J W Lenders

Carl Gustav Carus-Institut, Pforzheim, Baden-Württemberg, Germany

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Publications (271)1319.73 Total impact

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    ABSTRACT: Objective: Testing for succinate dehydrogenase subunit B (SDHB) mutations is recommended in all patients with metastatic phaeochromocytomas and paragangliomas (PPGLs), but may not be required when metastatic disease is accompanied by adrenaline production. This retrospective cohort study aimed to establish the prevalence of SDHB mutations among patients with metastatic PPGLs characterised by production of adrenaline compared to those without production of adrenaline, and to establish genotype-phenotype features of metastatic PPGLs according to underlying gene mutations. Design & Methods: Presence of SDHB mutations or deletions was tested in 205 patients (114 males) aged 42±16 yrs (range 9 to 86 yrs) at diagnosis of metastatic PPGLs with and without adrenaline production. Results: Twenty-three of the 205 patients (11%) with metastatic PPGLs had disease characterized by production of adrenaline, as defined by increased plasma concentrations of metanephrine larger than 5% of the combined increase of both normetanephrine and metanephrine. None of these 23 patients had SDHB mutations. Of the other 182 patients with no tumoural adrenaline production, 51% had SDHB mutations. Metastases in bone were 36% to 41% more prevalent among patients with SDHB mutations or extra-adrenal primary tumours than those without mutations or with adrenal primary tumours. Liver metastases were 81% more prevalent among patients with adrenal than extra-adrenal primary tumours. Conclusion: SDHB mutation testing has no utility among patients with adrenaline-producing metastatic PPGLs, but is indicated in other patients with metastatic disease. Our study also reveals novel associations of metastatic spread with primary tumour location and presence of SDHB mutations.
    European journal of endocrinology / European Federation of Endocrine Societies. 11/2014;
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    ABSTRACT: Background Steroid profiling for diagnosis of endocrine disorders featuring disordered production of steroid hormones is now possible from advances in liquid chromatography with tandem mass spectrometry (LC–MS/MS). Adrenal venous (AV) measurements of aldosterone and cortisol are a standard practice in the clinical work-up of primary aldosteronism, but do not yet take advantage of steroid profiling. Methods A novel LC–MS/MS based method was developed for simultaneous measurement of 15 adrenal steroids: aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, pregnenolone, cortisone, cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, 21-deoxycortisol, 18-oxocortisol and 18-hydroxycortisol. These were compared in peripheral venous (pV) and AV plasma from 70 patients undergoing AV sampling with and without cosyntropin stimulation. Aldosterone and cortisol levels measured by LC–MS/MS were compared with those measured by immunoassay. Results Reproducibility of measurements with coefficients of variation ≤10% as well as analytical sensitivity sufficient to measure low pV levels particularly of aldosterone demonstrate the utility of the assay for profiling adrenal steroids in primary aldosteronism. Method comparisons indicated assay and concentration dependent differences of cortisol and aldosterone concentrations measured by immunoassay and LC–MS/MS. Median AV/pV ratios of 11-deoxycortisol (53.0), 17-hydroxyprogesterone (33.4), pregnenolone (62.4), androstenedione (40.6) and dehydroepiandrosterone (33.3) were 2.9- to, 5.4-fold larger than those for cortisol (11.6), with additionally generally larger increases than for cortisol with than without cosyntropin stimulation. Conclusion Our LC–MS/MS assay, in addition to improvements over existing immunoassay measurements of aldosterone and cortisol, offers profiling of 13 other adrenal steroids, providing a potentially useful method for the clinical work-up of patients with primary aldosteronism. In particular, the larger AV/pV ratios of several steroids compared to cortisol suggest more sensitive alternatives to the latter for assessing positioning of AV sampling catheters.
