Trametinib-Induced Hyponatremia in a Patient With Craniopharyngioma and Diabetes Insipidus.

Adamantinomatous craniopharyngiomas (ACPs) are rare, sellar-suprasellar benign tumors that cause considerable morbidity and mortality due to local invasion and treatment-related damage to surrounding structures, including central diabetes insipidus (CDI). Trametinib is a highly selective inhibitor of MEK1 and MEK2, which has been evaluated in both adult and pediatric cancers/ tumors with activation of the oncogenic mitogen-activated protein kinase (MAPK) pathway. Despite being thought to have fewer side effects than conventional cytotoxic chemotherapy, off-target toxicities such as hyponatremia have been described.

Increased insulin-like growth factor-1 concentrations in paediatric suprasellar low-grade glioma: an international multicentre study.

Objective: The objective of this study was to assess the prevalence of elevated insulin-like growth factor (IGF)-1 in children with suprasellar low-grade glioma (LGG) and explore the course of IGF-1 over time and its association with anthropometrics, hypothalamic syndrome, tumour characteristics, and tumour behaviour.

Design: This retrospective study included children from the Netherlands and the United Kingdom diagnosed with a suprasellar LGG under the age of 18 between 2003 and 2023, with a minimum 1-year follow-up. Elevated IGF-1 was defined as IGF-1 standard deviation score (SDS) >+2.

Hypothalamic obesity: from basic mechanisms to clinical perspectives.

Despite the diverse nature of obesity, there is compelling genetic, clinical, and experimental evidence that endorses the important contribution of brain circuits to this condition. The hypothalamus contains major regulatory circuits for bodyweight homoeostasis, the deregulation of which can lead to obesity. Although functional perturbation of hypothalamic pathways could lie at the basis of common forms of obesity, the term hypothalamic obesity has been created to define those rare forms of severe obesity where a clear hypothalamic substrate can be identified, either of genetic or acquired origin.

L-Dopa Might Be Insufficient to Suppress Development of Prolactinomas in Dihydropteridine Reductase-Deficiency Patients.

Dihydropteridine reductase (DHPR) deficiency is a disorder that prevents regeneration of tetrahydrobiopterin (BH4), causing hyperphenylalaninemia (HPA) and low levels of neurotransmitters, including dopamine. Due to low levels of dopamine, patients present with hyperprolactinemia. Treatment consists of a phenylalanine (Phe)-restricted diet, hydroxytryptophan and levodopa (L-Dopa) supplementation, leading to a rapid normalization of prolactin (PRL) levels.

Appetite- and Weight-Regulating Neuroendocrine Circuitry in Hypothalamic Obesity.

Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a background of an increasing prevalence of population-level common obesity, the number of survivors of congenital (eg, septo-optic dysplasia, Prader-Willi syndrome) and acquired (eg, central nervous system tumors) hypothalamic disorders is increasing, thanks to earlier diagnosis and management as well as better oncological therapies. Although to date the discovery of several appetite-regulating peptides has led to the development of a range of targeted molecular therapies for monogenic obesity syndromes, outside of these disorders these discoveries have not translated into the development of efficacious treatments for other forms of HyOb.

Tolvaptan and urea in paediatric hyponatraemia.

Background: The syndrome of inappropriate antidiuretic hormone (SIADH) is usually treated with fluid restriction. This can be challenging in patients with obligate fluid intake for nutrition or medication. Pharmaceutical treatment with tolvaptan and urea is available but minimal paediatric data are available.

Inaccuracies in plasma oxytocin extraction and enzyme immunoassay techniques.

Numerous studies have reported extensive associations between plasma oxytocin (OXT) concentrations and various human physiological and neurobehavioral processes. Measurement of OXT is fraught with difficulty due to its low molecular weight and plasma concentrations, with no consensus as to the optimal conditions for pre-analytical sample extraction, standards for immunoassay validation or the ideal protease inhibitors to prevent OXT degradation. Previous attempts at determining the efficacy of various purification techniques such as solid phase extraction (SPE) or ultrafiltration have only utilized human plasma samples, making it difficult to dissect out whether the effect of interference comes from the extraction process itself or cross-reactivity with other proteins.

Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance.

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses.

A new era for optic pathway glioma: A developmental brain tumor with life-long health consequences.

Optic pathway and hypothalamic glioma (OPHG) are low-grade brain tumors that arise from any part of the visual pathways frequently involving the hypothalamus. The tumors grow slowly and present with features driven by their precise anatomical site, their age at presentation and the stage of growth and development of the host neural and orbital bony tissues. Up to 50% of optic pathway glioma arise in association with Neurofibromatosis type 1 (NF1), which affects 1 in 3,000 births and is a cancer predisposition syndrome.

