Insights from the ACTION Teens Study: a survey of adolescents living with obesity, their caregivers and healthcare professionals in the UK.

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.

Semaglutide, A Long-Acting GLP-1 Analogue, for the Management of Early Onset Obesity due to MC4R defect - A Case Report.

INTRODUCTION: Childhood obesity is a global concern and has both nutritional and genetic causative factors. One of the most common monogenic causes of obesity is heterozygous mutations in the Melanocortin 4 receptor (MC4R), which are found in 5.7% to 8.6% of individuals with early-onset obesity. We report, the effect of Semaglutide, a long-acting Glucagon like peptide (GLP1) analogue, in the treatment of severe obesity in an adolescent boy with a heterozygous mutation in MC4R. CASE PRESENTATION: A 13-year-old boy with a history of excessive weight gain since infancy was referred to the specialised weight management team. He was born at full-term with a birth weight of 3.57kg (50th centile), but his weight consistently exceeded the 99.6th percentile after the age of one year. At the age of five years, he was diagnosed with autism spectrum disorder (ASD). Diagnostic investigations revealed insulin resistance, and dyslipidaemia, while genetic testing confirmed a heterozygous mutation in MC4R (E61K), inherited from his mother. Managing his condition was challenging due to his rapid weight gain, needle phobia, and behavioural difficulties. Despite intense multidisciplinary lifestyle interventions, he continued to gain weight, reaching a peak weight of 187.5kg [+16.65 standard deviation score (SDS)], body mass index (BMI) of 56.9kg/m2 (+4.19 SDS), body fat 63.9%] at the age of 13 years. Due to severe ASD and needle phobia, he was not keen on daily GLP-1 injections. He was commenced on Semaglutide subcutaneous injection at a dose of 0.25mg weekly, gradually increasing to the maximum dose of 1mg weekly. Over the course of 12 weeks, his BMI decreased to 52.2kg/m2 (+4.08SDS) and weight dropped to 176.8kg (+14.76SDS, body fat: 52.7%). At the 3-month and 12-month reviews post treatment, he achieved weight loss of 5.7% and 11% respectively. Quality of life questionnaire (QoL) showed improved scores from 35.95 to 60.36 at 12-month review indicating enhanced well-being. The CGM (continuous glucose monitor) demonstrated an improvement in TIR (time in range). CONCLUSION: Semaglutide, is approved by the FDA for weight management in adolescents aged 12 years and above in December 2022. A recent case series underscored the benefits of therapy with Liraglutide, a short-acting GLP-1 analogue, in rare genetic cases of early-onset obesity. To our knowledge, this is the first case report to highlight the efficacy and safety of Semaglutide in an adolescent with heterozygous MC4R mutation. Semaglutide could be a potential treatment option for monogenic obesity and will benefit from further research.

Improvements in Glucose Regulation in Children and Young People with Cystic Fibrosis-Related Diabetes following Initiation of Elexacaftor/Tezacaftor/Ivacaftor.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are increasingly used in children and young people with cystic fibrosis (CF). Data in adults show there may be an impact on glycaemic control in those with CF-related diabetes (CFRD). Paediatric data are rare. Case Series/Presentation: Children aged >12 years with CFRD, who were eligible for elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) were commenced on treatment. Glucose monitoring via the FreeStyle Libre system was commenced prior to, immediately after, and several months after commencing ELX/TEZ/IVA. Glycaemic control, shown by time in range (3-10 mmol/L), percentage of time spent hypoglycaemic (<3 mmol/L), and percentage of time spent hyperglycaemic (>10 mmol/L) on Insulin doses were recorded. Following ELX/TEZ/IVA, four of seven children stopped insulin, two required substantially reduced doses of insulin, one showed no response. Glycaemic control remained similar on lower doses or no insulin. Hypoglycaemia was detected in those not requiring insulin. CONCLUSION: ELX/TEZ/IVA has a positive impact on glycaemic control and insulin requirements in children with CFRD. Close monitoring is required when commencing treatment. Children with CFRD need counselling regarding possible reductions in insulin requirement and re-education regarding symptoms, signs, and management of hypoglycaemia.

Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus.

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.

Klinefelter syndrome: going beyond the diagnosis.

