Neurogenic myocardial dysfunction post craniopharyngioma resection: A diagnostic dilemma.

Endoscopic transsphenoidal resection of craniopharyngioma is a commonly used technique. Cerebral vasospasm may occur in nearly 10% of cases leading to adverse neurological outcomes. Cardiopulmonary dysfunction may be seen in patients with severe vasospasm. The literature describing the occurrence of neurogenic stunned myocardium following craniopharyngioma resection in pediatric patients is very sparse. Here, we describe such a case managed with a combination of milrinone (to relieve vasospasm and improve cardiac pump function), noradrenaline (to obtain target blood pressure), and vasopressin (to control urine output). This case report proposes the treatment plan of neurogenic stunned myocardium following vasospasm in pediatric patients.

Craniopharyngioma, Chronotypes and Metabolic Risk Profile.

AIM: To investigate the potential association among Craniopharyngioma (CP), chronotypes and metabolic risk profile. SUBJECTS AND METHODS: The study population included 28 patients (46.4% males; 42.6 ± 15.8 years) and 28 controls, age, gender and BMI matched (46.4% males; 46.5 ± 12.9 years). In this study sample, we evaluated: anthropometric measurements (waist circumference, WC; BMI), plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure. Morningness-Eveningness was measured with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ), which included 19 questions about preferred sleep time and daily performance. RESULTS: in both patients and controls grade I obesity was detected in 15 subjects (53.6%), grade II obesity in 13 subjects (46.4%). In the patient group, the mean score of chronotype was 47.8 ± 12.6. In particular, 9 patients (32.1%) exhibited the morning chronotype, 6 (21.4%) the intermediate chronotype and 13 (46.4.%) the evening chronotype. No significant difference was found in gender and age among the chronotype categories. Patients with the evening chronotype had higher blood pressure values and worse metabolic parameters than those with the morning chronotype. In the control group, the mean score of the chronotype was 57.6 ± 9.5. In particular, 16 (57.1%) subjects exhibited the morning chronotype, 10 (35.7%) the intermediate chronotype and only 2 (7.1.%) the evening chronotype. The prevalence of intermediate and evening chronotypes was higher in females than males (p = 0.021), while males have a higher prevalence of the morning chronotype. Subjects with intermediate and evening chronotypes had worse metabolic parameters than those with the morning chronotype. In patients, the chronotype score was inversely correlated to WC, BMI, SBP, DBP, plasma glucose, total cholesterol, triglycerides, LDL cholesterol and positively correlated with HDL cholesterol. No correlation was found between age and chronotype. In controls, the chronotype score was inversely correlated to WC, BMI, plasma glucose, total cholesterol, LDL cholesterol. No correlation was found among chronotype and age, blood pressure, triglycerides, HDL cholesterol. Considering the whole population of the study (patients and controls), at logistic regression the chronotype score was significantly associated with the presence of CP. CONCLUSIONS: for the first time thus far, our study puts the light on the association of the CP with chronotypes and metabolic alterations in this disease, which are the main determinants of the reduced quality of life, higher morbidity and mortality in this setting of patients. This finding suggests that alterations of chronotype might represent an adjunctive risk for CP patients and a possible target for their integrate management.

Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis.

