G Brabant

University of Duisburg-Essen, Essen, North Rhine-Westphalia, Germany

Are you G Brabant?

Claim your profile

Publications (259)902.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To study the interaction between copeptin and hypothalamic-pituitary-adrenal (HPA) activation in men and women during hypoglycaemic stress.Design and patientsA prospective study in 118 patients (mean age 47.7±13.6 yrs., n=52 women) undergoing insulin tolerance testing for suspected pituitary dysfunction.MeasurementsSerum copeptin was measured in serially collected blood samples and assessed in relation to ACTH, cortisol and other endocrine parameters.ResultsSymptomatic hypoglycaemia (mean glucose nadir, 1.6±0.5 mmol/l) resulted in a rapid significant increase of serum copeptin. Individuals with impaired pituitary function had lower stress-induced copeptin levels (median, 6.26 pmol/l) than patients with intact pituitary (8.46 pmol/l, P < 0.001). A weak overall correlation between stress-induced copeptin and cortisol levels was observed (rs = 0.31, P < 0.001). In female individuals, there was a positive correlation between stress-induced copeptin and ACTH (rs = 0.47, P < 0.001) or cortisol levels (rs = 0.42, P = 0.002), while in males no correlation to ACTH (rs = 0.03, P = 0.75) and poor correlation to cortisol levels (rs = 0.24, P = 0.045). was observed. Patients with central diabetes insipidus showed lowest baseline (2.20 pmol/l) and stimulated copeptin levels (3.68 pmol/l).Conclusions The data from this study indicate that stress-induced release of AVP in women, but not in men, is linked to the co-activation of the hypothalamic-pituitary-adrenal system.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 09/2014; · 3.40 Impact Factor
  • H. Biersack, G. Brabant
    [Show abstract] [Hide abstract]
    ABSTRACT: Spätschäden einer Krebserkrankung sind durch die therapiebedingt verbesserten Überlebensraten ein rasch zunehmendes, aber bislang zu wenig wahrgenommenes Problem. Zu diesen Folgeerkrankungen, die definitionsgemäß Jahre nach der initialen Erkrankung auftreten, zählen nicht nur Zweittumoren, sondern auch eine Reihe nichtonkologischer internistischer Probleme. Diese kardiovaskulären, gastrointestinalen, renalen oder endokrinen Spätschäden wurden bislang unzureichend beachtet und müssen bei der häufig schleichenden Symptomatik gezielt adressiert werden.
    Der Internist 12/2013; 54(10). · 0.33 Impact Factor
  • H Biersack, G Brabant
    [Show abstract] [Hide abstract]
    ABSTRACT: Due to therapy-associated improvements in survival rates, delayed effects of cancer are a rapidly increasing but as yet only poorly recognized problem. These delayed sequelae, which by definition occur years after the primary disease, include secondary tumors and many non-oncological internal medical problems. Little attention has so far been paid to the cardiovascular, gastrointestinal, renal and endocrinal delayed side effects and must be specifically addressed due to the often slowly progressing symptoms.
    Der Internist 09/2013; · 0.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Headache is very common in pituitary disease and is reported to be present in more than a third of all patients with pituitary adenomas. Tumour size, cavernous sinus invasion, traction or displacement of intracranial pain-sensitive structures such as blood vessels, cranial nerves and dura mater, and hormonal hypersecretion are implicated causes. The present review attempts to systematically review the literature for any combination of headache and pituitary or hormone overproduction or deficiency. Most data available are retrospective and/or not based on the International Headache Society (IHS) classification. Whereas in pituitary apoplexy a mechanical component explains the almost universal association of the condition with headaches, this correlation is less clear in other forms of pituitary disease and a positive impact of surgery on headaches is not guaranteed. Similarly, invasion into the cavernous sinus or local inflammatory changes have been linked to headaches without convincing evidence. Some studies suggest that oversecretion of GH and prolactin may be important for the development of headaches and treatment, particularly with somatostatin analogues, has been shown to improve symptoms in these patients. Otherwise, treatment rests on general treatment options for headaches based an accurate clinical history and a precise classification which includes assessment of the patient's psychosocial risk factors. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2013; · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Direct measurement of arginine-vasopressin/antidiuretic hormone (AVP/ADH) concentrations is not included in the standard diagnostic procedures for paraneoplastic syndrome of inappropriate ADH secretion (SIADH). Here, we evaluate the potential of copeptin measurement as a surrogate marker of AVP/ADH secretion for the direct diagnosis of suspected SIADH in cancer patients. Forty-six unselected cancer patients with serum sodium concentrations permanently below 135 mmol/L were included in this study. We compared standard diagnostic criteria for SIADH to the measurement of plasma copeptin in relation to osmolality. Normative data for comparison were constructed from 24 healthy controls studied under basal conditions, experimental dehydration, and hypotonic hypervolemia as well as from 222 hospital patients with no suspicion of an altered ADH regulation. Log transformation of copeptin revealed a linear relationship to plasma osmolality in the controls (R = 0.495, p < 0.001). Compared to these normative data, copeptin levels in most cancer patients were inappropriately high for plasma osmolality and were not significantly correlated. These results, suggestive for paraneoplastic SIADH, could be confirmed by conventional diagnostic procedures for SIADH. Current strategies to diagnose SIADH are difficult to perform under outpatients conditions. Our approach allows screening from a single plasma sample for true paraneoplastic ADH oversecretion and thus rapid selection for a specific therapy with an AVP receptor antagonist.
