Preoperative peripheral inflammatory markers are predictors of postoperative central diabetes insipidus in craniopharyngioma patients: a retrospective study.

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.

Antibodies Against Hypothalamus and Pituitary Gland in Childhood-Onset Brain Tumors and Pituitary Dysfunction.

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.

Prediction of calcification tendency in pediatric cystic adamantinomatous craniopharyngioma by using inflammatory markers, hormone markers, and radiological appearances.

PURPOSE: To compare the different levels of inflammatory markers, hormone markers, and radiological appearances between PCACP with and without calcification so as to explore the relationships between these markers and calcification. METHODS: The inflammatory markers, hormone markers, and radiological appearances were compared not only between PCACP with and without calcification, but also among its different forms of calcification. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic significance of all markers between these groups. RESULTS: It was showed that the white blood cell (WBC) count, neutrophil count, monocyte count, prognostic nutritional index (PNI), prolactin (PRL), and T1WI signal of cysts were higher in PCACP with calcification than in PCACP without calcification. The neutrophil count was significantly higher in PCACP with eggshell calcification than in other groups. The PCACP with mixed calcification had the highest PRL level in all kinds of PCACP with calcification. Only the area under curve (AUC) values of neutrophil count and PRL level were greater than 0.8. CONCLUSION: It is found that inflammation and hormone are related to PCACP's calcification. High neutrophil count and PRL level may indicate possible calcification tendency in PCACP. Improved intracystic therapies based on these results may help to inhibit the formation of calcification in PCACP in future.

Impact of neutrophil-lymphocyte ratio on long-term outcome in patients with craniopharyngioma.

Neutrophil-lymphocyte ratio (NLR) is a poor prognostic factor in many tumors including glioblastoma multiforme (GBM), colorectal, and prostate cancer. The aim of this study was to investigate the prognostic value of preoperative NLR in patients with craniopharyngioma.Around 149 patients of craniopharyngioma surgically were treated at the Department of Neurosurgery, West China Hospital from January 2008 to December 2010, including 84 males and 65 females aged from 6 to 70 years were retrospectively reviewed, and preoperative NLR was analyzed. Overall survival (OS), progression free survival (PFS), and quality of life (QOL) were evaluated.The 5-year OS and PFS rates were 81.21% and 75.84%. Preoperative NLR was significantly correlated with OS (HR = 1.44, 95% CI 1.16-1.79, P = .001) and PFS (HR = 1.46, 95% CI 1.22-1.74, P < .001). The best cut-off value of NLR was found to be 4 based on the receiver operator characteristics (ROC) curve. Patients with NLR ≥4 had a significantly worse QOL (P = .039), lower OS rate (P = .009), and PFS rate (P < .001).Preoperative NLR may be a simple, readily available, and valid predictor of long-term outcome in craniopharyngioma. We suggest that the NLR can provide effective guidance to neurosurgeons for more information about the tumor and prognostic evaluation.

A case series of atypical features of patients with biopsy-proven isolated IgG4-related hypophysitis and normal serum IgG4 levels.

BACKGROUND: IgG4-related hypophysitis is a rare clinical entity that forms part of an emerging group of multi-organ IgG4-related fibrosclerotic systemic diseases. The rare prevalence of the disease, presenting features that overlap with other sellar pathologies, and variable imaging features can make preoperative identification challenging. PURPOSE AND METHODS: We report three cases of isolated IgG4-related hypophysitis with atypical clinical and imaging features that mimicked those of pituitary apoplexy and other sellar lesions. Additionally, we review the literature of IgG4-related hypophysitis to provide context for individual patient data described herein. RESULTS: All patients presented with symptoms that mimicked those of pituitary apoplexy and visual disturbance, and MRI findings suggestive of pituitary macroadenoma, Rathke's cleft cyst and craniopharyngioma. The clinical presentation warranted surgical decompression, resulting in rapid symptomatic improvement. Preoperative high-dose followed by postoperative low-dose glucocorticoid replacement therapy was administered in all cases. Histopathology showed dense infiltrate of IgG4 cells. Post-operative follow-up monitoring for 12-26 months revealed normal serum IgG4 levels with no other organ involvement, while endocrinological testing revealed persistent pituitary hormone deficiencies. CONCLUSIONS: Our cases highlight the importance of considering IgG4-related hypophysitis in the differential diagnosis of solid and cystic sellar lesions presenting acutely with pituitary apoplexy symptoms. Existing diagnostic criteria may not be sufficiently precise to permit rapid and reliable identification, or avoidance of surgery in the acute setting. In contrast to other reports of the natural history of this condition, despite the severity of presenting features, the disease in our cases was pituitary-restricted with normal serum IgG4 levels.

