Altered endocannabinoid-dynamics in craniopharyngioma patients and their association with HPA-axis disturbances

in European Journal of Endocrinology
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  • 1 M Auer, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
  • 2 D Gebert, Neuroendocrinology, Max Planck Institute of Psychiatry , Munich, Germany
  • 3 S Biedermann, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 4 L Bindila, Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
  • 5 G Stalla, Neuroendocrinology, Medicover MVZ, Munich, Germany
  • 6 N Reisch, Endokrinologie, Medizinische Klinik Innenstadt, München, Germany
  • 7 A Kopczak, Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universitat Munchen, Munich, Germany
  • 8 J Fuss, Human Behavior Laboratory, University Hospital Hamburg Eppendorf Institute for Sex Research and Forensic Psychiatry, Hamburg, Germany

Correspondence: Matthias Auer, Email: matthias.auer@med.uni-muenchen.de
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Objective

Patients with craniopharyngioma (CP) frequently suffer from morbid obesity. Endocannabinoids (ECs) are involved in weight gain and rewarding behavior but have not been investigated in this context.

Design

Cross-sectional single-center study.

Methods

Eighteen patients with CP and 16 age- and sex-matched controls were included. Differences in endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and endocannabinoid-like molecules (oleoyl ethanolamide (OEA), palmitoyl ethanolamide (PEA), and arachidonic acid (AA) were measured at baseline and following endurance exercise. We further explored ECs-dynamics in relation to markers of HPA-axis activity (ACTH, cortisol, copeptin) and hypothalamic damage.

Results

Under resting conditions, independent of differences in BMI, 2-AG levels were more than twice as high in CP patients compared to controls. In contrast, 2-AG and OEA level increased in response to exercise in controls but not in CP patients, while AEA levels decreased in controls. As expected, exercise increased ACTH and copeptin levels in controls only. In a mixed model analysis across time and group, HPA measures did not provide additional information for explaining differences in 2-AG levels. However, AEA levels were negatively influenced by ACTH and copeptin levels, while OEA levels were negatively predicted by copeptin levels only. There were no significant differences in endocannabinoids depending on hypothalamic involvement.

Conclusion

Patients with CP show signs of a dysregulated endocannabinoid system under resting conditions as well as following exercise in comparison to healthy controls. Increased 2-AG levels under resting conditions and the missing response to physical activity could contribute to the metabolic phenotype of CP patients.

 

     European Society of Endocrinology

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