Presentation and outcomes of paediatric craniopharyngioma in the west of Scotland: a 25 year experience.

PURPOSE: Craniopharyngiomas can be aggressive leading to significant complications and morbidity. It is not clear whether there are any predictive factors for incidence or outcomes. Our aim was therefore to record the incidence, presentation, characteristics and progression of paediatric craniopharyngiomas in the West of Scotland. METHOD: Retrospective case note review for children diagnosed with paediatric craniopharyngiomas at the Royal Hospital for Children Glasgow, from 1995 to 2021 was conducted. All analyses were conducted using GraphPad Prism 9.4.0. RESULTS: Of 21 patients diagnosed with craniopharyngiomas, the most common presenting symptoms were headaches (17/21, 81%); visual impairment (13/21, 62%); vomiting (9/21, 43%) and growth failure (7/21, 33%). Seventeen (81%) patients underwent hydrocephalus and/or resection surgery within 3 months of diagnosis, usually within the first 2 weeks (13/21, 62%). Subtotal resection surgeries were performed in 71% of patients, and median time between subsequent resection surgeries for tumour recurrence was 4 years (0,11). BMI SDS increased at 5 year follow-up (p = 0.021) with 43% being obese (BMI > + 2SD). More patients acquired hypopituitarism post-operatively (14/16, 88%) compared to pre-operatively (4/15, 27%). A greater incidence of craniopharyngiomas were reported in more affluent areas (10/21, 48%) (SIMD score 8-10) compared to more deprived areas (6/10, 29%) (SIMD score 1-3). Five patients (24%) died with a median time between diagnosis and death of 9 years (6,13). CONCLUSION: Over 25 years the management of craniopharyngioma has changed substantially. Co-morbidities such as obesity are difficult to manage post-operatively and mortality risk can be up to 25% according to our cohort.

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study.

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.

ADVANCING THE UNDERSTANDING OF CLINICAL SEPSIS USING GENE EXPRESSION-DRIVEN MACHINE LEARNING TO IMPROVE PATIENT OUTCOMES.

ABSTRACT: Sepsis remains a major challenge that necessitates improved approaches to enhance patient outcomes. This study explored the potential of machine learning (ML) techniques to bridge the gap between clinical data and gene expression information to better predict and understand sepsis. We discuss the application of ML algorithms, including neural networks, deep learning, and ensemble methods, to address key evidence gaps and overcome the challenges in sepsis research. The lack of a clear definition of sepsis is highlighted as a major hurdle, but ML models offer a workaround by focusing on endpoint prediction. We emphasize the significance of gene transcript information and its use in ML models to provide insights into sepsis pathophysiology and biomarker identification. Temporal analysis and integration of gene expression data further enhance the accuracy and predictive capabilities of ML models for sepsis. Although challenges such as interpretability and bias exist, ML research offers exciting prospects for addressing critical clinical problems, improving sepsis management, and advancing precision medicine approaches. Collaborative efforts between clinicians and data scientists are essential for the successful implementation and translation of ML models into clinical practice. Machine learning has the potential to revolutionize our understanding of sepsis and significantly improve patient outcomes. Further research and collaboration between clinicians and data scientists are needed to fully understand the potential of ML in sepsis management.

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.

The effect of COVID-19 on the presentation of thyroid disease in children.

Introduction: Although studies suggest a potential link between COVID-19 and thyroid dysfunction in adults, there are insufficient data to confirm that association in children, and whether there is any effect on presentation to healthcare services. Aims: To identify whether presentations of thyroid dysfunction in children to a tertiary paediatric hospital changed as a result of the COVID-19 pandemic. Methods: A retrospective case note review was conducted of all children with abnormal thyroid function tests between 1st January 2016 and 31st December 2021 at a tertiary paediatric endocrine centre in the United Kingdom. Results: Overall, 244 children whose first presentation was within the timeframe of interest were included in this study, with a median age (range) of 11.5 (6.1, 16.8) years. Of these, 43 (18%) were hyperthyroid and 201 (82%) were hypothyroid. The greatest number of thyroid presentations occurred in 2021 (n=60, 25% of total over time period) and the fewest in 2020 (n=10, 4% of total over time period). Prior to this, the median (range) number of presentations per year was 34 (28, 39). There were no statistically significant differences in biochemistry, antibody status or other clinical characteristics between those who presented with hyperthyroidism prior to the pandemic or after. In those with hypothyroidism, baseline biochemistry was similar between the 2 groups, but the presence of other autoimmune conditions was greater pre-pandemic (17.2% vs 15.0%, p=0.03). In addition, patients were more likely to have transient thyroid dysfunction, which did not require treatment post-pandemic (70.0% vs 49.6%, p=0.0086). Conclusions: Although overall rates of presentation with thyroid dysfunction have not altered since the first wave of the COVID-19 pandemic, presentations with transient thyroid dysfunction, not requiring ongoing treatment have increased. Further research regarding the relationship between COVID-19 and thyroid function in children and young people, is needed.

