Long-Term Effect of Adrenalectomy on Cardiovascular Remodeling in Patients With Pheochromocytoma.

Context: Catecholamines may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial and myocardial wall due to various mechanisms. Reversibility of this process has not been studied on both structures simultaneously. Objective: To clarify the long-term effect of excess normalization of catecholamines on carotid and myocardial wall changes in patients with pheochromocytoma or functional paraganglioma (PHEO) after tumor removal. Design, Settings, and Patients: Carotid intima-media thickness (IMT) and the left ventricular (LV) mass index were studied in 50 patients with PHEO before tumor removal and 5 years after tumor removal, and in 50 blood pressure- and age-matched essential hypertensive patients before follow-up and after 5 years of follow-up. Main Outcome Measures: Common carotid artery (CCA)-IMT and LV mass indexed to lean body mass (LBM). Results: Elimination of catecholamine excess in the PHEO group resulted in a significant decrease in CCA-IMT and LV mass index from 0.86 ± 0.17 to 0.83 ± 0.18 mm (P < 0.05) and from 3.2 ± 0.9 to 2.9 ± 0.9 g/LBM (P < 0.001), respectively. In contrast, CCA-IMT and LV mass index increased significantly from 0.78 ± 0.14 to 0.81 ± 0.15 mm (P < 0.05) and from 3.1 ± 0.7 to 3.2 ± 0.6 g/LBM (P < 0.05), respectively, in patients with essential hypertension. Conclusion: In patients with PHEO, carotid IMT and LV mass index can significantly regress after tumor removal, in contrast to the impairment of these parameters in essential hypertensive patients during the same long-term period.

Factors influencing arterial stiffness in pheochromocytoma and effect of adrenalectomy.

The aim of the study was to evaluate arterial stiffness and its modulating factors measured by carotid-femoral pulse wave velocity (PWV) and central augmentation index (AI) in patients with pheochromocytoma (PHEO) before and after surgery. Forty-five patients with PHEO and 45 healthy controls were investigated using an applanation tonometer (SphygmoCor, AtCor Medical). The gender, age, BMI and lipid profiles were comparable among both groups. The main difference in basic characteristic was as expected for fasting plasma glucose (P<0.001) and all blood pressure modalities. PWV in PHEO was significantly higher than in controls (7.2+/-1.4 vs. 5.8+/-0.5 ms(-1); P<0.001). Between-group difference in PWV remained significant even after the adjustment for age, heart rate, fasting plasma glucose and each of brachial (P<0.001) and 24 h blood pressure parameters (P<0.01). The difference in AI between groups did not reach the statistical significance (19+/-14 vs. 16+/-13%; NS). In multiple regression analysis, age (P<0.001), mean blood pressure (P=0.002), high-sensitive C-reactive protein (hs-CRP) (P=0.007) and 24 h urine norepinephrine (P=0.007) were independently associated with PWV in PHEO. In addition, 27 patients with PHEO were studied 1 year after tumor removal. Successful tumor removal led to a significant decrease in PWV (7.0+/-1.2 vs. 6.0+/-1.1 ms(-1); P<0.001). In conclusion, patients with PHEO have an increase in PWV, which is reversed by the successful tumor removal. Age, mean blood pressure, hs-CRP and norepinephrine levels are independent predictors of PWV.

Increased blood pressure variability in pheochromocytoma compared to essential hypertension patients.

OBJECTIVE: Catecholamines are responsible for short and long-lasting blood pressure (BP) elevations in pheochromocytoma. We investigated whether in patients with pheochromocytoma this catecholamine excess would result in higher BP variability in comparison with patients suffering from essential hypertension (EH). DESIGN: We examined retrospectively 54 (26 treated with alpha1-blockers) patients with pheochromocytoma (30 patients also investigated after tumour removal) and 108 (42 treated with alpha1-blockers) patients with EH. They all underwent 24-h ambulatory BP monitoring. To assess the BP variability, coefficient of BP variability (SD of average BP/average BP) was used. RESULTS: In subjects with pheochromocytoma, a higher coefficient of BP variability was shown compared with EH during the 24-h period (0.12 +/- 0.03 versus 0.10 +/- 0.02, P = 0.003 for systolic BP in the treated group) and mainly during the daytime (0.11/0.13 +/- 0.04/0.03 versus 0.09/0.11 +/- 0.03/0.04, P = 0.007/0.06 for systolic/diastolic BP in the untreated group and 0.12/0.13 +/- 0.04/0.04 versus 0.09/0.12 +/- 0.04/0.02, P < 0.001/0.01 in the treated group). Tumour removal resulted in a decrease of the previously increased 24-h (0.11 +/- 0.03 versus 0.10 +/- 0.03, P = 0.04) and daytime (0.11 +/- 0.03 versus 0.09 +/- 0.03, P = 0.03) coefficient of systolic BP variation. Twenty-seven subjects with pheochromocytoma and inverted circadian BP rhythm (night-time BP > daytime BP) had a significantly higher 24-h (0.13 +/- 0.03 versus 0.10 +/- 0.03, P < 0.001 for systolic BP) and daytime coefficient of BP variation (0.13/0.15 +/- 0.04/0.03 versus 0.09/0.12 +/- 0.02/0.02, P < 0.001/<0.001) and also a higher occurrence of the isolated excretion of norepinephrine (14 versus seven subjects, P = 0.05) compared with the 27 subjects with pheochromocytoma without inverted circadian BP rhythm. CONCLUSION: The excess of catecholamines in patients with pheochromocytoma is associated with higher long-term BP variability in comparison with patients suffering from EH especially in subjects with inverted circadian BP rhythm. Tumour removal resulted in the amelioration of the previously increased BP variability.

Preparation and testing of stationary phases and modified capillaries for affinity chromatography and affinity capillary electrophoresis of pepsin.

Three stationary phases have been prepared for affinity liquid chromatography isolation and separation of porcine and human pepsin. The phases contain 3,5-diiodo-L-tyrosine (DIT) bound to the supports HEMA BIO VS, HEMA BIO E and EPOXY TOYOPEARL. These phases have been tested on a model sample of porcine pepsin A and applied to human pepsin. Fractions have been collected and the chymase activity determined in selected analyses. For affinity CE, capillaries have been prepared by modifying the wall with 3-aminopropyltriethoxysilane, followed either by direct binding of DIT, or by binding L-tyrosine that was subsequently iodated. The dissociation constant K(d) has been determined for the pepsin-DIT complex from the changes in the electrophoretic mobilities.

Simple plasma work-up for a fast chromatographic analysis of homocysteine, cysteine, methionine and aromatic amino acids.

Simplified sample workup obviating protein precipitation and eluent evaporation commonly employed in earlier reports using chloroformate-mediated derivatization of aminothiols prior to mass spectrometric (MS) detection is presented. The reduction of disulfides in plasma is accomplished with dithiothreitol within minutes. A simultaneous derivatization with ethyl chloroformate (ECF) and extraction of derivatives into organic phase takes place within seconds. Along with S-amino acids, also aromatic amino acids can be determined during a 5-min run. Gas chromatography with flame ionization detection (GC-FID) proved to be sensitive enough to reach plasma homocysteine levels. A prerequisite for a reliable quantitation was fulfilled under the given conditions. Intra-assay precision was <5%, recoveries from spiked plasma complete (101.2%), detection and quantitation limits for homocysteine came to <1 and 3 micro mol/l. Our results were in full agreement with those obtained by liquid chromatography (r=0.999 for homocysteine and 0.987 for cysteine), and were close to two homocysteine immunoassays (r=0.991 and 0.939, respectively).