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

TY - JOUR

T1 - Altered endocannabinoid-dynamics in craniopharyngioma patients and their association with HPA-axis disturbances

AU - Auer, Matthias

AU - Gebert, Dorothea

AU - Biedermann, Sarah V

AU - Bindila, Laura

AU - Stalla, Günter

AU - Reisch, Nicole

AU - Kopczak, Anna

AU - Fuß, Johannes

PY - 2021

Y1 - 2021

N2 - ObjectivePatients 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.DesignCross-sectional single-center study.MethodsEighteen 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), palmitoylethanolamide (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.ResultsUnder 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.ConclusionPatients 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.

AB - ObjectivePatients 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.DesignCross-sectional single-center study.MethodsEighteen 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), palmitoylethanolamide (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.ResultsUnder 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.ConclusionPatients 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.

U2 - 10.1530/EJE-21-0178

DO - 10.1530/EJE-21-0178

M3 - SCORING: Journal article

VL - 185

SP - 231

EP - 239

JO - EUR J ENDOCRINOL

JF - EUR J ENDOCRINOL

SN - 0804-4643

IS - 2

ER -