    Endocrine 03/2013; · 1.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to examine potential implications of changes in the approach to adult growth hormone (GH) replacement (GHR) over the last 15 years. Therefore, we analysed the German KIMS database as one of the largest single country pharmacoepidemiological databases on adult GH deficiency (GHD). Based on the date of their first GH application patients were assigned to three intervals (1995-1999, 2000-2004, 2005-2009). A multivariate analysis of variance with interval and sex as independent variables was conducted. Differences were analysed with respect to IGF-I standard deviation score (SDS), quality of life, latency between GHD diagnosis and first GH dose, body mass index, waist-hip ratio, lipid profile, and GH dose. All analyses were conducted at baseline, 1 year, and 3 years of GHR. We detected significant associations between time interval and patient characteristics at baseline and with treatment effects. Recently, patients with less severe GHD (mean IGF-I SDS: -2.1, -1.6, -1.0 in the 1st, 2nd and 3rd interval; p = 0.000) are treated with lower GH starting doses (mean 0.30, 0.19, 0.21 mg/day in the 1st, 2nd and 3rd interval; p = 0.000). In the first time interval, IGF-I SDS was not normalized in females after 3 years of GHR. The results of our analysis demonstrate prominent changes in patient characteristics and handling of GHR. They highlight that approach to therapy and patient inclusion criteria change over time and may represent an important confounder for any analysis in epidemiological surveillance surveys.
    Pituitary 07/2012; · 2.67 Impact Factor
  • C Hubold, G Brabant
    [Show abstract] [Hide abstract]
    ABSTRACT: Ectopic hormone production is a rare complication in neuroendocrine tumors. Tumors producing corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) are most commonly observed, leading to the classical symptoms of Cushing’s syndrome. Additionally, a very low percentage of neuroendocrine tumors can produce growth hormone-releasing hormone (GHRH) leading to classical features of acromegaly. Moreover, ectopic antidiuretic hormone (ADH) secretion has been described in neuroendocrine tumors presenting as hyponatremia due to the syndrome of inappropriate ADH secretion. Other ectopic hormone secretions, such as paraneoplastic gonadotropin release are rarely observed. Ectopic hormone secretion is not usually associated with a detectable pituitary mass and diagnosis is based on the measurement of circulating peptides. This is frequently assisted by imaging techniques, such as somatostatin receptor scintigraphy. Therapeutically a curative approach is the primary goal but in advanced tumors palliative treatment aims to control symptoms with the help of specific antihormonal compounds, such as somatostatin analogues.
    Der Internist 02/2012; 53(2):145-51. · 0.33 Impact Factor
  • Endocrine Practice 01/2012; 18(3):325-34. · 2.49 Impact Factor
  • Annals of Oncology 12/2011; 22(12):2696. · 7.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The clinical picture of pituitary abscesses may resemble features of other pituitary pathologies including endocrine deficiencies. The characteristic radiological changes, namely the ring enhancement, may aid in the diagnostic work-up of this very rare condition. A 40-year-old patient with longstanding HIV infection presented with headache and fatigue. Testing for pituitary function confirmed panhypopitutarism. MRI scanning demonstrated an inhomogeneous pituitary gland with ring-like enhancement and sphenoid sinus mucosa thickening. Transsphenoidal surgery was performed. Histologically CD68 positive macrophages were found supporting the diagnosis of infectious hypophysitis. Under hormone replacement therapy and retroviral treatment the patient clinically normalized. A pituitary abscess due to infectious hypophysitis is a rare cause of pituitary failure. Diagnostic signs on imaging may help to rapidly distinguish the cause of pituitary deficiency in patients with HIV infection.
