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OBJECTIVES: The Awareness, Care and Treatment In Obesity maNagement (ACTION) Teens study explored attitudes, behaviours, perceptions and barriers regarding effective obesity care among adolescents living with obesity (ALwO), caregivers and healthcare professionals (HCPs). DESIGN: Cross-sectional online survey study. SETTING: Study across 10 countries; here, we report data from UK respondents. PARTICIPANTS: Overall, 416 ALwO (aged 12 to <18 years; body mass index ≥95th percentile for age and sex (WHO charts)), 498 caregivers and 250 HCPs in the UK completed the survey (August-December 2021). PRIMARY AND SECONDARY OUTCOME MEASURES: Survey questions addressed key aspects of obesity management for ALwO. RESULTS: Overall, 46% of ALwO perceived their weight as normal or below normal and 86% believed their health was at least good; 56% and 93% of caregivers responded similarly for their ALwO. Despite this, most ALwO (57%) had attempted to lose weight in the past year and 34% felt highly motivated to lose weight. YouTube and social media were most often used by ALwO for information about weight management (41% and 39%); few ALwO and caregivers sought information from a doctor (13% and 22%). Among ALwO who had discussed weight with an HCP (n=122), 49% trusted their weight-management advice. Only 10% of ALwO and 8% of caregivers were told by a doctor that they/their child had obesity. For HCPs, obesity-related comorbidities were the most common reason for initiating weight conversations with ALwO (73%), while short appointment times were the most common barrier (46%). Overall, 30% of ALwO and 11% of caregivers did not feel comfortable bringing up weight with an HCP. CONCLUSIONS: Improved education and communication are needed among ALwO, caregivers and HCPs in the UK to help improve awareness of obesity, its aetiology and its impact on health, and to support HCPs to proactively initiate weight-related conversations and build trust with ALwO and caregivers. TRIAL REGISTRATION NUMBER: NCT05013359.
Subject(s)
Caregivers , Health Personnel , Pediatric Obesity , Humans , Adolescent , Male , Female , Cross-Sectional Studies , United Kingdom , Caregivers/psychology , Pediatric Obesity/therapy , Pediatric Obesity/psychology , Health Personnel/psychology , Child , Surveys and Questionnaires , Health Knowledge, Attitudes, Practice , AdultABSTRACT
Actinic keratosis (AK) and seborrheic keratosis (SK) represent prevalent dermatological conditions with distinct clinical characteristics and potential health implications. This article investigates recent strides in dermatological diagnostics, centered on the development and application of artificial intelligence (AI) technology for discerning between AK and SK. The objective of this study is to develop and evaluate an artificial intelligence (AI) model capable of accurately distinguishing between stage one and stage two gastric carcinoma based on pathology slides. Employing a dataset of high-resolution images obtained from Kaggle.com, consisting of 1000 AK and 1000 SK images, a novel AI model was trained using cutting-edge deep learning methodologies. The dataset underwent meticulous partitioning into training, validation, and testing subsets to ensure robustness and generalizability. The AI model showcased exceptional proficiency in distinguishing AK from SK images, attaining notable levels of accuracy, precision, recall, specificity, F1-score, and area under the curve (AUC). Insights into the etiology and clinical ramifications of AK and SK were presented, emphasizing the critical significance of precise diagnosis and tailored therapeutic approaches. The integration of AI technology into dermatological practice holds considerable potential for enhancing diagnostic precision, refining treatment decisions, and elevating patient outcomes. This article underscores the transformative impact of AI in dermatology and the importance of collaborative efforts between clinicians, researchers, and technologists in advancing the realm of dermatological diagnosis and care.
