Novel clinical algorithm for hypothalamic obesity in youth with brain tumours and factors associated with excess weight gain.

BACKGROUND: A standardized approach for identifying and treating hypothalamic obesity (HO) in children with hypothalamic tumours is lacking. OBJECTIVES: To describe children with hypothalamic tumours at risk for obesity, assess outcomes of a novel HO clinical algorithm, and identify factors associated with weight gain. METHODS: Retrospective analysis of youth with hypothalamic and suprasellar tumours, seen at a paediatric tertiary care centre from 2010 to 2020. RESULTS: The study cohort (n = 130, 50% female, median age at diagnosis 5 [range 0-17]y) had a median duration of follow up of 5 (0.03-17)y. At last recorded body mass index (BMI) measurement, 34% had obesity, including 17% with severe obesity. Median onset of overweight and obesity after diagnosis was 6.2 (0.3-134) and 8.9 (0.7-65) months, respectively. After algorithm implementation (n = 13), the proportion that had an early dietitian visit (within 6 months) increased from 36% to 54%, (p = 0.498) and weight management referrals increased from 51% to 83% (p = 0.286). Higher BMI z-score at diagnosis was associated with overweight and obesity development (p < 0.001). CONCLUSION: Patients with hypothalamic tumours commonly develop obesity. Use of a clinical algorithm may expedite recognition of HO. Further research is needed to identify predictors of weight gain and to develop effective treatment.

Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report.

BACKGROUND: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. CASE PRESENTATION: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. CONCLUSIONS: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.

Generalizability of "GWAS Hits" in Clinical Populations: Lessons from Childhood Cancer Survivors.

With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.70, p = 6.2 × 10-8). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (n = 4,212; observed-to-expected replication ratio = 0.55, p = 5.6 × 10-15). Finally, in direct comparisons of survivor samples against independent equivalently powered general population samples from the UK Biobank, we consistently observed lower meta-GWAS hit replication rates and poorer polygenic risk score predictive performance in survivor samples for multiple phenotypes. As a possible explanation, we found that meta-GWAS hits were less likely to be replicated in survivors who had been exposed to cancer therapies that are associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

Metástasis hipofisarias de tumores sólidos: 2 casos de diferente presentación / Pituitary metastasis of solid tumors: 2 cases of different presentation

No disponible

Hypothalamic-pituitary function following childhood brain tumors: Analysis of prospective annual endocrine screening.

BACKGROUND: Outcomes for childhood brain tumors are now associated with a five-year survival rate of 75%. Endocrine effects of brain tumors are common, occurring in 43% of patients by 10 years from tumor diagnosis. Optimal timing of screening for endocrinopathies remains undefined. We aim to identify incidence and timing of endocrinopathies following brain tumor diagnosis, to better refine screening guidelines. METHODS: Retrospective chart review of patients referred to our hospital's neuro-oncology clinic for evaluation and treatment of brain tumors. Inclusion criteria were a positive history for brain tumor diagnosis and evaluation at our center. Data collection included demographics, tumor diagnosis, tumor therapy, and endocrinopathy diagnosis and timing. Laboratory data and clinical documentation were reviewed. RESULTS: Four hundred nineteen subjects were included for analysis. Tumor locations included supratentorial 158 (38%), posterior fossa 145 (35%), suprasellar 96 (23%), and upper spinal cord 20 (5%). Only 61% had undergone endocrine screening. Forty-five percent of screened patients had endocrinopathies. Endocrinopathy diagnosis typically occurred within six years after tumor diagnosis. Tumor recurrence and repeated therapies increased the risk for endocrinopathies within the subsequent six years after tumor therapy. Higher rates of endocrinopathies were identified in patients who had received cranial irradiation for posterior fossa, supratentorial, or suprasellar tumors. CONCLUSION: Endocrine screening should occur in childhood brain tumor survivors, particularly those who have received irradiation. Our study suggests that in children with brain tumors, the highest yield for finding a pituitary deficiency is within the first six years after tumor diagnosis and treatment. Screening should continue annually beyond six years, but with special attention in the subsequent six years after therapy for tumor recurrence. Prospective screening and endocrinology referral should be implemented in childhood brain tumor survivors.

