Objective: Fibroblast Growth Factor 21 (FGF-21) is a novel hepatokine with many beneficial effects on metabolism. The aim was to evaluate the relationship between plasma FGF-21, energy, lipid and glucose metabolism in patients with pheochromocytoma/functional paraganglioma (PPGL) in comparison with obese patients and lean healthy controls. Design and method: We examined 40 consecutive patients with PPGL, 21 obese and 26 lean healthy controls. 27 patients with PPGL were examined one year after adrenalectomy. Basic anthropometric and biochemical measurements were done. Energy metabolism was measured by indirect calorimetry (Vmax-Encore 29N). FGF-21 was measured by ELISA. Results: FGF-21 was significantly higher in PPGL than in controls (174.2 [283] pg/ml vs. 107.9 [116] pg/ml; P < 0.001) and comparable with obese (174.2 [283] pg/ml vs. 160.4 [180]; P = NS). After adrenalectomy FGF-21 decreased (176.4 [284] pg/ml vs. 131.3 [225] pg/ml, p < 0.001). Higher levels of FGF-21 have been expressed particularly in patients with diabetes. FGF-21 positively correlated in PPGL with age (p = 0.005), BMI (p = 0.028), fasting blood glucose (p = 0.002) and glycated hemoglobin (p = 0.014). Patients with pheochromocytoma showed hypermetabolic status compared to other groups. We did not find the relationship between indirect calorimetry parameters and FGF-21. Conclusions: Long-term catecholamine overproduction in PPGL leads to elevation in plasma FGF-21, especially in patients with secondary diabetes. FGF-21 levels were comparable between obese and PPGL patients despite different anthropometric indices. We didn’t find a link between FGF-21 and hypermetabolism in PPGL. It seems that hyperglycemia is basic stimulus for secretion of circulating FGF-21 regardless of etiology.

Background: Pheochromocytomas (PHEO) are tumors arising from chromaffin cells from the adrenal medulla, having the ability to produce, metabolize and secrete catecholamines. The overproduction of catecholamines leads by many mechanisms to the impairment in the left ventricle (LV) function, however, endocardial measurement of systolic function did not find any differences between patients with PHEO and essential hypertension (EH). The aim of the study was to investigate whether global longitudinal strain (GLS) derived from speckle-tracking echocardiography can detect catecholamine-induced subclinical impairments in systolic function. Methods: We analyzed 17 patients (10 females and seven males) with PHEO and 18 patients (nine females and nine males) with EH. The groups did not differ in age or in 24-h blood pressure values. Results: The patients with PHEO did not differ in echocardiographic parameters including LV ejection fraction compared to the EH patients (0.69 ± 0.04 vs. 0.71 ± 0.05; NS), nevertheless, in spackle-tracking analysis, the patients with PHEO displayed significantly lower GLS than the EH patients (−14.8 ± 1.5 vs. −17.8 ± 1.7; p < 0.001). Conclusions: Patients with PHEO have a lower magnitude of GLS than the patients with EH, suggesting that catecholamines induce a subclinical decline in LV systolic function.

Primary aldosteronism (PA) is associated with objectively measured lower physical fitness and blunted response of the renin-angiotensin-aldosterone system to exercise. The purpose of this pilot study was to objectively measure exercise response of the renin-angiotensin-aldosterone system and cardiopulmonary fitness changes after laparoscopic adrenalectomy (ADE) in patients with unilateral PA. We examined a total of 14 patients with confirmed PA before and after ADE, by means of spiroergometry and hormonal evaluation. As expected, after adrenalectomy basal aldosterone (Aldo) levels before exercise decreased significantly, with a concomitant increase in plasma renin (PR). The increase in Aldo (285.9 +/- 171.3 to 434.1 +/- 278.2 ng/l; p=0.02) and blunted increase in PR (7.1 +/- 0.4 to 8.9 +/- 10.4 pg/ml; NS) post-exercise before ADE became significant after ADE Aldo post-ADE (46.8 +/- 18.8 to 106.5 +/- 68.1 ng/l; p<0.0001) and PR post-ADE (20.1 +/- 14.5 to 33.9 +/- 30.7 pg/ml; p=0.014). After adrenalectomy, the patients had a non-significant increase in peak workload and VO2peak. We found normalization of the renin-angiotensin-aldosterone system response to exercise with little changes in cardiopulmonary fitness six months after ADE.

