bluuebunny/crossref_metadata_2025_split huggingface dataset:
6379 Clonidin does not stimulate copeptin release
Authors: Binder G , Weber K , Peter A , Schweizer R 
Published: October 2024

Abstract
Disclosure: G. Binder: None. K. Weber: None. A. Peter: None. R. Schweizer: None.
Background: Copeptin is secreted in isomolar amounts along with arginine vasopressin peptide from the posterior pituitary. Its stability makes it a perfect candidate for a biomarker of AVP deficiency. In children, the infusion of arginine and bolus of insulin stimulate copeptin; the respective stimulation test could be an alternative to the water deprivation test. Here, we retrospectively studied the effect of clonidine on copeptin release. Design and patients: This is a monocentric retrospective analysis of donated residual serum samples from 42 children with suspected of GH deficiency who underwent clonidine stimulation between 2020 and 2023. Measurements: Copeptin was measured in baseline, 30-, 60-, 90- and 120-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. GH was measured using an in-house RIA calibrated against the WHO International Reference Preparation 98/574. Results: According to the test results (clonidine and arginine test), there were 20 patients with GHD and 16 without GHD. No patient had polyuria-polydipsia syndrome. Median age was 6.7 years (quartiles; 5.6-7.8), the median height was -2.92 SDS (-3.42- -2.34), and the median BMI was-0.29 SDS (-1,32 - +0,16). The median baseline level of copeptin was 5,6 pmol/l (3.4-9.6). Median copeptin mildly decreased to 4.5 pmol/l (3.0-10.0) after 30 min; this change was not significant (P=0.45). Thereafter, median values remained low at 4.6, 4.6 and 4.6 pmol/l (60, 90 and 120 min). There was no correlation between baseline copeptin levels and the diagnosis of GHD. Conclusion: The clonidine stimulation test does not stimulate copeptin release and is therefore not suitable for the assessment of AVP deficiency in children.
Presentation: 6/2/2024
8644 Dynamic Insights into Glucocorticoid Receptor Dysfunction: Novel patient-derived T437I Mutation and Its Impact on Glucocorticoid Receptor Function
Authors: Tettey Theophilus , Kim Sohyoung , Wagh Kaustubh , Lao Qizong , Schiltz Louis R , Lafuente Agustina , Stavreva Diana A , Presman Diego Martin , Merke Deborah P , Hager Gordon L 
Published: October 2024

Abstract
Disclosure: T. Tettey: None. S. Kim: None. K. Wagh: None. Q. Lao: None. L.R. Schiltz: None. D.A. Stavreva: None. D.M. Presman: None. D.P. Merke: None. G.L. Hager: None.
The glucocorticoid receptor (GR) is a hormone regulated transcription factor which binds chromatin to regulate many genes, including stress-response and inflammatory genes. Dexamethasone, a GR agonist, is widely used in the treatment of severe inflammation, including COVID-19. GR is vital for life and several GR mutations have been linked to severe pathophysiological conditions. Here we report a novel mutation in the DNA binding domain (DBD) of GR (T437I) in a patient with partial glucocorticoid resistance, a rare genetic disorder characterized by generalized insensitivity to glucocorticoids and a consequent hyperactivation of the hypothalamic pituitary adrenal axis. While the clinical manifestations of this hT437I GR mutation are apparent, its molecular mechanisms remain unexplored. Employing a comprehensive approach that integrates biophysical methods, molecular biology, and genomics, we investigate the molecular underpinnings of this genetic anomaly. Using CRISPR/Cas9 gene editing, we introduce GFP or Halo-tagged hT437I GR mutant into GR null mouse cells. Our findings indicate that the T437I GR variant exhibits normal hormone binding and nuclear translocation. Live-cell imaging using number and brightness analysis reveals that the mutant receptor maintains a wildtype-like oligomeric state but adopts a heterodimeric conformation in the presence of endogenous GR. Global transcriptomics analyses of the mouse hT437I mutant show that most dexamethasone-regulated genes are unresponsive following hormone treatment. We hypothesize that this mutation within the DBD compromises the binding of GR to regulatory sites of target genes. Leveraging fluorescence high-resolution microscopy, we employ single molecule tracking to study the dynamic behavior of Halo-tagged hT437I GR in mouse cells. Our results indicate that the GR mutant has a higher dwell-time on chromatin compared to the wild-type receptor. This suggests that the hT437I mutation impairs the receptor's binding to genomic sites, potentially leading to a failure in regulating GR target genes. This ongoing exploration of the molecular intricacies aims to deepen our understanding of the clinical phenotype observed in the patient.
Presentation: 6/2/2024
12599 Early Remission Of Chromosome 6 Q 24-related Neonatal Diabetes Mellitus
Authors: Pratibha Rana , Dummula Krishna 
Published: October 2024