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Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, affecting approximately 6.1 million people worldwide, according to estimates from the Parkinson's Foundation. Early and accurate diagnosis of PD is crucial for effective management and treatment. In this study, we aimed to develop an artificial intelligence (AI) model capable of distinguishing between magnetic resonance imaging (MRI) scans of individuals with PD and those without PD. A total of 442 MRI scans were utilized for training the AI model, comprising 221 scans of individuals diagnosed with PD and 221 scans of healthy controls. The dataset, obtained from a publicly available image dataset on Kaggle.com, was randomly split into three sets: training, validation, and testing, with 80%, 10%, and 10% of the data allocated to each set, respectively. Leveraging Google's Collaboration platform for model training, the AI model achieved exceptional performance, with accuracy, precision, recall (sensitivity), specificity, and F1-score all measuring at high levels. Additionally, the area under the receiver operating characteristic curve (AUC) for the model was found to be 1, indicating strong discrimination between PD and non-PD cases. This study presents a novel AI model capable of accurately identifying PD from MRI scans with high precision and reliability, offering promise for enhancing early diagnosis and personalized treatment strategies for individuals affected by PD.
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Persistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does not identify a disease-causing variant. Large deletions have previously been used to identify novel regulatory regions causing HI. Here, we used genome sequencing to search for novel large (>1 Mb) deletions in 180 probands with HI of unknown cause and replicated our findings in a large cohort of 883 genetically unsolved individuals with HI using off-target copy number variant calling from targeted gene panels. We identified overlapping heterozygous deletions in five individuals (range 3-8 Mb) spanning chromosome 20p11.2. The pancreatic beta-cell transcription factor gene, FOXA2, a known cause of HI was deleted in two of the five individuals. In the remaining three, we found a minimal deleted region of 2.4 Mb adjacent to FOXA2 that encompasses multiple non-coding regulatory elements that are in conformational contact with FOXA2. Our data suggests that the deletions in these three children may cause disease through the dysregulation of FOXA2 expression. These findings provide new insights into the regulation of FOXA2 in the beta-cell and confirm an aetiological role for chromosome 20p11.2 deletions in syndromic HI.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 20 , Congenital Hyperinsulinism , Hepatocyte Nuclear Factor 3-beta , Humans , Hepatocyte Nuclear Factor 3-beta/genetics , Hepatocyte Nuclear Factor 3-beta/metabolism , Congenital Hyperinsulinism/genetics , Congenital Hyperinsulinism/pathology , Chromosomes, Human, Pair 20/genetics , Female , Male , Regulatory Sequences, Nucleic AcidABSTRACT
There have been over 100 cases of Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome reported, but there is currently no curative treatment for children with this condition. We aimed to better characterise adipose cells from a child with ROHHAD syndrome. We isolated pre-adipocytes from a 4 year-old female patient with ROHHAD syndrome and assessed proliferation rate of these cells. We evaluated levels of DLP-Pref-1(pre-adipocyte marker) using western blotting, and concentrations of interleukin-6(IL-6) using ELISA. We performed next-generation sequencing (NGS) and bioinformatic analyses on these cells compared to tissue from an age/sex-matched control. The two most up-/down-regulated genes were validated using QPCR. We successfully isolated pre-adipocytes from a fat biopsy, by confirming the presence of Pref-1 and differentiated them to mature adipocytes. Interleukin 6, (Il-6) levels were 5.6-fold higher in ROHHAD cells compared to a control age/sex-matched biopsy. NGS revealed 25,703 differentially expressed genes (DEGs) from ROHHAD cells vs. control of which 2,237 genes were significantly altered. The 20 most significantly up/down-regulated genes were selected for discussion. This paper describes the first transcriptomic analysis of adipose cells from a child with ROHHAD vs. normal control adipose tissue as a first step in identifying targetable pathways/mechanisms underlying this condition with novel therapeutic interventions.