BACKGROUND: The incidence of growth hormone deficiency (GHD) in adamantinomatous craniopharyngioma (aCP) is significantly higher than in other sellar region tumors, but the possible mechanism is still elusive. A high level of inflammatory responses is another feature of aCP. We investigated the internal connection between interleukin-1α (IL-1α) and GHD, while focusing on its biological activities in pituitary fibrosis. MATERIALS AND METHODS: To diagnosis of GHD, the Body Mass Index (BMI), Insulin Like Growth Factor-1(IGF-1) and peak growth hormone (GH) values after insulin stimulation test of 15 aCP patients were recorded. Histological staining was performed on the aCP samples. Levels of 9 proinflammatory cytokines in tumor tissue and cell supernatant were detected using Millipore bead arrays. The effect of IL-1α on GH secretion was evaluated in vivo and in vitro. Western blot, qRT-PCR and cell functional assays were used to explore the potential mechanism through which IL-1α acts on GH secretion. The stereotactic ALZET osmotic pump technique was used to simulate aCP secretion of proinflammatory cytokines in rats. Recombinant IL-1α (rrIL-1α) and conditioned media (CM) prepared from the supernatant of aCP cells was infused directly into the intra-sellar at a rate of 1 µl/h over 28 days, and then the effects of IL-1α treatment on pathological changes of pituitary gland and GH secretion were measured. To further confirm whether IL-1α affects GH secretion through IL-1R1, an IL-1R1 blocker (IL-1R1a, 10 mg/kg body weight, once daily) was administered subcutaneously from the first day until day 28. RESULTS: There was a significant positive correlation between pituitary fibrosis and GHD (rS = 0.756, P = 0.001). A number of cytokines, in particular IL-1α, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), were elevated in tumor tissue and cell supernatant. Only IL-1α showed a significant difference between the GHD group and the No-GHD group (P < 0.001, F = 6.251 in tumor tissue; P = 0.003, F = 1.529 in cell supernatant). IL-1α significantly reduced GH secretion in coculture of GH3 and pericytes. The activation of pericytes induced by IL-1α was mediated by the IL-1R1 signaling pathway. In vivo, IL-1α induces pituitary fibrosis, further leading to a decreased level of GH. This pathological change was antagonized by IL-1R1a. CONCLUSION: This study found that the cross talk between aCP cells and stroma cells in the pituitary, i.e. pericytes, is an essential factor in the formation of GHD, and we propose that neutralization of IL-1α signaling might be a potential therapy for GHD in aCP.

Origin of craniopharyngiomas: implications for growth pattern, clinical characteristics, and outcomes of tumor recurrence.

OBJECT Craniopharyngiomas are associated with a high rate of recurrence. The surgical management of recurrent lesions has been among the most challenging neurosurgical procedures because of the craniopharyngioma's complex topographical relationship with surrounding structures. The aim of this study was to define the determinative role of the site of origin on the growth pattern and clinical features of recurrent craniopharyngiomas. METHODS The authors performed a retrospective analysis of 52 patients who had undergone uniform treatment by a single surgeon. For each patient, data concerning symptoms and signs, imaging features, hypothalamic-pituitary function, and recurrence-free survival rate were collected. RESULTS For children, delayed puberty was more frequent in the group with Type I (infradiaphragmatic) craniopharyngioma than in the group with Type TS (tuberoinfundibular and suprasellar extraventricular) lesions (p < 0.05). For adults, blindness was more frequent in the Type I group than in the Type TS group (p < 0.05). Nausea or vomiting, delayed puberty, and growth retardation were more frequent in children than in adults (p < 0.05). Overall clinical outcome was good in 48.07% of the patients and poor in 51.92%. Patients with Type TS recurrent tumors had significantly worse functional outcomes and hypothalamic function than patients with the Type I recurrent tumors but better pituitary function especially in children. CONCLUSIONS The origin of recurrent craniopharyngiomas significantly affected the symptoms, signs, functional outcomes, and hypothalamic-pituitary functions of patients undergoing repeated surgery. Differences in tumor growth patterns and site of origin should be considered when one is comparing outcomes and survival across treatment paradigms in patients with recurrent craniopharyngiomas.

[Craniopharyngiomas: progress in pathogenesis and therapeutics]. / Craniopharyngiomes: progrès en pathogénie et thérapeutique.

This review focuses on new aspects in craniopharyngiomas with emphasis on pathogenic mechanisms and treatment strategies that were presented at the joined Endocrine Society/International Society of Endocrinology meeting in Chicago in June 2014. Craniopharyngiomas are benign epithelial tumors arising from the pituitary stalk or gland. Two subtypes could be distinguished: an adamatinomatous form that is more common in children, and a papillary form that is observed almost exclusively in adults. Besides these histological differences, these two variants differ in some molecular features that have been recently identified and could have important therapeutic implications. Despite its histologically benign nature, the morbidities related to the tumor itself or its treatment raise many concerns and excess mortality rates up to nine times higher than in the general population has been reported. Among the potential sequelae of craniopharyngiomas, obesity seems the most frequent. The difficulty in the management of this obesity lies in its complex underlying pathophysiological mechanisms. Complete resection of localized tumors should be attempted while a limited hypothalamus-sparing surgery followed or not by radiotherapy should be adopted in tumors involving the hypothalamus. A multidisciplinary approach including, in particular, a dedicated neurosurgeon, and a therapeutic strategy tailored to the individual presentation of the craniopharyngioma in any patient should be initiated at diagnosis for improving the prognosis of these tumors.

[Biology of the craniopharyngioma].