    The Journal of Steroid Biochemistry and Molecular Biology. 10/2014;
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    ABSTRACT: Objective: Diagnosis of pheochromocytoma during pregnancy can be difficult and the tumor carries an unfavorable prognosis if not diagnosed and treated in a timely manner.Methods: To present a case, of Takotsubo-like cardiomyopathy, characterized by transient left ventricular apical ballooning due to pheochromocytoma following delivery.Results: A few hours after Caesarean section a 32-year-old Caucasian woman presented with pulmonary edema followed by cardiac arrest, with echocardiographic and ventriculographic evidence of reversible acute myocardial failure characteristic of Takotsubo-like cardiomyopathy. A previously unrecognized adrenal pheochromocytoma was found during further clinical work-up. Left ventricle function normalized after surgical removal of the tumor carried out after implementing alpha-adrenoreceptor blockade. Hemorrhagic necrosis of the pheochromocytoma was seen on histopathology, which might have triggered the sequence of events leading to the development of Takotsubo-like cardiomyopathy and hemodynamic collapse.Conclusion: To the best of our knowledge we describe here the first reported case of Takotsubo-like cardiomyopathy related to pheochromocytoma following the delivery. This emphasizes the increased cardiovascular risk if pheochromocytoma is not diagnosed and treated in a timely manner especially during pregnancy.
    08/2014;
  • B.J. Kramers, C. Kramers, J.W.M. Lenders, J. Deinum
    Clinical Therapeutics 08/2014; 36(8):e12. · 2.23 Impact Factor
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    ABSTRACT: Context: Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. Objective: We assessed whether altered succinate dehydrogenase product-precursor relationships, manifested by differences in tumor ratios of succinate to fumarate or other metabolites, might aid in identifying and stratifying patients with SDHx mutations. Design, Setting and Patients: PPGL tumor specimens from 233 patients, including 45 with SDHx mutations, were provided from eight tertiary referral centers for mass spectrometric analyses of Krebs cycle metabolites. Main outcome measure: Diagnostic performance of the succinate:fumarate ratio for identification of pathogenic SDHx mutations. Results: SDH-deficient PPGLs were characterized by 25-fold higher succinate and 80% lower fumarate, cis-aconitate and isocitrate tissue levels than PPGLs without SDHx mutations. Receiver-operating characteristic curves for use of ratios of succinate to fumarate or to cis-aconitate and isocitrate to identify SDHx mutations indicated areas under curves of 0.94 to 0.96; an optimal cut-off of 97.7 for the succinate:fumarate ratio provided a diagnostic sensitivity of 93% at a specificity of 97% to identify SDHX-mutated PPGLs. Succinate:fumarate ratios were higher in both SDHB-mutated and metastatic tumors than in those due to SDHD/C mutations or without metastases. Conclusions: Mass spectrometric-based measurements of ratios of succinate:fumarate and other metabolites in PPGLs offer a useful method to identify patients for testing of SDHx mutations, with additional utility to quantitatively assess functionality of mutations and metabolic factors responsible for malignant risk.
    The Journal of clinical endocrinology and metabolism. 07/2014;
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    ABSTRACT: Pheochromocytomas and paragangliomas (PPGLs) can be localized by (18)F-FDG PET. The uptake is particularly high in tumors with an underlying succinate dehydrogenase (SDH) mutation. SDHx-related PPGLs are characterized by compromised oxidative phosphorylation and a pseudohypoxic response, which mediates an increase in aerobic glycolysis, also known as the Warburg effect. The aim of this study was to explore the hypothesis that increased uptake of (18)F-FDG in SDHx-related PPGLs is reflective of increased glycolytic activity and is correlated with expression of different proteins involved in glucose uptake and metabolism through the glycolytic pathway.
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 06/2014;
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    ABSTRACT: Objective: The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. Conclusions: The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines. Consideration should be given to preanalytical factors leading to false-positive or false-negative results. All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications. Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas. Partial adrenalectomy is an option for selected patients. Lifelong follow-up is suggested to detect recurrent or metastatic disease. We suggest personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes.
    The Journal of clinical endocrinology and metabolism. 06/2014; 99(6):1915-1942.
