Assessment of hypothalamic syndrome in adult craniopharyngioma patients.

ObjectiveRapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare syndrome manifesting in childhood. Diagnosis of ROHHAD syndrome remains challenging due to the diversity of symptoms that may be missed easily, especially for autonomic dysfunction, and partly develop later in time. The 2023 hypothalamic syndrome (HS) diagnostic criteria are a novel tool for recognizing symptoms of hypothalamic dysfunction. However, symptoms of autonomic dysregulation are lacking in these criteria. They are therefore insufficient for use in ROHHAD patients. No other scoring system for autonomic dysfunction in ROHHAD syndrome exists. We aim to improve the diagnostic criteria for HS by including a score for autonomic dysregulation, supporting early diagnosis of ROHHAD syndrome.MethodsA score for autonomic dysregulation in ROHHAD syndrome supplementary to the 2023 HS diagnostic criteria was developed based on existing instruments to assess autonomic dysfunction symptoms adjusted for specific symptoms in ROHHAD syndrome, with a score ranging from 0 to 10. The diagnostic criteria for HS including our add-on were tested retrospectively in four ROHHAD patients.ResultsFour ROHHAD patients, median age 9.4 years (range 4.6–25.7), were assessed regarding signs and symptoms of HS and autonomic dysfunction. All patients had HS and scored on at least three different domains of autonomic dysregulation. Median score was 9 out of 10 (range 4–9).ConclusionsThe 2023 HS diagnostic criteria are not sufficient to recognize autonomic dysfunction due to hypothalamic dysfunction in ROHHAD syndrome. Our add-on score is clinically easy to use and may help in early recognition and follow-up in ROHHAD syndrome and other causes of HS.Significance statementRapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare cause of HS in childhood. In the recently developed diagnostic criteria for HS, the autonomic manifestations of hypothalamic dysfunction, which are common in ROHHAD syndrome, are not represented sufficiently. Children with ROHHAD may, for example, experience ophthalmological problems (strabismus or oculomotor apraxia), altered pain threshold, increased or impaired sweating, cold extremities, and/or heart rate dysregulation. Many of these symptoms are mostly unnoticed by the clinician or caregivers, leading to a delay in diagnosis and treatment. An add-on to the diagnostic criteria for HS including parameters of autonomic dysregulation will support early recognition of ROHHAD syndrome, follow-up during treatment and research purposes.

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known •Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. •There are few reports on aAVP-D, most of which focus on adult patients. •The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New •Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. •Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. •Early recognition and structured management of ADI lowered the risk of complications.

Fatigue in patients with hypothalamic syndrome – A cross-sectional analysis of the German childhood-onset craniopharyngioma cohort

BACKGROUNDPatients with tumors of the sellar region are at risk of developing hypothalamic syndrome. Survivors experience fatigue and excessive daytime sleepiness even years after tumor treatment. The aim of this cross-sectional study was to determine the severity of fatigue in patients with and without hypothalamic syndrome. METHODSPatients diagnosed with CP or pilocytic astrocytoma were recruited from the KRANIOPHARYNGEOM 2000/2007/Registry 2019 studies and included in this analysis. Eligibility criteria were regular participation in outpatient after-care, one completed Multidimensional Fatigue Inventory-20 (MFI-20) questionnaire and complete medical records on criteria for hypothalamic syndrome. With univariable and multivariable linear regression, the relation of hypothalamic syndrome and levels of fatigue symptoms (MFI-20 sum score) were assessed. MFI-20 scores were compared to sex- and age-matched reference values from a German normative population using paired t-test. RESULTSData on 46 patients, with a median age of 20 years, was available for this analysis of which 28 (61%) patients presented with hypothalamic syndrome. After adjustment for age and sex, patients with hypothalamic syndrome reported higher scores in the physical (= 3.61 [95% CI: 1.38–5.85]), mental (= 2.80 [95% CI: 0.28–5.32]) and sum MFI-20 (= 12.02 [95% CI: 2.93–21.10]) domain than patients without hypothalamic syndrome. Compared to reference values from a general German population, all patients reported higher mean scores in each fatigue domain. Regardless of the level of daytime sleepiness in patients with hypothalamic syndrome, the reported fatigue scores were high. Daytime sleepiness did not correlate with fatigue. CONCLUSIONSFatigue symptoms are present in patients with CP. However, patients with hypothalamic syndrome are more affected in mental, physical and overall fatigue. It is crucial in clinical practice, to distinguish between sleep disorders and fatigue and to target patients with hypothalamic syndrome.

