Childhood Craniopharyngioma Patients Research Articles

Cognitive interference processing in adults with childhood craniopharyngioma using functional magnetic resonance imaging

PurposeTo assess cognitive interference processing in adults with childhood craniopharyngioma (CP), with and without hypothalamic injury, respectively, in terms of behavioral performance and functional magnetic resonance imaging (fMRI) activity, using the multi-source interference task (MSIT).MethodsTwenty-eight CP patients (median age 34.5 [29.0–39.5] years) were investigated at median 20.5 (16.3–28.8) years after treatment with surgical resection and in some cases additional radiotherapy (n = 10) and compared to 29 matched controls (median age 37.0 [32.5–42.0] years). The subjects performed the MSIT during fMRI acquisition and behavioral performance in terms of response times (ms) and accuracy performance (%) were recorded.ResultsThe MSIT activated the cingulo-fronto-parietal (CFP) attention network in both CP patients and controls. No differences were found in behavioral performance nor fMRI activity between CP patients (interference effect 333.9 [287.3–367.1] ms and 3.1 [1.6–5.6]%, respectively) and controls (309.1 [276.4–361.0] ms and 2.6 [1.6–4.9]%). No differences were found in behavioral performance nor fMRI activity between the two subgroups with (332.0 [283.6–353.4] ms and 4.2 [2.3–5.7]%, respectively) and without hypothalamic injury (355.7 [293.7–388.7] ms and 2.1 [1.0–5.2]%, respectively), respectively, and controls.ConclusionAdults with childhood CP performed cognitive interference processing equally well as controls and demonstrated no compensatory fMRI activity in the CFP attention network compared to controls. This was also true for the two subgroups with and without hypothalamic injury. The results can be useful to better characterize this condition, and to optimize treatment and support for these individuals.

First experiences with neuropsychological effects of oxytocin administration in childhood-onset craniopharyngioma.

The hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions. In our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire. All patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions. Oxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.

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.

A systematic review of cognitive performance in patients with childhood craniopharyngioma.

Craniopharyngiomas are rare brain tumors of the sellar/suprasellar region, often adversely affecting patients' physical and psychosocial functioning. Until a few years ago, knowledge on cognitive deficits in craniopharyngioma patients was based on little valid evidence, with considerable inconsistencies across studies. Findings from recent research, with partly larger sample sizes, add to existing evidence to provide a more clear and reliable picture. The current review aims to summarize and systemize current findings on cognitive deficits in childhood craniopharyngioma, taking account of patient- and treatment-related variables where possible. Those studies were included that reported results of childhood craniopharyngioma patients tested with formalized neuropsychological tests (irrespective of their age at study, group size ≥10). A systematic assignment of test results to subcomponents of broader cognitive domains (e.g. to specific memory systems and processes) allows for a first comprehensive overview of patterns of spared and impaired cognitive functions. We show that episodic memory recall in particular is impaired, largely sparing other memory components. In accordance with recent knowledge on mammillary function, patients with hypothalamic involvement appear to be at particular risk. Deficits in higher cognitive processes, relying on the integrity of the prefrontal cortex and its subcortical pathways, may also occur, but results are still inconsistent. To gain deeper insight into the pattern of deficits and their association with patient- and treatment-related variables, further multi-site research with larger cohorts is needed.

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

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. 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. 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. 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. 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.

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

As a result of hypothalamic involvement and/or treatment-related hypothalamic damage, up to 75% of childhood craniopharyngioma patients develop hypothalamic obesity. 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). 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. 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.

Childhood craniopharyngioma with hypothalamic obesity - no long-term weight reduction due to rehabilitation programs

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. 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. 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. 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.

Long-term weight development and psychosocial status in childhood Craniopharyngioma patients

Background: Craniopharyngioma (CP) are the most common sellar tumors in children. Patients often develop excessive weight gain and obesity due to several factors as involvement or damage of the hypothalamus. Previous studies on the weight development in CP patients have shown an increase in weight before and in the first ten years after diagnosis leading to an impaired quality of life. The long-term weight development in these patients has not been investigated till now.

Eating behaviour and weight problems in long-term survivors of childhood craniopharyngioma – results of the HIT ENDO trial

Background: Due to hypothalamic tumour involvement and/or treatment related hypothalamic damage, up to 75% of childhood craniopharyngioma patients (CP) develop hypothalamic obesity.

Diagnostics, treatment, and follow-up in craniopharyngioma.