  • A van Berkel, K Pacak, J W M Lenders
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    ABSTRACT: Localization of phaeochromocytomas and paragangliomas (PPGLs) should involve functional imaging since anatomical imaging modalities can either fail to locate the tumor or can be suboptimal due to an anatomical abnormality or previous surgery. Functional imaging is particularly useful to fully delineate the extent of disease by using the whole body scan and the evaluation of multifocality, metastatic or recurrent disease. An increasing number of radiolabeled tracers have become available for tumor visualization during the past decade. (123) I-meta-iodobenzylguanidine scintigraphy is the most widely used functional imaging modality and its sensitivity to identify chromaffin cell tumors varies from 85-88% for phaeochromocytomas and 56-76% for paragangliomas, while specificity ranges between 70-100% and 84-100%, respectively. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 05/2014; · 3.40 Impact Factor
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    ABSTRACT: Context: Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia. Objective: The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs. Design and Methods: We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi. Results: Glands contained a solitary adenoma in 43% and nodular hyperplasia in 53% of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes. Conclusions: Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.
    The Journal of Clinical Endocrinology and Metabolism 04/2014; · 6.31 Impact Factor
  • Jacques W M Lenders, Graeme Eisenhofer
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    ABSTRACT: The principal function of the adrenal medulla is the production and secretion of catecholamines. During stressful challenging conditions, catecholamines exert a pivotal homeostatic role. Although the main adrenomedullary catecholamine, epinephrine, has a wide array of adrenoreceptor-mediated effects, its absence does not cause life-threatening problems. In contrast, excess production of catecholamines due to an adrenomedullary tumor, specifically pheochromocytoma, results in significant morbidity and mortality. Despite being rare, pheochromocytoma has a notoriously bad reputation because of its potential devastating effects if undetected and untreated. The paroxysmal signs and symptoms and the risks of missing or delaying the diagnosis are well known for most physicians. Nevertheless, even today the diagnosis is still overlooked in a considerable number of patients. Prevention and complete cure are however possible by early diagnosis and appropriate treatment but these patients remain a challenge for physicians. Yet, biochemical proof of presence or absence of catecholamine excess has become more easy and straightforward due to developments in assay methodology. This also applies to radiological and functional imaging techniques for locating the tumor. The importance of genetic testing for underlying germline mutations in susceptibility genes for patients and relatives is increasingly recognized. Yet, the effectiveness of genetic testing, in terms of costs and benefits to health, has not been definitively established. Further improvement in knowledge of genotype-phenotype relationships in pheochromocytoma will open new avenues to a more rationalized and personalized diagnostic approach of affected patients. © 2014 American Physiological Society. Compr Physiol 4:691-713, 2014.
    Comprehensive Physiology. 04/2014; 4(2):691-713.
  • Hypertension 04/2014; 63(4):e89. · 6.87 Impact Factor
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    ABSTRACT: Higher plasma concentrations of catecholamines in winter than in summer have been established, but whether this impacts the plasma concentrations of metanephrines used for the diagnosis of pheochromocytoma is unknown. In this study, we examined seasonal variations in the plasma concentrations of metanephrines, the impact of this on diagnostic test performance and the influences of forearm warming ('arterialization' of venous blood) on blood flow and measured concentrations. The measurements of the plasma concentrations of metanephrines were recorded from 4052 patients tested for pheochromocytoma at two clinical centers. Among these patients, 107 had tumors. An additional 26 volunteers were enrolled for the measurements of plasma metanephrines and forearm blood flow before and after forearm warming. There was no seasonal variation in the plasma concentrations of metanephrines among patients with pheochromocytoma, whereas among those without tumors, the plasma concentrations of normetanephrine were higher (P<0.0001) in winter than in summer. Lowest concentrations of normetanephrine were measured in July, with those recorded from December to April being more than 21% higher (P<0.0001). These differences resulted in a twofold higher (P=0.0012) prevalence of false-positive elevations of normetanephrine concentrations in winter than in summer, associated with a drop in overall diagnostic specificity from 96% in summer to 92% in winter (P=0.0010). Forearm warming increased blood flow and lowered (P=0.0020) plasma normetanephrine concentrations. The plasma concentrations of normetanephrine are subject to seasonal variation with a resulting higher prevalence of false-positive results in winter than in summer. Lowered plasma concentrations of normetanephrine with forearm warming suggest an effect of temperature. These results have implications for considerations of temperature to minimize false-positive results.