Severe hypertension in pediatric diabetic ketoacidosis a case report and review of literature.

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus in children. Despite the presence of dehydration, hypertension occurs in a significant proportion of children with DKA. There is a lack of clarity in the literature regarding the management of hypertension in patients with paediatric DKA. Herein, we report the case of an adolescent boy who presented with DKA and severe hypertension. His neurological status was closely monitored. There was a gradual decline in his blood pressure with an improvement in the pH over the next 72 hours. The combination of severe DKA and hypertension can be a challenging clinical dilemma, especially regarding fluid management. Studies on severe DKA in children are exacting, given the rarity of this condition. A multi-centre study is suggested to provide a meaningful analysis of this aspect of DKA.

Genetic Analysis of Pediatric Primary Adrenal Insufficiency of Unknown Etiology: 25 Years' Experience in the UK.

CONTEXT: Although primary adrenal insufficiency (PAI) in children and young people is often due to congenital adrenal hyperplasia (CAH) or autoimmunity, other genetic causes occur. The relative prevalence of these conditions is poorly understood. OBJECTIVE: We investigated genetic causes of PAI in children and young people over a 25 year period. DESIGN SETTING AND PARTICIPANTS: Unpublished and published data were reviewed for 155 young people in the United Kingdom who underwent genetic analysis for PAI of unknown etiology in three major research centers between 1993 and 2018. We pre-excluded those with CAH, autoimmune, or metabolic causes. We obtained additional data from NR0B1 (DAX-1) clinical testing centers. INTERVENTION AND OUTCOME MEASUREMENTS: Genetic analysis involved a candidate gene approach (1993 onward) or next generation sequencing (NGS; targeted panels, exomes) (2013-2018). RESULTS: A genetic diagnosis was reached in 103/155 (66.5%) individuals. In 5 children the adrenal insufficiency resolved and no genetic cause was found. Pathogenic variants occurred in 11 genes: MC2R (adrenocorticotropin receptor; 30/155, 19.4%), NR0B1 (DAX-1; 7.7%), CYP11A1 (7.7%), AAAS (7.1%), NNT (6.5%), MRAP (4.5%), TXNRD2 (4.5%), STAR (3.9%), SAMD9 (3.2%), CDKN1C (1.3%), and NR5A1/steroidogenic factor-1 (SF-1; 0.6%). Additionally, 51 boys had NR0B1 variants identified through clinical testing. Although age at presentation, treatment, ancestral background, and birthweight can provide diagnostic clues, genetic testing was often needed to define the cause. CONCLUSIONS: PAI in children and young people often has a genetic basis. Establishing the specific etiology can influence management of this lifelong condition. NGS approaches improve the diagnostic yield when many potential candidate genes are involved.

An appraisal of current service delivery and future models of care for young people with gender dysphoria.