[A rare case of diencephalic cachexia in an adult female with cranio-pharyngioma]. / Redkii sluchai razvitiia diéntsefal'noi kakheksii u vzrosloi zhenshchiny s kraniofaringiomoi.

Diencephalic cachexia (DС) is progressive weight loss despite a normal caloric intake and a satisfactory state of health, which is caused by hypothalamic lesions. This is a rare (about 100 cases were reported) and potentially fatal disorder of unknown pathogenesis. At present, there is no effective pharmacological therapy for the disorder. Cachexia may regress only if the tumor reduces in size, therefore the timely diagnosis and treatment are of vital importance for the patient. DС is typical of early childhood, and only a few cases have been reported in adults. We present a rare case of DС in a 24-year-old female with papillary craniopharyngioma.

The purine receptor P2X7R regulates the release of pro-inflammatory cytokines in human craniopharyngioma.

Craniopharyngiomas (CPs) are usually benign, non-metastasizing embryonic malformations originating from the sellar area. They are, however, locally invasive and generate adherent interfaces with the surrounding brain parenchyma. Previous studies have shown the tumor microenvironment is characterized by a local abundance of adenosine triphosphate (ATP), infiltration of leukocytes and elevated levels of pro-inflammatory cytokines that are thought to be responsible, at least in part, for the local invasion. Here, we examine whether ATP, via the P2X7R, participates in the regulation of cytokine expression in CPs. The expression of P2X7R and pro-inflammatory cytokines were measured at the RNA and protein levels both in tumor samples and in primary cultured tumor cells. Furthermore, cytokine modulation was measured after manipulating P2X7R in cultured tumor cells by siRNA-mediated knockdown, as well as pharmacologically by using selective agonists and antagonists. The following results were observed. A number of cytokines, in particular IL-6, IL-8 and MCP-1, were elevated in patient plasma, tumor tissue and cultured tumor cells. P2X7R was expressed in tumor tissue as well as in cultured tumor cells. RNA expression as measured in 48 resected tumors was positively correlated with the RNA levels of IL-6, IL-8 and MCP-1 in tumors. Furthermore, knockdown of P2X7R in primary tumor cultures reduced, and stimulation of P2XR7 by a specific agonist enhanced the expression of these cytokines. This latter stimulation involved a Ca2+-dependent mechanism and could be counteracted by the addition of an antagonist. In conclusion, the results suggest that P2X7R may promote IL-6, IL-8 and MCP-1 production and secretion and contribute to the invasion and adhesion of CPs to the surrounding tissue.

Nutritional and endocrinologic evaluation of patients with craniopharyngioma.

BACKGROUND & AIMS: Lesions of hypothalamus or adjacent brain structures by the craniopharyngioma (CP) and/or its treatment, as well as changes in orexigenic and anorexigenic hormones, are possible pathogenic factors for the obesity observed in CP patients. This study assessed anthropometric measurements, food intake, and biochemical markers of CP patients. METHODS: Weight, height, skinfold thicknesses, circumferences, body composition, food intake evaluation, basal glucose, lipids, insulin, ghrelin, PYY, and HOMA-IR calculation were obtained from CP children (n = 10, 4F, aged 12 ± 4.2yr) and CP adults (n = 27,13F aged 42 ± 13 yr) and from 32 gender and age matched controls. RESULTS: Overweight/obesity was observed in 51.4% of the patients at the diagnosis and increased to 86.5% at the time of the study. Obesity was more frequent in patients with grade 2 hypothalamic involvement. Most anthropometric measurements were similar in patients and controls. Caloric intake was lower in CP adults, without difference between children. Lipid intake was higher in CP patients. Carbohydrate and protein intakes were lower in CP children, with no difference between adult groups. There were no differences in micronutrients intake as well as in insulin and PYY levels, and HOMA-IR between patients and controls. HDL-c was lower in CP adults and ghrelin higher in CP children. CONCLUSIONS: There is a high rate of overweight/obesity in CP patients at the diagnosis and throughout the follow-up period. Obesity was associated with degree of hypothalamic involvement but not with caloric intake. Obesity and a lipid rich diet may have contributed to the dyslipidemia observed in CP patients.

Analysis of short- and long-term metabolic effects of growth hormone replacement therapy in adult patients with craniopharyngioma and non-functioning pituitary adenoma.

