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Lukas Engler Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Christian Adolf Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Daniel A Heinrich Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Anna-Katharine Brem Max-Planck-Institute of Psychiatry, Munich, Germany
Division of Interventional Cognitive Neurology, Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

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Anna Riester Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Anna Franke Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Felix Beuschlein Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Martin Reincke Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Axel Steiger Max-Planck-Institute of Psychiatry, Munich, Germany

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Heike Künzel Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Primary aldosteronism is a natural model for chronic aldosterone excess in humans and associated with symptoms of anxiety and depression. Cognitive deficits are inherent to the symptomatology of depression and anxiety disorders. Mineralocorticoid receptors and aldosterone appear to play a role in memory. Aldosterone was additionally supposed to be a risk factor for cognitive decline in patients with essential hypertension. The objective of this study was to investigate possible effects of chronically high aldosterone concentrations on cognitive function. A range of cognitive dimensions were assessed in 19 patients (9 males, 10 females); mean age 47.1 (12.5) under standardized treatment and several rating scales for anxiety, depression, quality of life and sleep were administered. Cognitive parameters were compared to standard norms from a large, healthy standardization sample. Patients showed increased levels of anxiety and depression without meeting diagnostic criteria for a disorder. Besides a numerically lower attention score, patients did not show any significant differences in the cognitive dimensions. Anxiety and depression were negatively correlated with quantitative performance in males. In females, a negative correlation between sleep disturbances and abstract reasoning and a positive correlation with quantitative performance were found. Our data showed no specific effect of chronic aldosterone in the tested cognitive parameters overall at least in younger patients, but they indicate sexually dimorphic regulation processes.

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Natalie Rogowski-Lehmann Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

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Aikaterini Geroula Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden, Germany

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Aleksander Prejbisz Department of Hypertension, Institute of Cardiology, Warsaw, Poland

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Henri J L M Timmers Section of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands

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Felix Megerle Medizinische Klinik und Poliklinik I des Universitätsklinikums Würzburg, Würzburg, Germany

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Mercedes Robledo Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Madrid, Spain

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Martin Fassnacht Medizinische Klinik und Poliklinik I des Universitätsklinikums Würzburg, Würzburg, Germany

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Stephanie M J Fliedner First Department of Medicine, University Medical Center Schleswig-Holstein, Lübeck, Germany

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Martin Reincke Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

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Anthony Stell Department of Computing and Information, University of Melbourne, Melbourne Australia

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Andrzej Januszewicz Department of Hypertension, Institute of Cardiology, Warsaw, Poland

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Jacques W M Lenders Section of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
Medizinische Klinik III, Universitätsklinikum Carl Gustav Carus an der Technische Universität Dresden, Dresden, Germany

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Graeme Eisenhofer Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden, Germany
Medizinische Klinik III, Universitätsklinikum Carl Gustav Carus an der Technische Universität Dresden, Dresden, Germany

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Felix Beuschlein Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland

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Background

Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure.

Objective

To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL).

Design

Prospective study protocol, which has enrolled patients from six European centers with confirmed PPGLs. Data were analyzed from 235 patients (37 iPPGLs, 36 sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. iPPGL patients were diagnosed at a significantly higher age than fPPGLs (P < 0.001), found to have larger tumors (P = 0.003) and higher metanephrine and normetanephrine levels at diagnosis (P = 0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs 4.3 symptoms, P < 0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than that in fPPGL (60.9%) and sPPGL (21.5%). Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients, the PPGL diagnosis had been delayed.

Précis

Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes.

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