David Michalský

The endocrine profile of subcutaneous and visceral adipose tissue of obese patients

The aim of the present study was to evaluate the expression profile of genes potentially related to metabolic complications of obesity in the whole adipose tissue and isolated adipocytes from subcutaneous (SAT) and visceral adipose tissue (VAT) from 12 non-diabetic obese women and 12 lean women. Real-time polymerase chain reaction was used for expression analysis of 41 genes of interest and two housekeeping genes. We found increased expression of specific proinflammatory and adipogenic genes and reduced expression of specific lipogenic and insulin signaling pathway genes in obese relative to lean women with no preferable localization in SAT or VAT depot. The gene expression significantly differed between adipocytes and adipose tissue but both contributed to the proinflammatory profile in obesity. We conclude that both SAT and VAT exhibit alterations in the expression of specific genes possibly contributing to proinflammatory and insulin resistance state and consequently to metabolic complications of obesity.

High incidence of cardiovascular complications in pheochromocytoma.

Excess of catecholamines in pheochromocytoma is usually accompanied with classical symptoms and signs. In some cases, severe cardiovascular complications (e. g., heart failure, myocardial infarction) may occur. We performed a retrospective analysis focused on the incidence of cardiovascular complications (classified as follows: arrhythmias, myocardial involvement or ischemia and atherosclerosis, cerebrovascular impairment) before the establishment of diagnosis of pheochromocytoma among 145 subjects treated in our hospital. Cardiovascular complications occurred in 28 subjects, but these subjects did not differ significantly from subjects without complications in age, gender, body mass index, paroxysmal symptoms, symptom duration, tumor dimension, catecholamine secretory phenotype, and incidence of hypertension or diabetes mellitus. Arrhythmias occurred in 15 subjects (2 arrhythmia types in 2 subjects): atrial fibrillation in 9 subjects, supraventricular tachycardia in 3 cases, and ventricular tachycardia in 2 patients. Significant bradycardia was noted in 3 cases. Five subjects presented with heart failure with decreased systolic function (takotsubo-like cardiomyopathy found in 2 cases). One subject suffered from hypertrophic obstructive cardiomyopathy. Seven subjects presented with non-ST-segment elevation myocardial infarction, 2 patients with ST-segment myocardial infarction, and 1 subject underwent coronary artery bypass grafting. Two subjects suffered from significant peripheral atherosclerosis. Among cerebrovascular complications, transient ischemic attack was found in 3 cases, 2 subjects suffered from stroke, and subarachnoidal bleeding occurred in 1 patient. One subject suffered from diffuse neurological impairment due to multiple ischemic white matter lesions. These data show relatively high incidence of cardiovascular complications (19.3%) in subjects with pheochromocytoma. Early diagnosis is mandatory to prevent severe complications in pheochromocytoma.

Changes in Energy Metabolism in Pheochromocytoma

CONTEXT Catecholamine overproduction in pheochromocytoma affects basal metabolism, resulting in weight loss despite normal food intake. OBJECTIVE The objective of the study was to evaluate changes in energy metabolism expressed as resting energy expenditure (REE) in patients with pheochromocytoma before and after adrenalectomy and the possible relationship with circulating inflammatory markers. DESIGN We measured REE in 17 patients (8 women) with pheochromocytoma by indirect calorimetry (Vmax-Encore 29N system) before and 1 year after adrenalectomy. Body fat percentage was measured with a Bodystat device. Inflammatory markers (leukocytes count and C-reactive protein) and cytokines (TNF-α, IL-6, and IL-8) were analyzed with a Luminex 200. RESULTS REE measured in the pheochromocytoma group was 10.4% higher than the predicted value (1731 ± 314 vs 1581 ± 271 kcal/d; P = .004). Adrenalectomy significantly increased body mass index (P =0.004) and the percentage of body fat (P = .01), with a proportional increase in fat distribution (waist circumference, P = .045; hip circumference, P = .001). REE significantly decreased after adrenalectomy (1731 ± 314 vs 1539 ± 215 kcal/d; P = .002), even after adjustments in body surface and body weight (P < .001). After adrenalectomy, we found a significant decrease in leukocyte counts (P = .014) and in the levels of TNF-α (P < .001), IL-6 (P = .048), and IL-8 (P = .007) but not C-reactive protein (P = .09). No significant correlations among calorimetry parameters, hormones, and proinflammatory markers were detected. CONCLUSIONS Chronic catecholamine overproduction in pheochromocytoma may lead to a proinflammatory and hypermetabolic state characterized by increased REE. Adrenalectomy leads to the normalization of energy metabolism followed by an increase in body mass index and body fat content and decreases in inflammatory markers and cytokines.

Long-term effect of specific treatment of primary aldosteronism on carotid intima-media thickness.

