bluuebunny/crossref_metadata_2025_split huggingface dataset:
7080 Copy Number Variation (CNV) in Self-Limited Delayed Puberty (SLDP)
Authors: Al-Sayed Y , Ishida M , Hall C L , Howard S 
Published: October 2024

Abstract
Disclosure: Y. Al-Sayed: None. M. Ishida: None. C.L. Hall: None. S. Howard: None.
SLDP is where the onset of puberty is more than 2-2.5 standard deviations later than the population mean age and is often familial with strong genetic determinants. The reproductive axis is regulated by gonadotropin-releasing hormone (GnRH), which plays a crucial role in initiating puberty and maintaining fertility through its pulsatile secretion. Disruption in GnRH neuron development or hypothalamic function can lead to DP. UK Biobank data has identified negative health outcomes associated with SLDP including early menopause/andropause and cognitive and psychosocial disabilities. Consequently, there has been extensive research to investigate genes affecting the hypothalamic-pituitary-gonadal (HPG) axis that might be implicated in the pathogenesis of DP by our group and others which has identified sequence variation contributing to the aetiology of SLDP. However, factors beyond nucleotide variations, such as epigenetic changes and CNVs can also lead to pubertal timing disorders. Moreover, CNVs are seen in multiple individuals (n=92) from the Deciphering Developmental Disorders study (https://www.deciphergenomics.org) with a phenotype including DP (HP:0000823). We performed whole genome sequencing on 49 probands with SLDP and subsequently, analysed the data for CNV. The data was initially called, annotated, filtered then partitioned for classification of CNVs using a command-line tool that implements the ACMG guidelines to evaluate the pathogenicity of germline duplications and deletions. Using an unbiased candidate gene approach, we identified several deletions that affected 60 known/predicted dosage sensitive genes and combines with functional enrichment analysis; This approach revealed potential molecular pathways and biological processes involved in the pathogenesis of SLDP, including histone acetylation, and neural plate development. To refine our findings, we applied additional filters, including known HPG axis genes, GWAS loci associated with pubertal timing, decipher CNV tracks, and DP gene panels, to narrow down large number of rare predicted damaging CNVs and prioritize those with potential relevance to DP. Our study highlights the potential role of CNVs in DP and expands our understanding of the molecular pathways and biological processes involved in this condition, shedding light on the complex mechanisms underlying DP.
Presentation: 6/2/2024
12288 Diabetes Wearable Technology In Children Less Than Six Years At A Large Urban Diabetes Center
Authors: Citron-Zafrin Kate , Richter Laruen , Williams Kristen , Gandica Rachelle , Vargas Ileana , Leibel Natasha 
Published: October 2024

Abstract
Disclosure: K. Citron-Zafrin: None. L. Richter: None. K. Williams: None. R. Gandica: None. I. Vargas: None. N. Leibel: None.
Introduction/Background: Type 1 diabetes (T1D) is one of the most common chronic diseases in pediatrics. T1D is particularly challenging to manage in children under 6 years old due to unpredictable eating patterns, rapid growth, and risk of extreme blood glucose levels. Diabetes wearable technology (insulin pumps and continuous glucose monitors (CGMs)) has become increasingly prominent, but its use has not been well described in this age group. Objectives: We sought to characterize our experience with technology use in children with T1D less than 6 years old. Design/Methods: Retrospective chart review of 82 youth diagnosed with T1D before 6 years old, seen at our center from 2019-2023. Data was collected on demographic information, insurance type, use of insulin pump and CGM, hemoglobin A1c (A1c), diabetic ketoacidosis (DKA) and hypoglycemic events. We used chi-square statistics to compare variables in our population with reported national data. Results: In this cohort, 80% used insulin pumps and 100% used CGMs, an increase from previously reported data (56% insulin pump use and 44% CGM use in those less than 6yo, p&lt;0.001). 54% had private insurance. There were more individuals with family members with T1D compared to reported data (35% vs. 22%, p=0.0041). The median age at diagnosis was 34 months, median time from diagnosis to pump start was 3.5 months. After diagnosis, 1 pump user and 1 multiple daily injections (MDI) user had DKA. One MDI user had hypoglycemia requiring intervention. Average A1C 12 months after diagnosis was 7.9% in the pump group and 8.2% in the MDI group. Hybrid closed loop pump users had an average A1C 6 months after placement of 7.7%. Conclusions: At our urban academic diabetes center, there was higher use of diabetes wearable technology as compared with previously reported data in this age group. There were more individuals with relatives with T1D compared to reported averages. The low rates of DKA and hypoglycemic events seen in this population support that these technologies can be used safely and soon after diagnosis. Although improved from national data, tight glycemic control remains a challenge in this very young age group.
Presentation: 6/1/2024
7697 Co-existing Overt Cushing Syndrome And Primary Aldosteronism Secondary To Unilateral Adrenal Adenoma
Authors: Tarrazona - Dominisac R , Lantican M , Aragon J B 
Published: October 2024

