Anthe S. Sterkenburg

Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes

BACKGROUND Quality of life (QoL) and long-term prognosis are frequently, and often severely, impaired in craniopharyngioma (CP) patients. Knowledge of risk factors for long-term outcome is important for optimization of treatment. METHODS Overall survival (OS) and progression-free survival (PFS), body mass index (BMI), neuropsychological status (EORTCQLQ-C30, MFI-20), and psychosocial status were analyzed in 261 patients with childhood-onset CP diagnosed before 2000 and longitudinally observed in HIT-Endo. RESULTS Twenty-year OS was lower (P = .006) in CP with hypothalamic involvement (HI) (n = 132; 0.84 ± 0.04) when compared with CP without HI (n = 82; 0.95 ± 0.04). OS was not related to degree of resection, sex, age at diagnosis, or year of diagnosis (before/after 1990). PFS (n = 168; 0.58 ± 0.05) was lower in younger patients (<5 y at diagnosis) (n = 30; 0.39 ± 0.10) compared with patients aged 5-10 years (n = 66; 0.52 ± 0.08) and older than 10 years (n = 72; 0.77 ± 0.06) at diagnosis. PFS was not associated with HI, degree of resection, or sex. HI led to severe weight gain during the first 8-12 years of follow-up (median BMI increase: +4.59SD) compared with no HI (median increase: +1.20SD) (P = .00). During >12 years of follow-up, patients with HI presented no further increase in BMI. QoL in CP patients with HI was impaired by obesity, physical fatigue, reduced motivation, dyspnea, diarrhea, and nonoptimal psychosocial development. CONCLUSIONS OS and QoL are impaired by HI in long-term survivors of CP. HI is associated with severe obesity, which plateaus after 12 years. OS/PFS are not related to degree of resection, but gross-total resection should be avoided in cases of HI to prevent further hypothalamic damage, which exacerbates sequelae.

Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma

Abstract Background: As a result of hypothalamic involvement and/or treatment-related hypothalamic damage, up to 75% of childhood craniopharyngioma patients develop hypothalamic obesity. Methods: Eating behavior was analyzed in 101 survivors of childhood craniopharyngioma, recruited from 1980 to 2001 in the HIT-Endo multicenter study, and in 85 body mass index (BMI)-matched healthy controls using the Inventory for Eating Behavior and Weight Problems (IEG) and the Inventory for Eating Disorders (ESI). Results: Severely obese patients (BMI>8 SD; n=9) presented with pathological eating behavior, more weight problems, and eating disorders, as compared to obese (BMI 3–8 SD; n=44) and normal or overweight patients (BMI<3 SD; n=48). Craniopharyngioma patients with different degrees of obesity showed similar or even less pathological findings as compared to BMI-matched normal controls. Conclusion: Severe obesity is associated with pathological eating behavior/disorders in craniopharyngioma patients. As these disorders are not disease-specific, risk factors for hypothalamic obesity should be the focus of further craniopharyngioma research.

Hydrocephalus and hypothalamic involvement in pediatric patients with craniopharyngioma or cysts of Rathke's pouch: impact on long-term prognosis.

OBJECTIVE Pediatric patients with sellar masses such as craniopharyngioma (CP) or cyst of Rathkes pouch (CRP) frequently suffer disease- and treatment-related sequelae. We analyzed the impact and prognostic relevance of initial hydrocephalus (HY) and hypothalamic involvement (HI) on long-term survival and functional capacity (FC) in children with CP or CRP. SUBJECTS AND METHODS Using retrospective analysis of patient records, presence of initial HY or HI was assessed in 177 pediatric patients (163 CP and 14 CRP). Twenty-year overall survival (OS) and progression-free survival (PFS), FC, and BMI were analyzed with regard to initial HY, degree of resection, or HI. RESULTS Of the 177 patients, 105 patients (103/163 CP and 2/14 CRP) presented with initial HY and 96 presented with HI. HY at diagnosis was associated (P=0.000) with papilledema, neurological deficits, and higher BMI at diagnosis and during follow-up. OS, PFS, and FC were not affected by HY at initial diagnosis. HI at diagnosis (96/177) had major negative impact on long-term prognosis. Sellar masses with HI were associated with lower OS (0.84±0.04; P=0.021), lower FC (P=0.003), and higher BMI at diagnosis and last follow-up (P=0.000) when compared with sellar masses without HI (OS: 0.94±0.05). PFS was not affected by HI or degree of resection. CONCLUSIONS Initial HY has no impact on outcome in patients with sellar masses. OS and FC are impaired in survivors presenting with initial HI. PFS is not affected by HY, HI, or degree of resection. Accordingly, gross-total resection is not recommended in sellar masses with initial HI to prevent further hypothalamic damage.

Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma

OBJECTIVE Hypothalamic obesity in childhood craniopharyngioma (CP) patients carries a high risk for development of metabolic syndrome. In metabolic syndrome, the development of nonalcoholic fatty liver disease (NAFLD) is known. The aim of this study is to detect the risk for NAFLD in childhood-onset CP. DESIGN This cross-sectional study included liver computed tomography (CT); ultrasound analysis of abdomen; measurements of serum parameters, height, weight and body composition; and daily medication of patients with childhood-onset CP. METHODS A total of 384 patients recruited in trials HIT Endo and KRANIOPHARYNGEOM 2000 were analyzed. Ninety-four survivors were included by fulfilling the criteria of proven hypothalamic involvement (HI), a minimum time interval of 5 years between diagnosis and study, and a minimum age of 18 years at the time of evaluation. A total of 19 patients agreed to participate. To quantify the degree of steatosis hepatis, analyses of liver density were performed once by non-contrasted CT of liver sections. RESULTS NAFLD occurs in about 50% of CP patients with HI and is associated with elevated liver enzymes and homeostasis model assessment index. BMI is not an effective predictive factor but body fat mass measured by near-infrared spectroscopy (NIRS) is. Over half of CP patients (60%) with NAFLD are treated with stimulating agents, with risk of hepatic side effects. CONCLUSIONS NAFLD is a major adverse late effect in childhood-onset CP. NIRS rather than BMI should be used to measure body composition and predict NAFLD. Stimulating agents for treatment of fatigue and daytime sleepiness in CP should be prescribed judiciously.

Diencephalic Syndrome in Childhood Craniopharyngioma—Results of German Multicenter Studies on 485 Long-term Survivors of Childhood Craniopharyngioma

CONTEXT Childhood craniopharyngiomas (CPs) are known to be associated with an increased risk of excessive weight gain and hypothalamic obesity. Atypical clinical manifestations include the development of a diencephalic syndrome (DS) with a failure to thrive or maintain weight at appropriate body mass index. CASES AND METHODS In a retrospective study, we analyzed 21 of 485 childhood CP patients (4.3%) who presented with a low weight (< -2 body mass index SD) at the time of diagnosis. Eleven of the 21 patients were identified with a DS due to proven hypothalamic involvement. We show the clinical manifestations of DS and weight development before and after diagnosis in these 11 patients. The first significant differences between patients with low weight at diagnosis and normal-weight patients at diagnosis are observed at 5 years of age. Within the first 2 years after diagnosis, the weight of DS patients and normal-weight patients converge to a similar level. Tumor size does not play a role with respect to DS development. Finally, tumor characteristics of DS patients were compared with magnetic resonance imaging scans of obese CP patients at the time of diagnosis. CONCLUSIONS DS is a rare clinical manifestation in childhood CP and should be considered as a discrete diagnosis in failure to thrive. DS at the time of diagnosis does not preclude weight gain after diagnosis of a CP with hypothalamic involvement.

Childhood Craniopharyngioma with Hypothalamic Obesity - No Long-term Weight Reduction due to Rehabilitation Programs