    Experimental and Clinical Endocrinology & Diabetes 09/2011; 119(10):633-5. · 1.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypopituitarism is not a rare disease and its clinical signs and symptoms deserve the attention of the clinically practising neurologist. Next to the classical cause of hypopituitarism mediated by tumours of the hypothalamo-pituitary region, a number of recent articles have highlighted the high frequency of central endocrine disturbances in patients with brain damage, i. e. not only after traumatic brain injury and subarachnoid haemorrhage but also as a consequence of the treatment of childhood brain tumours. This article provides an overview of the clinical symptomatology and pathophysiology of hypopituitarism as well as the current knowledge about neuroendocrine disturbances in the adult patient suffering from the above-mentioned disorders.
    Fortschritte der Neurologie · Psychiatrie 04/2011; 79(4):213-20. · 0.85 Impact Factor
  • G Brabant
    MMW Fortschritte der Medizin 04/2010; 152(13):37-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 57 yr old man presented to endocrinology clinic with a six year history of poorly controlled hypertension which was treated with Metoprolol 200 mg/day and Enalapril 20 mg/day. He was asymptomatic but incidentally hypokalaemia was detected while having cholecystectomy, two years prior to his clinic appointment. He had never been on diuretics or laxatives. He was started on potassium supplements (120 mmol/d) and advised to increase dietary potassium by the surgical team. A detailed personal history revealed ingestion of 300-500 g licorice per day. Physical examination was unremarkable apart from increased blood pressure of 180/105 mmHg. Following the initial visit, his serum electrolyes (K+3.7 mmol/l) were normal with potassium supplementation and as were morning cortisol, ACTH, 11-deoxycortisol and plasma metanephrines. 17 OH-P, DHEAS and androstenedione were normal but testosterone was low. Morning ambulant aldosterone was slightly increased at 801 pmol/L and renin activity was undetectable. Urinary 24 h aldosterone excretion was significantly increased at 162 ng/24 h with normal cortisol and catecholamine excretion. Four weeks following advice to stop licorice, serum potassium decreased to 3.4 mmol/L despite continuous supplementation. Morning plasma aldosterone increased to 1 449 pmol/ml, renin activity remained undetectable but 24 h urine aldosterone excretion increased to 434 ng/24 h with a reduction in urinary cortisol excretion. Interestingly 17 OH-P and androstenedione levels, although within the reference range, were slightly higher compared to the levels whilst on licorice. Testosterone level had significantly increased to be within normal range. Abdominal imaging with US and MRI showed a 2.7 cmx2.2 cmx1.7 cm left adrenal mass. He underwent laparoscopic left adrenalectomy and histology confirmed aldosterone producing adrenal adenoma. Post-operatively his aldosterone and serum potassium levels normalized and he became normotensive without any antihypertensive medication.
    Experimental and Clinical Endocrinology & Diabetes 03/2010; 118(4):250-3. · 1.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of water and electrolyte disturbances following traumatic brain injury (TBI) is considerable and has been attributed to a dysregulation of the hypothalamic peptide arginine-vasopressin (AVP). Copeptin, the C-terminal part of the AVP prohormone, reflects AVP activity. In 71 TBI patients we measured copeptin in serum by a sandwich immunoassay. Injury severity was assessed by Glasgow Coma Score (GCS) and computed tomography, and recovery by Glasgow Outcome Score (GOS). Neuroendocrine and osmoregulation regulation were examined on day 0, 3 and 7, and 24 months post-injury. Copeptin was highest on admission (40.0 +/- 72.3 pmol/l), stabilized on day 3 and 7 (21.2 +/- 18.3 resp. 20.3 +/- 17.1 pmol/l), and normalized at follow-up (4.2 +/- 1.7 pmol/l). On admission, there was a correlation between serum sodium and urine excretion (p = 0.003), but the correlation got lost on day 3 and 7. Copeptin did not reflect the individual 24 h urine excretion or serum sodium levels indicating an uncoupling of copeptin/AVP release and renal water excretion. High copeptin level on day 3 were correlated with a low GCS (p < 0.001), midline shift (p = 0.019), intracerebral hemorrhage (p = 0.026), SAPS score (p = 0.001), as well as with a low GOS (p = 0.031). Copeptin was significantly decreased following skullbase fracture (p = 0.016).Our data reveal a loss of hypothalamic osmoregulation following TBI. The measurement of Copeptin/AVP release reveals a significant predictive function for the severity of TBI.