In the recent years a considerable number of different studies devoted to craniopharyngioma morphology were performed. There are more than 35 factors known up to date that could be related to the craniopharyngioma growth (Ki-67, p53, beta-catenin, p63, Retinoid acid receptors, Galectin-3, MIF, MVD, CK et al.). Despite the such a variety of factors, none of them, except for the Ki-67, strongly correlates with the risk of tumour recurrence and none can be associated with a particular tumour type. Most studies, by the way, focused on a very small number of factors and were performed in relatively small groups of patients. Most publications are devoted to the Ki-67, beta-catenin and p53 studies, and the highest number of patients enrolled to the study was 67. This survey made an attempt to review the literature on the craniopharyngioma biology and to identify further areas of research to obtain data that could affect the choice of treatment and outcome in this complex disease.

Pathology and pathogenesis of craniopharyngiomas.

Craniopharyngiomas are benign but locally invasive tumours of the sellar region that occur as two subtypes. The adamantinomatous type (aCP) occurs mainly during childhood while the papillary type (pCP) is found almost exclusively in adults. It is thought that aCPs arise from ectopic embryonic remnants of Rathke's pouch and these tumours share features with odontogenic tumours suggesting a common origin. The pathogenesis of pCPs is less understood but these tumours may arise from metaplastic transformation of anterior pituitary epithelial cells. Mutations in CTNNB1 that encodes ß-catenin are found in around 70 % of aCPs. These mutations stabilise ß-catenin, which evades destruction and accumulates in the nucleus and cytosol leading to constitutive activation of the Wnt signaling pathway. Expression of mutant ß-catenin early in mouse pituitary development promotes the formation of tumours similar to aCPs. However, accumulation of ß-catenin occurs only in small clusters of tumour cells even though the mutation is ubiquitous. These cell clusters are slow-growing and share some characteristics with pituitary stem cells. They are often present at the invading edge and express growth factors that may participate in paracrine signaling to surrounding cells. ß-Catenin nuclear translocation may also occur in the absence of CTNNB1 mutations, suggesting that other genetic or epigenetic events can activate Wnt signaling in aCP. These mechanisms, as well as those underlying the molecular pathogenesis of pCPs remain to be identified.

Coexistence of adamantinomatous and squamous-papillary type craniopharyngioma: case report and discussion of etiology and pathology.

Craniopharyngiomas are histopathologically classified as adamantinomatous type (AD) and squamous-papillary type (SP). However coexistence of a mixed type seen on histopathologic specimens has not been reported. In this report, a patient diagnosed with mixed type craniopharyngioma is presented and the etiology and pathologic features are discussed.

Rathke cleft cysts: a review of clinical and surgical management.

The aim of this paper is to provide a comprehensive review of clinical, imaging, and histopathological features, as well as operative and nonoperative management strategies in patients with Rathke cleft cysts (RCCs). A literature review was performed to identify previous articles that reported surgical and nonsurgical management of RCCs. Rathke cleft cysts are often incidental lesions found in the sellar and suprasellar regions and do not require surgical intervention in the majority of cases. In symptomatic RCCs, the typical clinical presentation includes headache, visual loss, and/or endocrine dysfunction. Visual field testing and endocrine laboratory studies may reveal more subtle deficiencies associated with RCCs. When indicated, the transsphenoidal approach typically offers the least invasive and safest method for treating these lesions. Various surgical strategies including cyst wall resection, intralesional alcohol injection, and sellar floor reconstruction are discussed. Although headache and visual symptoms frequently improve after surgical drainage of RCCs, hypopituitarism and diabetes insipidus are less likely to do so. A subset of more aggressive, atypical RCCs associated with pronounced clinical symptoms and higher recurrence rates is discussed, as well as the possible relationship of these lesions to craniopharyngiomas. Rathke cleft cysts are typically benign, asymptomatic lesions that can be monitored. In selected patients, transsphenoidal surgery provides excellent rates of improvement in clinical symptoms and long-term cyst resolution. Complete cyst wall resection, intraoperative alcohol cauterization, and sellar floor reconstruction in the absence of a CSF leak are not routinely recommended.

Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans.

