (18 women, 36 men) with essential hypertension (aged 39.6 +/- 9.7 years) and 25 healthy volunteers (10 women, 15 men; aged 36.0 +/- 7.2 years). A decrease in erythrocyte deformability (p < 0.01) was found in the hypertensive men compared with the hypertensive women. Hematocrit (p < 0.01), blood viscosity at the shear rates of 0.3 s-1 (p < 0.01) and 6 s-1 (p < 0.01), plasma viscosity (p < 0.01), erythrocyte aggregation (p < 0.01), and neuropeptide Y (p < 0.02) concentrations were higher in the hypertensive men than in the hypertensive women. A positive correlation between blood fibrinogen and serotonin was found in the pooled hypertensive group and in the hypertensive men (p < 0.01) and between blood viscosity (shear rate 6 s-1) and neuropeptide Y in the pooled hypertensive group (p < 0.01). Neuropeptide Y correlated with filtration time of 1 mL blood in the hypertensive men (p < 0.05) and in the pooled normotensive group (p < 0.01) and with beta-thromboglobulin in the hypertensive women (p < 0.001). A positive correlation was also found in the hypertensive men between erythrocyte and platelet aggregation (p < 0.01) and between beta-thromboglobulin and adrenaline (p < 0.01). Hemorrheological and humoral abnormalities are more pronounced in men than in women with essential hypertension and may contribute to the increased incidence of cardiovascular events in men.

Evaluation of plasma aldosterone to plasma renin activity ratio in patients with primary aldosteronism.

The plasma aldosterone to renin activity ratio (A/PRA) was assessed retrospectively in 103 patients with primary aldosteronism including 74 patients with surgically proven adrenal cortical adenoma (APA) and 29 patients with idiopathic adrenal cortical hyperplasia (IHA). The results were compared with those obtained in 31 patients with essential hypertension (EH) and 45 healthy normotensive controls. The upper limit of normal A/PRA ratio, as obtained in the controls was 17.8. This value was exceeded in 89% of patients with APA; postoperatively it decreased in 97% of the APA group, and returned to normal in 81%. In the IHA group the A/PRA was elevated in 70% of patients. The normal ratios in patients with primary aldosteronism were associated with unsuppressed plasma renin activity (PRA). Although the mean values of the A/PRA ratio differed significantly between the groups, complete separation was not obtained. The serum potassium level at time of testing did not influence the diagnostic value of the A/PRA ratio, although an inverse correlation between serum potassium and the A/PRA ratio was found in the patients with APA. This study supports the high sensitivity of the A/PRA ratio in diagnosis of primary aldosteronism, however, a single determination with a normal result may not be sufficient for exclusion of the disease.

[Evaluation of the usefulness for measuring catecholamines and their principle metabolites in the diagnosis of pheochromocytoma]. / Ocena przydatnosci oznaczania katecholamin i ich glównych metabolitów w diagnostyce guzów chromochlonnych.

Objective of the study was assessment of the usefulness of determination of noradrenaline (NA) and adrenaline (A) in urine and blood as well as the total methoxycatecholamines (MNA +MA), vanillylmandelic acid (VMA), DOPA and dopamine (DA) urinary excretion in diagnosis of pheochromocytoma. The experience based on 155 patients with pheochromocytoma (105F, 50M, age 18-82 yrs) diagnosed in the Department of Hypertension and Angiology Academy of Medicine in Warsaw will be discussed. In all patients excluding 2 cases pheochromocytoma has been proven histopathologically. The most considerable diagnostic usefulness of MNA + MA indication was proven. MNA + MA was increased in 96.6 patients. In 89.6% patients an increased excretion of NA and A or one of this catecholamines was demonstrated. An increased excretion of VMA was demonstrated in 75%. The excretion of DOPA and dopamine was tested in 120 cases. An increased excretion of DA was shown in 31% and DOPA in 16%.