    European Journal of Endocrinology 03/2014; 170(3):349-57. · 3.14 Impact Factor
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    ABSTRACT: Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing chromaffin cell tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To explore whether phenotypic differences among PPGLs reflect a MAX-mediated mechanism and opposing influences of HIF2α and HIF1α, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. Among PPGLs from 140 patients, tumors due to MAX mutations were characterized by gene expression profiles and intermediate phenotypic features that distinguished these tumors from other PPGLs, all of which fell into two expression clusters: one cluster with low expression of HIF2α and mature phenotypic features and the other with high expression of HIF2α and immature phenotypic features due to mutations stabilizing HIFs. Max-mutated tumors distributed to a distinct sub-cluster of the former group. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2α, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1α had opposing actions to HIF2α in both cell lines, supporting evolving evidence of their differential actions on tumorigenic processes via a MYC/MAX related pathway. Requirement of a fully functional MYC/MAX complex to facilitate differentiation explains the intermediate phenotypic features in tumors due to MAX mutations. Overexpression of HIF2α in chromaffin cell tumors due to mutations affecting HIF stabilization explains their proliferative features and why the tumors fail to differentiate even when exposed locally to adrenal steroids. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 03/2014; · 6.20 Impact Factor
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    ABSTRACT: Adrenal phaechromocytomas and extra-adrenal sympathetic paragangliomas (PPGLs) are rare neuroendocrine tumours characterised by production of the catecholamines noradrenaline, adrenaline and dopamine. Tumoural secretion of catecholamines determines their clinical presentation which is highly variable among patients. Up to 10-15% of patients present entirely asymptomatically and in 5% of all adrenal incidentalomas a PPGL is found. Therefore, prompt diagnosis of PPGL remains a challenge for every clinician. Early consideration of the presence of a PPGL is of utmost importance since missing the diagnosis can be devastating due to potential lethal cardiovascular complications of disease. First step in diagnosis is proper biochemical analysis to confirm or refute the presence of excess production of catecholamines or their metabolites. Biochemical testing is not only indicated in symptomatic patients, but also in asymptomatic patients with adrenal incidentalomas or identified genetic predispositions. Measurements of metanephrines in plasma or urine offers the best diagnostic performance and are the tests of first choice. Paying attention to sampling conditions, patient preparation and use of interfering medications is important since these factors can largely influence test results. When initial test results are inconclusive, additional tests can performed such as the clonidine suppression test. Test results can also be used for estimation of tumour size or prediction of tumor location and underlying genotype. Furthermore, tumoural production of 3-methoxytyramine is associated with presence of an underlying SDHB mutation and may be a biomarker of malignancy.
    European Journal of Endocrinology 12/2013; · 3.14 Impact Factor
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    ABSTRACT: Adrenal venous sampling is recommended by current guidelines to identify surgically curable causes of hyperaldosteronism but remains markedly underused. Key factors contributing to the poor use of adrenal venous sampling include the prevailing perceptions that it is a technically challenging procedure, difficult to interpret, and can be complicated by adrenal vein rupture. In addition, the lack of uniformly accepted standards for the performance of adrenal venous sampling contributes to its limited use. Hence, an international panel of experts working at major referral centers was assembled to provide updated advice on how to perform and interpret adrenal venous sampling. To this end, they were asked to use the PICO (Patient or Problem, Intervention, Control or comparison, Outcome) strategy to gather relevant information from the literature and to rely on their own experience. The level of evidence/recommendation was provided according to American Heart Association gradings whenever possible. A consensus was reached on several key issues, including the selection and preparation of the patients for adrenal venous sampling, the procedure for its optimal performance, and the interpretation of its results for diagnostic purposes even in the most challenging cases.
