B Allolio

University of Wuerzburg, Würzburg, Bavaria, Germany

Are you B Allolio?

Claim your profile

Publications (439)1818.78 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To evaluate current management time lines in adrenal crisis (AC) and to establish time targets and limits for emergency treatment.Design/patientsPatients from a prospective study who had reported an AC (n=46) were contacted and asked about management of their AC. A survey among 24 European endocrinologists collected expert recommendations concerning time targets and limits for contact - arrival time of emergency health professionals and presentation of emergency card - glucocorticoid (GC) injection time.ResultsMedian time targets and limits regarded by experts as adequate for contact – arrival time were 45 and 90 min, respectively and for card – injection time 15 and 30 min, respectively. 37 of 46 patients could be interviewed. All patients were equipped with an emergency card but only 23 (62%) with an emergency kit. Seven patients (19%) were trained in GC self-injection. The median time interval between contacting a health professional and arrival was 20 min (range 2-2880min); ≤45 min: n=32 (86%), <90 min: n=34 (92%), The median time interval between arrival and administration of GC was 30 min (range 2-2400min); ≤15 min: n=17 (46%), ≤30 min: n=20 (54%).Conclusion While the time between contacting health professionals and their arrival was within the limits set by experts, initiation of GC administration was delayed in 46% of patients. Thus improved management of AC needs to focus on shortening the presentation of card - injection time. Given the current reality in the management of AC, promotion of self-injection of GC (s.c. or i.m.) is warranted.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 09/2014; · 3.40 Impact Factor
  • Article: Erratum.
    08/2014; 29(8):1611.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Kaposi sarcoma (KS) is a malignant disease most commonly diagnosed in the setting of a human immunodeficiency virus (HIV) infection and in patients receiving immunosuppressive treatment. Pulmonary KS has never been reported in association with endogenous Cushing's syndrome (CS).
    BMC Endocrine Disorders 07/2014; 14(1):63. · 2.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context. Somatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found in a high proportion of sporadic adenomas associated with Cushing's syndrome (CS). The aim was to analyze the PRKACA mutation in a large cohort of patients with adrenocortical masses. Methods. Samples from nine European centers were included (Germany, n=4; Italy, n=4; France, n=1). Samples were drawn from 149 patients with non-secreting adenomas (n=32 + 2 peritumoral), subclinical hypercortisolism (n=36), CS (n=64 + 2 peritumoral), androgen-producing tumors (n=4), adrenocortical carcinomas (n=5 + 2 peritumoral), and primary bilateral macronodular adrenal hyperplasias (n=8). Blood samples were available from patients with non-secreting adenomas (n=15), subclinical hypercortisolism (n=10), and CS (n=35). Clinical and hormonal data were collected. DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct sequencing were performed. Results. PRKACA heterozygous mutations were found in 22/64 samples of CS patients (34%). No mutations were found in peritumoral tissue and blood samples or in other tumors examined. The c.617A>C (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were identified: c.600 601insGTG/p.Cys200 Gly201insVal in three patients and c.639C>G+c.638 640insATTATCCTGAGG/p.Ser213Arg+p.Leu212 Lys214insIle-Ile-Leu-Arg) in one. All the mutations involved a region implicated in interaction between PKA regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed higher levels of cortisol after dexamethasone test and a smaller adenoma size, compared to non-mutated subjects. Conclusions. These data confirm and extend previous observations that somatic PRKACA mutations are specific for adrenocortical adenomas causing CS.