The clinical needs of young people with gender dysphoria (GD) have outpaced the capacity of health services to provide appropriate care. The study aimed to explore the interface of Paediatric Endocrinology and young people with GD, detailing the clinical characteristics and the clinical care provided, in order to inform future service development. Medical records of all young people with GD (n=91, 59 (65%) birth-assigned females and 32 (35%) birth-assigned males) referred to Paediatric Endocrinology during 2011-2019 for puberty suppression were reviewed. Median age at initial assessment was 14.6 years (range 8.8-17.6 years). There was a threefold increase from 2016 (n=22) to 2019 (n=73). Mental health disorders were present in 34 (37%) and autistic spectrum disorder in 21 (23%), while 54 (59%) had at least one comorbidity. Sixty-four (70%) young people fulfilled the criteria for consideration of fertility preservation, with 6 (9%) of them preserving their gametes. Seventy-nine (87%) young people commenced treatment with gonadotrophin-releasing hormone analogue, at a median age of 14.8 years (range 9.7-18.0 years). Six (8%) of those discontinued treatment, following a median duration of 6 months (range 6-18 months). Forty-one young people commenced gender-affirming hormones. One (2%) of those who started gender-affirming hormones discontinued treatment.Conclusions: We have witnessed increasing numbers of young people with GD attending Paediatric Endocrinology, with an over-representation of comorbidities, necessitating provision of an individualised approach to treatment. Addressing young people's acceptability of fertility services and ongoing close collaboration between endocrinology and mental health professionals require innovative models of multidisciplinary care. What is Known: • A worldwide increase in presentation of gender dysphoria has been mirrored in our service, with majority assigned female at birth and post-pubertal. • An over-representation of comorbidities exists, notably mental health disorders and autistic spectrum disorder. What is New: • Coordination of interprofessional care to meet complex needs, at an individual level, while improving efficiency of working, at a systemic level, can be met by the development of specialist centres. • The reasons for low uptake of fertility services demand further exploration.

The use of growth hormone therapy in adults with Prader-Willi syndrome: A systematic review.

OBJECTIVE: Despite clear benefits in the management of children with Prader-Willi syndrome (PWS), the role of growth hormone (GH) in adults is unclear. The aim of this study was to conduct a systematic review to evaluate the effects of GH on body composition, bone health and cardiovascular health in adults with PWS. DESIGN: A systematic computerized literature search of the PubMed database was conducted by two independent reviewers. Inclusion criteria were individuals over the age of 16 years with a genetic diagnosis of PWS who had received GH therapy, together with assessment of body composition, bone health or cardiovascular health. RESULTS: Twenty full-text papers met the inclusion criteria, encompassing 364 unique patients. No differences in body mass index (BMI) were noted, although 2 studies reported increased BMI after GH cessation. Data demonstrated statistically significant increases in lean body mass and reductions in percentage fat mass. Studies reported inconsistent effects of GH on cholesterol and echocardiography parameters. No studies reported differences in bone mineral density, although one reported improved bone geometry. Minor adverse events including pretibial oedema, headache and transient impaired glucose tolerance were reported in 7 studies. CONCLUSIONS: These data suggest that GH is safe and well tolerated in adults with PWS, with evidence of improvement in body composition. Further longitudinal studies are still required to investigate the effects of GH on bone and cardiovascular health. Where GH is used in adults with PWS, this should be managed by a specialist multidisciplinary team with regular monitoring initiated.

Parent-reported outcomes in young children with disorders/differences of sex development.

BACKGROUND: There is a paucity of tools that can be used in routine clinical practice to assess the psychosocial impact of Disorders/Differences of Sex Development (DSD) on parents and children. OBJECTIVE: To evaluate the use of short Parent Self-Report and Parent Proxy-Report questionnaires that can be used in the outpatient setting. METHODS: Previously validated DSD-specific and generic items were combined to develop a Parent Self-Report questionnaire and a Parent Proxy-Report questionnaire for children under 7 years. Of 111 children approached at one tertiary paediatric hospital, the parents of 95 children (86%) with DSD or other Endocrine conditions completed these questionnaires. RESULTS: Questionnaires took under 10 min to complete and were found to be easy to understand. Compared to reference, fathers of children with DSD reported less stress associated with Clinic Visits (p = 0.02) and managing their child's Medication (p = 0.04). However, parents of children with either DSD or other Endocrine conditions reported more symptoms of Depression (p = 0.03). Mothers of children with DSD reported greater Future Concerns in relation to their child's condition (median SDS - 0.28; range - 2.14, 1.73) than mothers of children with other Endocrine conditions (SDS 1.17; - 2.00, 1.73) (p = 0.02). Similarly, fathers of children with DSD expressed greater Future Concerns (median SDS -1.60; - 4.21, 1.00) than fathers of children with other Endocrine conditions (SDS 0.48; - 2.13, 1.52) (p = 0.04). CONCLUSION: DSD was associated with greater parental concerns over the child's future than other Endocrine conditions. Brief parent-report tools in DSD can be routinely used in the outpatient setting to assess and monitor parent and patient needs.