Hypokalemia as a typical feature of primary aldosteronism (PA) is associated with muscle weakness and could contribute to lower cardiopulmonary fitness. The aim of this study was to describe cardiopulmonary fitness and exercise blood pressure and their determinants during a symptom-limited exercise stress test in patients with PA. We performed a cross-sectional study of patients with confirmed PA who were included before adrenal vein sampling on whom a symptom-limited exercise stress test with expired gas analysis was performed. Patients were switched to the treatment with doxazosin and verapamil at least two weeks before the study. In 27 patients (17 male) the VO(2peak) was 25.4+/-6.0 ml/kg/min which corresponds to 80.8+/-18.9 % of Czech national norm. Linear regression analysis shows that VO(2peak) depends on doxazosin dose (DX) (p=0.001) and kalemia (p=0.02): VO(2peak) = 4.2 - 1.0 * DX + 7.6 * Kalemia. Patients with higher doxazosin doses had a longer history of hypertension and had used more antihypertensives before examination, thus indicating that VO(2peak) also depends on the severity of hypertension. In patients with PA, lower cardiopulmonary fitness depends inversely on the severity of hypertension and on lower plasma potassium level.

Objective: This randomised, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data.Design and method: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomised to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after one year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in 5 patients. Results: Similar and comparable reduction of 24-hour systolic blood pressure after RDN or spironolactone addition after randomisation was observed, 9.1 mmHg (p = 0.001) and 10.9 mmHg (p = 0.001), respectively. Similar decrease of office blood pressure was observed, 17.7 mmHg (p < 0.001) versus 14.1 mmHg (p < 0.001), while the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed non-significantly better efficacy of spironolactone addition in 24 h systolic and office systolic blood pressure reduction than RDN (3.7 mmHg, p = 0.27 and 4.6 mmHg in favour of spironolactone addition, p = 0.28, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, p = 0.001). Conclusions: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in blood pressure reduction over a period of 24 months. However, by contrast to the 12-month results, blood pressure changes are not significantly greater.

Objective: The aim of the study was to evaluate differences between patients with pheochromocytoma presenting with hypermetabolism and normometabolism according to resting energy expenditure (REE), and to estimate factors affecting metabolic state. Design and method: We have measured REE in 34 patients (17 women) with pheochromocytoma by indirect calorimeter (Vmax-Encore 29N system) before adrenalectomy. The hypermetabolic state was defined as measured REE above 10% higher than the predicted value. Body fat percentage was measured by Bodystat device. The diagnosis of PHEO was based on plasma metanephrines and the demonstration of tumor by CT scan. The diagnose was confirmed histopathologically. Results: The hypermetabolic state was confirmed in 16 patients with pheochromocytoma (47%). Hypermetabolism was more frequent in patients with adrenergic phenotype. Hypermetabolic state was characterized by higher age (56 ± 13 vs 48 ± 15 years, P = 0.07), serum cholesterol levels (4.1 ± 0.9 vs 5.1 ± 1.0 mmol/l, P = 0.005), especially LDL (P = 0.006) and serum chromogranin A levels (P = 0.041) in comparison with normometabolic pheochromocytoma. No differences were found in BMI, body fat percentage, blood pressure, glucose levels, TSH, plasma normetanephrine levels and pharmacotherapy. No significant correlations between calorimetry parameters and hormones were detected. Conclusions: Chronic catecholamine overproduction in pheochromocytoma may lead to a proinflammatory and hypermetabolic state characterized by increased REE. A hypermetabolic state was found in 47% patients with pheochromocytoma and was more common in older patients with adrenergic phenotype and higher chromogranin A levels as a possible indicator of disease activity. We did not observe a correlation between catecholamine metabolites and calorimetry parameters.

Objective: 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 stiffness. Our previous study showed significant reduction of arterial stiffness assessed by carotid- femoral pulse wave velocity (PWV) in patients with primary aldosteronism in a short interval -1 year after adrenalectomy in comparison with patients treated with spironolactone, Thera are no data about the long-term effect of both treatment methods on arterial stiffness. Thus this study was aimed at comparing the long-term effect of adrenalectomy versus spironolactone therapy on arterial stiffness. Design and method: Fifty patients with confirmed primary aldosteronism (25 with aldosterone-producing adenoma) successfully treated by unilateral laparoscopic adrenalectomy, 25 treated with spironolactone were investigated by Sphygmocor device (carotid-femoral PWV and aortic augmentation index) at baseline and 6 years after the specific treatment. Results: There was a significant decrease in PWV from 9.6 ± 2.3 to 8.6 ± 1.6 m/s (P = 0.001) and also in aortic augmentation index from 29 ± 9 to 24 ± 9% (P < 0.001) 6 years after adrenalectomy; in the spironolactone group, the PWV decrease was not statistically significant – from 9.3 ± 2.2 to 8.8 ± 2.0 m/s (P = 0.11) and also a non-significant aortic augmentation index decrease from 25 ± 7 to 23 ± 8% (P = 0,17) after 6 years of treatment. In both groups, there was a significant decrease of office and 24 hr blood pressure with non-significant difference in blood pressure decrease between both treatment arms. Conclusions: In long term, the surgical treatment in patients with unilateral forms of primary aldosteronism has significant effect on long-lasting improvement of arterial stiffness (carotid-femoral PWV and aortic augmentation index) in comparison with conservative treatment with spironolactone, despite comparable effect on blood pressure reduction. This suggests that in patients treated with aldosterone receptor blockers they probably do not fully prevent negative effects of aldosterone on the arterial wall. Therefore, for better long-lasting outcome, it is preferable to seek for unilateral forms of primary aldosteronism treatable by adrenalectomy.