Although Klinefelter syndrome (KS) is common, it is rarely recognised in childhood, sometimes being identified with speech or developmental delay or incidental antenatal diagnosis. The only regular feature is testicular dysfunction. Postnatal gonadotropin surge (mini-puberty) may be lower, but treatment with testosterone needs prospective studies. The onset of puberty is at the normal age and biochemical hypogonadism does not typically occur until late puberty. Testosterone supplementation can be considered then or earlier for clinical hypogonadism. The size at birth is normal, but growth acceleration is more rapid in early and mid-childhood, with adult height greater than mid-parental height. Extreme tall stature is unusual. The incidence of adolescent gynaecomastia (35.6%) is not increased compared with typically developing boys and can be reduced or resolved by testosterone supplementation, potentially preventing the need for surgery. Around two-thirds require speech and language therapy or developmental support and early institution of therapy is important. Provision of psychological support may be helpful in ameliorating these experiences and provide opportunities to develop strategies to recognise, process and express feelings and thoughts. Boys with KS are at increased risk of impairment in social cognition and less accurate perceptions of social emotional cues. The concept of likely fertility problems needs introduction alongside regular reviews of puberty and sexual function in adolescents. Although there is now greater success in harvesting sperm through techniques such as testicular sperm extraction, it is more successful in later than in early adolescence. In vitro maturation of germ cells is still experimental.

Burosumab Therapy in a Paediatric Patient with McCune-Albright Syndrome: A Case Report.

INTRODUCTION: McCune-Albright syndrome is characterized by the triad of fibrous dysplasia, café au lait skin pigmentation, and hyperfunctioning endocrinopathies. It is a sporadic condition caused by a missense mutation in the GNAS locus, located on chromosome 20q13.3, resulting in mosaic activation of the G protein alpha subunit. CASE PRESENTATION: We pre­sent a paediatric patient diagnosed with McCune-Albright syndrome at the age of 5 years. During the course of his condition, he was medically managed for a number of complications, such as peripheral precocious puberty and growth hormone excess, and monitored for hyperprolactinaemia. Due to fibroblast growth factor 23-mediated phosphate wasting, the patient was commenced on oral phosphate supplements and alfacalcidol. After 2 years of treatment, this therapy did not optimize his bone biochemistry (phosphate 0.96 mmol/L, alkaline phosphatase 1,172 IU/L, and parathyroid hormone 9.1 pmol/L), and the patient was started on two-weekly burosumab therapy via subcutaneous injection. His bone biochemistry soon normalized (phosphate 1.52 mmol/L, alkaline phosphatase 358 IU/L, and parathyroid hormone 6.9 pmol/L) following this, and he remains on burosumab without any adverse effects. DISCUSSION: This case shows the positive effect that a short-term course of burosumab has on bone health in a paediatric patient with McCune-Albright syndrome. Further research is required to assess long-term effects. Our patient also presented with precocious puberty and growth hormone excess, a coexistence that can be challenging to diagnose and is less common in males. He received medical management for both conditions, but due to the similar presentations, this case highlights the importance to investigate and diagnose associated complications as early as possible, so they can be managed in a timely manner.

45,X male - rare case of unbalanced translocation of Y chromosome to chromosome 2 presenting with developmental delay, learning difficulty and obesity.

Summary: A male phenotype accompanied by a 45,X karyotype is rare. It may occur due to Y chromosomal translocation or insertion to X/autosome. Clinical presentation may vary depending on the presence of the Y chromosomal locus and the degree of loss of autosome material. 45,X males can present with short stature and Turner syndrome phenotype due to haploinsufficiency of genes which are normally expressed in both X and Y chromosomes. The presence of the sex-determining region Y (SRY) gene leads to the differentiation of bipotential gonads to testis. Most individuals go through puberty normally, but some may need pubertal induction for delayed puberty. Rarely some can have a pubertal arrest. The risk of gonadoblastoma is minimal in these individuals due to functioning testicular tissue. The azoospermia factor (AZF) region is found on the long arm of the Yq chromosome and is needed for spermatogenesis. In a 45,X male with unbalanced translocation of Y chromosome, spermatogenesis can be affected due to the lack of AZF leading to Sertoli cell-only syndrome. This will have an implication on fertility in adult life. We present a 14-year-old boy with developmental delay, learning difficulties and subtle dysmorphic features who was diagnosed with 45,X,der(2)t(Y:2)(?:p25). Fluorescence in situ hybridisation analysis revealed translocation of SRY (Yp11.3) to the terminal part of the short arm of chromosome 2 resulting in the deletion of most of the Y chromosome (Yp11.2-q12) and part of chromosome 2(2p25.3). This is the first case where SRY translocation to chromosome 2 presents with the above clinical presentation. Learning points: 45,X karyotype is rare in male. It may occur due to SRY translocation or an insertion to X/autosome. SRY gene translocation to chromosome 2 has been not reported in the literature. Clinical presentation can be varied due to degree of loss of chromosomal material. Due to loss of AZF region found on the long arm of the Yq, spermatogenesis can be affected. Loss of 2p25 leads to learning difficulty and obesity.