Abstract
Disclosure: R. Tarrazona - Dominisac: None. M. Lantican: None. J.B. Aragon: None.
Overt Cushing's syndrome and primary aldosteronism are two uncommon yet distinct adrenal disorders. Rarely do they coexist, complicating diagnosis and management. Here, we present a case of a 42 year old woman with a complex clinical profile for the past 21 months, marked by amenorrhea, weight gain, abdominal enlargement, new-onset hypertension, hyperglycemia, proximal myopathy, easy fatigability, and difficulty concentrating. A comprehensive physical examination and endocrine work-up confirmed coexistence of Cushing’s syndrome and primary hyperaldosteronism due to a left adrenal adenoma. Laparoscopic unilateral adrenalectomy was performed as definitive treatment of the functional tumor which resulted in substantial clinical improvement thereafter. This case highlights the importance of precise diagnosis and appropriate management in rare combined disorders, ultimately ensuring favorable patient outcomes.
Presentation: 6/1/2024
8347 EARLY CHILDHOOD GROWTH FOLLOWING PRE-PREGNANCY METABOLIC AND BARIATRIC SURGERY
Authors: Hilaire Maya J , Babcock Annelise , White Glenn , Masson Cynthia , LeDuc Charles A , Thaker Vidhu 
Published: October 2024

Abstract
Disclosure: M.J. Hilaire: None. A. Babcock: None. G. White: None. C. Masson: None. C.A. LeDuc: None. V. Thaker: None.
Background and Aims: Metabolic and bariatric surgery (MBS) is known to improve metabolic profile. There is conflicting data on the effects of pre-pregnancy MBS on the offspring growth. We aimed to assess offspring early life growth trajectory born to mothers with MBS before conception compared to those who did not. Methods: Records from pregnancies of women who gave birth at Columbia University Irving Medical Center between January 2020 and March 2023 were collected from the clinical databases and electronic health records. The gestational conditions and offspring early life weight, length and BMI trajectory were compared for: pre-pregnancy BMI &lt; 25, BMI 25-35, BMI &gt; 35 and prior MBS. Mixed effect models were used to compare the longitudinal anthropometric trajectories. Sensitivity analyses was done with propensity matching of the pre-pregnancy MBS group by maternal age, parity, pre-pregnancy BMI and race/ethnicity. Results: Of the 22,111 deliveries with data (51% Hispanic/Latino), 455 (76% Hispanic/Latino) had pre-pregnancy MBS- predominantly sleeve gastrectomy (SG, 57%) or Roux-en-Y Gastric Bypass (RYGB, 41%). Antepartum BMI was 32.5 kg/m2 (SD 6.3) for those with pre-pregnancy MBS with 89.8% pregnancies occurring 1-10 years after surgery. There was a higher proportion of multiparous individuals (42% vs 19-31%) in the MBS group. Pre-pregnancy MBS was associated with lower gestational weight-gain, diabetes, and hypertension compared to those with BMI &gt; 35. For offspring, there was no difference in the birth weight, proportion of SGA was higher (6.6% vs 2.5-2.7%, p &lt; 0.01), LGA was lower (2.0% vs 3.6-5.6%, p &lt; 0.01) and NICU admission rate was comparable (20% vs 15-25%). Offspring anthropometric data till age 36 months was available for approximately 50% of the births. Comparison of longitudinal weight trajectories showed no difference in the offspring between those born after RYGB and BMI &lt; 25 kg/m2 (p =0.8), while those born after SG had persistent rise (p =0.04), adjusting for maternal age, parity, time since surgery and race/ethnicity. In the SG group, boys had higher weight trajectories compared to girls. (p &lt; 0.001). The length trajectories and head circumference at birth were similar across groups. Conclusions: Gestational conditions improved with pre-pregnancy MBS. Pre-pregnancy RYGB, but not SG, was followed by favorable offspring weight trajectory that may have a role in long-term metabolic programming. This study is limited by lack of availability of information on pregnancy glycemic profiles, eating behaviors, dietary patterns, and other social determinants of health.
Presentation: 6/3/2024
7593 Early re-evaluation using levothyroxine dose requirements in infancy in patients with congenital hypothyroidism
Authors: Yoo Myungji , Joo Eunyoung , Kim Su Jin , Lee Ji-Eun 
Published: October 2024