The optimal surgical approach for pediatric craniopharyngiomas (CPs) remains a matter of debate, with selection bias classically precluding a fair comparison of outcomes between the transcranial approach (TCA) and endoscopic endonasal approach (EEA). The purpose of this systematic review was to analyze the current role of EEA in the treatment of pediatric CPs and to determine whether, upon expansion of its indications, a comparison with TCA is valid. A systematic review of English-language articles published between February 2010 and June 2022 was performed to identify studies in the MEDLINE (PubMed) and Embase databases reporting on the resection of pediatric CPs. Included were articles reporting on pediatric CPs removed through TCA or EEA. Case reports, review articles, and earlier or less comprehensive series by the same center were excluded. Baseline characteristics and outcomes were analyzed. Prediction intervals (PIs), heterogeneity (Q, I2, and τ2 statistics), and publication bias (funnel plot analysis) were assessed. A total of 835 patients underwent TCA (18 articles) and 403 patients underwent EEA (19 articles). Preoperatively, the mean patient age (p = 0.055, PI = 5.05-15.11), visual impairment (p = 0.08, PI = 19.1-90.5, I2 = 80%), and hypothalamic syndrome (p = 0.17, PI = 6.5-52.2, I2 = 62%) did not significantly differ between the EEA and TCA groups. Endocrine deficit (anterior pituitary deficit [p < 0.001, PI = 16.5-92.9, I2 = 81%] and diabetes insipidus [p < 0.001, PI = 6.3-60.6, I2 = 43%]) was more frequent in the EEA group. Hydrocephalus and signs/symptoms of raised intracranial pressure were significantly higher (p < 0.001, PI = 5.2-73.3, I2 = 70% vs p < 0.001, PI = 4.6-73, I2 = 62%, respectively) in the TCA group. Recurrent lesions (p = 0.52, PI = 2.7-87.3, I2 = 13%), tumor size (p = 0.25, PI = 22.1-56.8), third ventricle involvement (p = 0.053, PI = 10.9-81.3, I2 = 69%), and hypothalamic involvement (p = 0.06, PI = 8.5-83.6, I2 = 79%) did not differ significantly between the approaches. EEA was preferred (p = 0.006, PI = 26.8-70.8, I2 = 40%) for sellar-suprasellar CPs, whereas TCA was preferred for purely suprasellar CPs (p = 0.007, PI = 13.5-81.1, I2 = 61%). There was no difference between the approaches for purely intrasellar lesions (p = 0.94, PI = 0-62.7, I2 = 26%). The breadth of PIs, I2 values, and analysis of publication bias showed substantial variability among the pooled data, hindering the possibility of outcome meta-analyses. With the adoption of extended approaches, the use of EEA became appropriate for a wider spectrum of pediatric CPs, with associated excellent outcomes. Although a fair comparison between outcomes in the EEA and TCA groups was hindered because of the differences in patient populations and tumor subtypes, given the increased versatility of EEA and improved expertise in its use, surgeons can now select the optimal surgical approach based on the unique benefits and drawbacks of each pediatric CP.

Adult-onset craniopharyngiomas (CPs) often present after diagnostic delays, yet the prognostic relevance of duration of history (DOH) and specific clinical manifestations remains unexplored. Data of patients aged > 18 years at CP diagnosis between June 2012 and October 2024 at the First Affiliated Hospital of Nanchang University were retrospectively reviewed. Associations between DOH, specific symptoms, and tumor characteristics at diagnosis, as well as long-term outcomes, were systematically analyzed. Among 151 patients (median follow-up, 71 months) in our cohort, the median DOH was 5 months and showed no significant correlation with tumor volume at diagnosis, hypothalamic involvement, extent of resection, or long-term prognosis including mortality, recurrence, and hypothalamic syndrome at last visit. Patients with amenorrhea/sexual dysfunction in history demonstrated significantly longer DOH (p < 0.001), while those with neurological deficits (p = 0.043) or hydrocephalus (p = 0.044) were associated with shorter DOH. Neurological deficits in history was associated with larger tumor volume at diagnosis (p = 0.016). Headache presented as the first symptom was linked to significantly shorter DOH (p = 0.003) and neurological deficits as the first symptom was associated with worse progression-free survival (p = 0.047). Diagnostic delays are common in adult-onset CP patients but appear unrelated to tumor burden or long-term prognosis. Neurological deficits in history or as the first symptom should trigger prompt diagnostic workup and more rigorous follow-up, while prolonged diagnostic delays in those with endocrine symptoms underscore the need for heightened awareness among clinicians to expedite referral and diagnosis.

Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m2; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework.

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. 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. 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. 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.

Infundibulo-tuberal syndrome groups endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and adjacent basal hypothalamus (tuber cinereum). It was originally described by Henri Claude and Jean Lhermitte in 1917, in a patient with a craniopharyngioma. This study investigates the clinical, pathological and surgical evidence verifying the infundibulo-tuberal syndrome caused by craniopharyngiomas (CPs). A systematic retrospective review of craniopharyngiomas reported in French literature between 1705 and 1973 was conducted. A total of 128 well described reports providing a comprehensive clinical and pathological description of the tumors were selected. This series represents the historical French cohort of CPs reported in the pre-CT/MRI era. Three major syndromes caused by CPs were categorized: pituitary syndrome (35%), infundibulo-tuberal syndrome (52%) and hypothalamic syndrome (49%). CP topography was significantly related to the type of syndrome described (p < 0.001). Infundibulo-tuberal syndrome occurred in CPs which replaced or invaded the third ventricle floor. In contrast, the majority of sellar/suprasellar CPs growing below the third ventricle showed a pituitary syndrome (82%). Cases with hypothalamic syndrome were characterized by anatomical integrity of the pituitary gland and stalk (p = 0.033) and occurred predominantly in adults older than 41 years old (p < 0.005). Among infundibulo-tuberal symptoms, abnormal somnolence was not related with the presence of hydrocephalus. All squamous-papillary CPs presented psychiatric disturbances (p < 0.001). This historical CP cohort evidences a clinical-topographical correlation between the patient's type of syndrome and the anatomical structures involved by the tumor along the hypophysial-hypothalamic axis.

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 (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.

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. 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. 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. 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.

ObjectiveQuality of life (QoL) is frequently impaired in childhood-onset craniopharyngioma (CP) by hypothalamic syndrome. The debate, whether pretreatment hypothalamic involvement (HI) has apriori prognostic impact or surgical hypothalamic lesions (HL) determine outcome, is controversial.DesignSurvival and outcome of CPs recruited between 2007 and 2014 in KRANIOPHARYNGEOM 2007 were analyzed with regard to reference-confirmed presurgical HI and surgical HL.MethodsRadiological findings, BMI and QoL were assessed at diagnosis and during follow-up. QoL was assessed using Pediatric Quality of Life (PEDQOL) questionnaire.ResultsOne hundred sixty-nine CPs were included presenting with no HI (n = 11), anterior (n = 49) and anterior + posterior (a + p) HI (n = 109) prior to surgery. The latter 109 were analyzed for postoperative HL (no lesion: n = 23, anterior HL: n = 29, a + pHL: n = 57). Progression-free survival (PFS) was higher after complete resection. The highest PFS was observed in CP with a + pHL, especially when compared between non-irradiated subgroups (P = 0.006). Overall survival (OS) rates were 1.0 in all subgroups. CP with a + pHL developed higher BMI (P ≤ 0.001) during follow-up compared between subgroups. 55/109 pts with a + pHI completed PEDQOL at diagnosis (48/109 at 3 years follow-up). QoL was worse for a + pHL patients in terms of physical, social and emotional functionality when compared with the anterior HL and no HL subgroup. BMI development and QoL during follow-up were similar for patients with anterior HL and without HL.ConclusionsPosterior hypothalamus-sparing surgical strategies are associated with higher QoL, decreased development of obesity and lower PFS in CP.