Progression of pituitary tumours: impact of GH secretory status and long-term GH replacement therapy.

BACKGROUND: Most patients treated for hypothalamic-pituitary tumours develop GH deficiency. Long-term GH replacement treatment in adults with a previous history of hypothalamic-pituitary tumour could represent a concern about increasing the risk of tumour enlargement or recurrence. PURPOSE: To assess the progression risk of hypothalamic-pituitary tumours according to the GH secretory status (normal GH secretion, non-treated and treated GH deficiency). and determine the predictors of neoplasm recurrence. METHODS: We retrospectively reviewed 309 patients with tumours of the hypothalamic-pituitary region (294 subjects underwent neurosurgery while 81 radiotherapy) who were followed for 9.9 ± 8.3 years. RESULTS: Out of 309 patients, 200 were affected by severe GH deficiency; 90 of these underwent GH therapy. The tumour progression rate did not differ among GH-sufficient, not-treated and treated GH-deficient patients (16.5%, 16.4%. and 10.0%, respectively). In a multivariate analysis, previous radiotherapy (HR 0.12, CI 0.03-0.52, p < 0.005) and residual tumour (HR 8.20, CI 2.38-28.29, p < 0.001) were independent predictors of recurrence. After controlling for multiple covariates, the tumour recurrence risk in GH-sufficient and GH-treated patients was similar to that observed in not-treated GH-deficient patients. CONCLUSIONS: With limitations of retrospective analysis, GH therapy is not associated with an increased progression rate of tumours of the hypotalamic-pituitary region during long follow-up, thus supporting the long-term safety of GH treatment. The only predictors of tumour recurrence appear to be the presence of residual disease and the lack of radiotherapy.

Glioma del quiasma óptico en niños: complicaciones endocrinológicas en 14 casos / Optic chiasm glioma in children: Endocrine disorders in 14 cases

Fundamento y objetivos: Describir la frecuencia de endocrinopatías en niños con glioma del quiasma óptico y analizar los factores relacionados. Pacientes y métodos: Revisión de historias recogiendo las variables sexo, edad, antecedente de neurofibromatosis, forma de presentación, tratamiento del tumor y presencia de endocrinopatías. Pruebas estadísticas: Wilcoxon y Fisher. Resultados: Catorce pacientes (6 mujeres) con edad al diagnóstico de 0,5 a 7,0 años (media ± desviación típica: 2,97 ± 2,32) y tiempo de seguimiento de 10,64 ± 3,30 años (rango 6,0-16,0). Doce de 14 presentaban endocrinopatía al final del seguimiento: 8 pubertad precoz, 5 hipopituitarismo y 5 obesidad. La aparición de déficits se relacionó con la clínica neurooftalmológica antes de los 5 años de edad (p = 0,02) y con el requerimiento de tratamiento de la lesión (p = 0,03). Conclusiones: Los niños con gliomas del quiasma óptico pueden presentar endocrinopatías desde el momento del diagnóstico del tumor y, sobre todo, a lo largo de su evolución. La más frecuente es la pubertad precoz. Los déficits hipofisarios se relacionan con los tumores más agresivos (aquellos que debutan con clínica neurooftalmológica antes de los 5 años de edad y que requieren tratamiento) (AU)

Background and objectives: To describe the frequency of endocrine disorders in children with optic chiasm glioma and analyze related factors. Patients and methods: Review of medical records by collecting sex, age, history of neurofibromatosis, clinical presentation, treatment of tumour, and presence of endocrine abnormalities. Statistical tests Wilcoxon and Fisher. Results: 14 patients (6 female) with age at diagnosis of 0.5 to 7.0 years (mean ± standard deviation: 2.97 ± 2.32) and follow-up of 10.64 ± 3.30 years (range 6.0 to 16.0). 12/14 presented endocrinopathy at follow-up: 8 precocious puberty, 5 hypopituitarism, and 5 obesity. The onset of deficits was related to the neuroophthalmological symptoms under the age of five (P = .02)and treatment of the tumour was required.(P = .03). Conclusions: Children with optic chiasm gliomas may present endocrine disorders from the time of diagnosis of the tumor and, in particular as they develop on. The most common of these is precocious puberty. Pituitary deficits are associated with more aggressive tumours (those presenting with neuroophthalmological signs and symptoms before the age of five and requiring treatment) (AU)

Neuroendoscopic Intraventricular Biopsy in Children with Small Ventricles Using Frameless VarioGuide System.