PURPOSE: Adult patients operated for craniopharyngioma develop more frequently GH deficiency (GHD) than patients operated for non-functioning pituitary adenoma (NFPA). The aim of the study was to compare both short- (1 year) and long-term (5 years) effects of rhGH in 38 GHD adult patients (19 operated for Craniopharyngioma (CP) and 19 for NFPA). METHODS: IGF-I levels, body composition (BF%), BMI, lipid profile and glucose homeostasis were evaluated in all patients. Pituitary MRI was performed at baseline and during follow-up, as needed. RESULTS: At baseline no difference between the two groups was observed, apart from a higher prevalence of diabetes insipidus in CP patients (79 vs 21%). After 12 months, IGF-I SDS normalized and BF% significantly decreased only in the NFPA group. During long-term treatment, decrease in BF% and improvement in lipid profile shown by reduction in total- and LDL-cholesterol were present in NFPA group only, while increase in insulin levels and HbA1c and decrease of QUICKI were observed in CP patients only. Accordingly, after long-term therapy, the prevalence of metabolic syndrome (MS) was significantly higher in CP than in NFPA group (37% in CP and in 5% in NFPA group; p < 0.05). CONCLUSION: The present data suggest that CP patients are less sensitive to the positive rhGH effects on lipid profile and BF% and more prone to insulin sensitivity worsening than NFPA patients, resulting in increased prevalence of MS in CP only.

Endocrine aspects and sequel in patients with craniopharyngioma.

A craniopharyngioma (CP) is an embryonic malformation of the sellar and parasellar region. The annual incidence is 0.5-2.0 cases/million per year and approximately 60% of CP is seen in adulthood. The therapy of choice is surgery, followed by cranial radiotherapy in about half of the patients. Typical initial manifestations at diagnosis in children are symptoms of elevated intracranial pressure, visual disturbances and hypopituitarism. CPs have the highest mortality of all pituitary tumours. The standardised overall mortality rate varies from 2.88 to 9.28 in cohort studies. Adults with CP have a 3-19-fold higher cardiovascular mortality in comparison to the general population. Women with CP have an even higher risk. The long-term morbidity is substantial with hypopituitarism, increased cardiovascular risk, hypothalamic damage, visual and neurological deficits, reduced bone health and reduction in quality of life and cognitive function.

Sleep-wake and melatonin pattern in craniopharyngioma patients.

OBJECTIVE: To assess the influence of craniopharyngioma or consequent surgery on melatonin secretion, and the association with fatigue, sleepiness, sleep pattern and sleep quality. DESIGN: Cross-sectional study. METHODS: A total of 15 craniopharyngioma patients were individually matched to healthy controls. In this study, 24-h salivary melatonin and cortisol were measured. Sleep-wake patterns were characterised by actigraphy and sleep diaries recorded for 2 weeks. Sleepiness, fatigue, sleep quality and general health were assessed by Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Short-Form 36. RESULTS: Patients had increased mental fatigue, daytime dysfunction, sleep latency and lower general health (all, P≤0.05), and they tended to have increased daytime sleepiness, general fatigue and impaired sleep quality compared with controls. The degree of hypothalamic injury was associated with an increased BMI and lower mental health (P=0.01). High BMI was associated with increased daytime sleepiness, daytime dysfunction, mental fatigue and lower mental health (all, P≤0.01). Low midnight melatonin was associated with reduced sleep time and efficiency (P≤0.03) and a tendency for increased sleepiness, impaired sleep quality and physical health. Midnight melatonin remained independently related to sleep time after adjustment for cortisol. Three different patterns of melatonin profiles were observed; normal (n=6), absent midnight peak (n=6) and phase-shifted peak (n=2). Only patients with absent midnight peak had impaired sleep quality, increased daytime sleepiness and general and mental fatigue. CONCLUSION: Craniopharyngioma patients present with changes in circadian pattern and daytime symptoms, which may be due to the influence of the craniopharyngioma or its treatment on the hypothalamic circadian and sleep regulatory nuclei.

Treatment of craniopharyngioma in adults: systematic analysis of a 25-year experience.

