National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

Neuroendocrine Morbidity After Pediatric Optic Gliomas: A Longitudinal Analysis of 166 Children Over 30 Years.

CONTEXT: Fifty percent of pediatric low-grade gliomas affect the optic pathway, hypothalamus, and suprasellar areas (OP/HSGs), resulting in significant long-term neuroendocrinopathy. OBJECTIVE: This study aimed to dissect tumor- from treatment-related risk factors for OP/HSG-associated neuroendocrinopathy. DESIGN: This was a retrospective case notes analysis of 166 children with newly diagnosed OP/HSGs at our quaternary center between 1980 and 2010 by multivariate Cox, linear, and logistic regression. RESULTS: Patients were of median (range) age 4.9 (0.2-15.4) years at diagnosis and followed up for 8.3 (0.04-26.8) years. Despite high 20-year overall survival (81.0%), progression-free and endocrine event-free survival (EEFS) were 47.2 and 20.8%, respectively. EEFS declined up to 15 years post-diagnosis, with hypothalamic involvement (P < .001) being implicated more than radiotherapy (P = .008) in earlier endocrinopathy; the reverse being true of its density (radiotherapy P < .001; hypothalamic involvement P = .006). GH deficiency (GHD) was most common (40.3%), followed by central precocious puberty (CPP, 26.0%), gonadotropin (GnD; 20.4%), TSH (13.3%), and ACTH (13.3%) deficiencies. GHD increased with later treatment eras (P < .01), but replacement did not increase progression. CPP was associated with future GnD (P < .05). Posterior pituitary dysfunction (PPD; 7.2%) occurred in 57.9% after only biopsies or shunt procedures, and was associated with 6/13 deaths; 50.2% became obese. Tumor extent, surgery, and increased endocrinopathy, rather than radiotherapy, predicted visuocognitive morbidity. CONCLUSIONS: This first longitudinal OP/HSG-specific study demonstrates that hypothalamo-pituitary dysfunction evolves hierarchically over decades. Tumor location predicts its speed of onset and radiotherapy its density. GnD can evolve from previous CPP, whereas life-threatening PPD can occur after any surgery. Our data suggest that recent radiation-avoiding chemotherapeutic strategies have increased GHD without improving survival.

Treatment-resistant pediatric giant prolactinoma and multiple endocrine neoplasia type 1.

BACKGROUND: Pediatric pituitary adenomas are rare, accounting for <3 % of all childhood intracranial tumors, the majority of which are prolactinomas. Consequently, they are often misdiagnosed as other suprasellar masses such as craniopharyngiomas in this age group. Whilst guidelines exist for the treatment of adult prolactinomas, the management of childhood presentations of these benign tumors is less clear, particularly when dopamine agonist therapy fails. Given their rarity, childhood-onset pituitary adenomas are more likely to be associated with a variety of genetic syndromes, the commonest being multiple endocrine neoplasia type 1 (MEN-1). CASE DESCRIPTION: We present a case of an early-onset, treatment-resistant giant prolactinoma occurring in an 11-year-old peripubertal boy that was initially sensitive, but subsequently highly resistant to dopamine agonist therapy, ultimately requiring multiple surgical debulking procedures and proton beam irradiation. Our patient is now left with long-term tumor- and treatment-related neuroendocrine morbidities including blindness and panhypopituitarism. Only after multiple consultations and clinical data gained from 20-year-old medical records was a complex, intergenerationally consanguineous family history revealed, compatible with MEN-1, with a splice site mutation (c.784-9G > A) being eventually identified in intron 4 of the MEN1 gene, potentially explaining the difficulties in management of this tumor. Genetic counseling and screening has now been offered to the wider family. CONCLUSIONS: This case emphasizes the need to consider pituitary adenomas in the differential diagnosis of all pediatric suprasellar tumors by careful endocrine assessment and measurement of at least a serum prolactin concentration. It also highlights the lack of evidence for the optimal management of pediatric drug-resistant prolactinomas. Finally, the case we describe demonstrates the importance of a detailed family history and the role of genetic testing for MEN1 and AIP mutations in all cases of pediatric pituitary adenoma.