The hypoglycaemia error grid: A UK-wide consensus on CGM accuracy assessment in hyperinsulinism.

Objective: Continuous Glucose Monitoring (CGM) is gaining in popularity for patients with paediatric hypoglycaemia disorders such as Congenital Hyperinsulinism (CHI), but no standard measures of accuracy or associated clinical risk are available. The small number of prior assessments of CGM accuracy in CHI have thus been incomplete. We aimed to develop a novel Hypoglycaemia Error Grid (HEG) for CGM assessment for those with CHI based on expert consensus opinion applied to a large paired (CGM/blood glucose) dataset. Design and methods: Paediatric endocrinology consultants regularly managing CHI in the two UK centres of excellence were asked to complete a questionnaire regarding glucose cutoffs and associated anticipated risks of CGM errors in a hypothetical model. Collated information was utilised to mathematically generate the HEG which was then approved by expert, consensus opinion. Ten patients with CHI underwent 12 weeks of monitoring with a Dexcom G6 CGM and self-monitored blood glucose (SMBG) with a Contour Next One glucometer to test application of the HEG and provide an assessment of accuracy for those with CHI. Results: CGM performance was suboptimal, based on 1441 paired values of CGM and SMBG showing Mean Absolute Relative Difference (MARD) of 19.3% and hypoglycaemia (glucose <3.5mmol/L (63mg/dL)) sensitivity of only 45%. The HEG provided clinical context to CGM errors with 15% classified as moderate risk by expert consensus when data was restricted to that of practical use. This provides a contrasting risk profile from existing diabetes error grids, reinforcing its utility in the clinical assessment of CGM accuracy in hypoglycaemia. Conclusions: The Hypoglycaemia Error Grid, based on UK expert consensus opinion has demonstrated inadequate accuracy of CGM to recommend as a standalone tool for routine clinical use. However, suboptimal accuracy of CGM relative to SMBG does not detract from alternative uses of CGM in this patient group, such as use as a digital phenotyping tool. The HEG is freely available on GitHub for use by other researchers to assess accuracy in their patient populations and validate these findings.

Heterozygous CDC73 mutation causing hyperparathyroidism in children and adolescents: a report of 2 cases.

OBJECTIVES: Primary hyperparathyroidism (PHPT), whilst common in elderly populations, is rare in adolescents. Hereditary cases make up less than 10% of patients with PH. We report two patients with CDC73 mutation presenting in early adolescence. CASE PRESENTATION: Case 1: A 14-year-old patient was referred from an adolescent mental health unit with hypercalcaemia. Imaging revealed a parathyroid adenoma. Genetic testing of the patient showed a heterozygous deletion of CDC73. Case 2: A 10-year-old patient was admitted to the general paediatric ward with symptoms suggestive of hypercalcaemia. The patient was known to carry an autosomal dominant mutation of CDC73. Imaging of the parathyroid gland showed bilateral adenoma. CONCLUSIONS: We present two patients with CDC73 defects, who both presented with symptoms of hypercalcaemia. The cases highlight the difference in paediatric populations with PHPT who are often symptomatic at the time of diagnosis when compared to adult patients.

Insight into hypoglycemia frequency in congenital hyperinsulinism: evaluation of a large UK CGM dataset.

INTRODUCTION: Hypoglycemia is often recurrent and severe in patients with congenital hyperinsulinism (CHI). However, there is little information regarding frequency or patterns of episodes to inform clinical management and future trial design. RESEARCH DESIGN AND METHODS: We aimed to describe frequency and patterns of hypoglycemia by varying thresholds through a large continuous glucose monitoring (CGM) dataset. Through the UK CHI centers of excellence, data were analyzed from patients with CHI over a 5-year period. Hypoglycemia thresholds of 3.0 (H3.0), 3.5 (H3.5) and 3.9 (H3.9) mmol/L were used to test threshold change on hypoglycemia frequencies. RESULTS: From 63 patients, 3.4 million data points, representing 32 years of monitoring, were analyzed. By UK consensus threshold H3.5, patients experienced a mean 1.3 hypoglycemic episodes per day. Per cent time hypoglycemic increased from 1.2% to 3.3% to 6.9% when threshold changed from H3.0 to H3.5 and H3.9. Merged data showed periodicity of hypoglycemia risk in 24-hour periods in all patients. CONCLUSIONS: We have evaluated a large dataset to provide a comprehensive picture of the frequency and patterns of hypoglycemia for patients with CHI in the UK. These data establish a baseline risk of hypoglycemia by CGM and provide a framework for clinical management and clinical trial design.