Single-Centre Experience of Testosterone Therapy for Boys with Hypogonadism.

BACKGROUND: Hypogonadism in boys is one of the commonest conditions encountered in paediatric endocrinology. AIMS: To study variations in management in a contemporary group of boys at a single specialist centre. METHODS: Retrospective review of case records of all boys treated with testosterone at a tertiary endocrine service from 2012 to 2017. RESULTS: Of the 358 boys reviewed for hypogonadism, 46 (13%) were initiated on testosterone therapy at a median age (range) of 14.2 years (12.1, 17.7). Indications for therapy included a functional delay of puberty that was constitutional in 17 (37%) or related to chronic disease in 10 (22%) or organic hypogonadism due to primary gonadal failure in 7 (15%), multiple pituitary hormone deficiency in 6 (13%), and isolated hypogonadotropic hypogonadism in 6 (13%). Of the 46 boys, 40 (89%) were started on intramuscular testosterone, 4 (9%) on oral testosterone, and 1 (2%) on transdermal gel. Of the 19 boys (40%) with organic hypogonadism re-quiring long-term therapy, 12 (63%) had assessment of liver function, 6 (32%) had a haematocrit, and 2 (11%) had a DXA scan in the year of commencing treatment. CONCLUSIONS: Testosterone therapy is administered in about 13% of boys reviewed for hypogonadism and its monitoring requires standardisation.

Neonatal Features of the Prader-Willi Syndrome; The Case for Making the Diagnosis During the First Week of Life

Objective: Early diagnosis is of proven benefit in Prader-Willi syndrome (PWS). We therefore examined key perinatal features to aid early recognition. Methods: Data were collected from case records of subjects attending a multi-disciplinary clinic and from a retrospective birth questionnaire. Results: Ninety patients (54 male-36 female) were seen between 1991-2015, most with paternal deletion (n=56) or maternal isodisomy (n=26). Features included cryptorchidism in 94% males, preterm birth (26%), birthweight <2500 g (24%), polyhydramnios (23%), breech presentation (23%) and need for nasogastric feeding (83%). Reduced fetal movements (FM) were reported in 82.5% patients compared with 4% healthy siblings. Of 35 children born since 1999, 23 were diagnosed clinically within 28 days while diagnosis in 12 was >28 days: 1-12 months in seven; and 3.75-10.5 years in five. Typical PWS features in these 12 infants included hypotonia (100%), feeding difficulties (75%), cryptorchidism (83% males) and reduced FM (66%). Causes other than PWS including neuromuscular disease were considered in nine patients. Conclusion: Neonatal hypotonia, reduced FM, feeding difficulties and cryptorchidism should immediately suggest PWS, yet late diagnosis continues in some cases. Awareness of the typical features of PWS in newborn units is required to allow prompt detection even in the presence of confounding factors such as prematurity.

Permanent congenital hypothyroidism with blood spot thyroid stimulating hormone <10†mU/L.

BACKGROUND: The UK recommended lower threshold for neonatal blood spot thyroid stimulating hormone (TSH) screening for congenital hypothyroidism (CHT) is 10.0 mU/L. Some laboratories use lower thresholds. This will lead to referral of mildly or unaffected infants but some will require thyroxine therapy. METHODS: Laboratory referrals with a first or repeat capillary TSH between 8.0 and <10.0 mU/L were identified (January 2004 to March 2014). The outcome of these cases was examined. RESULTS: 26 infants had one or more blood spot TSH values between 8.0 and 9.99 mU/L; 65% had transient elevated neonatal TSH while one is awaiting diagnostic challenge. The remaining eight (31%) have permanent CHT; three with dyshormonogenesis, two with thyroid ectopia and the others met the criteria for definite CHT. Two out of three with dyshormonogenesis presented with decompensated hypothyroidism. CONCLUSIONS: Infants with permanent and occasionally severe CHT may have a screening TSH below the UK recommended lower cut-off.

Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature.