CRISPR/dCas9-VPR system resulted in an increase of the ratio between cardiac and skeletal muscle isoforms of Trdn (Figure 1b).Down-regulation of Trdn-AS expression using gapmeRs had no effect on the cardiac/skeletal muscle ratio.Figure 1 Conclusion: We identified a lncRNA named TRDN-AS which regulates the balance between cardiac and skeletal muscle isoforms of TRDN at the epigenetic level.Since TRDN is associated with heart failure, these results suggest a role for TRDN-AS in the development of heart failure.Figure 1.a) Expression levels of TRDN-AS, cardiac and skeletal muscle isoforms of TRDN in left ventricular biopsies from 23 control and 43 failing human hearts (HF).b) Regulation of Trdn isoforms by Trdn-AS.HL-1 cardiomyocytes were cotransfected with SP-dCas9-VPR and gRNA_Cloning Vector with specific guide RNA (sgRNA) or without (Control) target sequence.Cells were harvested after 48h. 5 independent experiments were performed.

Objective: Sympathetic tone is one of the main determinants of blood pressure (BP) variability. The aim of our study was to assess the changes in BP variability after renal sympathetic denervation (RDN) in resistant hypertensive patients, and, conversely, to look for the predictive value of baseline BP variability on mean BP changes after RDN. Design and method: Twenty-four hour BP measurements were analyzed in 167 resistant hypertensive patients recruited at 11 expert centers within the European Network Coordinating research on Renal Denervation (ENCOReD) (mean age 56.7 years; 40 % women; mean baseline office BP: 172/98 mmHg; 24-h ambulatory BP: 152/90 mmHg), both at baseline and after RDN. Blood pressure variability was assessed by the weighted standard deviation (SDw), average real variability (ARV), coefficient of variation (CV) and variability independent of the mean (VIM) of 24-h ambulatory BP. Results: After an average follow up of 6.7 months, mean office and 24-h ambulatory BP fell by 15.4/6.6 mmHg and 5.5/3.7 mmHg respectively (P < 0.0001 for both). Whereas no significant changes in ARV or CV were observed, SDw and VIM for 24-h systolic BP decreased by −1.29 mmHg (95%CI: −2.17 to −0.42; P < 0.01) and −1.11 mmHg (95%CI: −1.92 to −0.30; P < 0.01), respectively. Decrease in these systolic BP variability estimates remained significant in multivariable-adjusted analyses and was paralleled by similar changes for 24-h diastolic BP. Finally, baseline SDw (P = 0.0006), ARV (P = 0.012) and VIM (P = 0.04) were significantly correlated with mean changes in diastolic - but not systolic - BP after RDN. Conclusions: Renal denervation was associated with a significant decrease in BP variability independent of the mean, which in the long term may decrease cardiovascular risk. Furthermore, baseline BP variability was predictive of diastolic BP changes after RDN. These results are consistent with the known influence of sympathetic nervous system on BP variability and peripheral vascular resistances. Our findings need confirmation in randomized controlled studies testing second-generation RDN catheters, preferably including younger patients with higher sympathetic tone and less advanced vascular damage.