Wingless (Wnt)/ß-catenin signaling plays an essential role during normal development, is a critical regulator of stem cells, and has been associated with cancer in many tissues. Here we demonstrate that genetic expression of a degradation-resistant mutant form of ß-catenin in early Rathke's pouch (RP) progenitors leads to pituitary hyperplasia and severe disruption of the pituitary-specific transcription factor 1-lineage differentiation resulting in extreme growth retardation and hypopituitarism. Mutant mice mostly die perinatally, but those that survive weaning develop lethal pituitary tumors, which closely resemble human adamantinomatous craniopharyngioma, an epithelial tumor associated with mutations in the human ß-catenin gene. The tumorigenic effect of mutant ß-catenin is observed only when expressed in undifferentiated RP progenitors, but tumors do not form when committed or differentiated cells are targeted to express this protein. Analysis of affected pituitaries indicates that expression of mutant ß-catenin leads to a significant increase in the total numbers of pituitary progenitor/stem cells as well as in their proliferation potential. Our findings provide insights into the role of the Wnt pathway in normal pituitary development and demonstrate a causative role for mutated ß-catenin in an undifferentiated RP progenitor in the genesis of murine and human craniopharyngioma.

Primary cerebellopontine angle craniopharyngioma in a patient with Gardner syndrome.

Craniopharyngiomas usually involve the sella and suprasellar space. Ectopic craniopharyngiomas have rarely been reported at the cerebellopontine angle (CPA). We report a rare primary craniopharyngioma of the CPA without extension into the sellar region. The lesion was initially detected by MRI during investigation of multiple scalp fibromas. Multiple osteomas of the skull and face were detected 2years later, and colonic adenomatous polyposis was detected 4years later; typical features of Gardner syndrome. This is the third report of a primary CPA craniopharyngioma in a patient with Gardner syndrome.

Panhypopituitarism apparently caused by hypophysitis masking a rapid development of a craniopharyngioma. A case report.

We report the case of a 39-year-old male presenting with panhypopituitarism and diabetes insipidus. MR imaging showed focal thickening of the pituitary infundibulum and infiltration of the anterior pituitary lobe, suggesting hypophysitis. Hormonal replacement therapy induced a pronounced amelioration of general well-being. Eight months later the subject developed visual disturbances. MR imaging now showed a cystic sellar mass. Surgical drainage was performed. A second operation was necessary six weeks Later because of recurrent visual field defects. Diagnosis of papillary craniopharyngioma was finally made. This case demonstrates the remarkably rapid development of a craniopharyngioma, which initial radiological appearance was suggestive of hypophysitis. It also emphasizes the need of repeat MR examination in case of unusual presentation of hypopituitarism.

Ciliated craniopharyngioma--case report and pathological study.

BACKGROUND: Craniopharyngioma has two subtypes: adamantinomatous and squamous-papillary. Squamous-papillary craniopharyngioma may develop from remnants of the craniopharyngeal duct, anterior pituitary cells with squamous metaplasia, suprasellar epidermoid cyst, or Rathke cleft cyst. AIM: While ciliated craniopharyngioma is considered to represent a transitional stage between Rathke cleft cyst and squamous-papillary craniopharyngioma, ciliated craniopharyngioma following Rathke cleft cyst at the same site has not previously been described. RESULTS: We report a case of ciliated craniopharyngioma developing from Rathke cleft cyst. CONCLUSION: The clinical course for this case is discussed together with a review of the pathological literature for ciliated craniopharyngioma.

Non-adenomatous pituitary tumours.

Apart from pituitary adenomas, a number of tumours may arise from within the sella presenting a diagnostic and therapeutic challenge at a multidisciplinary specialist level. This article focus on the most commonly diagnosed non-adenomatous pituitary tumours (craniopharyngiomas, Rathke's cleft cysts and meningiomas) and provides data on their pathogenesis, diagnosis and treatment.

Pubertad precoz completa isosexual: hallazgos clínicos, de laboratorio y ecografía pélvica / Complete isosexual precocious puberty: clinical, pelvic ultrasound and laboratory features

