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 Arterial systemic blood samples were withdrawn before the ligation of the vessels supplying the tumour, during its surgical manipulations and after its removal, while haemodynamics was monitored.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.

Effect of removal of phaeochromocytoma on diurnal variability of blood pressure, heart rhythm and excretion of catecholamines.

Ambulatory 24 hour blood pressure and ECG monitoring with simultaneous estimation of the urinary excretion of noradrenaline and adrenaline were performed in seven patients with phaeochromocytoma, before and after removal of the tumour. Mean blood pressure during eight 3-hour periods, mean heart rate, and noradrenaline and adrenaline excretion during four 6-hour periods were estimated. Mean blood pressure before surgery did not show any significant circadian changes. After surgery both systolic and diastolic blood pressures were significantly lower at night than in the daytime periods. In contrast, mean heart rate before surgery was significantly lower at night than in the morning, and this relationship was greater after surgery. Ventricular arrhythmias during 24 hour monitoring were noted in three patients before and in six after surgery. These findings suggest that profound disturbances of autonomic blood pressure regulation improve after removal of phaeochromocytoma, and that ventricular arrhythmias, except for paroxysmal symptoms, tend to be less frequent before than after surgery.

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.

Influence of alpha-adrenergic blockade on ventricular arrhythmias, QTc interval and heart rate variability in phaeochromocytoma.

There are strong experimental evidences that alpha 1-adrenergic stimulation significantly influences cardiac arrhythmogenesis, especially during myocardial ischaemia and reperfusion. However, anti-arrhythmic effects of alpha-blockade in humans were scarcely utilised. Thus the purpose of our study was to assess these effects in patients with phaeochromocytoma. In 22 patients simultaneous 24 h ECG and blood pressure (BP) monitoring, as well as estimation of the urinary 24 h free catecholamine excretion, were performed twice: before and during the treatment with the non-selective alpha-blocker, phenoxybenzamine. The heart rate variability was measured during four 5 min periods, at 10.00, 16.00, 22.00 and 04.00. During alpha-blockade systolic blood pressure (SBP) decreased from 137.6 +/- 23.8 to 126.5 +/- 15.7 mm Hg (P < 0.01), heart rate increased from 83.0 +/- 9.9 to 88.5 +/- 10.0/min (P < 0.02) and duration of QTc interval unsignificantly increased. Incidence of frequent or repetitive ventricular arrhythmias was significantly higher before treatment (in 9 vs 3 of 22 patients, P < 0.05). Heart rate variability significantly decreased during the treatment, with regard to all parameters, representing both the sympathetic and parasympathetic activity. We conclude that non-selective alpha-blockade significantly decreases the incidence of frequent or repetitive ventricular arrhythmias in patients with phaeochromocytoma, although the lack of QTc interval shortening suggests that the effect of class I drugs may participate in the anti-arrhythmic effects of phenoxybenzamine. Moreover, non-selective alpha-blockade in phaeochromocytoma significantly diminishes vagal activity.

[Are there correlations of hormonal activity in pheochromocytoma and serum as well as erythrocyte sodium and potassium concentrations in patients with pheochromocytoma]. / Czy istnieje wspólzaleznosc miedzy czynnoscia hormonalna guza chromochlonneego a stezeniem sodu i potasu we krwi i erytrocytach u chorych z pheochromocytoma?

Interrelationship between serum Na+, K+ concentrations and the excretion of norepinephrine (NA), epinephrine (A) in the urine was studied in 69 patients aged 15-69 with pheochromocytoma (PH), and between serum Na+, K+ concentrations and serum NA, A levels in 53 patients. Furthermore, in 15 patients correlation between Na+, K+ concentrations in erytrocytes and serum NA, A levels was estimated. Na+ and K+ concentrations were determined using photometric analysis, NA and A excretion in the urine using fluorometric method and in blood by radiometry. Hypokalemia and hyponatremia were stated in 22% and 19% of patients with PH, respectively. Only in patients with electrolytic disorders correlation of serum as well as erythrocyte Na+ concentrations with serum NA level and between serum K+ and A concentrations were proved. In the part of studied patients with PH, the NA and A excess induced disorders of electrolytic homeostasis.

[Correlations between catecholamines and prostaglandins in patients with primary arterial hypertension and pheochromocytoma in basic conditions and after administration of clonidine]. / Wspólzaleznosc miedzy katecholaminami i prostaglandynami u chorych z nadcisnieniem tetniczym pierwotnym i z guzem chromochlonnym w warunkach podstawowych i po klonidynie.

Authors assessed correlation between venous blood catecholamines and prostaglandins concentrations before and after inhibition of sympathetic activity by clonidine in patients with primary hypertension or pheochromocytoma. 30 patients with essential uncomplicated hypertension and 11 with pheochromocytoma underwent the study. The control group consisted of 6 healthy volunteers. Serum norepinephrine (NA), epinephrine (A), prostaglandins: PGE2 PGF2 alpha and prostacyclin metabolite -6-keto-PGF1 alpha were determined before and 3 hours after oral administration of 0.3 mg clonidine. Negative correlation was stated between basic serum norepinephrine and 6-keto-PGF1 alpha concentrations in patients with pheochromocytoma, which could indicate prostacyclin metabolism disorders during persistent hypercatecholaminemia . There was no correlation between catecholamines and prostaglandins during the inhibition of sympathetic activity in patients with pheochromocytoma as well as essential hypertension. The positive correlation was observed between changes in serum NA and PGF2 alpha levels in patients with borderline hypertension. Thus, one may suppose, that correlation between na excretion and vasoconstrictive PGF2 proved in acute experiments, becomes evident within the early stage of hypertension also during sympathetic activity inhibition.

[Atrial natriuretic peptide in patients with primary arterial hypertension]. / Przedsionkowy peptyd natriuretyczny u chorych z nadcisineniem tetniczym pierwotnym.

Atrial natriuretic peptide (ANP) activity was studied in 33 males with borderline and established essential hypertension. No significant differences of serum ANP concentration were stated in patients with borderline and established uncomplicated hypertension in comparison with the control group.

[Correlations of atrial natriuretic peptide and catecholamine levels in the blood during surgical removal of pheochromocytoma]. / Wspólzaleznosc miedzy stezeniem przedsionkowego peptydu natriuretycznego a katecholaminami we krwi w czasie operacyjnego usuniecia guza chromochlonnego.

Atrial natriuretic peptide concentrations (ANP) were determined in 4 patients with pheochromocytoma during its surgical removal. There was no correlation among ANP level, plasma catecholamines concentrations and blood pressure. Increase of plasma ANP concentration after tumor removal can be explained by simultaneously observed hypervolemia. It proves that ANP secretion mostly depends on enlarged central blood volume.

[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%.