Abstract
Disclosure: R. Pratibha: None. K. Dummula: None.
Introduction: Chromosome 6q24 imprinting abnormalities represent the predominant cause of transient neonatal diabetes mellitus (TNDM), accounting for over two-thirds of cases with an estimated prevalence of 1 in 400,000. While remission typically manifests by 3 months of age, herein we detail a case of Chromosome 6q24-related TNDM exhibiting remission by 1.5 months of age. We share our clinical experience in managing this case without hypoglycemia and using C-Peptide levels as a monitoring tool to track the resolution. Case: A female infant, born at 36 weeks via elective C-section due to fetal growth restriction and oligohydramnios, was closely monitored in the nursery for potential hypoglycemia. Contrary to the expectation, she displayed escalating hyperglycemia, necessitating insulin infusion within 25 hours of birth. Apgar scores were 7 and 9, and the birth weight was 2095 g (6th percentile). Maternal history included impaired glucose tolerance in a previous pregnancy with borderline glucose tolerance during this gestation. The newborn physical exam was unremarkable except for mild macroglossia. Despite initial blood glucose (BG) of 52 mg/dl, it rose to 257 mg/dL by 16 hours. Insulin drip was started at 24 hours due to BG of 304 mg/dL. The monogenic diabetes panel obtained on day of life (DOL) #2 was negative; no acidosis was observed. The C- Peptide was low at 0.2 ng/ml. Insulin infusion was continued until DOL # 20. A trial of glyburide commenced on DOL #9 while on Insulin drip, yielded minimal response, prompting a transition to short-acting insulin for correction of hyperglycemia (&gt;250 mg/dL). C-peptide level during sulfonylurea (SU) trial remained low (0.5 ng/mL). The infant required 2 to 3 corrections per day with 0.05 units of Lispro Insulin, with the last dose administered at 44 days. She did not receive any long-acting Insulin. As of her last follow-up at the endocrine clinic at 57 days of age, the infant is thriving well and has normal blood glucose levels. The 6q24 Methylation-MLPA study showed duplication of 6q24 on the paternally inherited chromosome 6. Significantly, she never encountered hypoglycemia during her hospital stay. The C-peptide increased to 0.8 ng/ml at DOL#37 and had normalized to 1.3 ng/mL by DOL#57 indicating remission of TNDM. Conclusion: 6q24-related TNDM may often be characterized by features such as small for gestational age (SGA), macroglossia, umbilical hernia, cardiac and renal abnormalities. Early presentation of hyperglycemia with this phenotype must prompt its diagnostic evaluation. Early resolution by 1.5 months as seen in our case is uncommon. Uniquely, we used C-peptide as a tracking tool to guide resolution and manage insulin therapy.
Presentation: 6/3/2024
7866 Efficacy of Zinc and Myoinositol Supplementation on Metabolic Parameters In A Pediatric Population With Obesity: a Randomized Controlled Trial
Authors: Antoniotti Valentina , Mancioppi Valentina , Solito Arianna , Partenope Cristina , Petri Antonella , Rabbone Ivana , Scotti Lorenza , Prodam Flavia , Bellone Simonetta 
Published: October 2024