A novel technique for frame-based MR-guided laser ablation in an infant.

Hypothalamic hamartomata (HH) not only are usually associated with drug-resistant epilepsy but can also cause precocious puberty and developmental delay. Gelastic seizures are the most common type of seizures. Magnetic resonance image (MRI)-guided laser interstitial thermal therapy (LiTT) is a technique whereby a laser fibre is stereotactically implanted into a target lesion and heat is used to ablate whilst tissue temperature is monitored using MRI thermography.

A 40-Year Cohort Study of Evolving Hypothalamic Dysfunction in Infants and Young Children (<3 years) with Optic Pathway Gliomas.

Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.

Advances in differential diagnosis and management of growth hormone deficiency in children.

Growth hormone (GH) deficiency (GHD) in children is defined as impaired production of GH by the pituitary gland that results in growth failure. This disease might be congenital or acquired, and occurs in isolation or in the setting of multiple pituitary hormone deficiency. Isolated GHD has an estimated prevalence of 1 patient per 4000-10,000 live births and can be due to multiple causes, some of which are yet to be determined.

Adrenoleukodystrophy in the Differential Diagnosis of Boys Presenting with Primary Adrenal Insufficiency without Adrenal Antibodies.

Adrenoleukodystrophy (ALD) is an X-linked, metabolic disorder caused by deficiency of peroxisomal ALD protein resulting in accumulation of very-long chain fatty acids (VLCFA), primarily in the adrenal cortex and central nervous system. Approximately 35-40% of boys with ALD develop cerebral ALD (CALD), which causes rapidly progressive cerebral demyelination, loss of neurologic function, and death. Approximately 70-80% of boys with ALD have impaired adrenal function prior to the onset of neurologic symptoms.

Monogenic diabetes mellitus in cystic fibrosis.

We present a non-consanguineous family of three siblings who presented with diabetes mellitus (DM), two of whom had genetically confirmed cystic fibrosis (CF), with one pancreatic-sufficient mutation in the cystic fibrosis transmembrane conductance regulator () gene (ΔF508/R117H;IVS8-5T). A detailed history revealed family members from three successive generations diagnosed with 'type 1' or 'type 2' diabetes, leading to genetic investigations for monogenic DM. A heterozygous frameshift mutation in the hepatocyte nuclear factor 1 homeobox alpha () gene (c.

Congenital Epidermoid Cyst Presenting as Isolated Painful Trigeminal Neuropathy: Indications for Neuroimaging in the Diagnostic Process.

This article reports a case of a cerebellopontine angle epidermoid cyst presenting as isolated painful trigeminal neuropathy. The indolent nature of these uncommon benign tumors leads to frequent delays in their presentation and diagnosis, with patients often initially undergoing dental procedures. This is illustrated in the present case reported here, which highlights the difficulties in identifying trigeminal neuralgia (TN), particularly in its early phases, and supports current recommendations for routine neuroimaging in suspected cases of painful trigeminal neuropathy, which, unlike classic TN, is caused by a disorder other than neurovascular compression (even in the absence of additional neurologic symptoms or signs) and is present particularly in younger patients with atypical features.

Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin.

Do expanded seven-day NHS services improve clinical outcomes? Analysis of comparative institutional performance from the "NHS Services, Seven Days a Week" project 2013-2016.

Background: The cause of adverse weekend clinical outcomes remains unknown. In 2013, the "NHS Services, Seven Days a Week" project was initiated to improve access to services across the seven-day week. Three years on, we sought to analyse the impact of such changes across the English NHS.

Two Siblings with a Mutation in CCDC8 Presenting with Mild Short Stature: A Case of 3-M Syndrome.

Background: Short stature can be caused by mutations in a multitude of different genes. 3-M syndrome is a rare growth disorder marked by severe pre- and postnatal growth retardation along with subtle dysmorphic features. There have only been 2 prior reports of mutations in CCDC8 causing 3-M syndrome.

Optic pathway glioma in children: does visual deficit correlate with radiology in focal exophytic lesions?

Purpose: Unlike pilocytic astrocytomas in other parts of the brain, optic pathway gliomas (OPG) are usually diffuse lesions involving the anterior optic pathways and hypothalamus. Their infiltrative nature often precludes complete surgical resection. We sought to determine whether careful magnetic resonance (MR) analysis, correlated with visual deficits, could be sufficient to identify those focal lesions that may be amenable to more aggressive surgical resection at presentation.

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.

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.