bluuebunny/crossref_metadata_2025 huggingface dataset:
6703 Age-Related Reference Intervals for 11-Oxygenated Androgens in Children
Authors: IJsselstijn L , Zellerer R , Oude Engberink R , van Zelst B , van den Berg S A
Published: October 2024

Disclosure: L. IJsselstijn: None. R. Zellerer: None. R. Oude Engberink: None. B. van Zelst: None. S.A. van den Berg: None.

Context: 11-Oxygenated androgens have emerged as major components of several disorders of androgen excess. Levels of 11-keto androstenedione (11KA4), 11β-hydroxy androstenedione (11OHA4), 11-keto testosterone (11KT) and 11β-hydroxy testosterone (11OHT) have been mainly studied in adults and in relation to various disorders. Although it is known that 11-oxygenated androgens are pivotal in adrenarche and pubarche, well established reference intervals for children are lacking. Objective: To establish age-related reference intervals for 11-oxygenated androgens in children. Methods: Serum samples were collected from apparently healthy children with ages ranged 0-18 years (n=186, 108 boys and 78 girls). Concentrations of 11KA4, 11OHA4, 11KT and 11OHT were determined by isotope dilution mass spectrometry. Before measurement the serum was deproteinized and purified by solid-phase extraction. The lower limit of quantitation for 11KA4, 11KT and 11OHT were 3.0 ng/dL (0.10 nmol/L), and for 11OHA4 9.1 ng/dL (0.30 nmol/L). Results: For 11KA4 a difference between boys and girls was observed until the age of 6. In girls 11KA4 was undetectable where in boys concentration up to 9.61 ng/dL (0.32 nmol/L) were measured. From the age of 6 an increase of 11KA4 was observed with increasing age. From the age of 13 concentrations stabilized at 4.21-28.5 ng/dL (0.14-0.95 nmol/L) without a difference between boys and girls. 11OHA4 was detectable at all ages and showed no differences between boys and girls, except for an apparently slightly higher concentration for boys until the age of 4. The concentration 11OHA4 increased with age in an almost linear way. At the age of 18 concentrations were observed of 60.5- 296.4 ng/dL (2.00-9.80 nmol/L). For 11KT a similar relation between the concentration and age was observed until the age of 14. At the age of 14 a plateau seems to be reached at concentrations of 14.5-74.4 ng/dL (0.48-2.46 nmol/L), which slightly decreased from the age of 17. 11OHT was undetectable in both boys and girls up to the age of 9 years. After the age of 9 the concentration range increased by age up to 30.4 ng/dL (1.00 nmol/L). From the age of 12 11OHT was detectable in all girl samples, where as in boys samples with undetectable concentrations were present at all ages. Conclusions: Age-related reference ranges were established for 11KA4, 11OHA4, 11KT and 11OHT. Overall no differences were observed between boys and girls, except for 11KA4 at a young age. The concentrations measured at the age of 18 correspond to the adult values known from literature for all 4 11-oxygenated androgens.

Presentation: 6/1/2024
8400 An Unusual Case of Brittle Bone Disease
Authors: Middleton Sydney Michelle , Mogri Muniza
Published: October 2024

Disclosure: S.M. Middleton: None. M. Mogri: None.

Introduction: We present the case of a now 21-month-old F with prenatally suspected skeletal dysplasia; subsequent evaluation revealed concern for a form of brittle bone disease that has not been previously described. Clinical Case: The patient was delivered at 37.0 weeks gestational age via C-section. There had been prior prenatal concerns for a possible skeletal dysplasia. A skeletal survey done on day-of-life 2 noted generalized demineralization of her bones, shortening/bowing of the long bones, an acute right proximal ulnar fracture, and evidence of multiple discontinuous healed rib fractures. A repeat skeletal survey done at day-of-life 19 demonstrated worsening skeletal findings with a very poorly mineralized skull, shortening of the clavicles and extremities, progressive fractures in all extremities and further bowing of the limbs, progressive rib fractures with callus formation, and multiple vertebral bodies with stature loss concerning for compression fractures. Directed genetic testing for osteogenesis imperfecta was negative, so whole exome sequencing was pursued and identified variants of unknown significance in the KAT6B and WDR35 genes not previously described, noting that the patient was heterozygous for both. She was suspected to be a carrier for the WDR35 mutation as it is inherited in an autosomal recessive fashion, and parental genetic testing revealed that the patient’s father carried the same KAT6B mutation and was phenotypically normal. Mutations in these genes have been described in disorders associated with bone abnormalities (such as genitopatellar syndrome and cranioectodermal dysplasia 2), but with different clinical presentations. During the course of her care, she was also identified to have hypophosphatemia shortly after birth and concerns for phosphate wasting; she was noted to have a high fractional excretion of phosphate in the setting of low serum phosphorus despite enteral phosphorus supplementation. She additionally was found to have an elevated FGF23 level at the same time the suspected renal phosphate wasting was identified. Her total calcium has remained normal with normal PTH values; her 25-OH vitamin D has also been normal. She has subsequently been successfully managed on sodium phosphate and calcitriol supplementation, as well as regular zolendronate infusions, without recurrence of fractures, and is clinically doing well with improvements in her respiratory status and overall development. Conclusion: This patient illustrates a severe case of brittle bone disease that presently does not have a clear etiology, though could represent a novel genetic mutation that has not been described and could subsequently be identified with continued review of her genetic testing in the future. Reporting her case could be beneficial to other patients with similar skeletal disease in helping to identify an underlying cause.