Craniopharyngiomas are partly cystic embryogenic malformations of the sellar and parasellar region, with up to half the 0.5–2.0 new cases per million population per year occur in children and adolescents. Diagnosis profile for pediatric and adult craniopharyngioma is characterized by a combination of headache, visual impairment, and polyuria/polydipsia, which can also include significant weight gain. In children, growth retardation, and/or premature puberty often occur later or postoperatively. Recommended therapy with favorable tumor localization is complete resection; with unfavorable tumor localization (optic nerve and/or hypothalamic involvement), consensus is still pending whether a limited resection followed by local irradiation is more prudent. Even though overall survival rates are high (92%), recurrences after complete resection and progressions after incomplete resection can be expected. Accordingly, a randomized multinational trial (KRANIOPHARYNGEOM 2007) has been established to identify optimal diagnosis, treatment (particularly the ideal time point of irradiation after incomplete resection), and quality of life strategies of this chronic disease – most notably the morbid hypothalamic obesity in ∼50% of long-term survivors. We report on craniopharyngioma origins, its pathological manifestations, and specific challenges these sequelae pose regarding diagnosis, treatment, and life-long multi-discipline quality of life management for both adult and childhood craniopharyngioma patients.

Increased daytime sleepiness in patients with childhood craniopharyngioma and hypothalamic tumor involvement: review of the literature and perspectives.

Childhood craniopharyngiomas are rare embryogenic malformations of the sellar region, presumably derived from Rathke cleft epithelium. The overall survival rates after neurosurgical intervention and/or irradiation are high (92%). However, the quality of survival is frequently impaired due to endocrine deficiencies, sleep disturbances, daytime sleepiness, and severe obesity caused by hypothalamic lesions. Based on self-assessment using nutritional diaries, caloric intake was similar in patients and BMI-matched controls. Analyses of physical activity by accelerometric measurements showed a markedly lower level of physical activity. Significant daytime sleepiness and disturbances of circadian rhythms have been demonstrated in obese childhood craniopharyngioma patients. Daytime sleepiness and obesity in these patients were both correlated with low nocturnal and early morning melatonin levels. Polysomnographic studies in patients with severe daytime sleepiness revealed sleeping patterns typical for secondary narcolepsy. Reports on a beneficial effect of treatment with central stimulating agents supported the hypothesis that secondary narcolepsy should be considered as a rare cause for severe daytime sleepiness in patients with childhood craniopharyngioma.

Secondary narcolepsy may be a causative factor of increased daytime sleepiness in obese patients with childhood craniopharyngioma

Prognosis in childhood craniopharyngioma survivors hinges upon late effects such as pituitary deficiency and obesity. Observations indicate that reduced physical activity and increased daytime sleepiness might be risk factors for obesity. We analyzed the degree of daytime sleepiness in 115 childhood craniopharyngioma patients (47% obese) using the Epworth Sleepiness Scale (ESS). Thirty-five (30%) displayed increased daytime sleepiness (ESS score > 10) of whom 14 were obese (26% of obese cohort). Polysomnography (PSG) and Multiple Sleep Latency Tests (MSLT) were conducted with 10 obese patients presenting increased daytime sleepiness, with only two craniopharyngioma patients revealing a sleep related breathing disorder. Four patients had repeated episodes of SOREM (sleep onset rapid eye movement), the classic PSG criterion for narcolepsy. Three patients displayed hypersomnia. All but one patient qualified as acutely obese. We speculate that secondary narcolepsy is an exacerbating condition of childhood craniopharyngioma obesity, supported by recent reports on orexin and narcolepsy which suggest hypothalamic failure in idiopathic narcolepsy.

High rates of early relapses after complete resection and early tumor progressions after incomplete resection of childhood craniopharyngioma - update after three years of prospective evaluation in KRANIOPHARYNGEOM 2000

In HIT-ENDO we collected data on therapy and outcome of 306 patients with childhood craniopharyngioma (CP). The survival rates were 94±4% in irradiated and 93±5% in non-irradiated patients. The German multicenter prospective study KRANIOPHARYNGEOM 2000 was initiated in order to collect data on incidence and time course of relapses after complete surgery and tumor progressions after incomplete resection. Furthermore, the impact of irradiation (XRT) on relapse and recurrence rates was analyzed. Since 2001 ninety-six patients with newly diagnosed CP were recruited.. With a high degree of completeness (80–90%) data on neurosurgery, neuroradiology and XRT could be collected prospectively. Complete resection was achieved in 43%, subtotal resection in 45%. XRT was performed in 22 of 96 CP patients; in 18% immediately after subtotal resection, in 53% after progression of residual tumour and in 14% after (second surgery of) relapse. Data on XRT modalities were evaluable in 17 of 22 patients. XRT was performed at a median age of 11 years (4–18 y) and after a mean interval of 10 months after first diagnosis. All patients got a 3-dimensional CT-planning of XRT. The mean total dose was 52.5 Gray. An interim evaluation on event-free survival rates (EFS) after three years of follow-up showed a high rate of early events (EFS: 0.22±0.06) in terms of tumour progression after subtotal resection (n=48) and relapses (EFS: 0.60±0.10) after complete resection (n=37) during the first three years of follow-up. A high rate of early events (EFS: 0.57±0.15) was also found for patients after XRT (2 zystic progressions, 4 progressions of solid tumour parts after XRT). We conclude that progression after subtotal resection and relapse after complete resection of CP are frequent and early events even in irradiated patients during the first three years after diagnosis. Regular cerebral imaging is recommended in follow-up of patients with CP. There is controversial discussion on the adequate time point of irradiation after incomplete resection.