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

Context: In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic ß-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. Methods: Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018. Results: Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (SSRA) therapy. Fifty-five patients underwent surgery: 40 had immediate resolution of CHI, 10 had persistent hypoglycemia and a focus was not identified on biopsy in 5. In the 10 patients with persistent hypoglycemia, 7 underwent further surgery with resolution in 4 and ongoing hypoglycemia requiring SSRA in 3. Nine (15% of cohort) patients (1 complex surgical access; 4 biopsy negative; 4 declined surgery) were managed conservatively; medication was discontinued in 8 children at a median (range) age 2.4 (1.5-7.7) years and 1 remains on SSRA at 16 years with improved fasting tolerance and reduction in SSRA dose. Conclusion: Despite a unifying genetic basis of disease, we report inherent heterogeneity in focal CHI patients impacting outcomes of both surgical and medical management.

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. Synacthen 500 ng/1.73m2 administered as IV bolus, sampling at 0, 15, 25, and 35 minutes. Results: Mean (± 1SD) baseline cortisol was 221 ± 120 nmol/L, peak 510 ± 166 nmol/L and increment 210 ± 116 nmol/L. 336 (70%) patients had a normal response (baseline cortisol >100 nmol/L, peak >450 nmol/L), 78 (16%) a suboptimal response (peak cortisol 350-450 nmol/L) and were prescribed hydrocortisone to during periods of stress only, 67 (14%) an abnormal response (baseline <100nmol/L or peak <350nmol/L) and were prescribed daily hydrocortisone. Basal, peak, and incremental increases in cortisol were higher in females (P = .03, P < .001, P = .03, respectively). Abnormal results occurred most frequently in patients treated previously with pharmacological doses of glucocorticoids or structural brain abnormalities (P < .001). Conclusion: The low prevalence and strong association of abnormal results with indication for testing, suggests that over diagnosis occurred infrequently in this clinical setting.

Idiopathic intracranial hypertension in children with obesity.

AIM: Obesity is an under-recognised risk factor for raised intracranial pressure in the paediatric population. The pathophysiology remains unclear. The aim of our study was to investigate the association between idiopathic intracranial hypertension (IIH) and weight in children. METHODS: Patients diagnosed with IIH at a tertiary children's hospital were retrospectively identified between April 2017 and April 2019. Information regarding the patients' body mass index, presentation, investigation and treatment was collected and analysed. RESULTS: In total, 18 patients (M:F 7:11) were identified with a mean age of 11 years (±3.3SD; range: 6-15 years). The mean BMI was 30.3 kg/m2 and mean BMI SDS was +2.5. Twelve (66.6%) patients presented with both headaches and eye signs. Three patients were asymptomatic, with papilloedema noted on routine optician review. Of the 18 patients, 15 were treated medically, two had long-term neurosurgical interventions and one patient was managed conservatively. CONCLUSION: The results show that the majority of children with obesity who develop IIH were female. Awareness regarding IIH secondary to obesity needs to be highlighted to ensure detailed clinical evaluation takes place so that raised intracranial pressure can be diagnosed and managed earlier, to avoid more serious complications such as permanent visual loss.

Childhood obesity: A review of current and future management options.

Obesity is becoming increasingly prevalent in paediatric populations worldwide. In addition to increasing prevalence, the severity of obesity is also continuing to rise. Taken together, these findings demonstrate a worrying trend and highlight one of the most significant challenges to public health. Childhood obesity affects multiple organs in the body and is associated with both significant morbidity and ultimately premature mortality. The prevalence of complications associated with obesity, including dyslipidaemia, hypertension, fatty liver disease and psychosocial complications are becoming increasingly prevalent within the paediatric populations. Treatment guidelines currently focus on intervention with lifestyle and behavioural modifications, with pharmacotherapy and surgery reserved for patients who are refractory to such treatment. Research into adult obesity has established pharmacological novel therapies, which have been approved and established in clinical practice; however, the research and implementation of such therapies in paediatric populations have been lagging behind. Despite the relative lack of widespread research in comparison to the adult population, newer therapies are being trialled, which should allow a greater availability of treatment options for childhood obesity in the future. This review summarizes the current evidence for the management of obesity in terms of medical and surgical options. Both future therapeutic agents and those which cause weight loss but have an alternative indication are also included and discussed as part of the review. The review summarizes the most recent research for each intervention and demonstrates the potential efficacy and limitations of each treatment option.

Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management.

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.

Subcutaneous Calcification and Fixed Flexion Deformity of the Right Elbow Joint in a Child with a GNAS Mutation: A Case Report.

INTRODUCTION: The art of medicine glorifies when a clinician listens carefully to the patient's story, gives a thorough examination, performs appropriate investigations, and finally links findings together to reach a definite diagnosis. An interesting case was reported here, highlighting the integration of different symptoms and manifestations with some relevant biochemical investigations to reach a final diagnosis. To the best of our knowledge, fixed flexion deformity, as a complication of subcutaneous calcification, has not been previously reported in a child with Albright hereditary osteodystrophy (AHO). CASE PRESENTATION: A 2.5-year-old boy was born at term with a birth weight of 3.5 kg (-0.49 SDS). The child was referred to a general pediatrician with a history of right elbow joint swelling noticed initially at six months of age. He then developed the limitation of right upper arm movement, which slowly progressed afterward. The patient had no history of trauma. At nine months of age, he was diagnosed with hypothyroidism, preceded by cold skin, dry hair, and constipation. At nine years of age, he presented with a fixed flexion deformity of the right elbow associated with markedly limited joint movement and symmetrical hands with hyperpigmented knuckles of right metacarpal bones. Subcutaneous masses were felt along the right forearm, showing tenderness on palpation. Investigations revealed elevated serum parathyroid hormone and normal calcium indicating parathyroid hormone resistance. Further genetic testing revealed GNAS mutation. The child was obese throughout his childhood. CONCLUSIONS: This case report describes an obese child with subcutaneous calcification that led to fixed flexion deformity of the elbow, starting at an incredibly early age. Hypothyroidism and pseudohypoparathyroidism raised the suspicion of AHO, which was later confirmed by genetic testing. This is the first case report on fixed flexion deformity in a patient with GNAS mutation (c.719-1G > A Chr20: 57484737) in West Asia.

An eHealth Framework for Managing Pediatric Growth Disorders and Growth Hormone Therapy.

BACKGROUND: The use of technology to support health and health care has grown rapidly in the last decade across all ages and medical specialties. Newly developed eHealth tools are being implemented in long-term management of growth failure in children, a low prevalence pediatric endocrine disorder. OBJECTIVE: Our objective was to create a framework that can guide future implementation and research on the use of eHealth tools to support patients with growth disorders who require growth hormone therapy. METHODS: A total of 12 pediatric endocrinologists with experience in eHealth, from a wide geographical distribution, participated in a series of online discussions. We summarized the discussions of 3 workshops, conducted during 2020, on the use of eHealth in the management of growth disorders, which were structured to provide insights on existing challenges, opportunities, and solutions for the implementation of eHealth tools across the patient journey, from referral to the end of pediatric therapy. RESULTS: A total of 815 responses were collected from 2 questionnaire-based activities covering referral and diagnosis of growth disorders, and subsequent growth hormone therapy stages of the patient pathway, relating to physicians, nurses, and patients, parents, or caregivers. We mapped the feedback from those discussions into a framework that we developed as a guide to integration of eHealth tools across the patient journey. Responses focused on improved clinical management, such as growth monitoring and automation of referral for early detection of growth disorders, which could trigger rapid evaluation and diagnosis. Patient support included the use of eHealth for enhanced patient and caregiver communication, better access to educational opportunities, and enhanced medical and psychological support during growth hormone therapy management. Given the potential availability of patient data from connected devices, artificial intelligence can be used to predict adherence and personalize patient support. Providing evidence to demonstrate the value and utility of eHealth tools will ensure that these tools are widely accepted, trusted, and used in clinical practice, but implementation issues (eg, adaptation to specific clinical settings) must be addressed. CONCLUSIONS: The use of eHealth in growth hormone therapy has major potential to improve the management of growth disorders along the patient journey. Combining objective clinical information and patient adherence data is vital in supporting decision-making and the development of new eHealth tools. Involvement of clinicians and patients in the process of integrating such technologies into clinical practice is essential for implementation and developing evidence that eHealth tools can provide value across the patient pathway.

Liraglutide combined with intense lifestyle modification in the management of obesity in adolescents.