Abstract
Disclosure: M. Yoo: None. E. Joo: None. S. Kim: None. J. Lee: None.
Background: Congenital hypothyroidism (CH) is the most common endocrine disorder in the neonatal period. CH can lead to permanent mental retardation if left untreated. The prevalence of CH has recently increased due to neonatal screening programs for CH. Congenital Hypothyroidism: The 2020-2021 Consensus Guidelines Update, recently published in the Endo-European Reference Network (Endo-ERN), suggested that a reevaluation of early treatment withdrawal after 6 months could be performed in patients with CH. In Korea, there has been no study on early reevaluation after 6 months, so we conducted this study. Methods: As a retrospective study, patients diagnosed with CH from January 2013 to December 2022 at the Department of Pediatrics, Inha University evaluated thyroid function tests (TFT) at the time of diagnosis and LT4 dose and body weight during treatment. Results: A total of 105 patients were diagnosed with CH, 64 were classified as transient CH (TCH) and 41 as permanent CH (PCH). Patients younger than 2 years who did not complete the reevaluation were excluded. At diagnosis, thyroid stimulating hormone (TSH) levels were higher in the PCH group than in the TCH group (47.8 ± 58.0 mIU/L vs 69.2 ± 94.1 mIU/L, respectively). At 6 months, 1 and 2 years, the mean dose of levothyroxine (μg/kg/day) was significantly lower in the TCH group than in the PCH group. (3.34 ± 0.94 vs 3.63 ± 1.03 μg/kg/day, p&lt;0.05, 2.56 ± 0.95 vs 3.16 ± 1.14 μg/kg/day, p&lt;0.01 and 2.07 ± 0.57 vs 3.01 ± 1.14 μg/kg/day, p&lt;0.01). Based on the Receiver Operating Characteristic (ROC) curve, the optimal cutoff doses of LT4 for prediction of TCH at 6 month was 3.24 µg/kg/day (area under the curve=0.643; 95% CI, 0.529-0.757; sensitivity, 58.6%; specificity, 70.3%) Conclusion: Early re-evaluation after 6 month for withdrawal of LT4 treatment is possible in patients with CH if the patient has gland in situ, no family history, and low LT4 dose requirements.
Presentation: 6/1/2024
8118 Effect of Rurality on Diabetes Technology Use Among Medicaid-Insured Youth Enrolled in a Mid-Western Accountable Care Organization
Authors: Bell-Sambataro Esther Eunice , Kilbarger Joshua , Lahoti Amit , Ladd Jennifer M 
Published: October 2024