ABSTRACT
OBJECTIVES: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) is a rare syndrome associated with high morbidity and mortality. Diagnosis is often challenging. We describe three cases of ROHHAD with heterogeneous presentations but some consistent clinical features, including hyperprolactinaemia at diagnosis. We highlight when the diagnosis of ROHHAD should be considered at an early stage. CASE PRESENTATION: All three patients presented between 4 and 6 years old with rapid-onset obesity. They all have central hypoventilation requiring nocturnal BiPAP, varying degrees of hypothalamic dysfunction with hyperprolactinaemia being a consistent feature, and autonomic dysfunction. One patient has a neuro-endocrine tumour (NET) and two have glucose dysregulation. CONCLUSIONS: High prolactin was a consistent early feature. Central hypoventilation and NET may present later and therefore regular sleep studies and screening for NETs are required. A high suspicion of ROHHAD is warranted in patients with rapid, early-onset obesity and hyperprolactinaemia without structural pituitary abnormality.
Subject(s)
Autonomic Nervous System Diseases , Hyperprolactinemia , Hypothalamic Diseases , Neoplasms , Humans , Child, Preschool , Child , Hypoventilation/diagnosis , Hypoventilation/etiology , Obesity/complications , Obesity/diagnosis , Hypothalamic Diseases/complications , Hypothalamic Diseases/diagnosis , Syndrome , Autonomic Nervous System Diseases/complications , Autonomic Nervous System Diseases/diagnosisABSTRACT
OBJECTIVES: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation, and neural-crest tumour (ROHHAD(NET)) is a rare syndrome presenting in early childhood associated with high morbidity and mortality. There is no specific diagnostic biomarker and diagnosis is based on clinical features. An autoimmune origin has been postulated. CASE PRESENTATION: Management is largely supportive. We report a case of a five-year old female who presented in respiratory arrest after 6-months of rapid weight gain. She had central hypoventilation, central diabetes insipidus, growth hormone deficiency and hyperprolactinaemia. She displayed elevated interleukin-6 levels on cytokine serology which normalised after rituximab treatment. After rituximab treatment, her weight reduced significantly from greatly above the 99.6th to the 50th centile in 12 months. CONCLUSIONS: This response possibly reflects an underlying, immune-inflammatory pathology driving excess adiposity in this condition. Potentially, other aspects of ROHHAD(NET) may be mediated through autoimmune dysregulation in which case rituximab may provide benefits for prognosis and survival.
Subject(s)
Autonomic Nervous System Diseases , Hypothalamic Diseases , Child, Preschool , Female , Humans , Hypoventilation , Obesity , Rare Diseases , Rituximab/therapeutic use , Syndrome , Weight GainABSTRACT
Congenital hyperinsulinism (CHI) is a rare disease characterized by an unregulated insulin release, leading to hypoglycaemia. It is the most frequent cause of persistent and severe hypoglycaemia in the neonatal period and early childhood. Mutations in 16 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, KCNQ1, CACNA1D, FOXA2, EIF2S3, PGM1 and PMM2) that are involved in regulating the insulin secretion from pancreatic ß-cells have been described to be responsible for the underlying molecular mechanisms of CHI. CHI can also be associated with specific syndromes and can be secondary to intrauterine growth restriction (IUGR), maternal diabetes, birth asphyxia, etc. It is important to diagnose and promptly initiate appropriate management as untreated hypoglycaemia can be associated with significant neurodisability. CHI can be histopathologically classified into diffuse, focal and atypical forms. Advances in molecular genetics, imaging techniques (18F-fluoro-l-dihydroxyphenylalanine positron emission tomography/computed tomography scanning), novel medical therapies and surgical advances (laparoscopic pancreatectomy) have changed the management and improved the outcome of patients with CHI. This review article provides an overview of the background, clinical presentation, diagnosis, molecular genetics and therapy for children with different forms of CHI.