Objective: This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension (TRH) and assessed the effect of spironolactone addition. We present the 12-month data. Design and method: The entry criteria included office systolic blood pressure (BP) over 140 mmHg, ambulatory 24-hour mean systolic BP over 130 mmHg, treatment with at least 3 antihypertensive drugs including a diuretic, exclusion of secondary hypertension and excluding drug non-compliance. Thus, only patients with TRH were included after thorough examination in three tertiary hypertension centers. After randomization, patients selected for RDN were maintained on baseline medical therapy for 1 year unless changes were considered clinically necessary. Patients selected for intensified medical treatment received baseline medical therapy plus spironolactone (25 mg daily, as generally recommended), if tolerated, and if no contraindications were present. Results: A total of 106 patients with TRH were randomized: 52 patients to RDN and 54 patients to the spironolactone addition, with baseline systolic BP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable 24-hour systolic BP decline of 6.4 mmHg, p = 0.001 in RDN versus 8.2 mmHg, p = 0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic BP decline between complete RDN (6.3 mmHg, p = 0.004) and the subgroup where spironolactone was added and this continued within the 12 months (15 mmHg, p = 0.003). See Figure. Renal artery CT angiograms before and after one year post-renal denervation did not reveal any relevant changes.Conclusions: This study shows that, over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of TRH with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in BP reduction.

Objective: Sympathetic tone is one of the main determinants of blood pressure (BP) variability. The aim of our study was to assess the changes in BP variability after renal sympathetic denervation (RDN) in resistant hypertensive patients, and, conversely, to look for the predictive value of baseline BP variability on mean BP changes after RDN. Design and method: Twenty-four hour BP measurements were analyzed in 167 resistant hypertensive patients recruited at 11 expert centers within the European Network Coordinating research on Renal Denervation (ENCOReD) (mean age 56.7 years; 40 % women; mean baseline office BP: 172/98 mmHg; 24-h ambulatory BP: 152/90 mmHg), both at baseline and after RDN. Blood pressure variability was assessed by the weighted standard deviation (SDw), average real variability (ARV), coefficient of variation (CV) and variability independent of the mean (VIM) of 24-h ambulatory BP. Results: After an average follow up of 6.7 months, mean office and 24-h ambulatory BP fell by 15.4/6.6 mmHg and 5.5/3.7 mmHg respectively (P < 0.0001 for both). Whereas no significant changes in ARV or CV were observed, SDw and VIM for 24-h systolic BP decreased by −1.29 mmHg (95%CI: −2.17 to −0.42; P < 0.01) and −1.11 mmHg (95%CI: −1.92 to −0.30; P < 0.01), respectively. Decrease in these systolic BP variability estimates remained significant in multivariable-adjusted analyses and was paralleled by similar changes for 24-h diastolic BP. Finally, baseline SDw (P = 0.0006), ARV (P = 0.012) and VIM (P = 0.04) were significantly correlated with mean changes in diastolic - but not systolic - BP after RDN. Conclusions: Renal denervation was associated with a significant decrease in BP variability independent of the mean, which in the long term may decrease cardiovascular risk. Furthermore, baseline BP variability was predictive of diastolic BP changes after RDN. These results are consistent with the known influence of sympathetic nervous system on BP variability and peripheral vascular resistances. Our findings need confirmation in randomized controlled studies testing second-generation RDN catheters, preferably including younger patients with higher sympathetic tone and less advanced vascular damage.

Objective: Renal denervation (RDN) has been shown to be a feasible treatment in resistant hypertensive patients. Renal accessory arteries (RAs) are frequent (20–27%) but seldom accessible to RDN. As such, they may constitute an unaddressed source of sympathetic overactivity. The aim of this study was to investigate if the presence of accessory RAs influences blood pressure response to RDN in patients with resistant hypertension. Design and method: Patients were recruited from 6 expert centres, within the European Network Coordinating research on Renal Denervation (ENCOReD). All patients underwent 24-h BP measurements at baseline and 6 months after RDN. Patients were classified in type A (main RA > = 20 mm length and > = 4 mm diameter) or type B (main RA < 20 mm length or < 4 mm diameter) according to renal anatomy (Okada classification). Subtypes include A1 (no accessory RAs), A2 (with accessory RAs < 3 mm diameter), A3 (with accessory RAs > = 3 mm diameter), B1 (main RA < 20 mm in length) and B2 (RA < 4 mm diameter). Results: 114 resistant hypertensive patients (age 58.1 ± 11.2, 46% women) were included in the analysis. Seventy-six (66%) patients did not have accessory RAs (type A1) and 39 (34%) patients did have accessory RAs (on one or both sides). 24-hour ambulatory systolic/diastolic BP after RDN dropped by -6.4/-4.0 mmHg in patients with no accessory RAs (p < 0.006), compared to a non-significant + 0.2/-0.7 mmHg (p > 0.70) in patients with accessory RAs. (p > 0.08 for the baseline adjusted between-group difference). When adjusted for sex, age, body mass index, baseline 24-h systolic ambulatory blood pressure as fixed effects, and for centre as random effect, the difference in decrease in 24-h systolic ambulatory blood pressure between the 2 groups was -3.8 mmHg (95% CI: -10.7 to 3.1, p = 0.27). Conclusions: A significant blood pressure decrease after RDN was observed only in patients without RAs. However, the difference between blood pressure changes in patients with or without RAs did not reach statistical significance. Ongoing analyses will include more subjects, as well as information on performance of RDN in accessory RAs and the number of ablations on each side.