Abstract
Disclosure: V. Antoniotti: None. V. Mancioppi: None. A. Solito: None. C. Partenope: None. A. Petri: None. I. Rabbone: None. L. Scotti: None. F. Prodam: None.
Background: In the last decades, pediatric obesity and cardiovascular-associated risks have been relevant challenges. The first treatment against obesity is a lifestyle change, nevertheless, no intervention seems to be effective in the evolution of the condition, especially in the long term. Thus, the interest in non-pharmaceutical as well as pharmaceutical compounds is growing. Inositol compounds have recently been studied in adults with obesity and insulin resistance but have never been investigated in the pediatric age where insulin resistance is a specific trait of puberty. Furthermore, zinc is critical for insulin secretion and growth. Methods. This is a double-blind, randomized, placebo-controlled study aiming to explore the efficacy of 3 months of combined administration of Zinc (5 mg/die) and Myo-inositol (2000 mg/die) in children and adolescents with obesity. 56 patients aged 10- 17.9 years (starting from Tanner 3) with obesity and insulin resistance have been enrolled. The treatment group received 5 mg of Zinc, 2000 mg of Myo-inositol, and 1000 mg of galactooligosaccharides from Pisum sativum, while the placebo group only received 1000 mg of galactooligosaccharides from Pisum sativum. All patients were subjected to an isocaloric diet following the Mediterranean diet style consisting of 55% carbohydrates, 30-35% fat, and 15% protein. Clinical and biochemical evaluations were carried out for the determination of weight, lipid profile, liver function, and glucose-insulin metabolism. Results. At the end of the study, BMI, fasting insulin, and insulin resistance (HOMA-IR) were significantly improved in both groups, while the treatment group also had an increase in HDL cholesterol (p=0.0426). On the other hand, the placebo group significantly improved its eating habits showing greater adherence to the Mediterranean diet than the treatment group. Moreover, subjects were divided according to the degree of obesity. Fasting insulin (p= 0.0137), HOMA-IR (p= 0.0273), and systolic blood pressure (p= 0.0349) showed a significant improvement in treated patients with severe obesity compared to treated patients with low-grade obesity. Thus, subjects with a higher level of obesity respond better to both treatment and lifestyle change than those with a lower grade of obesity. Also, the improvement of the lifestyle and the presence of fiber allow an increase in the metabolic framework in placebo subjects. Conclusions. Supplementation with Zinc and Myo-inositol could be used as a non-pharmacological compound for the control of complications related to obesity also in the pediatric age.
Presentation: 6/1/2024
12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection
Authors: Pratibha R , Langner T R 
Published: October 2024

Abstract
Disclosure: R. Pratibha: None. T.R. Langner: None.
Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient.
Presentation: 6/3/2024
12606 Gamification In The Management Of Children And Adolescents With Diabetes: A Systematic Review
Authors: Hespanhol Larissa C , Lins de Menezes Vanessa , Souto Maia Paula Christianne G G , Balieiro Caroline Cristine Almeida , Oliveira Amador Wellgner Fernandes , Lira Rafaelle C 
Published: October 2024