Abstract
Disclosure: E.E. Bell-Sambataro: None. J. Kilbarger: None. A. Lahoti: None. J.M. Ladd: None.
Background: Diabetes technology (continuous glucose monitors (CGM) and insulin pumps), is associated with improved glycemic control and quality of life in children with type 1 diabetes (T1D), but technology use is not equitable. We explored whether rural/urban disparities exist in CGM and pump use among pediatric patients with T1D enrolled in an Accountable Care Organization (ACO) and thus on Medicaid. Methods: We conducted a retrospective cohort study using claims data from the central Ohio ACO database from January 1, 2018 to September 30, 2022. Individuals aged 1 to &lt;21years were identified using T1D-specific billing codes. CGM or pump use was defined using established prescription codes. Rurality was based on zip codes of residence linked to RUCA codes. For descriptive analyses, we calculated proportions, means and standard deviations. T-tests were used to compare continuous variables; chi-square tests were used to compare categorical variables. Multivariable Poisson regression was used to model the association between rurality and CGM or pump use, adjusted for age, sex, race, and era (pre-/post-COVID pandemic). Results: We identified 1079 enrolled individuals with T1D during the study period; 878 (81.4%) were using CGM and 259 (24%) were using insulin pumps. In descriptive analysis, CGM users were younger than non-users (users 11.4±4.4years vs non-users 15.3±3.8years, p&lt;0.01). The distribution of rurality between CGM users and non-users was similar (users 73.5% urban, 26.3% rural vs non-users 66.6% urban, 33.3% rural, p=0.05). There were no age or rurality differences between pump users and non-users (users 12.2±3.8years vs non-users 12.1±4.8years, p=0.86; users 72.6% urban vs non-users 72.1% urban, p=0.92). In regression modeling, rurality was not significantly associated with CGM use (adjusted risk ratio (aRR) 0.95, 95% confidence interval (CI) 0.89-1.02) whereas age, race, era, and pump use were significantly associated. Rurality was significantly associated with pump use (aRR 0.79, 95% CI 0.63-0.99) as were age, race and era. Conclusions: In this cohort limited to pediatric patients with T1D on Medicaid, rural residence did not have a significant effect on CGM use but did make pump use less likely. Those of older age or non-White race were significantly less likely to use CGM and pumps. Future efforts targeting these disparities should be undertaken to increase use of these standard of care technologies among all children.
Presentation: 6/2/2024
6971 Effects of the Hybrid Closed-loop System in Pediatric-Onset Type 1 Diabetes
Authors: Woo H , Yoo J , Shin S , Lee Y , Kim H , Gu M , Kim J , Kim J , Shin C , Lee Y 
Published: October 2024

Abstract
Disclosure: H. Woo: None. J. Yoo: None. S. Shin: None. Y. Lee: None. H. Kim: None. M. Gu: None. J. Kim: None. J. Kim: None. C. Shin: None. Y. Lee: None.
Purpose: We evaluated the effectiveness and limitations of the MiniMedTM 770G, a hybrid closed-loop (HCL) system which adjusts basal insulin every five minutes using continuous glucose monitoring (CGM) data, for glycemic control in pediatric-onset type 1 diabetes (T1D) in South Korea. Methods: We enrolled 20 patients (10 boys and 10 girls) who had been using the 770G pump for over three months, initiating its use between February 2022 and May 2023. Prior to this, they were CGM users and were followed for over a year post T1D diagnosis. Clinical and biochemical data, along with CGM metrics such as time in range (TIR), time below range (TBR), time above range (TAR), and coefficient of variation (CV), were analyzed. Additionally, the percentage of SmartGuard Auto Mode system usage was collected. Results: The median age at the start of 770G was 13.97 years (IQR 11.24–17.86), with a median of 6.5 years of duration of type 1 diabetes. After utilizing the 770G pump (n=20), TIR, TAR, and CV improved over the year (P&lt;0.05). Patients utilizing Auto Mode over 85% of the time exhibited significant improvements in HbA1c (P=0.02), TIR (P=0.04), CV (P&lt;0.01), and TAR 250 (P=0.02), in contrast to those who used Auto Mode 85% or less. Hyperglycemia and lack of calibration contributed to over 50% of the exits from Auto Mode. Conclusions: The implementation of HCL in adolescents and young adults with T1D enhanced glycemic control over one year. Educating patients on sustained Auto Mode use without interruptions is crucial.
Presentation: 6/2/2024
6729 Exploring the Body Composition of Pediatric Patients With Growth Hormone Deficiency and Idiopathic Short Stature Under RecombinantGH Treatment
Authors: Zaitoon Hussein , Yackobovitch-Gavan Michal , Midlij Eyas , Uretzky Adi , Laurian Irina , Dorfman Anna , Interator Hagar , Lebenthal Yael , Brener Avivit 
Published: October 2024