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P =0.001 in RDN versus 8.2 mm Hg, P =0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P =0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P = 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-alpha and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-alpha (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35+/-1.42 vs. 5.97+/-1.29 10(9) l); APA vs. IHA: TNF-alpha (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37+/-1.41 vs. 5.71+/-1.21 10(9) l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] microg/l, p</=0.003). No differences in inflammatory markers were observed between the followed groups, we confirmed higher levels of PINP in patients with PA.

Objective: Patients with resistant hypertension have a higher incidence of cardiovascular complications in comparison with controlled hypertension patients. Non-compliance to antihypertensive treatment represents perhaps one-half of all cases of resistant hypertension. This retrospective study set out to determine the influence of the non-compliance of patients with resistant hypertension influence on the development of subclinical organ damage. Design and method: The presence of antihypertensive drugs was analyzed in the toxicology laboratory using liquid chromatography with tandem mass spectrometry (LC-MS / MS) in serum of patients admitted to our department for investigation of resistant hypertension. To determine levels of antihypertensive drugs, unplanned blood sampling was taken in 65 patients in whom tests to assess subclinical organ damage, namely determination intima media thickness of the common carotid artery (IMT), an index of left ventricular mass (LVMI) and albuminuria were simultaneously performed. Results: Therapeutic levels of all analyzed administered drugs were found in 52 patients (80%). In the remaining of 13 patients (20%), plasma levels of one or more administered drugs were under therapeutic range or were not detected at all. In patients with true resistant hypertension, office blood pressure of 165 ± 21/98 ± 17 mm Hg, the IMT of 0.77 ± 0.14 mm, LVMI of 106 (91 to 122) g/m2 and albuminuria of 19 (5 - 368) g/min were determined, while office blood pressure values of 173 ± 23/107 ± 20 mm Hg, the IMT of 0.83 ± 0.17 mm, LVMI of 94 (88 - 117) g/m2 and albuminuria of 13 (5–74) g/min were observed in patients with documented non-compliance to antihypertensive treatment. Differences in all these parameters between both groups of patients were not statistically significant. Conclusions: This retrospective analysis did not reveal any significant difference in any of the parameters of subclinical organ damage among patients with non-compliance and true resistant hypertension. To demonstrate an expected higher incidence of cardiovascular complications in patients with non-compliance to treatment further prospective studies will be required.

Objective: Patients with resistant hypertension have a higher incidence of cardiovascular complications in comparison with controlled hypertension patients. Non-compliance to antihypertensive treatment represents perhaps one-half of all cases of resistant hypertension. This retrospective study set out to determine the influence of the non-compliance of patients with resistant hypertension influence on the development of subclinical organ damage. Design and method: The presence of antihypertensive drugs was analyzed in the toxicology laboratory using liquid chromatography with tandem mass spectrometry (LC-MS / MS) in serum of patients admitted to our department for investigation of resistant hypertension. To determine levels of antihypertensive drugs, unplanned blood sampling was taken in 65 patients in whom tests to assess subclinical organ damage, namely determination intima media thickness of the common carotid artery (IMT), an index of left ventricular mass (LVMI) and albuminuria were simultaneously performed. Results: Therapeutic levels of all analyzed administered drugs were found in 52 patients (80%). In the remaining of 13 patients (20%), plasma levels of one or more administered drugs were under therapeutic range or were not detected at all. In patients with true resistant hypertension, office blood pressure of 165 ± 21/98 ± 17 mm Hg, the IMT of 0.77 ± 0.14 mm, LVMI of 106 (91 to 122) g/m2 and albuminuria of 19 (5 - 368) g/min were determined, while office blood pressure values of 173 ± 23/107 ± 20 mm Hg, the IMT of 0.83 ± 0.17 mm, LVMI of 94 (88 - 117) g/m2 and albuminuria of 13 (5–74) g/min were observed in patients with documented non-compliance to antihypertensive treatment. Differences in all these parameters between both groups of patients were not statistically significant. Conclusions: This retrospective analysis did not reveal any significant difference in any of the parameters of subclinical organ damage among patients with non-compliance and true resistant hypertension. To demonstrate an expected higher incidence of cardiovascular complications in patients with non-compliance to treatment further prospective studies will be required.

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.