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      Long Term Sequelae of Pediatric Craniopharyngioma – Literature Review and 20 Years of Experience

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          Abstract

          Craniopharyngioma are rare histologically benign brain tumors that develop in the pituitary–hypothalamic area. They may invade nearby anatomical structures causing significant rates of neurological, neurocognitive, and endocrinological complications including remarkable hypothalamic damage. Information regarding long term implications of the tumors and treatment in the pediatric population is accumulating, and treatment goals appear to be changing accordingly. In this review we aim to present data regarding long term complications of craniopharyngioma in children and adolescents and our experience from a large tertiary center. Hypothalamic dysfunction was noted to be the most significant complication, adversely affecting quality of life in survivors. Obesity, fatigue, and sleep disorders are the most notable manifestations of this dysfunction, and treatment is extremely difficult. Changes in management in recent years show a potential for improved long term outcomes; we found a trend toward less aggressive surgical management and increasing use of adjuvant treatment, accompanied by a decrease in complication rates.

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          Most cited references66

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          Risk factors for the development of obesity in children surviving brain tumors.

          Hypothalamic obesity, a syndrome of intractable weight gain due to hypothalamic damage, is an uncommon but devastating complication for children surviving brain tumors. We undertook a retrospective evaluation of the body mass index (BMI) curves for the St. Jude Children's Research Hospital brain tumor population diagnosed between 1965 and 1995 after completion of therapy to determine risk factors for the development of obesity. Inclusion criteria were: diagnosis less than 14 yr of age, no spinal cord involvement, ambulatory, no supraphysiologic hydrocortisone therapy (>12 mg/m(2) x d), treatment and follow-up at St. Jude Children's Research Hospital, and disease-free survival greater than 5 yr (n = 148). Risk factors examined were age at diagnosis, tumor location, histology, extent of surgery, hydrocephalus requiring ventriculoperitoneal shunting, initial high-dose glucocorticoids, cranial radiation therapy, radiation dosimetry to the hypothalamus, intrathecal chemotherapy, and presence of endocrinopathy. Analyses were performed both between groups within a risk factor and against BMI changes for age in normal children older than 5.5 yr (the age of adiposity rebound). Risk factors were: age at diagnosis (P = 0.04), radiation dosimetry to the hypothalamus (51-72 Gy, P = 0.002 even after hypothalamic and thalamic tumor exclusion), and presence of any endocrinopathy (P = 0.03). In addition, risk factors when compared with BMI slope for the general American pediatric population included: tumor location (hypothalamic, P = 0.001), tumor histology (craniopharyngioma, P = 0.009; pilocytic astrocytoma, P = 0.043; medulloblastoma, P = 0.039); and extent of surgery (biopsy, P = 0.03; subtotal resection, P = 0.018). These results verify hypothalamic damage, either due to tumor, surgery, or radiation, as the primary cause of obesity in survivors of childhood brain tumors. In particular, hypothalamic radiation doses of more than 51 Gy are permissive. These results reiterate the importance of the hypothalamus in energy balance, provide risk assessment criteria for preventative measures before the development of obesity in at-risk patients, and suggest therapeutic strategies to reduce the future development of obesity.
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            Obesity after childhood craniopharyngioma--German multicenter study on pre-operative risk factors and quality of life.

            Craniopharyngiomas are tumorous embryogenic malformations. As the survival rate after craniopharyngioma is high (92 %), prognosis and quality of life (QoL) in survivors mainly depend on adverse late effects such as obesity.
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              Features of the metabolic syndrome after childhood craniopharyngioma.

              Obesity and multiple pituitary hormone deficiency are common complications after surgery for childhood craniopharyngioma. We hypothesized that post craniopharyngioma surgery, children are at high risk for the metabolic syndrome, including insulin resistance due to excess weight gain and GH deficiency. This study characterized body composition (anthropometry and dual energy x-ray absorptiometry) and metabolic outcomes in 15 children (10 males and 5 females; age, 12.2 yr; range, 7.2-18.5 yr) after surgical removal of craniopharyngioma. In 9 subjects, outcomes were compared with those of healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Insulin sensitivity was measured by 40-min iv glucose tolerance test. Seventy-three percent of subjects were overweight or obese. Sixty-six percent had normal growth velocity without GH treatment. Subjects had increased abdominal adiposity (P = 0.008) compared with controls. However, there was no significant difference in total body fat. Subjects had higher fasting triglycerides (P = 0.02) and lower high density lipoprotein cholesterol to total cholesterol ratio (P = 0.015). Insulin sensitivity was equally reduced for subjects and controls (P = 0.86). After craniopharyngioma removal, patients had more features of the metabolic syndrome compared with controls. This could be a result of hypothalamic damage causing obesity and GH deficiency. Further studies exploring predictors of the metabolic syndrome after craniopharyngioma surgery are required.
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                Author and article information

                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrin.
                Frontiers in Endocrinology
                Frontiers Research Foundation
                1664-2392
                29 August 2011
                28 November 2011
                2011
                : 2
                : 81
                Affiliations
                [1] 1simpleDivision of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto Toronto, ON, Canada
                [2] 2simpleDepartment of Psychology, The Hospital for Sick Children, University of Toronto Toronto, ON, Canada
                Author notes

                Edited by: Hermann Lothar Mueller, Klinikum Oldenburg gGmbH, Germany

                Reviewed by: Laurence Katznelson, Stanford University, USA; Sara DiVall, Johns Hopkins University School of Medicine, USA

                *Correspondence: Jill Hamilton, Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1×8. e-mail: jill.hamilton@ 123456sickkids.ca

                This article was submitted to Frontiers in Pituitary Endocrinology, a specialty of Frontiers in Endocrinology.

                Article
                10.3389/fendo.2011.00081
                3355823
                22645511
                120cdcda-3bce-4259-8741-518fa95b816e
                Copyright © 2011 Cohen, Guger and Hamilton.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                History
                : 05 August 2011
                : 09 November 2011
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 90, Pages: 10, Words: 10090
                Categories
                Endocrinology
                Review Article

                Endocrinology & Diabetes
                complications,neurocognitive,craniopharyngioma,hypothalamic obesity,child,recurrence,sleep,pituitary

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