    Hypertension 11/2013; · 6.87 Impact Factor
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    ABSTRACT: Adrenal vein sampling is used to establish the origins of excess production of adrenal hormones in primary aldosteronism. Correct catheter positioning is confirmed using adrenal vein measurements of cortisol, but this parameter is not always reliable. Plasma metanephrine represents an alternative parameter. The objective of our study was to determine the use of plasma metanephrine concentrations to establish correct catheter positioning during adrenal vein sampling with and without cosyntropin stimulation. We included 52 cosyntropin-stimulated and 34 nonstimulated sequential procedures. Plasma cortisol and metanephrine concentrations were measured in adrenal and peripheral venous samples. Success rates of sampling, using an adrenal to peripheral cortisol selectivity index of 3.0, were compared with success rates of metanephrine using a selectivity index determined by receiver operating characteristic curve analysis. Among procedures assessed as selective using cortisol, the adrenal to peripheral vein ratio of metanephrine was 6-fold higher than that of cortisol (94.0 versus 15.5; P<0.0001). There were significant positive relationships between adrenal to peripheral vein ratios of cortisol and metanephrine for cosyntropin-stimulated samplings but not for nonstimulated samplings. Receiver operating characteristic curve analysis indicated a plasma metanephrine selectivity index cutoff of 12. Using this cutoff, concordance in sampling success rates determined by cortisol and metanephrine was substantially higher in cosyntropin-stimulated than in nonstimulated samplings (98% versus 59%). For the latter procedures, sampling success rates determined by metanephrine were higher (P<0.01) than those determined by cortisol (91% versus 56%). In conclusion, metanephrine provides a superior analyte compared with cortisol in assessing the selectivity of adrenal vein sampling during procedures without cosyntropin stimulation.
    Hypertension 09/2013; · 6.87 Impact Factor
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    ABSTRACT: To document the influences of blood sampling under supine fasting versus seated non-fasting conditions on diagnosis of phaeochromocytomas and paragangliomas (PPGL) using plasma concentrations of normetanephrine, metanephrine and methoxytyramine. Biochemical testing for PPGL was performed on 762 patients at six centres, two of which complied with requirements for supine sampling after an overnight fast and four of which did not. PPGL were found in 129 patients (67 non-compliant, 62 compliant) and not in 633 patients (195 non-compliant, 438 compliant). Plasma concentrations of normetanephrine and methoxytyramine did not differ between compliant and non-compliant sampling conditions in patients with PPGL, but were 49-51% higher in patients without PPGL sampled under non-compliant compared to compliant conditions. The 97.5-percentiles of distributions were also higher under non-compliant compared to compliant conditions for normetanephrine (1.29 vs 0.79 nmol/l), metanephrine (0.49 vs 0.41 nmol/l) and methoxytyramine (0.42 vs 0.18 nmol/l). Use of upper cut-offs established from seated non-fasting sampling conditions resulted in substantially decreased diagnostic sensitivity (98% vs 85%). In contrast, use of upper cut-offs established from supine fasting conditions resulted in decreased diagnostic specificity for testing under non-compliant compared to compliant conditions (71% vs 95%). High diagnostic sensitivity of plasma normetanephrine, metanephrine and methoxytyramine for detection of PPGL can only be guaranteed using upper cut-offs of reference intervals established with blood sampling under supine fasting conditions. With such cut-offs, sampling under seated non-fasting conditions can lead to a 5.7-fold increase in false-positive results necessitating repeat sampling under supine fasting conditions. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 09/2013; · 3.40 Impact Factor