Endoscopic biopsy for intraventricular tumors in pediatric patients with small ventricles is a challenging procedure because of the risk of morbidity during the intraventricular approach. We describe the use of the VarioGuide system for intraventricular endoscopic biopsy in 9 consecutive pediatric patients with intraventricular lesions and small ventricular size. All patients had lesions in the anterior part of the third ventricle with a median frontal and occipital horn ratio of 0.33. Patients presented with growth failure (n = 4), visual disturbances (n = 4), and seizures (n = 1). The VarioGuide system consists of an ergonomic arm with 3 joints for gross adjustment. The 3 rotational joints on the distal side of the system are adjusted according to the angles of the planned trajectory. The endoscope is adjusted to the distal side of the VarioGuide and inserted through the ring, previously set for the diameter of the endoscope and for the planned trajectory. The accuracy of the trajectory and correct ventricular cannulation are confirmed under endoscopic guidance. The biopsy is carried out according to the standard technique. In all cases, the biopsy sample provided the definitive diagnosis. Diagnoses included germinomas in 4 patients, hamartoma in 1 patient, hypothalamic astrocytoma in 2 patients, and craniopharyngioma in 2 patients. The use of the VarioGuide system for intraventricular endoscopic biopsy is highly recommended for pediatric patients with small ventricle size. This technique may help minimize the risk of unnecessary brain damage during the entrance to small ventricles.

Paraneoplastic limbic encephalitis with associated hypothalamitis mimicking a hyperdense hypothalamic tumor: a case report.

BACKGROUND: Paraneoplastic limbic encephalitis is an uncommon association of common malignancies such as small cell lung carcinoma, testicular teratoma, and breast carcinoma. The nonspecific nature of the clinical presentation, lack of freely available diagnostic markers, and requirement for advanced imaging techniques pose a great challenge in the diagnosis of this disease in resource-poor settings. CARE PRESENTATION: A 64-year-old previously healthy Sri Lankan man was admitted to the general medical unit with subacute memory impairment regarding recent events that had occurred during the previous 3 weeks. Initial noncontrast computed tomography of the brain revealed a hyperdensity in the hypothalamic region surrounded by hypodensities extending toward the bilateral temporal lobes; these findings were consistent with a possible hypothalamic tumor with perilesional edema. The patient later developed cranial diabetes insipidus, which was further suggestive of hypothalamic disease. Interestingly, gadolinium-enhanced magnetic resonance imaging of the brain showed no such lesions; instead, it showed prominent T2-weighted signals in the inner mesial region, characteristic of encephalitis. The possibility of tuberculosis and viral encephalitis was excluded based on cerebrospinal fluid analysis results. Limbic encephalitis with predominant hypothalamitis was suspected based on the radiological pattern. Subsequent screening for underlying malignancy revealed a mass lesion in the right hilum on chest radiographs. Histological examination of the lesion showed small cell lung cancer of the "oat cell" variety. CONCLUSION: We suggest that the initial appearance of a hyperdensity in the hypothalamus region on noncontrast computed tomography is probably due to hyperemia caused by hypothalamitis. If hypothalamitis is predominant in a patient with paraneoplastic limbic encephalitis, magnetic resonance imaging will help to differentiate it from a hypothalamic secondary deposit. Limbic encephalitis should be considered in a patient with computed tomographic evidence of a central hyperdensity surrounded by bitemporal hypodensities. This pattern of identification will be useful for early diagnosis in resource-poor settings.

[Growing teratoma syndrome in a patient with intracranial germ cell tumor].