Subject(s)
Congenital Hyperinsulinism , Hyperinsulinism , Insulin-Secreting Cells , Child , Child, Preschool , Congenital Hyperinsulinism/diagnosis , Congenital Hyperinsulinism/genetics , Congenital Hyperinsulinism/therapy , Humans , Hyperinsulinism/metabolism , Infant, Newborn , Insulin/therapeutic use , Insulin Secretion , Insulin-Secreting Cells/metabolism , MutationABSTRACT
Objective: This preliminary review was conducted to inform the design of a new service to support families with children with Prader-Willi syndrome (PWS). Families were invited to attend a pilot clinic at a hospital outpatient department, comprising appointments with a multi-disciplinary team (MDT). Methods: Following the clinic, families (n=6) were invited to take part in semi-structured qualitative interviews that were audio-recorded, transcribed and analysed using thematic analysis. Results: Families reported that the clinic offered enhanced support in the following categories: integrated care; professional input; signposting to social support (respite and financial); connection with the wider PWS community; and behavioural support. Conclusion: This is the first paper that documents the parental perspective of an MDT clinic for children with PWS. The families felt an MDT clinic was superior to current care, offering more convenient access to an enhanced service, which would provide integrated and consistent care for their children's diverse, challenging and changing needs.
Subject(s)
Outpatient Clinics, Hospital , Parents , Patient Care Team , Patient Satisfaction , Prader-Willi Syndrome/therapy , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Qualitative ResearchABSTRACT
OBJECTIVES: Childhood obesity can lead to acute and chronic comorbidities and adult obesity, highlighting the need for prompt intervention. Families and caregivers play a vital role in treatment and when primary interventions fail, this may become a child protection issue. CASE PRESENTATION: We present two cases of severe childhood obesity where targeted lifestyle interventions failed to impact weight status. Both cases feature child welfare involvement with patients coming into the care of the local authority (under s20 of the Children Act 1989). Foster placement resulted in significant weight loss and improved BMI achieved through reduced portions, healthier choices, restricted calories to recommended daily intake for age and increased activity. Physical and emotional wellbeing benefits were observed and improvements in obesity related comorbidities. CONCLUSIONS: Failure to reduce a child's weight alone does not constitute a child protection issue. In severe cases, where maximum intervention has failed and when the child has obesity related comorbidites or at a higher risk of developing them, home environment change should be considered in the child's best interest as a treatment for severe childhood obesity.
Subject(s)
Foster Home Care/methods , Home Environment , Life Style , Pediatric Obesity/therapy , Weight Loss , Weight Reduction Programs/organization & administration , Child, Preschool , Female , Foster Home Care/psychology , Humans , Pediatric Obesity/psychologyABSTRACT
OBJECTIVE: This study seeks to understand family's perceptions of their care at a paediatric weight management service, with a view to informing service improvement. DESIGN: A qualitative service review conducted via semistructured interviews with parents (n=11) and children (n=3) who attended the clinic. The recruitment was open to all, but those who were not succeeding in their weight-loss goals self-selected to participate. Self-Determination Theory was used as a framework to explore families' experiences of the clinic. SETTING: Recruitment occurred during clinical appointments and interviews were conducted over the phone in the days following the appointments. PATIENTS: The service sees paediatric patients with a body mass index >99th percentile, with comorbidities or safeguarding concerns. INTERVENTIONS: The clinic's service includes appointments typically every 2 months, with a multidisciplinary team including consultant endocrinologists, a dietician, a clinical psychologist, a social worker and a clinical nurse specialist. MAIN OUTCOME MEASURES: Families' feedback on the multi-disciplinary team (MDT) clinic, and their perceptions of how improvements could be made. RESULTS: Families perceive a lack of autonomy, competency and feel a lack of connectivity both in their lives broadly and within their experience at the clinic. CONCLUSIONS: Interventions in families struggling with weight improvements should see the clinical team placing more emphasis on working alongside parents to develop young people's sense of self-determination. Expectations must be set that success originates from changes outside of clinical appointments and that the clinical team is in place to support the family's development of sustainable, self-determined lifestyle habits.
