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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.

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.

The interaction between catecholamines (CA) and ANP is not clearly established. The effects of excess endogenous CA on ANP secretion can be investigated in patients with pheochromocytoma. We studied 27 patients with surgically and histologically proven pheochromocytoma (P) aged 19-70 years. In 16 of these patients plasma ANP study was repeated after surgical removal of the tumour. The control group (C) consisted of 20 healthy volunteers aged 21-48 years. Moreover, 42 patients with uncomplicated mild to moderate essential hypertension (EH) aged 18-48 years were also studied. In P higher plasma ANP concentration versus C, EH was found (51.9 +/- 8.1; 25.5 +/- 1.5; 19.3 +/- 1.5 fmol/ml, respectively). In 16 patients with P, increased plasma ANP level (mean 63.3 +/- 12.6 fmol/ml) declined after surgical removal of the tumour (mean 22.4 +/- 2.9 fmol/ml). In the P patients no relationship was found between plasma ANP and hormonal patterns of the tumour or between plasma ANP and plasma catecholamines, whereas significant positive correlations between plasma ANP and both systolic and diastolic blood pressure and heart rate were demonstrated. These results suggest that excess CA produced by the chromaffin tumour induce ANP secretion via stimulation of adrenergic receptors. However, influence of the haemodynamic changes evoked by CA cannot be excluded. It is suggested that increased secretion of ANP may be of some importance in maintaining blood pressure homeostasis in patients with pheochromocytoma.

The purpose of our study was to assess the potential role of spin-echo (SE), chemical shift, and gadolinium-enhanced magnetic resonance imaging (MRI) in the differentiation of adrenal masses. Seventy-two adrenal masses (26 nonhyperfunctioning adenomas, 16 aldosterone-secreting adenomas and 6 other different benign cortical masses, 18 pheochromocytomas, and 6 malignant masses) in 63 patients were evaluated with spin-echo sequences, chemical shift imaging (CSI) and gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) dynamic studies. Ratios and indices of signal intensity for all examined MRI methods were calculated and examined for significance of difference between different types of adrenal masses. Quantitative magnetic resonance evaluation of adrenal masses showed significant differences (at least alpha < 0.01) between nonhyperfunctioning adenomas vs. pheochromocytomas or vs. malignant lesions or vs. aldosterone-secreting adenomas and between pheochromocytomas vs. malignant lesions. The most specific indicators of adrenal mass character proved to be the CSI ratio based on opposed-phase and in-phase two-dimensional fast low-angle shot (FLASH) images, reflecting lipid content in the lesion, and Gd-DTPA dynamic studies ratios reflecting contrast agent inflow and washout in the lesion: WoMAX/LAST and Dyn1.2-3.2. There was no overlap of CSI ratio between adenomas and pheochromocytomas. The overlap of ranges of CSI ratio between nonhyperfunctioning adenomas and aldosterone-secreting adenomas was only 18.5%. There was no overlap of WoMAX/LAST ratio between adenomas and pheochromocytomas, or adenomas and malignant lesions. The overlap of ranges of Dyn1.2-3.2 ratio between pheochromocytomas and malignant lesions was only 17.6%. MRI enables good visualization and specific characterization of adrenal masses. The optimal MRI protocol for the adrenal region is presented.

Neuropeptide-Y (NPY) is a peptide proposed to modulate the effect of the sympathetic nervous system on blood pressure control and contribute to the development of essential hypertension. To assess the possible influence of gender on its role, we evaluated plasma NPY, noradrenaline (NA) and adrenaline (A) concentrations in men and women with essential hypertension. No difference in NPY concentration was found between genders, but NPY concentration was elevated in both hypertensive men and women. NA levels were similar in all investigated hyper- and normotensives, while A was increased only in hypertensive men. These results suggest various patterns of sympatho-adrenal activity in gender subgroups of patients with essential hypertension.