    The Journal of clinical endocrinology and metabolism. 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background In patients with a relapse-free history of phaeochromcytoma/paraganglioma (PCC/PGL), persistent hypertension has been reported, but has not been well characterized.Methods In 28 patients (mean age 54.5 [26-81] years) with a relapse-free history of PCC/PGLs, we prospectively analysed resting, supine blood pressure (BP), ambulatory BP, echocardiography, exercise testing, metabolic parameters and retrospectively collected data from the time of diagnosis (baseline). Echocardiographic measures were compared to healthy (n=28) and hypertensive controls (n=15).ResultsMedian follow-up was 6 [1-16] years. Three patients had normal office and ambulatory BP and 3 patients had only elevated office BP. Fifty-four percent of patients had a blunted circadian rhythm. Comparing normal, hypertensive and PCC/PGL patients, we found significant differences in end-diastolic septal thickness (8.8±0.2, 13.8±0.4, 10.0±0.3 mm, p<0.05), septal basal thickness (9.0±0.3, 15.9±0.5, 11.2±0.4 mm, p<0.05) and left ventricular mass (143±8, 255±19, 169±9g, p<0.05). In 5 patients, 7 major cardiovascular events were observed. Compared to baseline, no significant difference was found in systolic (140±35 vs 137±18 mmHg) and diastolic (85±18 vs 83±10 mmHg) BP. An increase or a decrease in BP (>10 mmHg) was found in 36% and 39% of patients, respectively. The number of antihypertensive drugs had not changed (1 [0-3] vs 1 [0-4]). Fewer patients received insulin (1 vs 3) or oral antiglycemic drugs (2 vs 7).Conclusion Our data indicate that hypertension persists after removal of PCG/PGL in a substantial proportion of patients. Hypertensive heart disease is common and cardiovascular events are frequent in patients with a history of PCC/PGL.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2014; · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in aldosterone-producing adenomas (APAs). Our aim was to investigate the prevalence of somatic mutations in these genes in unselected patients with APA (n=474), collected through the European Network for the Study of Adrenal Tumors. Correlations with clinical and biochemical parameters were first analyzed in a subset of 199 patients from a single center and then replicated in 2 additional centers. Somatic heterozygous KCNJ5 mutations were present in 38% (180/474) of APAs, whereas ATP1A1 mutations were found in 5.3% (25/474) and ATP2B3 mutations in 1.7% (8/474) of APAs. Previously reported somatic CACNA1D mutations as well as 10 novel CACNA1D mutations were identified in 44 of 474 (9.3%) APAs. There was no difference in the cellular composition of APAs or in CYP11B2, CYP11B1, KCNJ5, CACNA1D, or ATP1A1 gene expression in APAs across genotypes. Patients with KCNJ5 mutations were more frequently female, diagnosed younger, and with higher minimal plasma potassium concentrations compared with CACNA1D mutation carriers or noncarriers. CACNA1D mutations were associated with smaller adenomas. These associations were largely dependent on the population structure of the different centers. In conclusion, recurrent somatic mutations were identified in 54% of APAs. Young women with APAs are more likely to be KCNJ5 mutation carriers; identification of specific characteristics or surrogate biomarkers of mutation status may lead to targeted treatment options.
    Hypertension 05/2014; · 6.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the β-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.
    Nature Genetics 04/2014; · 35.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated copeptin concentrations independent of serum osmolality (type A); 14% had copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal copeptin concentrations independent of osmolality (type C), and 12% had suppressed copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype.
    Journal of the American Society of Nephrology 04/2014; · 8.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Corticotropin-independent Cushing's syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol-producing adrenal adenomas is not well understood. Methods We performed exome sequencing of tumor-tissue specimens from 10 patients with cortisol-producing adrenal adenomas and evaluated recurrent mutations in candidate genes in an additional 171 patients with adrenocortical tumors. We also performed genomewide copy-number analysis in 35 patients with cortisol-secreting bilateral adrenal hyperplasias. We studied the effects of these genetic defects both clinically and in vitro. Results Exome sequencing revealed somatic mutations in PRKACA, which encodes the catalytic subunit of cyclic AMP-dependent protein kinase (protein kinase A [PKA]), in 8 of 10 adenomas (c.617A→C in 7 and c.595_596insCAC in 1). Overall, PRKACA somatic mutations were identified in 22 of 59 unilateral adenomas (37%) from patients with overt Cushing's syndrome; these mutations were not detectable in 40 patients with subclinical hypercortisolism or in 82 patients with other adrenal tumors. Among 35 patients with cortisol-producing hyperplasias, 5 (including 2 first-degree relatives) carried a germline copy-number gain (duplication) of the genomic region on chromosome 19 that includes PRKACA. In vitro studies showed impaired inhibition of both PKA catalytic subunit mutants by the PKA regulatory subunit, whereas cells from patients with germline chromosomal gains showed increased protein levels of the PKA catalytic subunit; in both instances, basal PKA activity was increased. Conclusions Genetic alterations of the catalytic subunit of PKA were found to be associated with human disease. Germline duplications of this gene resulted in bilateral adrenal hyperplasias, whereas somatic PRKACA mutations resulted in unilateral cortisol-producing adrenal adenomas. (Funded by the European Commission Seventh Framework Program and others.).