Abstract
Disclosure: L.C. Hespanhol: None. V. Lins de Menezes: None. P. Souto Maia: None. C.A. Balieiro: None. W. Oliveira Amador: None. R. Lira: None.
Background: Educating children and adolescents with diabetes about their own condition presents a significant challenge. Gamification has been proposed as an innovative approach to ease the transition to self-care by engaging and empowering children and adolescents in their diabetes management. Purpose: The purpose of this systematic review is to examine published research on using gamification and technology within diabetes care for young patients. Methods: PubMed, Lilacs and EMBASE were systematically searched in January 2024 to include articles focusing on the use of new virtual technologies to improve the clinical and laboratory conditions of children and adolescents with diabetes. The protocol was registered in PROSPERO (ID: CRD42024499381) adhering to PRISMA recommendations. We assessed the risk of bias using RoB-2 and ROBINS-I. Results: A total of 24 studies were included, of which 7 were randomized trials. Age of participants ranged from 5 to 19 years. We identified five gamification strategies (i.e., applications, video games, minigame, robot, or web game) within seven clinical domains (i.e., psychosocial impairment, glycemic control, autonomy, reduced frequency of error, health lifestyle, nutrition, or knowledge about disease). 246 (27%) patients demonstrated reduced emotional distress and increased enjoyment. Reduction of errors such as hypoglycemia and emergency preparedness was identified in 354 (39%) of patients and improvement in glycemic control measured by HbA1c was described in 277 (30%) of patients. Conclusion: Our systematic review gamification has shown promise in fostering autonomy by providing tools that educate young individuals regarding glycemic control, lifestyle choices, injection practices, carbohydrate counting, and other pertinent aspects of diabetes management.
Presentation: 6/1/2024
7795 Gender based differences in peripubertal growth patterns may offer insight into the twofold representation of boys compared to girls among children referred for growth hormone stimulation tests
Authors: Dekel Yuval , Horowitz Lee , Gendelman Raya , Cohen Michal 
Published: October 2024

Abstract
Disclosure: Y. Dekel: None. L. Horowitz : None. R. Gendelman: None. M. Cohen: None.
Background: Growth hormone (GH) stimulation tests are essential in the diagnostic assessment of pediatric GH deficiency (GHD). However, the tests bare multiple limitations, resulting from both intrinsic and child-related factors. Thus, referral decisions are key in making a correct diagnosis. Several studies demonstrated a gender bias in referral for short stature evaluation with a higher proportion of boys referred and diagnosed with GHD. Moreover, the boys had higher height z-scores upon referral. About 100 GH stimulation-tests are conducted annually at our pediatric endocrinology unit. We aimed to characterize the children that underwent GH stimulation-testing between 2017-2021, specifically focusing on differences based on: 1) gender 2) GH secretion status (deficient vs. sufficient). Methods: A retrospective review of charts of children aged 0-18 years that performed GH stimulation-tests at the Rambam pediatric endocrinology unit between the years 2017-2021 was conducted. Children followed at an outside clinic that had a first GH stimulation-test elsewhere, were excluded. Data was collected through the electronic database and by manually screening medical charts. The IBM SPSS statistics package 21 version was used for analysis. Results: Four-hundred children were included in the study, 266 boys (66.5%) and 134 girls (33.5%). Mean age 8.8±4.2 years, mean height z-score -2.3±0.7 and mean mid-parental height standard-deviation-scores (MPH-SDS) -0.6±0.7. The mean difference between MPH-SDS and child height-z-score was 1.7±0.8 SDS. Mean age was younger in girls compared with boys, 7.3±3.3 and 9.6±4.4 years respectively (p&lt;0.001). Age distribution differed between genders, while refferals peaked between 3-4 years of age in both girls and boys, a second peak at 13-14 years of age was evident only in boys. Interestingly, there was no significant difference between boys and girls in height z-score, difference from MPH-SDS or rates of GHD. Overall, 93 (23.3%) children were diagnosed with GHD, 32 girls (24%) and 61 boys (23%). Children with GHD were younger and had higher BMI-SDSs compared to GH sufficient children, age 7.8±3.8, 9.2±4.3 years respectively (p=0.003), BMI z-score 0.17±1.38, -0.47±1.15 respectively (p&lt;0.001). Conclusion: Twice as many boys than girls were referred for GH stimulation tests in our cohort. Based on differences in age distribution, the peripubertal physiologic growth deceleration that occurs later in boys, likely contributes to this finding. This male-to-female ratio is similar to ratios reported in the literature regarding short stature referrals; however, in contrast to the literature, in our cohort it could not be explained by an anthropometric bias in referral criteria.
Presentation: 6/3/2024
7003 Comparative Study Of The Properties And Differences Of Steroidogenesis Inhibitors In Vitro
Authors: Taki Yuki , Kono Takashi , Kono Satomi , Hashimoto Naoko , Nagano Hidekazu , Tanaka Tomoaki 
Published: October 2024