Presentation: 6/3/2024
7350 Association between thyroid function and insulin resistance indices in Korean adolescents: Findings from the 2014-2015 KNHANES
Authors: Mun Eunji , Lee Hye Ah , Choi Jung Eun , Lee Rosie , Kim Kyung Hee , Kim Hae Soon
Published: October 2024

Disclosure: E. Mun: None. H. Lee: None. J. Choi: None. R. Lee: None. K. Kim: None. H. Kim: None.

Purpose: Obesity and diabetes are rising concerns among adolescents. There are several studies regarding to the association between thyroid function and IR. However, there are limited studies focus on adolescents. Furthermore, there is a lack of studies evaluating various IR indices. We investigated the association between thyroid function and insulin resistance indices in adolescents with normal thyroid function. Methods: This cross-sectional study included 465 adolescents (aged 12-18, 255 boys, 210 girls) based on data from the Korea National Health and Nutritional Examination Survey2014-2015. Thyroid function was assessed using serum thyrotropin (TSH) and free thyroxine (fT4), while IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), glucose/insulin ratio (GIR), TyG (triglyceride-glucose index), and TG/HDL. Multiple linear regression analyzed the relationship between thyroid function and IR, stratified by sex. Nonlinearity was assessed through a restricted cubic spline model. Results: The mean TSH (uIU/mL) and fT4 (ng/dL) were 2.70 and 1.29, respectively. Boys had higher TSH (2.86 vs. 2.52, p = 0.013) and fT4 (1.33 vs. 1.24, p < 0.001) than girls, with significant gender differences. In girls, fT4 negatively correlated with HOMA-IR and positively with GIR. No significant relationship was found between thyroid function and IR in boys. When analyzed stratified by level of obesity, the association between IR and thyroid function was clear in the overweight/obese group in both sexes. Overweight and obese groups showed relationships between fT4 and HOMA-IR (β = 0.08, p = 0.04 in boys; β = -0.12, p < 0.01 in girls) and QUICKI (β = -4.14, p = 0.03 in boys; β = 6.60, p < 0.01 in girls). TSH correlated with TyG (β = 1.01, p = 0.04 in boys; β = 1.38, p = 0.01 in girls). In girls, fT4 was also related to TG/HDL (β = -0.06, p < 0.05) and GIR (β = 0.14, p < 0.01). Nonlinear analysis found no significant relationship between thyroid function and IR. Conclusion: The relationship between thyroid function and IR was more pronounced in the overweight and obese groups. Our study suggests that the correlation between thyroid function and insulin resistance in adolescents may vary based on gender and IR indices.

Presentation: 6/1/2024
6615 Clinical features and genetic etiology of primary ovarian insufficiency in 46,XX children
Authors: Wang F , Yin X , Lan X , Zang S , Li P
Published: October 2024

Disclosure: F. Wang: None. X. Yin: None. X. Lan: None. P. Li: None.