The aetiology of obesity has been attributed to several factors (environmental, dietary, lifestyle, host, and genetic factors); however none of these fully explain the increase in the prevalence of obesity worldwide. Gut microbiota located at the interface of host and environment in the gut are a new area of research being explored to explain the excess accumulation of energy in obese individuals and may be a potential target for therapeutic manipulation to reduce host energy storage. Several mechanisms have been suggested to explain the role of gut microbiota in the aetiology of obesity such as short chain fatty acid production, stimulation of hormones, chronic low-grade inflammation, lipoprotein and bile acid metabolism, and increased endocannabinoid receptor system tone. However, evidence from animal and human studies clearly indicates controversies in determining the cause or effect relationship between the gut microbiota and obesity. Metagenomics based studies indicate that functionality rather than the composition of gut microbiota may be important. Further mechanistic studies controlling for environmental and epigenetic factors are therefore required to help unravel obesity pathogenesis.

How well does the capillary thyroid-stimulating hormone test for newborn thyroid screening predict the venous free thyroxine level?

OBJECTIVES: To determine, in newborn infants referred with elevated capillary thyroid-stimulating hormone (TSH), a threshold below which a frankly subnormal venous free thyroxine (fT4) level of <10 pmol/L is unlikely, so that treatment with levo-thyroxine (L-T4) might be deferred until venous thyroid function tests (TFTs) become available. SUBJECTS AND METHODS: All infants referred in Scotland since 1979 with capillary TSH elevation were studied, with particular focus on infants screened using the AutoDELFIA assay between 2002 and 2013. RESULTS: Of the 321 infants referred with capillary TSH elevation using AutoDELFIA, 35 were excluded (fT4/TSH unavailable (12), venous sample either preceding or >10 days after capillary sampling (13, 10)), leaving 286 eligible for analysis (208 definite/probable hypothyroidism, 61 transient TSH elevation, 17 of uncertain thyroid status). Capillary TSH and venous T4 were strongly correlated (Spearman's rank correlation coefficient -0.707355). The optimal capillary TSH threshold for predicting a venous fT4 of <10 pmol/L was found to be >40 mU/L (90.3% sensitivity and 65.9% specificity compared with 90.25% and 59.1% for >35 mU/L and 88.3% and 68.2% for >45 mU/L). 93 infants (32.5%) had capillary TSH ≤40 mU/L at referral of whom 15 (9.7%) had venous fT4 <10 pmol/L, comprising seven with true congenital hypothyroidism, five with transient TSH elevation and three with uncertain status, two of whom died. CONCLUSION: For infants in whom capillary TSH is ≤40 mU/L, it is reasonable to defer L-T4 treatment until venous TFT results are known provided that the latter become available quickly.

The pitfalls associated with urinary steroid metabolite ratios in children undergoing investigations for suspected disorders of steroid synthesis.

BACKGROUND: Urinary steroid metabolite ratios may improve the diagnostic yield of potential disorders of steroid hormone synthesis. OBJECTIVES: To investigate the range of ratios and their predictive value in children with suspected disorders of steroid synthesis. DESIGN AND METHODS: Twelve ratios were calculated on steroid metabolite data analysed by gas chromatography-mass spectrometry in urine samples collected between 2008-2010 from 93 children. Urine samples were also analysed in 252 children with no known endocrine concerns. RESULTS: Of the 252 controls, 115 (46%) were male with a median age of 10 yr (range 1 month,18.5 years). Of the 93 cases, 38 (41%) were male with a median age of 6.5 yr (1 day,18.5 yrs). Of these, 41 (44%) had at least one ratio greater than the 95% percentile for controls. The most frequently abnormal ratio, found in 18/93 (19%) cases was (THS/(THE + THF + 5αTHF)) suggestive of 11ß-hydroxylase deficiency. Over this period, 8 (9%) children were subsequently diagnosed with a steroid hormone disorder; 4 with 21-hydroxylase deficiency, 2 with11ß-hydroxylase deficiency and 2 with 5α-reductase deficiency. All except one of these children had at least 1 raised ratio. CONCLUSIONS: Urinary steroid metabolite ratios in suspected disorders of hormone synthesis often exceed the reference range for normal children. The predictive value of steroid metabolite ratios in identifying a genetic abnormality may be condition specific and needs further study to improve its clinical utility.

Early identification of pituitary dysfunction in congenital nasal pyriform aperture stenosis: recommendations based on experience in a single centre.