    New England Journal of Medicine 02/2014; · 51.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Li-Fraumeni tumor syndrome is strongly associated with adrenocortical carcinoma (ACC), and caused by germline mutations in TP53 in 70% of cases. Also, TP53 polymorphisms have been shown to influence both cancer risk and clinical outcome in several tumor entities. We, therefore, investigated TP53 polymorphisms in a cohort of adult patients with ACC. Evaluation of the role of TP53 polymorphisms in adult patients with ACC. Peripheral blood for DNA extraction was collected from 72 ACC patients. Polymorphism analysis was performed by amplification and sequencing of exons and adjacent intron sections of TP53. Results were correlated with clinical data and the distribution of the polymorphisms was compared to published Caucasian control groups. Compared to control groups, genotype frequencies of analyzed TP53 polymorphisms amongst ACC patients were significantly different in 3 out of 4 polymorphisms: IVS2+38G>C (G/G, p=0.0248), IVS3ins16 (NoIns/NoIns, p<0.0001; NoIns/Ins, p<0.0001) and IVS6+62A>G (G/G, p<0.0001; G/A, p<0.0001). Overall survival of ACC patients, which harboured at least one of the less frequent genotype variants of four analyzed polymorphisms (n=23), was significantly inferior (median survival: 81.0 months in patients with the common homozygous genotypes vs. 20.0 months in patients with the less frequent genotypes, HR 2.56 1.66-7.07 95% CI. P=0.001). These results were confirmed by multivariable regression analysis (HR 2.84 1.52-7.17 95% CI. P=0.037). Some TP53 polymorphisms seem to influence overall survival in ACC patients. This effect was observed for a combination of polymorphic changes rather than for single polymorphisms.
    European Journal of Endocrinology 02/2014; · 3.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hyponatraemia, defined as a serum sodium concentration <135 mmol/L, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. Hyponatraemia is present in 15-20 % of emergency admissions to hospital and occurs in up to 20 % of critically ill patients. Symptomatology may vary from subtle to severe or even life threatening. Despite this, the management of patients remains problematic. Against this background, the European Society of Intensive Care Medicine, the European Society of Endocrinology and the European Renal Association-European Dialysis and Transplant Association, represented by European Renal Best Practice have developed a Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia.
    European Journal of Intensive Care Medicine 02/2014; · 5.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adrenocortical tumors comprise frequent adenomas (ACA) and rare carcinomas (ACC). Human cytochrome P450 2W1 (CYP2W1) is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins.
    PLoS ONE 01/2014; 9(8):e105855. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with primary adrenal insufficiency usually show pronounced impairment of aldosterone secretion and, therefore, require also mineralocorticoid replacement for full recovery. Clinical signs of mineralocorticoid deficiency comprise hypotension, weakness, salt craving and electrolyte disturbances (hyperkalemia, hyponatremia). Mineralocorticoid deficiency is confirmed by demonstration of profoundly decreased aldosterone and highly elevated plasma renin activity (PRA). Standard replacement consists of 9α-fluorocortisol given once daily as a single oral dose (0.05 – 0.2 mg). Monitoring of mineralocorticoid replacement consists of clinical assessment (well-being, physical examination, blood pressure, electrolyte measurements) and measurement of PRA aiming at a PRA level in the upper normal range. Current replacement regimens may often be associated with mild hypovolemia. Dose adjustments are frequently needed in pregnancy to compensate for the anti-mineralocorticoid activity of progesterone and in high ambient temperature to avoid sodium depletion. In arterial hypertension a dose reduction is usually recommended, but monitoring for hyperkalemia is required.