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    ABSTRACT: PURPOSE: Pheochromocytomas and paragangliomas (PGLs) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. The present study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors. EXPERIMENTAL DESIGN: Respiratory chain enzyme assays and 1H-NMR spectroscopy at 500 MHz, were performed on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in SDHB, SDHD, SDHAF-2, VHL, RET, NF1 and MAX. RESULTS: In SDHx related PGLs, a significant decrease in complex II activity (p<0.0001) and a significant increase in complex I, III and IV enzyme activities were observed when compared to sporadic, RET and NF1 tumors. Also, a significant increase in citrate synthase (p<0.0001) enzyme activity was observed in SDHx related PGLs when compared to sporadic, VHL, RET and NF1 related ones. An increase in succinate accumulation (p<0.001) and decrease in ATP/ADP/AMP accumulation (p<0.001) was observed when compared to sporadic PGLs and PGLs of other genotypes. Positive correlations (p<0.01) were observed between respiratory chain complex II activity and total catecholamine content and ATP/ADP/AMP and total catecholamine contents in tumor tissues. CONCLUSIONS: The present study for the first time establishes relationship between determinants of energy metabolism like activity of respiratory chain enzyme complex II, ATP/ADP/AMP content and catecholamine content in PGL tumors. Also, the present study for the first time successfully uses NMR spectroscopy to detect catecholamines in PGL tumors and provides ex vivo evidence for the accumulation of succinate in PGL tumors with a SDHx mutation.
    Clinical Cancer Research 05/2013; · 7.84 Impact Factor
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    ABSTRACT: BACKGROUND: Adrenal vein sampling (AVS) is the preferred test for subtyping primary aldosteronism. However, the procedure is technically demanding and costly. In AVS it is common practice to take duplicate blood samples at each location. In this paper we explore whether a single sample procedure leads to a different conclusion concerning the location of adrenal aldosterone secretion than a duplicate sample procedure. METHODS: AVS procedures with duplicate measurements performed in our university medical centre between 2005 and 2010 were evaluated retrospectively. We compared the conclusions regarding selectivity and lateralization based on the first sample taken (A) to the conclusions based on the average of duplicate samples (AB). We also calculated the number needed to sample in duplicate to prevent one misclassification. RESULTS: Ninety-six AVS procedures of 82 patients were included. The concordance in AVS conclusions between sample A and AB was 98-100%, depending on the criteria used for selectivity and lateralization. With permissive and strict criteria the number needed to sample in duplicate were infinite and 48, respectively. CONCLUSIONS: The incremental benefit of duplicate sampling compared to single sampling is low. Therefore, in case of technical difficulties during AVS, conclusions can also be reliably drawn from a single blood sample.
    Clinica chimica acta; international journal of clinical chemistry 04/2013; · 2.54 Impact Factor
  • Experimental and Clinical Endocrinology & Diabetes 03/2013; 121(03). · 1.56 Impact Factor

Publication Stats

5k Citations
1,319.73 Total Impact Points

Institutions

  • 2013–2014
    • Carl Gustav Carus-Institut
      Pforzheim, Baden-Württemberg, Germany
  • 2008–2014
    • Technische Universität Dresden
      • Institute of Chemistry and Laboratory Medicine
      Dresden, Saxony, Germany
  • 1988–2014
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 1986–2013
    • Radboud University Nijmegen
      • • Department of Medical Oncology
      • • Department of General Internal Medicine
      Nijmegen, Provincie Gelderland, Netherlands
  • 2012
    • University of Florence
      • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florence, Tuscany, Italy
  • 2003–2008
    • Maastricht University
      • Interne Geneeskunde
      Maastricht, Provincie Limburg, Netherlands
  • 2007
    • St. Antonius Ziekenhuis
      Nieuwegen, Utrecht, Netherlands
  • 2003–2007
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 2006
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada
  • 1993–2005
    • National Institutes of Health
      • Branch of Behavioral Neuroscience
      Maryland, United States
  • 1991
    • Leiden University Medical Centre
      • Department of Cardiology
      Leiden, South Holland, Netherlands