Subject(s)
Obesity/prevention & control , Patient Participation/psychology , Perception/physiology , Adolescent , Body Mass Index , Child , Child, Preschool , Comorbidity , Female , Humans , Interdisciplinary Communication , Interviews as Topic , Life Style , Male , Obesity/epidemiology , Obesity/psychology , Parents/psychology , Patient Participation/statistics & numerical data , Qualitative Research , Weight LossABSTRACT
Short-rib polydactyly syndromes are a heterogeneous group of disorders characterized by narrow thorax with short ribs, polydactyly and often other visceral and skeletal malformations. To date there have only been six reported patients with homozygous and compound heterozygous variants in IFT81, causing a short-rib thoracic dysplasia, with, or without, polydactyly (SRTD19: OMIM 617895). IFT81 is a protein integral to the core of the intraflagellar transport complex B (IFT-B), which is involved in anterograde transport in the cilium. We describe the case of a male infant with compound heterozygous variants in IFT81, who presented with short long bones, a narrow thorax, polydactyly, and multiple malformations. Three novel clinical features are reported including complete situs inversus, micropenis, and rectal atresia, which have not previously been associated with variants in IFT81. We reviewed the literature and identified the most consistent clinical features associated with this rare ciliopathy syndrome. We postulate that dolichocephaly and sagittal craniosynostosis may be associated with this condition, and provide a clue to considering IFT81 as the causative gene when deciphering complex ciliopathies.
Subject(s)
Ciliopathies/genetics , Craniosynostoses/genetics , Muscle Proteins/genetics , Short Rib-Polydactyly Syndrome/genetics , Cilia/pathology , Ciliopathies/diagnosis , Ciliopathies/physiopathology , Craniosynostoses/diagnosis , Craniosynostoses/physiopathology , Homozygote , Humans , Infant, Newborn , Male , Mutation/genetics , Phenotype , Short Rib-Polydactyly Syndrome/diagnosis , Short Rib-Polydactyly Syndrome/physiopathologyABSTRACT
INTRODUCTION: We present a patient with co-existence of 3ß-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency and Bartter syndrome, a unique dual combination of opposing pathologies that has not been reported previously in the literature. CASE: A female infant (46,XX) born at 34/40 weeks' gestation, weighing 2.67 kg (-1.54 standard deviation score) to non-consanguineous parents presented on day 4 of life with significant weight loss. Subsequent investigations revealed hyponatraemia, hypochloraemia, metabolic alkalosis, elevated 17-hydroxyprogesterone, ACTH, and renin. Urine steroid profile suggested HSD3B2 deficiency, which was confirmed by the identification of a homozygous HSD3B2 mutation. Due to the persistence of the hypochlo-raemic and hypokalemic alkalosis, an underlying renal tubulopathy was suspected. Sequence analysis of a targeted tubulopathy gene panel revealed a homozygous deletion in CLCNKB, consistent with Bartter syndrome type 3. The mother was found to be heterozygous for both mutations in -HSD3B2 and CLCNKB, and the father was negative for both. Single-nucleotide polymorphism microarray analysis confirmed 2 segments of homozygosity on chromosome 1 of maternal ancestry, encompassing both HSD3B2 and CLCKNB. DISCUSSION: Identification of a homozygous rare mutation in an offspring of non-consanguineous parents should raise suspicion of uniparental disomy, especially if the phenotype is unusual, potentially encompassing more than one disorder. The persistence of hypokalemic alkalosis, the biochemical fingerprint of hyperaldosteronism in a child with a form of CAH in which aldosterone production is severely impaired, challenges our current understanding of mineralocorticoid-mediated effects in the collecting duct.
