Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism-The UK Perspective.

Context: In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic β-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery.

Objective: We describe surgical and nonsurgical outcomes of focal CHI in a national cohort.

Baseline and Peak Cortisol Response to the Low-Dose Short Synacthen Test Relates to Indication for Testing, Age, and Sex.

Context: Meta-analyses report that the low dose short Synacthen test (LDSST) is more sensitive but less specific than the standard dose test for the diagnosis of adrenal insufficiency, and there are concerns regarding the accuracy of dosing in the LDSST.

Objective: Perform a retrospective, observational study to review the outcomes of LDSSTs performed in a tertiary endocrine service from 2008 to 2014 (N = 335) and 2016 to 2020 (N = 160), and examine for relationships between cortisol measurements and indication for testing, age and sex.

Methods: LDSST were performed by endocrine nurses.

Effect of Growth Hormone Therapy in Patients with Noonan Syndrome: A Retrospective Study.

Background: Noonan syndrome is an autosomal dominant condition with an incidence of 1:1000 to 1:2500. The disorder is associated with distinct dysmorphic features, cardiac anomalies, developmental delay and delayed puberty. Short stature is a recognised feature of Noonan syndrome.

Isolated premature menarche in two siblings with Neurofibromatosis type 1.

Objectives Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, caused by mutation in NF1. The condition is typified by the development of benign and malignant tumours in both the central nervous system and peripheral tissues. Isolated menarche is a sub-classification of incomplete isosexual precocious puberty typified by menarche in girls with no other features of pubertal development.

Congenital hyperinsulinism due to mutations in HNF1A.

Congenital hyperinsulinism is a rare but significant cause of severe and persistent hypoglycaemia in infancy. Although a biphasic phenotype of congenital hyperinsulinism in infancy followed by Maturity-Onset Diabetes of the Young (MODY) in later life has been established for HNF4A, the existence of a similar phenotype for a related MODY gene, HNF1A, is less clear. We describe two cases of congenital hyperinsulinism in association with dominantly inherited variants in HNF1A.

Heterozygous Insulin Receptor Mutation Associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series.

Mutations in the gene are associated with insulin resistance and hyperglycaemia. Various autosomal dominant heterozygous mutations leading to hyperinsulinemic hypoglycaemia (HH) have been described in adults and children (more than 3 years of age) but not in the neonatal period. Family 1: A small for gestational age (SGA) child born to a mother with gestational diabetes presented with persistent hypoglycaemia, was diagnosed with HH and responded well to diazoxide treatment.

Obesity is common at diagnosis of childhood pituitary adenoma and may persist following successful treatment.

Objective: There is a paucity of data describing long-term outcomes of paediatric patients with pituitary adenoma. In this report, we describe clinical features, treatment and outcomes of a paediatric cohort.

Design: Retrospective cohort study.

Continuous subcutaneous insulin infusion versus multiple daily injection regimens in children and young people at diagnosis of type 1 diabetes: pragmatic randomised controlled trial and economic evaluation.

Objective: To compare the efficacy, safety, and cost utility of continuous subcutaneous insulin infusion (CSII) with multiple daily injection (MDI) regimens during the first year following diagnosis of type 1 diabetes in children and young people.

Design: Pragmatic, multicentre, open label, parallel group, randomised controlled trial and economic evaluation.

Setting: 15 paediatric National Health Service (NHS) diabetes services in England and Wales.

Adrenal function of extremely premature infants in the first 5 days after birth.

Background There is limited data on adrenal function in the early days after birth in extremely premature infants. The relationship between plasma adrenocorticotrophic (ACTH) and cortisol hormone is central to the integrity of the hypothalamic-pituitary-adrenal (HPA) axis yet there are no studies examining this relationship in prematurity. Methods The aim of this study was to examine the relationship between early morning plasma cortisol and ACTH concentrations during the first 5 days after birth in infants born at less than 28 weeks' gestation and to identify any independent factors that determine plasma cortisol levels in these infants during extreme prematurity.

Hepatoblastoma and Wilms' tumour in an infant with Beckwith-Wiedemann syndrome and diazoxide resistant congenital hyperinsulinism.

Beckwith-Wiedemann syndrome (BWS) can be associated with embryonal tumours and congenital hyperinsulinism (CHI). We present an infant with BWS who developed congenital hepatoblastoma and Wilms' tumour during infancy. The infant presented with recurrent hypoglycaemia requiring high intravenous glucose infusion and was biochemically confirmed to have CHI.

A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8.

Background Congenital hyperinsulinism (CHI) occurs due to an unregulated insulin secretion from the pancreatic β-cells resulting in hypoglycaemia. Causative mutations in multiple genes have been reported. Phenotypic variability exists both within and between different genetic subgroups.

Continuous subcutaneous insulin infusion versus multiple daily injections in children and young people at diagnosis of type 1 diabetes: the SCIPI RCT.

Background: The risk of developing long-term complications of type 1 diabetes (T1D) is related to glycaemic control and is reduced by the use of intensive insulin treatment regimens: multiple daily injections (MDI) (≥ 4) and continuous subcutaneous insulin infusion (CSII). Despite a lack of evidence that the more expensive treatment with CSII is superior to MDI, both treatments are used widely within the NHS.

Objectives: (1) To compare glycaemic control during treatment with CSII and MDI and (2) to determine safety and cost-effectiveness of the treatment, and quality of life (QoL) of the patients.

The Challenges of Cortisol Replacement Therapy in Childhood: Observations from a Case Series of Children Treated with Modified-Release Hydrocortisone.