    Acta neurochirurgica. Supplement 01/2010; 106:221-4.
  • Growth Hormone & Igf Research - GROWTH HORM IGF RES. 01/2010; 20.
  • W. Karges, G. Brabant
    Onkologe. 01/2010; 16(7):657-665.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is upregulated by hypoxia and oncogenic signalling in many solid tumours. Its regulation and function in thyroid carcinomas are unknown. We evaluated the regulation of HIF-1 alpha and target gene expression in primary thyroid carcinomas and thyroid carcinoma cell lines (BcPAP, WRO, FTC-133 and 8505c). HIF-1 alpha was not detectable in normal tissue but was expressed in thyroid carcinomas. Dedifferentiated anaplastic tumours (ATCs) exhibited high levels of nuclear HIF-1 alpha staining. The HIF-1 target glucose transporter 1 was expressed to a similar level in all tumour types, whereas carbonic anhydrase-9 was significantly elevated in ATCs. In vitro studies revealed a functionally active HIF-1 alpha pathway in thyroid cells with transcriptional activation observed after graded hypoxia (1% O(2), anoxia) or treatment with a hypoxia mimetic cobalt chloride. High basal and hypoxia-induced expression of HIF-1 alpha in FTC-133 cells that harbour a phosphatase and tensin homologue (PTEN) mutation was reduced by introduction of wild-type PTEN. Similarly, pharmacological inhibition of the phosphoinositide 3-kinase (PI3K) pathway using LY294002 inhibited HIF-1 alpha and HIF-1 alpha targets in all cell lines, including those with B-RAF mutations (BcPAP and 8505c). In contrast, the effects of inhibition of the RAF/MEK/extracellular signal-regulated kinase pathway were restricted by environmental condition and B-RAF mutation status. HIF-1 is functionally expressed in thyroid carcinomas and is regulated not only by hypoxia but also via growth factor signalling pathways and, in particular, the PI3K pathway. Given the strong association of HIF-1 alpha with an aggressive disease phenotype and therapeutic resistance, this pathway may be an attractive target for improved therapy in thyroid carcinomas.
    Endocrine Related Cancer 10/2009; 17(1):61-72. · 5.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obese patients with sepsis have higher morbidity and mortality rates than normal weight subjects. One crucial factor is the disease-associated disturbed energy balance. Ghrelin is an orexigenic peptide, mainly produced in the stomach. Leptin is an adipose-tissue derived peptide, circulating as free (fl) and receptor-bound protein (bl) acting antagonistically to ghrelin's effects on food intake. In the present study we tested the weight dependent influence of an intravenous (i.v.) ghrelin injection on leptin levels as well as hepatic protein expression in healthy and endotoxemic rats. Male Lewis rats were randomly divided into four diet-induced obese and four normal weight groups. Application of either ghrelin or NaCl was followed by a bolus injection of LPS or NaCl. Blood was collected at five time points (up to 24 h) to measure fl and bl by radioimmunoassay. Furthermore, hepatic leptin, leptin receptor and ghrelin expression were investigated immunohistochemically. Results revealed a late shift from high elevated fl to significantly enhanced levels of bl in ghrelin treated obese animals. Both fl and bl levels remained unaffected in lean rats. The findings suggest that an increased body weight of the treated animals is associated with altered hormone levels after therapeutic interventions with ghrelin.
    Experimental and Clinical Endocrinology & Diabetes 10/2009; 117(9):473-9. · 1.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is an increasing socio-economic health problem. Diet-induced obese (DIO) rodents are widely used as a model of obesity in humans. However, there is no comprehensive data about the behavioral phenotype of DIO rodents. Therefore, the aim of the present study was to determine whether a high-fat-diet changes behavioral patterns of DIO Fischer 344 (F344) rats in comparison with lean littermates. The behavioral tests (homecage, holeboard, social interaction, and hotplate) were performed in 28 normal-weight and 28 male DIO F344 rats (mean age: 16 weeks) and revealed a significantly higher level of anxiety- and aggression-related parameters in obese rats, whereas their pain threshold was significantly lower. Fitting to a different behavioral response, basal corticosterone levels (measured by RIA) of obese animals were significantly elevated (16.0ng/ml vs. 12.5ng/ml; p<0.01). We conclude that obese rats differ in various aspects from their lean littermates. The altered behavioral characteristics displayed by DIO F344 rats have to be considered in further experiments involving DIO rodents.