BACKGROUND Severe obesity due to hypothalamic involvement has major impact on prognosis in long-term survivors of childhood craniopharyngioma. The long-term effects of rehabilitation efforts on weight development and obesity in these patients are not analyzed up to now. PATIENTS AND METHODS 108 patients with childhood craniopharyngioma recruited in HIT Endo before 2001 were included in the study. Long-term weight development (BMI SDS after >10 yrs follow-up) was analyzed in regard to rehabilitation, which was performed in 31 of 108 (29%) patients (one rehabilitation in 4 patients (13%), more than one in 21 patients (68%), 6 patients unknown) in 13 German rehabilitation -clinics. RESULTS 84% of patients underwent rehabilitation in order to reduce hypothalamic obesity (BMI>+ 2 SD), whereas 12% of patients were normal weight. Childhood craniopharyngioma pa-tients with rehabilitation presented with higher BMI at diagnosis (median BMI: +1.32 SD; range: -1.08 to + 7.00 SD) and at last evaluation (median BMI: +4.93 SD; range: -0.20 to + 13.13 SD) when compared with patients without rehabilitation (median BMI at diagnosis: +0.24 SD; range: -2.67 to + 6.98 SD; BMI at evaluation: +2.09 SD; range: -1.48 to + 10.23 SD). A long-term weight reducing effect of rehabilitation was no detectable regardless of degree of obesity, frequency of rehabilitation, and hospital of rehabilitation. CONCLUSION Treatment options for hypothalamic obesity in terms of rehabilitation are limited. Accordingly, strategies for prevention of hypothalamic lesions and psychosocial effects of rehabilitation are currently in focus for improvement of prognosis in childhood craniopharyngioma patients.

CR-06HYDROCEPHALUS AND HYPOTHALAMIC INVOLVEMENT IN PEDIATRIC PATIENTS WITH CRANIOPHARYNGIOMA OR CYSTS OF RATHKE'S POUCH: IMPACT ON LONG-TERM PROGNOSIS

Objective: Pediatric patients with sellar masses such as craniopharyngioma (CP) or cyst of Rathke’s pouch (CRP) frequently suffer disease- and treatment-related sequelae. We analyzed the impact and prognostic relevance of initial hydrocephalus (HY) and hypothalamic involvement (HI) on long-term survival and functional capacity (FC) in children with CP or CRP. Subjects and methods: Using retrospective analysis of patient records, presence of initial HY or HI was assessed in 177 pediatric patients (163 CP and 14 CRP). Twenty-year overall survival (OS) and progression-free survival (PFS), FC, and BMI were analyzed with regard to initial HY, degree of resection, or HI. Results: Of the 177 patients, 105 patients (103/163 CP and 2/14 CRP) presented with initial HY and 96 presented with HI. HY at diagnosis was associated (PZ0.000) with papilledema, neurological deficits, and higher BMI at diagnosis and during followup. OS, PFS, and FC were not affected by HY at initial diagnosis. HI at diagnosis (96/177) had major negative impact on longterm prognosis. Sellar masses with HI were associated with lower OS (0.84G0.04; PZ0.021), lower FC (PZ0.003), and higher BMI at diagnosis and last follow-up (PZ0.000) when compared with sellar masses without HI (OS: 0.94G0.05). PFS was not affected by HI or degree of resection. Conclusions: Initial HY has no impact on outcome in patients with sellar masses. OS and FC are impaired in survivors presenting with initial HI. PFS is not affected by HY, HI, or degree of resection. Accordingly, gross-total resection is not recommended in sellar masses with initial HI to prevent further hypothalamic damage.

Reactive pituitary enlargement mimicking a sellar mass.

Introduction ▼ Diagnosis and treatment of patients with sellar masses is a multidisciplinary challenge due to the close proximity to optical, endocrine, and hypothalamic structures. Appropriate interpretation of primary imaging is necessary in order to achieve risk adapted surgical and radiooncological strategies focusing on the preservation of visual and hypothalamic function. The diff erential diagnosis in imaging of sellar masses include hypothalamic glioma and optical tract glioma, Langerhans cell histiocytosis (LCH), Rathke’s cleft cyst, xanthogranuloma, germinoma, epidermoid tumor, thrombosis of arachnoidal cysts, colloidal cyst of the third ventricle, pituitary adenoma, aneurysma, and rare infl ammatory variations [ 7 ] . Magnetic resonance imaging (MRI) before and after gadolinium application is the standard imaging for detection of sellar/parasellar masses, further imaged by native computerized tomography to detect calcifi cations [ 2 , 7 ] . Primary insuffi ciencies of peripheral endocrine organs, such as hypothyroidism due to Hashimoto thyroiditis, lead to an increased release of stimulating pituitary hormones due to feedback control mechanisms. The increase of pituitary hormonal activity results in reactive hyperplasia of the pituitary gland. In radiology, the distinction between hyperplasia and adenoma may be diffi cult. We report on a patient presenting with reactive enlargement of the pituitary gland due to Hashimoto thyroiditis, initially suspected as a sellar tumor.