BACKGROUND: Congenital nasal pyriform aperture stenosis (CNPAS) is an increasingly recognised cause of upper airway obstruction associated with midline abnormalities. Studies have described pituitary dysfunction in 40% of patients. We aimed to develop guidelines for: (a) the early identification of pituitary insufficiency to minimise surgical risk and (b) to stratify patients for follow-up. METHODS: Retrospective case note review of patients with CNPAS between 2000 and 2014 in a tertiary paediatric unit. RESULTS: 20 patients (12 female:8 male) were analysed; 16 were diagnosed during the neonatal period while 4 were diagnosed later. There was no consistent approach in the evaluation of the pituitary axis at diagnosis. Pituitary dysfunction was identified in 3 (15%) patients, 2 of whom were found during evaluation of short stature in mid-late childhood. Hypoglycaemia and conjugated hyperbilirubinaemia, but not the degree of stenosis, were highly predictive of pituitary dysfunction (p < 0.05). Available height standard deviation score (SDS) data at 1 year of 70% of our patients identified both of the late-diagnosed growth hormone-deficient patients, with SDS of -2.6 and -3.6, respectively. CONCLUSION: All CNPAS patients should have MRI of the brain and baseline endocrine investigations at diagnosis. Growth monitoring for at least 1 year is recommended as low, or falling, height SDS at 1 year is a good predictor of pituitary dysfunction.

Deficits in Trabecular Bone Microarchitecture in Young Women With Type 1 Diabetes Mellitus.

The pathophysiological mechanism of increased fractures in young adults with type 1 diabetes mellitus (T1DM) is unclear. We conducted a case-control study of trabecular bone microarchitecture and vertebral marrow adiposity in young women with T1DM. Thirty women with T1DM with a median age (range) age of 22.0 years (16.9, 36.1) attending one outpatient clinic with a median age at diagnosis of 9.7 years (0.46, 14.8) were compared with 28 age-matched healthy women who acted as controls. Measurements included MRI-based assessment of proximal tibial bone volume/total volume (appBV/TV), trabecular separation (appTb.Sp), vertebral bone marrow adiposity (BMA), and abdominal adipose tissue and biochemical markers of GH/IGF-1 axis (IGF-1, IGFBP3, ALS) and bone turnover. Median appBV/TV in cases and controls was 0.3 (0.22, 0.37) and 0.33 (0.26, 0.4), respectively (p = 0.018) and median appTb.Sp in T1DM was 2.59 (2.24, 3.38) and 2.32 (2.03, 2.97), respectively (p = 0.012). The median appBV/TV was 0.28 (0.22, 0.33) in those cases with retinopathy (n = 15) compared with 0.33 (0.25, 0.37) in those without retinopathy (p = 0.02). Although median visceral adipose tissue in cases was higher than in controls at 5733 mm(3) (2030, 11,144) and 3460 mm(3) (1808, 6832), respectively (p = 0.012), there was no difference in median BMA, which was 31.1% (9.9, 59.9) and 26.3% (8.5, 49.8) in cases and controls, respectively (p = 0.2). Serum IGF-1 and ALS were also lower in cases, and the latter showed an inverse association to appTbSp (r = -0.30, p = 0.04). Detailed MRI studies in young women with childhood-onset T1DM have shown clear deficits in trabecular microarchitecture of the tibia. Underlying pathophysiological mechanisms may include a microvasculopathy.

Review of growth hormone therapy in adolescents and young adults with Prader-Willi syndrome.

Consensus guidelines from the Growth Hormone Research Society Workshop recommend growth hormone therapy in all children with genetically confirmed Prader-Willi syndrome (PWS) in combination with dietary, lifestyle and environmental interventions. As yet, however, there are limited published data regarding the use of growth hormone therapy in adolescents and young adults with PWS. This review focuses on the advantages and disadvantages of growth hormone therapy in this particular group. The risk of complications, challenges with consent for therapy, the need for contraception in females with PWS and the appropriate monitoring required are all factors which must be carefully considered in this challenging patient group. Transition from paediatric to adult services can be difficult for most adolescents, but especially so for PWS adolescents and should be undertaken under the care of experienced paediatric and adult endocrinologists and a multidisciplinary team approach. Further research is, however, still required in the management of PWS patients during adolescence.