Abstract
Disclosure: H. Zaitoon: None. M. Yackobovitch-Gavan, PhD: None. E. Midlij: None. A. Uretzky: None. I. Laurian: None. A. Dorfman: None. H. Interator: None. Y. Lebenthal, MD: None. A. Brener: None.
Background: Growth hormone (GH) is an anabolic hormone that stimulates protein accretion in skeletal muscle. Treatment for growth hormone deficiency (GHD) and idiopathic short stature (ISS) in children and adolescents by means of recombinant human growth hormone (rGH) is mainly aimed at linear growth augmentation, while its impact on body composition remains obscure. Methods: This retrospective observational study included 305 bioimpedance analysis (BIA) reports of pediatric patients with GHD and those with ISS whose clinical data were extracted from medical records. Generalized estimating equations linear models were used to explore the contributing factors for body composition components of the appendicular skeletal muscle mass (ASMM) and the muscle-to-fat ratio (MFR) z-scores while adjusting for cumulative doses of rGH. Results: Of the 135 pediatric patients enrolled in the study, 89 (65.9%) were boys. This group included 64 patients diagnosed with GHD and 71 with ISS. Those with GHD exhibited significantly higher body mass index z-scores (p&lt;0.001), higher fat percentages (FATP), higher truncal FATP scores, lower MFR z-scores, and higher diastolic blood pressure percentiles than the ISS group (p=0.010, p=0.027, p=0.050, and p=0.050, respectively). Female sex (p=0.049) and ISS diagnosis (p=0.005) were major contributors to higher MFR z-scores, while female sex (p&lt;0.001), older age (p&lt;0.001), and higher insulin-like growth factor 1 (IGF1) z-scores (p=0.021) were major contributors to higher ASMM z-scores. Socioeconomic position and cumulative rGH dose did not significantly contribute to body composition parameters. Conclusion: This study demonstrated an inclination towards increased adiposity in young individuals with GHD compared to those with ISS, while the muscle component remained unaffected. Considering the influence of IGF1 on the regulation of muscle mass, treating GHD with rGH with the aim of attaining normal IGF1 levels could temper the elevated adiposity in affected patients.
Presentation: 6/3/2024
7494 Glycerol Phenylbutyrate Treatment of Two Patients with Monocarboxylate Transporter 8 Deficiency
Authors: Zung A , Sonntag N , Schweizer U , Banne E , Braun D 
Published: October 2024

Abstract
Disclosure: A. Zung: None. N. Sonntag: None. U. Schweizer: None. E. Banne: None. D. Braun: None.
Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Currently, the two thyromimetic agents 3,5-diiodothyropropionic acid (DITPA) and triiodothyroacetic acid (TRIAC) have been evaluated in the treatment of these patients, as they both partially restore intracellular TH action independent of MCT8. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods: We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, serum markers of peripheral hyperthyroidism, vital signs, anthropometric measurements and neurocognitive functions by several neurodevelopment validated tests. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P32[1]L mutation. Results: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment yielded a dose-dependent decrease in FT3 and an increase in FT4 serum levels. The patients showed an elevation in cholesterol levels in parallel with GPB dose, but sex-hormone binding protein (SHBG), another marker of peripheral hyperthyroidism was not affected. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, mainly in hyperreflexia score, slight improvement in gross motor functions and a mild progression in cognitive functions. Serum metabolites of GPB did not exceed the toxic range but elevated liver transaminases restricted the dose intensification of GPB. Conclusions: In the first report of GPB treatment in MCT8 deficiency patients we found an improvement in TH profile and body-mass index (BMI). The reduction in T3 levels could contribute to the remarkable increase in BMI-SDS, since various aspects of peripheral hyperthyroidism in MCT8 deficiency, including poor weight gain, were attributed to elevated T3. The limited effects of GPB treatment on cognitive and motor functions can derive from the advanced age of the patients at the time of the intervention.
Presentation: 6/2/2024