Subject(s)
Adrenal Hyperplasia, Congenital/complications , Bartter Syndrome/complications , Chloride Channels/genetics , Mutation , Progesterone Reductase/genetics , Uniparental Disomy , Adrenal Hyperplasia, Congenital/genetics , Bartter Syndrome/genetics , Female , Humans , Infant , Infant, NewbornABSTRACT
Background Congenital hyperinsulinism (CHI), a condition characterized by dysregulation of insulin secretion from the pancreatic ß cells, remains one of the most common causes of hyperinsulinemic, hypoketotic hypoglycemia in the newborn period. Mutations in ABCC8 and KCNJ11 constitute the majority of genetic forms of CHI. Case presentation A term macrosomic male baby, birth weight 4.81 kg, born to non-consanguineous parents, presented on day 1 of life with severe and persistent hypoglycemia. The biochemical investigations confirmed a diagnosis of CHI. Diazoxide was started and progressively increased to 15 mg/kg/day to maintain normoglycemia. Sequence analysis identified compound heterozygous mutations in ABCC8 c.4076C>T and c.4119+1G>A inherited from the unaffected father and mother, respectively. The mutations are reported pathogenic. The patient is currently 7 months old with a sustained response to diazoxide. Conclusions Biallelic ABCC8 mutations are known to result in severe, diffuse, diazoxide-unresponsive hypoglycemia. We report a rare patient with CHI due to compound heterozygous mutations in ABCC8 responsive to diazoxide.
Subject(s)
Congenital Hyperinsulinism/drug therapy , Congenital Hyperinsulinism/genetics , Diazoxide/therapeutic use , Sulfonylurea Receptors/genetics , Vasodilator Agents/therapeutic use , Humans , Infant, Newborn , Male , Treatment OutcomeABSTRACT
Background The hyperinsulinism/hyperammonaemia (HI/HA) syndrome is the second most common cause of hyperinsulinaemic hypoglycaemia, caused by activating mutations in GLUD1. In this article, we report a series of three unrelated patients with HI/HA syndrome who demonstrated variable phenotypes, ranging from delayed presentation to spontaneous resolution of hypoglycaemia, thereby expanding the current knowledge and understanding of GLUD1 mutations. Case presentation This paper is a retrospective analysis of patients with HI/HA syndrome who demonstrated a variable disease course. Patient 1 presented with hypoglycaemic seizures at the age of 7 months and was diagnosed with HI/HA syndrome. Patient 2, a 5-year-old boy, on anti-convulsants since 8 months of age, was diagnosed with HI/HA at the age of 4 years. Patient 3, an 11-year-old girl with a history of transient neonatal hypoglycaemia, was diagnosed with HI/HA at the age of 12 months following evaluation for absence seizures. Patients 1 and 2 had raised ammonia levels, whilst patient 3 had normal ammonia level. The genetic analysis in all three patients confirmed GLUD1 mutation. Good glycaemic control was observed in all following diazoxide treatment. All patients have learning difficulties. Patient 1 demonstrated spontaneous resolution of hypoglycaemia at the age of 8 years, enabling discontinuation of diazoxide. Conclusions The cases highlight the diagnostic challenges in HI/HA syndrome due to a highly variable presentation. Knowledge of variable phenotypes would enable early diagnosis, thereby decreasing the risk of long-term neurological damage. Spontaneous resolution of hyperinsulinism could occur, and it is important to consider a trial off diazoxide therapy especially if the patients are on a small dose of diazoxide.
