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Oxytocin in Survivors of Childhood-Onset Craniopharyngioma

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Oxytocin in Survivors of Childhood-Onset Craniopharyngioma Oxytocin in survivors of childhood-onset craniopharyngioma Anna M. M. Daubenbüchel, Anika Hoffmann, Maria Eveslage, Jale Özyurt, Kristin Lohle, Julia Reichel, Christiane M. Thiel, et al. Endocrine International Journal of Basic and Clinical Endocrinology ISSN 1355-008X Volume 54 Number 2 Endocrine (2016) 54:524-531 DOI 10.1007/s12020-016-1084-5 1 23 Your article is protected by copyright and all rights are held exclusively by Springer Science +Business Media New York. This e-offprint is for personal use only and shall not be self- archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com”. 1 23 Author's personal copy Endocrine (2016) 54:524–531 DOI 10.1007/s12020-016-1084-5 ORIGINAL ARTICLE Oxytocin in survivors of childhood-onset craniopharyngioma 1,2 1 3 4 Anna M. M. Daubenbüchel ● Anika Hoffmann ● Maria Eveslage ● Jale Özyurt ● 1 1 4,5 6 Kristin Lohle ● Julia Reichel ● Christiane M. Thiel ● Henri Martens ● 6 1 Vincent Geenen ● Hermann L. Müller Received: 19 July 2016 / Accepted: 9 August 2016 / Published online: 1 September 2016 © Springer Science+Business Media New York 2016 Abstract Quality of survival of childhood-onset cranio- irradiation were analyzed. Patients with preoperative pharyngioma patients is frequently impaired by hypotha- hypothalamic involvement showed similar oxytocin levels lamic involvement or surgical lesions sequelae such as compared to patients without hypothalamic involvement obesity and neuropsychological deficits. Oxytocin, a pep- and controls. However, patients with surgical hypotha- tide hormone produced in the hypothalamus and secreted lamic lesions grade 1 (anterior hypothalamic area) pre- by posterior pituitary gland, plays a major role in regula- sented with lower levels (p = 0.017) of oxytocin under tion of behavior and body composition. In a cross- fasting condition compared to patients with surgical lesion sectional study, oxytocin saliva concentrations were ana- of posterior hypothalamic areas (grade 2) and patients lyzed in 34 long-term craniopharyngioma survivors with without hypothalamic lesions (grade 0). Craniophar- and without hypothalamic involvement or treatment- yngioma patients’ changes in oxytocin levels before and related damage, recruited in the German Childhood Cra- after breakfast correlated (p = 0.02) with their body mass niopharyngioma Registry, and in 73 healthy controls, index. Craniopharyngioma patients continue to secrete attending the Craniopharyngioma Support Group Meeting oxytocin, especially when anterior hypothalamic areas are 2014. Oxytocin was measured in saliva of craniophar- not involved or damaged, but oxytocin shows less varia- yngioma patients and controls before and after standar- tion due to nutrition. Oxytocin supplementation should be dized breakfast and associations with gender, body mass explored as a therapeutic option in craniopharyngioma index, hypothalamic involvement, diabetes insipidus, and patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypotha- lamic areas. Clinical trial number: KRANIOPHAR- * Hermann L. Müller YNGEOM 2000/2007(NCT00258453; NCT01272622). [email protected] Keywords Craniopharyngioma ● Hypothalamus ● Obesity ● 1 Department of Pediatrics, Klinikum Oldenburg AöR, Medical Oxytocin ● Behavior Campus University Oldenburg, 26133 Oldenburg, Germany 2 University Medical Centre Groningen (UMCG), University of Groningen, 9712 Groningen, The Netherlands 3 Institute of Biostatistics and Clinical Research, University of Münster, 48149 Münster, Germany Introduction 4 Biological Psychology Lab, Department of Psychology, Faculty of Medicine and Health Sciences, Carl von Ossietzky University, 26129 Oldenburg, Germany Childhood-onset craniopharyngioma (CP) are rare intra- 5 cranial embryonal malformations of the sellar region arising Research Center Neurosensory Science and Cluster of Excellence ’ “Hearing4all”, Carl von Ossietzky University, 26129 Oldenburg, from remnants of Rathke s pouch [1]. CP show low-grade Germany histological malignancy (WHO °I) and frequently effect 6 GIGA-I3 Center of Immunoendocrinology, University of Liege hypothalamic and pituitary regions due to their location [2]. Liege-Sart Tilman, 4000 Liege, Belgium This hypothalamic involvement (HI) of CP and/or Author's personal copy Endocrine (2016) 54:524–531 525 treatment-related lesions of this region usually result in Oxytocin concentrations were analyzed at a median endocrine