Objetivo: El objetivo de este estudio ha sido determinar si la forma de presentación inicial de la pubertad precoz central (PPC) varía en relación con la etiología y permite el diagnóstico diferencial entre formas idiopáticas y orgánicas (neurogénicas), lo que haría innecesarias las pruebas de imagen del sistema nervioso central (SNC) en determinados pacientes. Pacientes y métodos: Los niños con PPC evaluados fueron incluidos de forma consecutiva en un estudio prospectivo observacional. Se recogieron los hallazgos clínicos, de laboratorio y ecográficos. Se compararon los hallazgos de PPC idiopática (3 niños y 49 niñas) y orgánica (2 niños y 8 niñas). Resultados: No hubo diferencias en cuanto al estadio puberal, edad de inicio puberal (7,0 [5,8-7,5] frente a 7,3 [5,1-8,3] años), cociente edad ósea/edad cronológica (1,26 [1,2-1,3] frente a 1,23 [1,1-1,3]) y menarquia materna (11,7 ± 0,2 frente a 11,7 ± 0,6 años) entre PPC idiopática y orgánica, respectivamente. Los pacientes con PPC orgánica presentaron una menor desviación estándar (DE) de la talla (0,35 ± 0,4 frente a 1,6 ± 0,1; p < 0,01), predicción de talla adulta y DE de la velocidad de crecimiento (0,8 ± 0,9 frente a 3,7 ± 0,7). Las niñas con PPC orgánica presentaban de forma significativa unas mayores concentraciones plasmáticas de estradiol (47,5 [25-68] frente a 27 [14-43] pg/ml) que las niñas con PPC idiopática. La ecografía pélvica realizada en el momento del diagnóstico reveló la presencia de cambios puberales en genitales internos en el 43,9 % de las niñas (el 37,2 % en la subpoblación con PPC idiopática frente al 62,5 % en el grupo de PPC orgánica; p = 0,18). Conclusiones: Existe un solapamiento clínico-ecográfico entre PPC idiopática y orgánica. Las pruebas de imagen del SNC siguen siendo necesarias en todos los casos de PPC y los estudios ecográficos no pueden sustituir a otras investigaciones diagnósticas (AU)

Objective: To determine whether initial presentation varies according to aetiology, whether such differences allow differential diagnosis between idiopathic and organic forms, and whether CNS imaging can be avoided in some patients with central precocious puberty (CPP). Patients and methods: Children referred for evaluation of precocious puberty were evaluated, and the subpopulation of children with CPP was enrolled in this prospective observational study. Clinical, laboratory and ultrasound features of 62 consecutive patients with CPP (5 boys and 57 girls) were recorded. We compared the characteristics of idiopathic (3 boys, 49 girls) and organic (2 boys, 8 girls) CPP. Results: There were no differences in pubertal staging, age at puberty onset (7.0 [5.8-7.5] vs. 7.3 [5.1-8.3] years), bone age/chronological age ratio (1.26 [1.2-1.3] vs. 1.23 [1.1-1.3]), maternal menarche (11.7 ± 0.2 vs. 11.7 ± 0.6 years) between idiopathic and organic CPP, respectively. Organic CPP patients had a poorer height SD (0.35 ± 0.4 vs. 1.6 ± 0.1; p < 0.01), predicted adult height, growth rate and growth rate SD (0.8 ± 0.9 vs. 3.7 ± 0.7). Girls with organic CPP had significantly higher oestradiol levels (47.5 [25-68] vs. 27 [14-43] pg/ml) than girls with idiopathic CPP. Pelvic ultrasound at the time of diagnosis revealed the presence of pubertal changes in internal genitalia in 43.9 % of girls (37.2 % idiopathic versus 62.5 % organic CPP subpopulation; p=0.18). Conclusions: There is a clinical-ultrasound overlap between idiopathic and organic CPP. Imaging remains necessary in all cases of central precocious puberty, and ultrasound data should not be replaced by other diagnostic investigations (AU)

Craniopharyngioma: modern concepts in pathogenesis and treatment.

PURPOSE OF REVIEW: Craniopharyngioma is a benign tumour. Its tendency to recur after excision and the high surgical risk due to involvement of the most vital structures of the brain mean that alternatives to radical surgery should be considered, namely limited surgical procedures followed by radiotherapy. Since both options present inherent risks, optimal craniopharyngioma treatment remains controversial. This paper aims to critically review the recent literature on craniopharyngioma. RECENT FINDINGS: The management of children with craniopharyngioma has benefited from concerted efforts by national and international groups to improve outcome and reduce morbidity. From the current literature it is evident that there is a trend to better integrate all treatment modalities available, tailoring therapies to specific risk factors. Modern imaging and new surgical and radiotherapy techniques are increasing the possibility of cure. Biological markers are under investigation and this will increase our knowledge on craniopharyngioma. SUMMARY: Studies on treatment, biology and pathogenesis of craniopharyngioma, available in the current literature, grew considerably in the last year. Although a consensus has not been reached on all aspects of this complex disease, there is a trend in the field to move quickly towards a better understanding of the disease to improve treatment strategies and to produce clinical cooperative trials.