Background: Aldosterone has been shown to substantially contribute to the accumulation of different types of collagen fibres and growth factors in the arterial wall, thus increasing wall thickness. A previous study showed reduction of increased common carotid intima–media thickness (IMT) in patients with primary aldosteronism 1 year after adrenalectomy. Our study in patients with primary aldosteronism was aimed at comparing the long-term effect of adrenalectomy vs. spironolactone therapy on common carotid IMT regression. Method: Forty-two patients with confirmed primary aldosteronism (21 with aldosterone-producing adenoma treated by unilateral laparoscopic adrenalectomy, 21 treated with spironolactone) were investigated by carotid ultrasound at baseline and 1 and 6 years after the specific treatment. Results: There was a decrease in common carotid IMT from 0.956 ± 0.140 to 0.900 ± 0.127 mm (−5.9%; P < 0.05) at 1 year and to 0.866 ± 0.130 mm (−9.4%; P < 0.01) at 6 years after adrenalectomy; in the spironolactone group, common carotid IMT decreased from 0.917 ± 0.151 to 0.900 ± 0.165 mm (−1.8%; NS) at 1 year and to 0.854 ± 0.176 mm (−6.8%; P < 0.01) at 6 years of treatment. The magnitude of improvement at 1 year was significantly higher (by 70%; P < 0.05) in the adrenalectomy group; however, the difference (by 27%) became nonsignificant at 6 years. Comparing the adrenalectomy and spironolactone groups, there was no significant difference in blood pressure decrease after treatment. Conclusion: In the long term, spironolactone therapy in patients with primary aldosteronism had significant effect on regression of IMT, which was comparable to surgical treatment in patients with unilateral forms of primary aldosteronism.

Discrepant Results of Adrenal Venous Sampling in Seven Patients with Primary Aldosteronism

Background: Adrenal venous sampling serves as a discrimination between uni- and bilateral forms of primary aldosteronism (PA). Even correctly performed adrenal venous sampling may lead to non-diagnostic results in some cases. Results: We describe 7 subjects with PA in whom correct cannulation of adrenal veins (high selectivity index defined as cortisol(adrenal)/cortisol(periphery) ratio) was associated with aldosterone (ALDO) suppression (ALDO/cortisol(adrenal)/ALDO/cortisol(periphery) ratio <1) in the left adrenal gland and in whom all subjects underwent a successful adrenalectomy on the right side. In 3 subjects, samples from the right side with lower selectivity indexes (1.11–1.7) compared to those samples with a higher index of selectivity (10.4–44.9) pointed to lateralization. Next, 2 subjects were operated because of relatively large adrenal masses in the right adrenal gland on CT despite ALDO suppression on this side. One subject presented with high selectivity indexes from the right side (19.5 and 37.6), but only one sample showed ALDO secretion. Patient 7 was treated with right-sided adrenalectomy despite a low lateralization index (ALDO/cortisol(right)/ALDO/cortisol(left) 1.78). Conclusions: Our results document some uncertainties in interpreting results of adrenal venous sampling in subjects with PA which may result from deep catheter insertion, anomalous venous drainage, or fluctuations in ALDO secretion.

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.

Biochemical Testing After Pheochromocytoma Removal: How Early?

Pheochromocytomas are catecholamine-producing tumors with typical clinical presentation. Tumor resection is considered as an appropriate treatment strategy. Due to its unpredictable clinical behavior, biochemical testing is mandatory to confirm the success of tumor removal after surgery. The aim of the study was to investigate the feasibility of a shorter interval of postoperative testing (earlier than the recommended 2-4 weeks according to recently published Guidelines). We investigated 81 patients with pheochromocytoma before and after surgery. Postoperative examination was performed of stable subjects after their transport from the surgical to the internal ward (7.1±2.2 days after surgery). Plasma metanephrines were used for the diagnosis of pheochromocytoma and confirmation of successful tumor removal. All subjects with pheochromocytoma had markedly elevated plasma metanephrines before surgery. No correlation between postoperative interval (the shortest being 3 days) and plasma metanephrine levels was found. Postoperative plasma metanephrine levels did not differ significantly from those taken at the one-year follow-up. In conclusion, we have shown that early postoperative diagnostic workup of subjects with pheochromocytoma is possible and may thus simplify early postoperative management of this clinical condition.

CSN Society News

Nephrology has a long tradition in the Czech Republic. The first acute dialysis was performed in 1955, a chronic dialysis programme started in the early 60ies, and a transplantation programme in 1966. This was reflected by many important international meetings held in Prague: The 2nd Congress of the International Society of Nephrology (1963), 17th Congress of the European Dialysis and Transplantation Association (1980) and the 15th Congress of the European Society of Artificial Organs (1988). More recently, the 17th and 25th meetings of the International Society of Blood Purification (1999 and 2007), 11th ANCA and Vasculitis Workshop (2003), 7th European Peritoneal Dialysis Meeting (2005), 13th Congress of the European Society of Organ Transplantation (2007) and finally, this year, the 48th Congress of ERA-EDTA.