    Best Practice & Research: Clinical Endocrinology & Metabolism 01/2014; · 4.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In subjects at high risk for sleep apnea (SA), aldosterone concentrations correlate with severity of SA and primary aldosteronism (PA) is very often diagnosed. Patients with PA show a high prevalence of SA. Treatment of PA either by adrenalectomy (ADX) or mineralocorticoid receptor (MR) blockade is thought to abolish the increased comorbidities. However, no data are available regarding effectiveness of different PA treatments on quality of sleep. This prospective multi-center study included 15 patients with newly diagnosed PA evaluated before and 0.7±0.2 years after treatment initiation, and a second cohort including 81 patients who were evaluated 5.3 and 6.8 years after treatment initiation. Biochemical parameters, 24h blood pressure and three validated self-assessment questionnaires (Giessen Complaint List (GBB-24), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality-Index (PSQI)) were analyzed. Z-scores of exhaustion tendency of GBB significantly improved in newly diagnosed PA patients after treatment initiation (1.8±1.4 vs. 1.0±1.2, p=0.034). In the second cohort no differences were found in GBB-24, ESS and PSQI. No differences were found in all three questionnaires independently of type of PA therapy. However, female patients scored significantly higher than males in the PSQI (8.7±3.6 vs 5.7±4.2, p<0.005), indicating lower sleep quality, independently of the type of therapy. For the first time, we analyzed quality of sleep in patients with PA, demonstrating that therapy initiation improves exhaustion tendency. Surprisingly, female PA patients showed significantly more sleep disturbances than male PA patients several years after treatment initiation.
    Hormones (Athens, Greece) 01/2014; 13(1):57-64. · 2.01 Impact Factor
  • Surgery 12/2013; · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In dialysis patients, the prevalence of thyroid disorders and their impact on specific cardiovascular (CV) events and mortality are largely unknown. The aim of the present study was to analyze whether subclinical thyroid disorders were associated with CV events and mortality. Prospective multicenter cohort study. Thyroid status and clinical outcomes were explored in 1,000 diabetic hemodialysis patients from 178 centers in Germany. Thyroid status, defined by the following cutoff values: euthyroidism (thyrotropin [TSH], 0.30-4.0mIU/L; free triiodothyronine [T3], 2.7-7.6pmol/L; and free thyroxine [T4], 11.0-24.0pmol/L), subclinical hyperthyroidism (TSH<0.3mIU/L and free T3/free T4 within reference ranges), subclinical hypothyroidism (TSH, 4.1-15.0mIU/L and free T3/free T4 within reference ranges), euthyroid sick syndrome (free T3<2.7pmol/L and TSH/free T4 low or within reference ranges). During 4 years' follow-up, prespecified adjudicated end points were determined: sudden cardiac death, myocardial infarction, stroke, combined CV events, and overall mortality. Short-term effects within the first 12 months were contrasted to long-term effects (years 2-4). TSH, free T3, and free T4 levels at baseline. Euthyroidism was present in 78.1% of patients; subclinical hyperthyroidism, in 13.7%; and subclinical hypothyroidism, in 1.6%. Euthyroid sick syndrome was exhibited by 5.4% of patients. The adjusted short-term risk of sudden cardiac death was more than doubled (HR, 2.03; 95% CI, 0.94-4.36) in patients with subclinical hyperthyroidism, and similarly for patients with euthyroid sick syndrome (HR, 2.74; 95% CI, 0.94-7.98) compared with patients with euthyroidism. Short-term mortality was increased almost 3-fold for patients with euthyroid sick syndrome (HR, 2.97; 95% CI, 1.66-5.29), but this effect was not seen in the long term. Subclinical hypothyroidism was not associated with CV events or all-cause mortality. Risks of stroke and myocardial infarction were not affected meaningfully by thyroid disorders. Observational study design. Sudden cardiac death may be influenced by subclinical hyperthyroidism and euthyroid sick syndrome in the short term. Furthermore, euthyroid sick syndrome is associated strongly with mortality in hemodialysis patients. Regular assessment of thyroid status may help estimate the cardiac risk of dialysis patients.