An effect of peptide released by the heart atria of mammals and called the atrial natriuretic factor (ANF) on blood pressure and heart contractions was studied in rats with genetically determined arterial hypertension (SHR) and in normotensive Wistar-Kyoto rats (WKY). Nine male SHR rats and 11 male WKY rats, aged between 12 and 16 weeks, were given normal saline infusion for 30 minutes through implanted catheters to both ulnar vein and artery. Then, an infusion of ANF at the rate of 0.3 microgram/kg per hour followed for 35 minutes. An infusion of ANF produces significant decrease in the mean arterial blood pressure, systolic and diastolic pressures without significant effect on pulse pressure and heart contractions. AFN infusion with the same rate did not produce any significant differences in the arterial blood pressure and heart contractions in Wistar-Kyoto rats. The obtained results suggest that ANF may play a role in pathogenesis of the arterial blood hypertension.

The aim of the study was to find out whether vasopressin (AVP) modifies hypotensive and heart rate accelerating effects of atrial natriuretic peptide (ANP) in normotensive (WKY) and spontaneously hypertensive (SHR) conscious rats. The effect of i.v. administration of 1; 2 and 4 micrograms of ANP on blood pressure (MP) and heart rate (HR) was compared during i.v. infusion of 0.9% NaCl (NaCl), NaCl+AVP (1.2 ng kg-1 min-1) and NaCl+dEt2AVP (V1 receptors antagonist, 0.5 microgram kg-1 min-1). AVP increased MP in SHR and WKY and decreased HR in SHR. V1 antagonist decreased MP and increased HR only in SHR. In SHR ANP decreased MP and increased HR during NaCl, AVP and V1 antagonist infusion. In WKY these effects were observed only during AVP administration. In each experimental situation hypotension and tachycardia induced by ANP were greater in SHR than in WKY. In both strains ANP induced changes in MP and HR were enhanced during AVP in comparison to NaCl infusion. V1 antagonist did not modify effects of ANP in WKY and SHR. The results indicate that ANP abolishes hypertensive response induced by blood AVP elevation and that the basal levels of endogenous vasopressin acting through V1 receptors does not interfere with hypotensive action of ANP neither in WKY nor in SHR.

Concentration of atrial natriuretic peptide (ANP) was studied in acute myocardial infarction (AMI), its association with ventricular arrhythmias (VA), left ventricular dysfunction and infarct size. Plasma ANP concentrations were measured at time: 0, 4, 8, 16, 24, 48 and 72 hours after admission in 11 patients (pts) with first AMI, up to 6 hours after the first symptoms. Ventricular arrhythmia was assessed by 24 hour Holter monitoring, left ventricular dysfunction by echocardiography and infarct size by serial CK-MB measurement in first 72 hours of AMI. In subsequent measurements the average plasma concentration of ANP (mean +/- SEM) was elevated: 42.2 +/- 9.9, 35.3 +/- 12.5, 33.9 +/- 8.3, 42.3 +/- 8.3, 36.9 +/- 6.4, 60.7 +/- 9.3, 47.8 +/- 12.0 fmol/ml. The maximal plasma ANP concentration was significantly higher (p less than 0.01) in 4 pts with VA 4th grade acc. to Lown than in 7 pts without VA (102.6 +/- 17.9 vs 41.1 +/- 6.4). The maximal level of ANP--153.3 fmol/ml in a patient with paroxysmal supraventricular tachycardia was observed. There were no significant correlations between plasma ANP and infarct size, size of left atrium and contractility disturbances of left ventricle.

Plasma atrial natriuretic factor (ANF) and catecholamine concentrations were determined in 11 untreated patients with uncomplicated essential hypertension and seven normotensive subjects during graded submaximal exercise on a treadmill (loads: I 40%, II 60%, III 80% of maximal oxygen consumption). No significant differences in plasma ANF and catecholamine concentrations were found between the hypertensive and the normotensive subjects. The results do not support the presence of significant differences in the release of ANF and catecholamines during dynamic exercise between patients with uncomplicated essential hypertension and normotensive subjects.