Relapse Pattern After Complete Resection and Early Progression After Incomplete Resection of Childhood Craniopharyngioma

In HIT Endo data on therapy and prognosis of 306 patients with childhood craniopharyngioma (CP) were analyzed. The 5 years-overall survival rate was 94 +/- 4 % in irradiated patients and 93 +/- 5 % in non-irradiated patients. Aims of the prospective study KRANIOPHARYNGEOM 2000 were to collect data on the incidence and time course of relapses after complete surgery and tumour progressions after incomplete resection. Furthermore, the impact of irradiation therapy (XRT) on tumour relapse and recurrence rates was analyzed. Since 2001 ninety-eight patients with CP were recruited at a median age at diagnosis of 9.9 years ranging from 1.8 to 18.0 years. Complete resection was achieved in 44 %, incomplete resection in 54 %. XRT was performed in 24 of 98 CP patients; in 10 early after incomplete resection, in 14 of 24 after progression of residual tumour or relapse, in 3 of 14 after second surgery of relapse. XRT was performed at a median age of 12.0 years ranging from 5.0 to 18.9 years and in median after an interval of 9 months after first diagnosis. The analysis of event-free survival rates (EFS) in patients with CP showed a high rate of early events in terms of tumour progression after incomplete resection (3y-EFS: 0.22 +/- 0.09) and relapses after complete resection (3y-EFS: 0.60 +/- 0.10) during the first three years of follow-up. A high rate of early events (1y-EFS: 0.78 +/- 0.10; 2y-EFS: 0.57 +/- 0.15) was also found for patients after XRT (3 cystic progressions, 3 progressions of solid tumour; in 24 patients after XRT). We conclude that tumour progression and relapse are frequent and early events even in irradiated patients. Monitoring of cerebral imaging and clinical status is recommended in follow-up of patients with childhood CP. In order to analyze the appropriate time point of XRT after incomplete resection, QoL, EFS and overall survival in patients (age > or = 5 years) will be analyzed in KRANIOPHARYNGEOM 2007 after stratified randomization of the time point of irradiation after incomplete resection (early irradiation versus irradiation at progression of residual tumour).

High rates of early relapses after complete resection and early tumor progressions after incomplete resection of childhood craniopharyngioma – Update after three years of prospective evaluation in KRANIOPHARYNGEOM 2000 and study design of KRANIOPHARYNGEOM 2007

In our multicenter cross-sectional study HIT-ENDO we collected data on therapy and outcome of 306 patients with childhood craniopharyngioma (CP). The survival rates were 94±4% in irradiated and 93±5% in non-irradiated patients. The German multicenter prospective study KRANIOPHARYNGEOM 2000 (www.kraniopharyngeom.de) was initiated in order to collect data on incidence and time course of relapses after complete surgery and tumor progressions after incomplete resection. Furthermore, the impact of irradiation (XRT) on relapse and recurrence rates was analyzed. Since 2001 ninety-six patients with newly diagnosed CP were recruited. With a high degree of completeness (80–90%) data on neurosurgery, neuroradiology and XRT could be collected prospectively. Complete resection was achieved in 43%, subtotal resection in 45%. XRT was performed in 22 of 96 CP patients; in 18% immediately after subtotal resection, in 53% after progression of residual tumour and in 14% after (second surgery of) relapse. Data on XRT modalities were evaluable in 17 of 22 patients. XRT was performed at a median age of 11 years (4–18 y) and after a mean interval of 10 months after first diagnosis. All patients got a 3-dimensional CT-planning of XRT. The mean total dose was 52.5 Gray. An interim evaluation on event-free survival rates (EFS) after three years of follow-up showed a high rate of early events (EFS: 0.22±0.06) in terms of tumour progression after subtotal resection (n=48) and relapses (EFS: 0.60±0.10) after complete resection (n=37) during the first three years of follow-up. A high rate of early events (EFS: 0.57±0.15) was also found for patients after XRT (2 zystic progressions, 4 progressions of solid tumour parts after XRT). We conclude that progression after subtotal resection and relapse after complete resection of CP are frequent and early events even in irradiated patients during the first three years after diagnosis. Regular monitoring of cerebral imaging and clinical status is recommended in follow-up of patients with CP. There is controversial discussion on the adequate time point of irradiation after incomplete resection. Accordingly, the multicenter prospective study KRANIOPHARYNGEOM 2007 will focus on this issue. Patients at age ≥5 years at diagnosis will be randomized after incomplete resection for the time point of irradiation (immediate XRT after surgery versus XRT at progression of residual tumour). Endpoints of the study will be quality of life (PEDQOL domaine: physical function), progression-free survival and overall survival). The time point of evaluation will be 3 years after randomisation.

Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients – First experiences in therapeutic melatonin substitution

Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently suffer from endocrine deficiencies, sleep disturbances and obesity due to pituitary and hypothalamic lesions. A self-assessment daytime sleepiness questionnaire (German version of the Epworth Sleepiness Scale [ESS]) was used to evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic lesions may explain daytime sleepiness in craniopharyngioma patients, salivary melatonin and cortisol concentrations were examined in obese and non-obese craniopharyngioma patients (n=79), patients with hypothalamic pilocytic astrocytoma (n=19), and control subjects (n=30). Using a linear prediction model analyzing the influence of BMI and tumor diagnosis on diurnal salivary melatonin and cortisol levels we found that morning salivary melatonin levels were significantly and independently related to BMI (p-value in F-test: 0.004) and tumor diagnosis (p-value in F-test: 0.032). Also for nighttime salivary melatonin levels significant relations with BMI (p-value in F-test: <0.001) and tumor diagnosis (p-value in F-test: 0.025) were detectable. Melatonin concentrations in saliva of craniopharyngioma patients collected at nighttime or in the morning showed a significant (p<0.01; p<0.05) inverse correlation (Spearman r: –0.42; –0.31) with the patient's ESS score. Severely obese craniopharyngioma patients and severely obese hypothalamic tumor patients had similar patterns of melatonin secretion. Differences in terms of morning and nighttime salivary melatonin concentrations were not detectable between normal weight controls and normal weight patients with craniopharyngioma or hypothalamic tumor. Differences in salivary cortisol concentrations were not related to impaired melatonin secretion in patients with childhood craniopharyngioma. A pilot study on efficacy of melatonin substitution (6mg/d) in childhood craniopharyngioma patients with severe daytime sleepiness (n=12) showed a significant improvement based on ESS and activity protocols. We speculate that hypothalamic lesions might be responsible for both obesity and daytime sleepiness. As decreased nocturnal melatonin levels were associated with increased daytime sleepiness, BMI and hypothalamic tumor diagnosis, further studies on the beneficial effects of melatonin substitution on daytime sleepiness and weight control in these patients are warranted. (www.kraniopharyngeom.com)

Melatonin Secretion and Increased Daytime Sleepiness in Childhood Craniopharyngioma Patients

Melatonin Secretion and Increased Daytime Sleepiness in Childhood Craniopharyngioma Patients

Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients.

Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently suffer from endocrine deficiencies, sleep disturbances, and obesity due to pituitary and hypothalamic lesions. A self-assessment daytime sleepiness questionnaire (German version of the Epworth Sleepiness Scale) was used to evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic lesions may explain daytime sleepiness in craniopharyngioma patients, salivary melatonin and cortisol concentrations were examined in obese and nonobese craniopharyngioma patients (n = 79), patients with hypothalamic pilocytic astrocytoma (n = 19), and control subjects (n = 30). Using a general linear model procedure analyzing the influence of body mass index (BMI) and tumor diagnosis on diurnal salivary melatonin, we found that morning salivary melatonin levels were related to BMI (by F test, P = 0.004) and tumor diagnosis (by F test, P = 0.032). Also for nighttime salivary melatonin levels significant relations with BMI (by F test, P < 0.001) and tumor diagnosis (by F test, P = 0.025) were detectable. Melatonin concentrations in saliva of craniopharyngioma patients collected at night or in the morning showed a negative correlation (night: Spearman's rho = -0.42; P = 0.001; morning: Spearman's rho = -0.31; P = 0.020) with the patient's Epworth Sleepiness Scale score. Severely obese craniopharyngioma patients and severely obese hypothalamic tumor patients had similar patterns of melatonin secretion. Differences in terms of diurnal salivary cortisol concentrations were not detectable when patient groups and controls were compared. We speculate that hypothalamic lesions might be responsible for both obesity and daytime sleepiness. As decreased nocturnal melatonin levels were associated with increased daytime sleepiness, BMI, and hypothalamic tumor diagnosis, further studies on the beneficial effects of melatonin substitution on daytime sleepiness and weight control in these patients are warranted.