OBJECTIVES: Childhood obesity is a public health concern worldwide, with rates continuing to rise, despite preventive measures. Lifestyle modification remains the mainstay in the treatment of patients with excessive weight, but unfortunately, this is not always successful. Options for medical management of obesity in the paediatric population are limited. METHODS: Seven adolescents (all girls, mean age 14.9 years) with a body mass index (BMI) above 98th percentile and serious complications secondary to obesity were offered an intense weight management programme. The participants were reviewed by a multidisciplinary team every two weeks for advice and support, and treated with daily subcutaneous injections of liraglutide (dose range 1.2-3.0 mg). Scores for anxiety and depression were evaluated using the Revised Child Anxiety and Depression Scale. RESULTS: The results showed a significant weight loss over the three months with an average reduction of 5.4 kg (4.2%; 95% CI 1.93-8.78; p=0.0087). The mean drop in BMI was 2.1 kg/m2, which is statistically significant (95% CI 0.973-3.199; p=0.0037). Resolution of complications (raised intracranial pressure and steatohepatitis) was noted following weight loss. Anxiety and depressive symptoms improved over the three-month intervention course, especially features of separation anxiety disorder. Liraglutide was well tolerated by all patients. CONCLUSIONS: Liraglutide medication, alongside a dedicated multidisciplinary team guided lifestyle therapy, is effective and safe in the treatment for excessive weight in adolescents, leading to the reversal of the complications related to obesity and improvement in the psychological symptoms.

The Efficacy of Denosumab in the Management of a Tibial Paediatric Aneurysmal Bone Cyst Compromised by Rebound Hypercalcaemia.

Surgery is the main treatment option for patients with aneurysmal bone cyst (ABC). We report our experience of using denosumab as an alternative treatment in a child with a multiply recurrent and unresectable tibial ABC. The efficacy and safety of denosumab in the paediatric population, and in the treatment of ABC, are still to be fully evaluated. We describe a 13-year-old boy with an extensive and aggressive ABC involving the proximal tibia, which had recurred following multiple previous surgeries. The patient had ongoing severe pain, was unable to weight-bear, and was at significant risk of pathological fracture. En bloc resection and embolization were not deemed viable, and a decision to use denosumab was made. He received 17 doses of subcutaneous denosumab (70 mg/m2) over a 27-month period, at increasing dose intervals. His symptoms significantly improved, and bony consolidation was observed within six months of treatment. He was able to walk without protection and fully weight-bear without any pain by 18 months. With an increase to a six-month dosing interval, the patient presented with a severe, symptomatic rebound hypercalcaemia requiring bisphosphonate therapy. This reoccurred on two further occasions. This case adds to the evidence that denosumab is effective in the treatment of ABC in paediatric patients, but there is a risk of rebound hypercalcaemia. Therefore, patient awareness and biochemical monitoring for rebound hypercalcaemia are essential.

Posaconazole-Induced Hypertension Masquerading as Congenital Adrenal Hyperplasia in a Child with Cystic Fibrosis.

BACKGROUND: Deficiency of 11ß-hydroxylase is the second most common cause of congenital adrenal hyperplasia (CAH), presenting with hypertension, hypokalaemia, precocious puberty, and adrenal insufficiency. We report the case of a 6-year-old boy with cystic fibrosis (CF) found to have hypertension and cortisol insufficiency, which were initially suspected to be due to CAH, but were subsequently identified as being secondary to posaconazole therapy. Case Presentation. A 6-year-old boy with CF was noted to have developed hypertension after administration of two doses of Orkambi™ (ivacaftor/lumacaftor), which was subsequently discontinued, but the hypertension persisted. Further investigations, including echocardiogram, abdominal Doppler, thyroid function, and urinary catecholamine levels, were normal. A urine steroid profile analysis raised the possibility of CAH due to 11ß-hydroxylase deficiency, and a standard short synacthen test (SST) revealed suboptimal cortisol response. Clinically, there were no features of androgen excess. Detailed evaluation of the medical history revealed exposure to posaconazole for more than 2 months, and the hypertension had been noted to develop two weeks after the initiation of posaconazole. Hence, posaconazole was discontinued, following which the blood pressure, cortisol response to the SST, and urine steroid profile were normalized. CONCLUSION: Posaconazole can induce a clinical and biochemical picture similar to CAH due to 11ß-hydroxylase deficiency, which is reversible. It is prudent to monitor patients on posaconazole for cortisol insufficiency, hypertension, and electrolyte abnormalities.