deficiencies, neuropsychological deficits, patho- patient age of 20 years (range 7–41 years), with a median logical patterns of eating behavior, and obesity with major interval between initial CP diagnosis and this study of 11.0 negative impact on prognosis and quality of life in surviving years (range: 0.5–31.0 years). They were analyzed for patients [3–7]. Substitution therapy for endocrine defi- height, weight, and body mass index (BMI), as well as ciencies—hydrocortisone, sex steroids, growth hormone, oxytocin concentrations in saliva, for which samples were vasopressin, and thyroid hormones—is an elemental part in taken shortly before and 60 min after breakfast. For the CP treatment for patients with disturbances involving the oxytocin concentration comparisons, a standardized and hypothalamic and pituitary regions [2]. comparable breakfast for all participants was ensured The peptide hormone oxytocin, which is primarily syn- (approx. 10–15 kcal/kg body weight; 8 a.m.). The study was thesized in the paraventricular and supraoptic nuclei of the conducted during the 17thAnnual Meeting of the German hypothalamus and released by the posterior pituitary, has Craniopharyngioma Support Group, Bad Sassendorf, not been analyzed in the context of CP before this study [8]. Germany, 2014. A total of 73 healthy children, adolescents, It can be assumed that oxytocin synthesis and release is and adults, also attending the 17th Annual Craniophar- disturbed in patients with CP, similar to the other hormones yngioma Support Group Meeting, 2014, served as controls. of the pituitary gland. Oxytocin is similar to the peptide Body composition and the degree of obesity were eval- hormone vasopressin, as its structure differs only by two uated by calculating the BMI standard deviation score amino acids [9]. However, in contrast to vasopressin, whose (SDS) according to the references of Rolland-Cachera et al. function is well understood and the clinical symptoms in [17]. The histological diagnosis of anadamantinomatous CP vasopressin-deficient patients are well known [10], little is was confirmed by reference assessment in all cases. HI of known about the role of oxytocin in CP patients. Oxytocin CP was assessed by magnetic resonance imaging (MRI), is involved in metabolism [11] and in the regulation of a computed tomography, and/or microscopic inspection dur- wide variety of social and non-social behaviors such as non- ing surgery. Preoperative HI was defined as involvement of social memory, anxiety, depression, and stress [12–16]. hypothalamic structures either by tumor growth into the To evaluate the role of oxytocin in CP patients, we hypothalamus or displacement of hypothalamic structures conducted a pilot cross-sectional study analyzing a small by the tumor. Surgical hypothalamic lesions were assessed group of patients recruited in the German Craniophar- on postoperative MRI and reference-confirmed by a neu- yngioma Registry to assess oxytocin concentrations in sal- roradiologist blinded for the clinical data based on a pre- iva of patients with childhood-onset CP in comparison to viously published grading system [18, 19]. healthy controls. The study was approved by the local standing committee on ethical practice and written parental and/or patient con- sent was obtained in all cases. Patients and methods Oxytocin analysis in saliva Patients We compared saliva levels of the 34 CP patients with the saliva of a healthy control group consisting of 41 female This study analyzed patients with adamantinomatous and 32 male participants with a median age of 39 years childhood-onset CP, recruited in the German Craniophar- (range 8–63 years). Oxytocin saliva levels were measured yngioma Registry and prospectively evaluated in the multi- under fasting conditions as well as directly after a standar- center trials HIT Endo and KRANIOPHARYNGEOM 2000/ dized breakfast meal. In addition, we quantified changes in 2007 (Clinical Trial No.: NCT00258453; NCT01272622), oxytocin levels before and after breakfast (Δ oxytocin is who attended the 17th Annual Meeting of the German defined as the difference in oxytocin after breakfast−oxy- Craniopharyngioma Support Group, Bad Sassendorf, Ger- tocin before breakfast). To measure oxytocin saliva levels, many, 2014. Thirty-four of 40 patients (85 %) attending this saliva was collected from each participant (patients and meeting agreed to participate in the study. These 34 CP controls) before and after breakfast using a standardized patients (19 female, 15 male) had been initially diagnosed at method for saliva sampling.
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