BACKGROUND AND AIMS: Craniopharyngioma is a rare and mostly benign epithelial tumor of the central nervous system, mostly affecting children. Considering that most of the published series of craniopharyngioma are based on pediatric populations, studies in adults gain importance based mainly on the reduced number of cases and the possible differences emerging from a mostly different histological type. We undertook this study to establish the pattern of presentation, morphological features and specific characteristics of craniopharyngioma in an adult Mexican population, as well as discussing the long-term outcome and how it may be influenced by surgical, anatomic and clinical factors. METHODS: A total of 153 adult patients (16 years or older) underwent transcranial and transsphenoidal surgery between January 1985 and December 2009, all with histological confirmation of craniopharyngioma. Hypothalamic involvement, surgical complications, rate of tumor resection and endocrinological outcome were evaluated. RESULTS: Seventy nine males (51.6%) and 74 females (48.4%) were included. Mean age at diagnosis was 32.4 years (range: 16-77 years). Mean initial tumor volume was 28.44 mL (range: 0.18-100.44 mL). Partial or complete hypothalamic involvement (Samii Grades III, IV and V) was found in 90.2%. The overall rate of new endocrinopathies was 37.25% after surgery (95% CI = 33.9-41.2). CONCLUSIONS: Gross total removal of craniopharyngiomas with large hypothalamic involvement was related to poor neuroendocrine outcome in adults. Partial removal should be indicated, associated with adjuvant therapy, in order to improve postoperative neuroendocrine status.

Hyperinsulinemia may promote growth without GH in children after resection of suprasellar brain tumors.

It remains elusive what factors induce growth without growth hormone (GWGH) in children after neurosurgery of brain tumors. Growth velocity and endocrinological data were compared between the patients with and without GWGH. We experienced three patients with GWGH (median, 12 years; 2 germinoma and 1 craniopharyngioma; three females; group 1) and 11 patients without (12 years; 8 craniopharyngioma, 2 germinoma and 1 medulloblastoma; 7 males; group 2) after neurosurgery. All patients in group 2 received GH replacement therapy. Growth velocity and endocrinological data were compared. Median height velocity was normal in group 1 (5.5 cm/year), but low in group 2 (2.2 cm/year), which improved after GH replacement therapy (7.0 cm/year). Median serum insulin level was increased in group 1 (87.0 µU/ml, P < 0.05) compared with normal level in group 2 (10.0 µU/ml). Despite hyperinsulinemia, serum glucose level was normal in group 1. Three of 5 with hyperinsulinemia and 2 of 9 without were obese or overweight, but the difference was not significant. Current body mass index and serum levels of IGF-1, IGFBP-3, leptin, and prolactin were similar between groups. Serum estradiol was prepuberty level in group 1. Hyperinsulinemia may induce GWGH in children with brain tumors after neurosurgery.

[Severe thrombotic complications in the postoperative period in a child after removal of craneopharyngeoma].

The paper describes a rare clinical case of severe thrombotic complications (thrombosis of the subclavian, superior vena cava and femoral veins) of the child in the postoperative period, after removal of craniopharyngeoma. The development of complications was diagnosed based on clinical symptoms and results of ultrasound. Genesis of thrombotic complications has been clarified with the help of special hemostasiological studies that confirmed the presence of acquired protein S deficiency. The matters of discussion are the problems of diagnosis and therapy of this complication.

Appetite-regulating hormone changes in patients with craniopharyngioma.

Patients with craniopharyngioma (CP), an embryological tumor located in the hypothalamic and/or pituitary region, often suffer from uncontrolled eating and severe obesity. We aimed to compare peripherally secreted hormones involved in controlling food intake in normal weight and obese children and adolescents with CP vs. controls. Plasma insulin, glucose, total ghrelin, and peptide-YY (PYY) levels were assessed under fasting conditions as well as 60 min after liquid mixed meal in four groups: Normal weight (n = 12) and obese (n = 15) CP patients, and 12 normal weight and 15 obese otherwise healthy BMI-, gender- and age-matched controls. Homeostasis model assessment of insulin resistance (HOMA(IR)), as well as quantitative insulin sensitivity check index (QUICKI) were calculated. Obese CP subjects had significantly higher HOMA(IR), higher baseline and postmeal insulin but lower ghrelin levels, weaker postmeal changes for PYY, and lower QUICKI compared to obese controls. QUICKI data from all CP patients correlated positively with ghrelin and PYY % postmeal changes (ghrelin: r = 0.38, P = 0.023; PYY r = 0.40, P = 0.017) and negatively with standard deviation score-BMI (SDS-BMI: r = -0.49, P = 0.002). Tumor growth of 87% obese and 58% of normal weight CP patients affected the hypothalamic area which was associated with higher SDS-BMI and weaker % postmeal ghrelin changes (P = 0.014) compared to CP patients without hypothalamic tumor involvement. Blunted postmeal ghrelin and PYY responses in obese CP subjects are likely due to their higher degree of insulin resistance and lower insulin sensitivity compared to matched obese controls. Thus, insulin resistance in CP patients seems to affect eating behavior by affecting meal responses of gut peptides.