A six-year-old patient with non-germinomatous germ cell tumor of the chiasmatic-sellar area developed polyuria and polydipsia as the first symptoms of the disease. Then there were signs of precocious puberty and vision impairment. MRI examination revealed a shiasmatic sellar tumor and occlusive hydrocephalus. Tumor marker levels in blood serum were elevated. The alpha-fetoprotein level was increased 5-fold; human chorionic gonadotropin 20-fold. These levels increased over time. The patient received 2 cycles of PEI multiagent chemotherapy (Ifosfamide 1.5 g/m(2), Cisplatin 20 mg/m(2), Etoposide 100 mg/m(2)) during 5 days and 1 cycle of second-line multiagent chemotherapy (Cisplatin 100 mg/m(2) for 1 day and Endoxan 1500 mg/m(2) for 2 days). Despite the decrease in tumor marker levels to normal values, the patient's vision still deteriorated. MRI examination revealed that tumor size increased and its structure changed. Total tumor resection led to vision improvement and regression of intracranial hypertension. Histological analysis of tumor tissue only revealed a mature teratoma. This phenomenon, known as growing teratoma syndrome, is very rare among patients with intracranial non-germinomatous germ cell tumors.

An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

BACKGROUND: Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. CASE PRESENTATION: We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. CONCLUSIONS: Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

Rosette-forming glioneuronal tumor originating in the hypothalamus.

Rosette-forming glioneuronal tumors (RGNT) of the fourth ventricle are slow-growing tumors that primarily involve the fourth ventricular region. We here report the first patient, an 8-year-old girl, with an RGNT originating in the hypothalamus and manifesting with precocious puberty. After partial removal, the remaining tumor showed rapid enlargement, and the pathologic diagnosis at the second surgery revealed histopathologic features similar to those found in the initial samples, including biphasic patterns of neurocytic rosettes and GFAP-stained astrocytic components. These tumor cells had mildly atypical nuclei; however, mitotic figures and necrosis were absent. Eosinophilic granular bodies and a glomeruloid vasculature were found, but Rosenthal fibers were absent. The Ki-67 proliferative index was 3.5 % (vs 1.1 % at the initial surgery). No recurrence was recorded during the 3-year period after the proton radiotherapy.

Formas de presentación clínica del hamartoma hipotalámico / Forms of clinical presentation of hypothalamic hamartoma

No disponible

A rare case of multicystic disseminated astrocytoma with pilomyxoid characteristics in a 4-year-old child.

Pilomyxoid astrocytomas are a more aggressive variant of pilocytic astrocytoma. Over the last 14 years, there has been increasing evidence to suggest that these tumours are distinct pathological entities to pilocytic astrocytomas. Radiological features of these tumours are slowly emerging in the neuroradiological literature. We report a unique radiological appearance of a multicystic, disseminated astrocytoma with pilomyxoid characteristics presenting in a 4-year-old boy and highlight the importance of considering this diagnosis with similar imaging.

Endocrine dysfunction in Taiwanese children with human chorionic gonadotropin-secreting germ cell tumors.

BACKGROUND/PURPOSE: Human chorionic gonadotropin (HCG)-secreting germ cell tumors (GCTs) are rare childhood malignancies with unique clinical manifestations but delayed diagnosis is common. The purpose of this study is to investigate the clinical manifestations and endocrine dysfunction of Taiwanese children with HCG-secreting GCTs. METHODS: From 1991 to 2011, 24 children (19 boys and five girls) with HCG-secreting GCTs were evaluated for their clinical findings and endocrine functions. RESULTS: The mean age at diagnosis of the study patients was 10.8 ± 3.1 years. Of the 24 patients, 20 had central nervous system (CNS) GCTs and four had primary mediastinal GCTs (PMGCTs). The most common pathologic findings were germinomas and mixed type GCTs. The common initial symptoms and signs included polyuria, polydipsia, rapid growth, neurologic deficit,sexual precocity, and growth retardation. There was a delay in diagnosis in about 60% of patients. Diabetes insipidus and hypopituitarism were common endocrine dysfunctions in patients with CNSGCTs. Twelve boys had gonadotropin-independent puberty upon diagnosis, which were related to their high serum ß-hCG levels. None of the five girls had this disorder despite their high serum ß-hCG levels. Three of the four PMGCTs patients had the classic form of Klinefelter syndrome. CONCLUSION: Taiwanese children with HCG-secreting GCTs often have clinical manifestations related to endocrine dysfunction. High index of suspicion is important to avoid delayed diagnosis in these children.