    American Journal of Kidney Diseases 12/2013; · 5.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction of the adrenal cortex. Consequently, patients with PAI are at higher risk of developing other autoimmune diseases. The diagnosis of PAI is often delayed by many months, and most patients present with symptoms of acute adrenal insufficiency. Because PAI is rare, even medical specialists in this therapeutic area rarely manage more than a few patients. Currently, the procedures for diagnosis, treatment and follow-up of this rare disease vary greatly within Europe. The common autoimmune form of PAI is characterized by the presence of 21-hydroxylase autoantibodies; other causes should be sought if no autoantibodies are detected. Acute adrenal crisis is a life-threatening condition that requires immediate treatment. Standard replacement therapy consists of multiple daily doses of hydrocortisone or cortisone acetate combined with fludrocortisone. Annual follow-up by an endocrinologist is recommended with the focus on optimization of replacement therapy and detection of new autoimmune diseases. Patient education to enable self-adjustment of dosages of replacement therapy and crisis prevention is particularly important in this disease. The authors of this document have collaborated within an EU project (Euadrenal) to study the pathogenesis, describe the natural course and improve the treatment for Addison's disease. Based on a synthesis of this research, the available literature, and the views and experiences of the consortium's investigators and key experts, we now attempt to provide a European Expert Consensus Statement for diagnosis, treatment and follow-up.
    Journal of Internal Medicine 11/2013; · 6.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although prognostic parameters are important to guide adjuvant treatment, very few have been identified in patients with completely resected adrenocortical carcinoma (ACC). To assess the prognostic role of clinical symptoms of hypercortisolism in a large series of patients with completely resected ACC. A total of 524 patients followed at referral centers for ACC in Europe and the United States entered the study. Inclusion criteria were ≥18 yr of age, a histologic diagnosis of ACC, and complete surgery (R0). Exclusion criteria were a history of other malignancies and adjuvant systemic therapies other than mitotane. All ACC patients were completely resected, and adjuvant mitotane therapy was prescribed at the discretion of the investigators. The primary end point was overall survival (OS). The secondary end points were recurrence-free survival (RFS) and the efficacy of adjuvant mitotane therapy according to cortisol secretion. Overt hypercortisolism was observed in 197 patients (37.6%). Patients with cortisol excess were younger (p=0.002); no difference according to sex and tumor stage was observed. The median follow-up of the series was 50 mo. After adjustment for sex, age, tumor stage, and mitotane treatment, the prognostic significance of cortisol excess was highly significant for both RFS (hazard ratio [HR]: 1.30; 95% confidence interval [CI], 1.04-2.62; p=0.02) and OS (HR: 1.55; 95% CI, 1.15-2.09; p=0.004). Mitotane administration was associated with a reduction of disease progression (adjusted HR: 0.65; 95% CI, 0.49-0.86; p=0.003) that did not differ according to the patient's secretory status. A major limitation is that only symptomatic patients were considered as having hypercortisolism, thus excluding information on the prognostic role of elevated cortisol levels in the absence of a clinical syndrome. Clinically relevant hypercortisolism is a new prognostic factor in patients with completely resected ACC. The efficacy of adjuvant mitotane does not seem to be influenced by overt hypercortisolism.
    European Urology 11/2013; · 10.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: End-stage renal disease (ESRD) patients exhibit an extraordinarily high annual mortality secondary to cardiac and vascular causes, particularly sudden cardiac death (SCD). Left ventricular (LV) hypertrophy is a frequent finding and constitutes an independent predictor of mortality risk in these patients. Mineralocorticoid receptor antagonists (MRAs) are cardioprotective in heart failure patients and effectively reduce LV mass, but are considered inappropriate in patients with severe renal impairment, given their potential to cause hyperkalaemia. Recent data from small clinical studies suggest that MRAs may be safe in patients undergoing regular haemodialysis, but cardiovascular (CV) protection in these patients is unclear. We here review the literature on CV effects of MRA in dialysis patients and report the design of the Mineralocorticoid Receptor antagonists in End-stage renal Disease (MiREnDa) trial. The MiREnDa trial is a prospective randomized, placebo-controlled, double-blind, parallel group, multi-centre, intervention study investigating the effects of spironolactone (50 mg daily) compared with placebo in maintenance haemodialysis patients. The change in LV mass index (LVMI) as assessed by cardiac magnet resonance imaging (CMR) constitutes the primary efficacy end point. Secondary end points include changes in LV geometry and function, office and 24-h ambulatory blood pressure, cardiac arrhythmias, vascular function parameters, measures of heart failure and quality of life. Pre-dialysis potassium levels and the incidence of threatening hyperkalaemia (pre-dialysis potassium ≥6.5 mmol/L) constitute safety end points. MiREnDa will investigate CV efficacy and safety of spironolactone in haemodialysis patients [clinical trials.gov NCT01691053].