Delayed ghrelin suppression following oral glucose tolerance test in children and adolescents with hypothalamic injury secondary to craniopharyngioma compared with obese controls.

Ghrelin, released from the stomach, acts at the hypothalamus and is associated with initiation of food intake. We hypothesised that patients with craniopharyngioma and hypothalamic obesity (CRHO) would have ghrelin abnormalities. Fifteen CRHO patients and 15 BMI-matched controls underwent oral glucose tolerance test with dynamic ghrelin measurement. From 0-30 minutes, ghrelin (pg/ml) decreased less (43.4 ? 38.8 vs. 70.8 ? 35.8, p < 0.05) and insulin (pmol/l) increased more (1 669.2 ? 861.7 vs. 1 049.1 ? 560.4, p = 0.04) in CRHO compared with controls, respectively. Insulin area-under-the-curve was a weak negative predictor of the 0?30 minutes ghrelin decrease (r(2) = 0.29, p = 0.02). Delayed ghrelin suppression may contribute to obesity in CRHO.

Obesity, metabolic syndrome, and insulin dynamics in children after craniopharyngioma surgery.

INTRODUCTION: Children after craniopharyngioma surgery often develop rapid weight gain and hyperphagia. We investigate the metabolic syndrome features, risk factors, and the insulin dynamics in these patients. MATERIALS AND METHODS: Standard oral glucose tolerance tests (OGTT) were performed in 12 subjects, aged 7.7-18.1 years, after surgical removal of craniopharyngioma and their healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Blood samples were obtained for measurement of levels of plasma glucose, insulin, lipids, liver enzymes, baseline hormonal profiles with calculation of insulin secretion, and insulin sensitivity indices derived from OGTT. RESULTS AND DISCUSSION: Nine of 12 subjects were severely obese. All patients exhibited significant weight gain after surgery. The waist to hip ratio was higher in subjects compared to controls (P = 0.023). Subjects had higher fasting triglycerides (P = 0.019) and lower HDL/total cholesterol ratio (P = 0.012). Five of 12 subjects met the criteria for the metabolic syndrome, compared with one of 12 in controls. One patient had prediabetes and another patient had overt type 2 diabetes. Six of 12 subjects had nonalcoholic steatohepatitis. No significant risk factors were found between each group of patients with and without the metabolic syndrome. There were no differences of insulin secretion and insulin sensitivity indices between craniopharyngioma and control subjects. CONCLUSION: Children after craniopharyngioma surgery are at risk of rapid weight gain and the development of metabolic syndrome. Further studies to better understand the mechanism are required to design effective treatment and prevention.

Reduced energy expenditure and impaired feeding-related signals but not high energy intake reinforces hypothalamic obesity in adults with childhood onset craniopharyngioma.

CONTEXT: Obesity is a frequent manifestation of hypothalamic damage from a craniopharyngioma (CP). It is not yet clarified whether the obesity is due to alterations in energy expenditure, i.e. basal metabolic rate (BMR) and physical activity, or to increased energy intake (EI). OBJECTIVE: The aim was to investigate whether energy expenditure and EI differed between childhood onset CP patients and matched population controls and whether these measures were related to hypothalamic damage, as tumor growth into the third ventricle (TGTV). DESIGN AND METHODS: Forty-two CP patients (20 women) aged 28 yr (range, 17-57 yr) operated between 1958 and 2000 in the South Medical Region of Sweden (population, 2.5 million) were studied. Body composition, satiety hormones, BMR (indirect calorimetry), physical activity, EI, and attitudes toward eating were assessed. Comparisons were made with matched controls and between patients with (n=25) and without (n=17) TGTV. RESULTS: After adjustment, patients had lower BMR compared to controls (-90 kcal/24 h; P=0.02) and also had lower EI (1778 vs. 2094 kcal/24 h; P=0.008), and the EI/BMR ratio was significantly lower in TGTV patients. Similar dietary macronutrient composition was found, and only significantly higher scales in restricting food intake were recorded in patients. Ghrelin levels were significantly lower in patients, whereas serum insulin and leptin levels were higher (P<0.001), and both ghrelin and insulin correlated significantly to tumor growth. Lower levels of physical activity (P<0.01) were recorded in patients. CONCLUSIONS: The major mechanisms that reinforced obesity were hypothalamic damage causing disrupted or impaired sensitivity to feeding-related signals for leptin, insulin, and ghrelin, and reductions in both BMR and physical activity.