Background: Hydrocortisone is the preferred treatment for adrenal insufficiency in childhood. A small minority of children experience low cortisol concentrations and symptoms of cortisol insufficiency, poorly responsive to modifications in dosing. We speculated that treatment with modified-release hydrocortisone Plenadren may be beneficial in these selected patients.

Correction to: Open resection of hypothalamic hamartomas for intractable epilepsy revisited, using intraoperative MRI.

The authors apologize to have sent a final manuscript draft omitting "Athanasius Chawira" from the list of authors. The correct list of authors is given in this article.The original article has been corrected.

Mode of clinical presentation and delayed diagnosis of Turner syndrome: a single Centre UK study.

Background: Early diagnosis of girls with Turner syndrome (TS) is essential to provide timely intervention and support. The screening guidelines for TS suggest karyotype evaluation in patients presenting with short stature, webbed neck, lymphoedema, coarctation of aorta or ≥ two dysmorphic features. The aim of the study was to determine the age and clinical features at the time of presentation and to identify potential delays in diagnosis of TS.

Open resection of hypothalamic hamartomas for intractable epilepsy revisited, using intraoperative MRI.

Introduction: Hypothalamic hamartomas (HHs) are rare non-neoplastic lesions which cause drug-resistant epilepsy with associated behavioural, psychiatric and endocrine issues. With the development of new minimally invasive techniques for the treatment of HH, there is a need to reappraise the effectiveness and safety of each approach. We review the outcomes of HH patients treated surgically, utilizing intraoperative magnetic resonance imaging (IOMRI), by a team of Alder Hey NHS Foundation Trust tumour and epilepsy neurosurgeons since 2011.

Continuous Flash Glucose Monitoring in children with Congenital Hyperinsulinism; first report on accuracy and patient experience.

Background: The factory calibrated FreeStyle Libre (FSL) flash glucose monitoring system has been recently introduced for use in patients with diabetes mellitus. There are no reports available regarding its use in patients with congenital hyperinsulinism (CHI). We have assessed the accuracy of FSL compared to the finger prick capillary blood glucose (CBG) over 2 weeks period in patients with CHI and evaluated the parents' experience of using FSL.

Ketotic Hypoglycemia in Children with Previous Transient Congenital Hyperinsulinism.

Congenital Hyperinsulinism (CHI) is a major cause of neonatal hypoglycemia characterised by non-ketotic hypoglycemia. We describe the occurrence and higher prevalence of ketotic hypoglycemia (KH) in 5 children with transient CHI. Four children had required diazoxide to control the persistent hypoglycemia that was discontinued at a mean age of 11.

Novel Splicing Mutation in Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies.

, encoding -1,3-glucuronyltransferase 3, has an important role in proteoglycan biosynthesis. Homozygous mutations have been associated with short stature, skeletal deformities, and congenital heart defects. We describe for the first time a novel heterozygous splice site mutation in contributing to severe short stature, growth hormone (GH) deficiency, recurrent ketotic hypoglycaemia, facial dysmorphism, and congenital heart defects.

Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities.

Congenital hypopituitarism (CH) is characterized by the deficiency of one or more pituitary hormones and can present alone or in association with complex disorders. Congenital hyperinsulinism (CHI) is a disorder of unregulated insulin secretion despite hypoglycaemia that can occur in isolation or as part of a wider syndrome. Molecular diagnosis is unknown in many cases of CH and CHI.

Testosterone Therapy Improves the First Year Height Velocity in Adolescent Boys with Constitutional Delay of Growth and Puberty.

Background: Constitutional delay of growth and puberty (CDGP) can cause significant psychological distress in adolescent boys. Although testosterone usage in this group has not been shown to affect the final adult height, the effect on the first year height velocity has not been widely reported.

Objectives: The aim is to determine whether testosterone treatment improves the first year height velocity in boys with CDGP when compared to boys with CDGP who go through puberty spontaneously.

Novel compound heterozygous mutation causing Bainbridge-ropers like syndrome and primary IGF1 deficiency.

Background: De novo truncating and splicing mutations in the additional sex combs-like 3 () gene have been implicated in the development of Bainbridge-Ropers syndrome (BRPS) characterised by severe developmental delay, feeding problems, short stature and characteristic facial features.

Case Presentation: We describe, for the first time, a patient with severe short stature, learning difficulties, feeding difficulties and dysmorphic features with a novel compound heterozygous mutation in .Additionally the patient also has primary insulin like growth factor-1 (IGF1) deficiency.

Glycolate oxidase deficiency in a patient with congenital hyperinsulinism and unexplained hyperoxaluria.

Background: A baby girl was born at 39 weeks gestation to consanguineous Asian parents. From day 1 of life she had severe hypoglycaemia with an inappropriately elevated insulin concentration consistent with congenital hyperinsulinism (CHI), confirmed by the finding of a homozygous mutation in ABCC8 (encoding the sulfonylurea receptor 1).

Case Diagnosis/treatment: Urine organic acid analysis showed an incidentally elevated excretion of glycolate.

Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome.

Background: Recent data indicates that adults with Down syndrome (DS) are at increased risk for cardiovascular disease (CVD) that significantly contributes to their morbidity and mortality. Although identification of cardiometabolic risk factors during childhood is desirable to design preventive interventions, the data on such risk factors in children with DS is scarce. The aim of this study was to study the cardiometabolic risk factors such as insulin resistance (IR), leptin and adiponectin concentrations, lipid abnormalities and leptin resistance in non-obese children with DS.