Abstract
Disclosure: Y. Taki: None. T. Kono: None. S. Kono: None. N. Hashimoto: None. H. Nagano: None. T. Tanaka: None.
Objective: Osilodrostat (Osi) is utilized as an inhibitor of cortisol (F) synthesis and is a potent inhibitor of CYP11B2, in addition to CYP11B1. Therefore, we investigated the aldosterone (Ald) and cortisol concentration-dependent inhibitory effects of Osi in vitro, using tissues from 9 cases [5 Aldosterone-producing adenoma (APA) and 4 Cortisol-producing adenoma (CPA)] operated at our institution. Methods: Adrenal tumor surgery specimens were treated with collagenase and cultured on plates. After 3 days, the medium was changed and incubated with osilodrostat or metyrapone (0.0001 to 10 µM). After another 3 days, the medium was collected, and Ald/F concentrations were measured. The IC50 of both drugs for Ald/F were then compared. Results: In APA cases, Osi inhibited at significantly lower concentrations (IC50: 0.003 µM) than Met (0.782 µM; p=0.0159) for Ald; in CPA cases, Osi inhibited with similar potency to Met (IC50: 0.061 µM vs 0.466 µM, p=0.2286) for F. In all cases, Osi inhibited at significantly lower concentrations for Ald than F (IC50: 0.003 µM vs 0.028 µM, p=0.0008). Discussion: Osi is a potent inhibitor of Ald and F production, and its use for PA alone is challenging because clinical trials of Osi for PA were terminated due to concerns about adrenal insufficiency. Therefore, we suggest that Osi may be useful in PA-associated CPA patients for whom surgery is not indicated or as a preoperative drug therapy.
Presentation: 6/1/2024
8304 Growth trajectories of children born preterm and full-term with low birth weight to preschool ages; a nationwide study
Authors: Kang E , Cha J , Na J , Ryu S , Choi Y J , Kim J 
Published: October 2024

Abstract
Disclosure: E. Kang: None. J. Cha: None. J. Na: None. S. Ryu: None. Y. Choi: None. J. Kim: None.
Context: Children born preterm (PT) and full-term with low birth weight (FT-LBW) are known to be at considerable risk of poor growth outcomes. Objective: To investigate the growth trajectories of children born PT and FT-LBW from birth to preschool ages. Methods: A total of 1,150,508 newborns were included in the study, comprising 41,454 children born PT and 38,250 children born FT-LBW, who participated in the first three rounds (4-6, 9-12, 18-24 months) of the National Health Screening Program for Infants and Children (NHSPIC). Growth measurements were obtained from the NHSPIC database and converted into the Z-scores. Growth data at two, four, and six years of age were measured as outcome variables. The impact of being born small on poor growth outcomes was investigated using a generalized estimating equation and Cox proportional hazards regression analysis. Results: The median birth weight of three groups was 2.3kg for PT, 2.4kg for FT-LBW, and 3.2kg for FT control group, respectively. The incidence of short stature defined as height Z-score &lt; -2 standard deviation score (SDS) and failure to thrive (BMI Z-score &lt; -2 SDS) was highest in FT-LBW group, followed by the PT group, and control group. At four years of age, the incidence rates were 6.0% vs. 5.2% vs. 1.9% for short stature and 4.6% vs. 3.9% vs. 1.7% in FTT. The β estimate of height outcome was lower in both the PT and FT-LBW groups with -0.326 SDS in PT and -0.456 SDS in FT-LBW group. Conclusion: The FT-LBW group was consistently shorter and lighter throughout the preschool period than the PT group. This highlights the significance of growth monitoring in high-risk populations.
Presentation: 6/3/2024