Subject(s)
Glutamate Dehydrogenase/genetics , Hyperammonemia/genetics , Hyperinsulinism/genetics , Mutation , Phenotype , Ammonia/blood , Blood Glucose/metabolism , Child , Child, Preschool , Diazoxide/therapeutic use , Female , Humans , Hyperammonemia/blood , Hyperammonemia/drug therapy , Hyperinsulinism/blood , Hyperinsulinism/drug therapy , Infant , Male , Treatment Outcome , Vasodilator Agents/urineABSTRACT
Background Congenital hyperinsulinism (CHI) occurs due to an unregulated insulin secretion from the pancreatic ß-cells resulting in hypoglycaemia. Causative mutations in multiple genes have been reported. Phenotypic variability exists both within and between different genetic subgroups. Case presentation A male infant born at 35+6 weeks' gestation with a birth weight of 4.3 kg [+3.6 standard deviation score (SDS)] had recurrent hypoglycaemic episodes from birth. Biochemical investigations confirmed a diagnosis of CHI. Diazoxide was started and the dose was progressively increased to maintain euglycaemia. His father was slim and had been diagnosed with type 2 diabetes in his 30s. Sequence analysis identified a heterozygous hepatocyte nuclear factor 4 alpha (HNF4A) mutation (p.Arg245Pro, c.734G>C) and compound heterozygous ABCC8 mutations (p.Gly92Ser, c.274G>A and p.Ala1185Val, c.3554C>T) in the patient. The p.Ala1185Val ABCC8 mutation was inherited from his unaffected mother and the p.Arg245Pro HNF4A and p.Gly92Ser ABCC8 mutations from his father. All three mutations were predicted to be pathogenic. Identification of the HNF4A mutation in the father established a diagnosis of maturity-onset diabetes of the young (MODY), which enabled medication change resulting in improved glycaemic control. Conclusions We report a rare patient with CHI due to dual genetic aetiology. Although he is currently responsive to the maximum dose of diazoxide, the long-term prognosis remains unclear.
Subject(s)
Congenital Hyperinsulinism/genetics , Hepatocyte Nuclear Factor 4/genetics , Sulfonylurea Receptors/genetics , Birth Weight , Blood Glucose/analysis , Humans , Infant, Newborn , Male , MutationABSTRACT
Activating mutations in thyrotropin receptor (TSHR) have been previously described in the context of nonautoimmune hyperthyroidism and thyroid adenomas. We describe, for the first time, a mutation in TSHR contributing to follicular thyroid carcinoma (FTC) in an adolescent. A 12-year-old girl presented with a right-sided neck swelling, increasing in size over the previous four weeks. Clinical examination revealed a firm, nontender thyroid nodule. Ultrasound scan of the thyroid showed a heterogeneous highly vascular mass. Thyroid function tests showed suppressed TSH [<0.03mU/L], normal FT4 [10.1pmol/L, 9-19], and raised FT3 [9.1pmol/L, 3.6-6.4]. Thyroid [TPO and TRAB] antibodies were negative. A right hemithyroidectomy was performed and the histology of the sample revealed follicular carcinoma with mild to moderate nuclear pleomorphism and evidence of capsular and vascular invasion (pT1b). Sanger sequencing of DNA extracted from the tumour tissue revealed a missense somatic mutation (c.1703T>C, p.Ile568Thr) in TSHR. Papillary thyroid carcinomas constitute the most common thyroid malignancy in childhood, while FTC is rare. FTC due to TSHR mutation suggests an underlying, yet to be explored, molecular pathway leading to the development of malignancy. The case is also unique in that the clinical presentation of FTC as a toxic thyroid nodule has not been previously reported in children.
ABSTRACT
AIMS: To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. METHODS: A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). RESULTS: The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. CONCLUSIONS: Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.
Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems , Insulin/administration & dosage , Practice Patterns, Physicians'/statistics & numerical data , Adolescent , Adult , Blood Glucose/drug effects , Blood Glucose/metabolism , Blood Glucose Self-Monitoring/methods , Blood Glucose Self-Monitoring/standards , Calibration , Child , Diabetes Mellitus, Type 1/epidemiology , Dose-Response Relationship, Drug , Europe/epidemiology , Female , Geography , Humans , Insulin Infusion Systems/standards , Israel/epidemiology , Longitudinal Studies , Male , South America/epidemiology , Young AdultABSTRACT
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 11.25 (+5.25) months. KH developed after an average time period of 6.7 months following the resolution of CHI. Children with transient CHI may be at risk of subsequently developing KH at a variable age period.