    Nephrology Dialysis Transplantation 10/2013; · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adrenocortical carcinoma (ACC) is an orphan malignancy that has attracted increasing attention during the last decade. Here we provide an update on advances in the field since our last review published in this journal in 2006.The Wnt/β-catenin pathway and insulin-like growth factor-2 (IGF-2) signaling have been confirmed as frequently altered signaling pathways in ACC but recent data suggest that they are probably not sufficient for malignant transformation. Thus, major players in the pathogenesis are still unknown.For diagnostic workup, comprehensive hormonal assessment and detailed imaging are required, because in most ACCs evidence for autonomous steroid secretion can be found and computed tomography or magnetic resonance imaging (if necessary combined with functional imaging) can differentiate benign from malignant adrenocortical tumors. Surgery is potentially curative in localized tumors. Thus, we recommend to perform complete resection including lymphadenectomy by an expert surgeon. The pathology report should demonstrate the adrenocortical origin of the lesion (e.g. by SF1 staining) and provide Weiss score, resection status and quantitation of the proliferation marker Ki67 to guide further treatment. Even after complete surgery recurrence is frequent and adjuvant mitotane treatment improves outcome, but uncertainty exists whether all patients benefit from this therapy.In advanced ACC, mitotane is still standard of care. Based on the FIRM-ACT trial, mitotane plus etoposide, doxorubicin, and cisplatin is now the established first-line cytotoxic therapy. However, most patients will experience progress and require salvage therapies. Thus, new treatment concepts are urgently needed. The ongoing international efforts including comprehensive "omic approaches" and next generation sequencing will improve our understanding of the pathogenesis and hopefully lead to better therapies.
    The Journal of clinical endocrinology and metabolism 09/2013; · 6.50 Impact Factor

Publication Stats

7k Citations
1,818.78 Total Impact Points

Institutions

  • 1993–2014
    • University of Wuerzburg
      • • Department of Internal Medicine I
      • • Institute for History of Medicine
      • • Department of Internal Medicine II
      Würzburg, Bavaria, Germany
  • 2013
    • Ludwig-Maximilian-University of Munich
      • Department of Internal Medicine IV
      München, Bavaria, Germany
    • Maxima Medical Center
      Veldhoven, North Brabant, Netherlands
  • 2007–2012
    • Università degli Studi di Torino
      • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
  • 2003–2011
    • University of Birmingham
      • • School of Clinical and Experimental Medicine
      • • Institute for Biomedical Research
      • • Group of Medical Science and Education
      Birmingham, ENG, United Kingdom
  • 2010
    • University of Tuebingen
      • Institute of Pathology and Neuropathology
      Tübingen, Baden-Wuerttemberg, Germany
  • 2009
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2008
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 2002–2003
    • Marienkrankenhaus Hamburg
      Hamburg, Hamburg, Germany
  • 2000
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 1998–2000
    • University of Freiburg
      • Department of Internal Medicine
      Freiburg, Lower Saxony, Germany
  • 1999
    • University of Hamburg
      • Department of Pathology
      Hamburg, Hamburg, Germany
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 1988–1997
    • University of Cologne
      • • Department of Internal Medicine
      • • Department of Neurosurgery
      Köln, North Rhine-Westphalia, Germany
  • 1986–1990
    • Christian-Albrechts-Universität zu Kiel
      • • Institut für Medizinische Klimatologie
      • • Institute for Infection Medicine
      Kiel, Schleswig-Holstein, Germany
  • 1989
    • MediaPark Klinik Köln
      Köln, North Rhine-Westphalia, Germany
  • 1987
    • HELIOS Klinik Kiel
      Kiel, Schleswig-Holstein, Germany