    Physiology & Behavior 09/2009; 98(5):563-9. · 3.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous work has examined potential links between the etiology of GH deficiency (GHD) and the baseline characteristics of the patients including biochemical and psychometric parameters. Using an update of the KIMS pharmaco-epidemiological database (Pfizer International Metabolic Database), we addressed the question how well such results can be generalized and whether regional differences may play a role. From 30 different countries, 13 167 GH-deficient patients were included in KIMS at the data close in December 2008. In order to explore country-specific differences of baseline characteristics documented in KIMS, separate analyses of baseline characteristics of adult-onset GHD patients (n=7708) were performed for the six largest contributing European countries and the United States. This analysis revealed striking regional variations in the pathogenesis of the disease, clinical characteristics such as body mass index, and in the classical features of the metabolic syndrome such as blood pressure or lipid status between countries. Moreover, the approach to endocrine function testing was widely different between countries, as well as the distribution of etiologies of GHD. These data suggest that a complex relation between biochemical and clinical signs of GHD exists, and that the spectrum of adult GHD syndrome is influenced by regional diagnostic and clinical particularities.
    European Journal of Endocrinology 09/2009; 161 Suppl 1:S25-31. · 3.14 Impact Factor

Publication Stats

5k Citations
902.90 Total Impact Points

Institutions

  • 2013
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
  • 2012–2013
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
    • Universität zu Lübeck
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2008–2012
    • RWTH Aachen University
      • Department of Neurosurgery
      Aachen, North Rhine-Westphalia, Germany
  • 2011
    • Universitätsklinikum Erlangen
      • Department of Neurosurgery
      Erlangen, Bavaria, Germany
  • 2010
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
  • 1984–2010
    • Hannover Medical School
      • • Department of Gastroenterology, Hepatology and Endocrinology
      • • Department of Nuclear Medicine
      Hannover, Lower Saxony, Germany
  • 2009
    • The University of Manchester
      • School of Pharmacy and Pharmaceutical Sciences
      Manchester, ENG, United Kingdom
    • University of Greifswald
      • Institute of Clinical Chemistry and Laboratory Medicine
      Greifswald, Mecklenburg-Vorpommern, Germany
  • 2006
    • German Institute of Human Nutrition
      • Department of Clinical Nutrition
      Potsdam, Brandenburg, Germany
  • 2005
    • University of Leipzig
      Leipzig, Saxony, Germany
    • Bielefeld University
      • CeBiTec - Center for Biotechnology
      Bielefeld, North Rhine-Westphalia, Germany
  • 2004
    • Philipps University of Marburg
      Marburg, Hesse, Germany
    • Universität Ulm
      • Department of Internal Medicine
      Ulm, Baden-Wuerttemberg, Germany
  • 2001–2004
    • Otto-von-Guericke-Universität Magdeburg
      Magdeburg, Saxony-Anhalt, Germany
    • Charité Universitätsmedizin Berlin
      • Department of Gastroenterology, Infectiology and Rheumatology
      Berlin, Land Berlin, Germany
  • 1986–2003
    • Hochschule Hannover
      Hanover, Lower Saxony, Germany
  • 1999
    • The University of Warwick
      • Biological Sciences
      Warwick, ENG, United Kingdom
  • 1998
    • Academy of Sciences of the Czech Republic
      • Ústav informatiky
      Praha, Hlavni mesto Praha, Czech Republic
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 1996–1998
    • Private Institute for Endocrinology, Reproductive and Preventive Medicine Dr. Verhoeven
      Düsseldorf, North Rhine-Westphalia, Germany
    • Martin Luther University of Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 1995
    • Kyoto University
      • Graduate School of Medicine / Faculty of Medicine
      Kioto, Kyōto, Japan
  • 1990–1994
    • University of Amsterdam
      • • Faculty of Medicine AMC
      • • Department of Intensive Care
      Amsterdam, North Holland, Netherlands
  • 1991
    • Free University of Brussels
      • Institute of Interdisciplinary Research (IRIBHM)
      Brussels, BRU, Belgium