Background: Quality of survival (QoS) is frequently impaired in childhood-onset craniopharyngioma (CP) patients by hypothalamic syndrome. The debate, whether pretreatment hypothalamic involvement (HI) has apriori prognostic impact or treatment-related hypothalamic lesions (HL) determine outcome, is controversial. Methods: In cross-sectional prospective study, survival and outcome of 109 CPs recruited 2007-2014 in KRANIOPHARYNGEOM 2007 with reference-confirmed presurgical, anterior and posterior HI were analyzed with regard to surgical HL (no, anterior or anterior and posterior HL). Body mass index (BMI), QoS assessed by PEDQOL, and functional capacity (FMH) were measured at diagnosis, during follow-up, and at last visit (median follow-up: 6 years). Results: Surgical HL were reference-confirmed in 86 of 109 (79%) CP (29 anterior, 57 anterior and posterior HL). PFS and BMI at diagnosis were similar in CP subgroups with different degree of HL. CP with anterior and posterior HL presented with higher BMI at one-year follow-up (median BMI: +5.21 SD) and at last visit (BMI: +5.74 SD), when compared to patients without HL (BMI, one year: +1.72 SD, p=0.001; last visit BMI: +2.27 SD, p<0.001) and when compared to patients with anterior HL (BMI, 1 year: +2.46 SD, p=0.002; last visit: +2.87 SD, p=0.001). QoS improved during follow-up in CP without HL for physical functionality (p=0.047), emotional stability (p=0.040), and social functionality (p=0.002) when compared to CP with anterior and posterior HL. Functional capacity was not associated with degree of HL. Conclusions: Based on appropriate preoperative staging, posterior hypothalamus-sparing surgical strategies do not increase risk for relapse/progression, improve QoS and ameliorate development of obesity in CP at risk for obesity due to presurgical anterior and posterior HI.

Hypothalamic syndrome (HS) is a rare disorder caused by disease-related and/or treatment-related injury to the hypothalamus, most commonly associated with rare, non-cancerous parasellar masses, such as craniopharyngiomas, germ cell tumours, gliomas, cysts of Rathke's pouch and Langerhans cell histiocytosis, as well as with genetic neurodevelopmental syndromes, such as Prader-Willi syndrome and septo-optic dysplasia. HS is characterized by intractable weight gain associated with severe morbid obesity, multiple endocrine abnormalities and memory impairment, attention deficit and reduced impulse control as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition but treatments for general obesity are often used in patients with HS, including surgery, medication and counselling. However, these are mostly ineffective and no medications that are specifically approved for the treatment of HS are available. Specific challenges in HS are because the syndrome represents an adverse effect of different diseases, and that diagnostic criteria, aetiology, pathogenesis and management of HS are not completely defined.

Many patients treated for craniopharyngioma (CP) complain of a relative incapacity for physical activity. Whether this is due to an objective decrease in adaptation to exercise is unclear. We assessed exercise tolerance in children with surgically treated CP and appropriate pituitary hormone replacement therapy compared with healthy controls and we examined the potential relationships with hypothalamic involvement, GH replacement, and the catecholamine deficiency frequently observed in these subjects. Seventeen subjects (12 males and five females) with CP and 22 healthy controls (14 males and eight females) aged 15.3±2.5 years (7.3-18 years) underwent a standardized cycle ergometer test. Maximum aerobic capacity was expressed as the ratio of VO(2max) to fat-free mass (VO(2max)/FFM), a measure independent of age and fat mass in children. VO(2max)/FFM was 20% lower in children with CP compared with controls (P<0.05), even after adjustment for gender. Children with hypothalamic involvement (n=10) had a higher percentage of fat mass (P<0.05) than those without hypothalamic involvement (n=7) and lower VO(2max)/FFM (P<0.05), whereas children without hypothalamic involvement had VO(2max)/FFM close to that of controls (P>0.05). GH treatment was associated with a significant positive effect on aerobic capacity (P<0.05) only in the absence of hypothalamic involvement. No relationship was found between exercise capacity parameters and daily urine epinephrine excretion or epinephrine peak response to insulin-induced hypoglycemia. Children with CP have a decrease in aerobic capacity mainly related to hypothalamic involvement. The hypothalamic factors altering aerobic capacity remain to be determined.