Purpose: The clinical features of primary ovarian insufficiency in 46,XX children were analyzed, the pathogenic genes of POI were screened, and the genetic etiology of primary ovarian insufficiency in children 46,XX was clarified. Method: The clinical data of 46,XX POI patients were collected, including uterine and ovarian ultrasound, serum follicle-stimulating hormone (FSH), estrogen, anti-mullerian hormone (AMH), chromosomal karyotype analysis, adrenal and thyroid function, and immune function. Whole exome sequencing (WES) and CNV were used to screen POI candidate genes. Novel mutations such as MCM8 gene were used to verify cell function. HE staining, immunohistochemistry, cell fluorescence, and Tunnel method were used to observe the changes in ovarian tissue structure. Construction overexpression plasmids of Mutant MCM8 gene in Hela cells. Result: 1. Clinical features of 46,XX POI: The age of onset of the children was 11.9∼16.1 years old. In addition to POI, the clinical phenotype showed height growth retardation. Among them, 4 cases were short stature, 3 cases were growth hormone deficiency, and 5 cases were backward in bone age. All of them showed elevated FSH (>25 IU/L), and 7 cases had low serum AMH (<0.5 ng/ml). 2.The Screening of POI candidate genes and pathogenicity analysis: 5 of the 10 children carried the mutations of the pathogenic genes with POI, that is, 2 cases (sisters of the same family) carried two novel heterozygous mutations of MCM8 gene, one infant carried two novel heterozygous mutations of CYP19A1 gene, and one case with delayed puberty carried one homozygous mutation of ZSW1M7 gene. 3.The MCM8 mutant were functionally validated: The sisters carried two novel mutations, namely p.C242R and p.S445*. The elder sister (the proband) showed POI, short stature and tumor susceptibility, while the younger sister showed a trend of gradual increase in FSH level and ovarian decline. The follicles of the proband disappeared and fibrous tissue proliferation, the MCM8 expression was lower, and the positive rate of cell apoptosis was higher than normal control. The downregulation of Bax and Capase3 expression in mutant MCM8 of Hela cell was delayed compared with wild type, indicating the persistence of apoptosis. Conclusion: 1. The clinical characteristics of 46,XX POI in children are ovarian hypoplasia, often combined with height growth retardation, biochemical manifestations of hypergonadotropic hypogonadism, decreased serum AMH, and karyotype 46,XX. 2.46,XX POI genetic etiology analysis found that five known POI-related pathogenic genes, namely CYP19A1, MCM8, and ZSW1M7, in which five novel mutations were identified.3.Mutant MCM8 promotes ovarian apoptosis by activating the Bcl-2/Bax/Caspase 3 pathway. Keywords: Primary ovarian insufficiency, short stature, apoptosis

Presentation: 6/3/2024
6860 Cognitive Capacity in Children with Growth Hormone Deficiency
Authors: Leal V , Alvarez V , Awadalla S S
Published: October 2024

Disclosure: V. leal: None. V. Alvarez: None. S.S. Awadalla: None.

Growth hormone (GH) is necessary for longitudinal growth and also has multiple other functions including neurologic development. Cognitive function in children with idiopathic isolated growth hormone deficiency (IGHD) has been poorly studied. This study aims to prospectively investigate cognitive capacity in children with IGHD.Cognitive function of 10 children with IGHD (peak GH <10 μg/L) was studied using Wechsler Intelligence Scales for Children IV: Intelligence Quotient, Verbal Comprehension Index, Perceptual Reasoning Index, and Working Memory and Processing Speed Indices.6 females and 4 males were included , Age was 10.04 ±2.01 years (M± DS) , height SDS was -1.86 ±0.19 . The IQ was 100.6 ±8.5, Verbal Comprehension was 99.3 ±8.5, Perceptual Reasoning was 102.5 ±9.1, Working Memory was 99.9 ±9.8, and Processing Speed was 98.9 ±13.1. Using Spearman correlation test ; a moderate positive correlation was observed between the GH peak and the intellectual coefficient IQ and peak GH: r=0.45, p=0.18, Perceptual reasoning and GH: r=0.43, p=0.2 without a statistical significance probably because of the sample size. In conclusion; The overall IQ score fell within the normal range, with lower scores in processing speed and working memory. These findings underscore the importance of considering not only the impact on linear growth but also on cognitive development when addressing growth hormone deficiency in the pediatric population

Presentation: 6/3/2024
6941 Congenital Generalized Lipodystrophy - An Undiagnosed Case in an Underserved Border Community
Authors: Evans D , Gutierrez A , Echetebu S , Zerah M
Published: October 2024

Disclosure: D. Evans: None. A. Gutierrez: None. S. Echetebu: None. M. Zerah: None.

Introduction: Congenital Generalized Lipodystrophy (Berardinelli-Seip Syndrome) is estimated to occur 1-10/10 million people1. Patients may present with specific clinical features and/or hormonal imbalances such as hyperinsulinemia and hypertriglyceridemia. Complications of CGL result in a decreased average life expectancy of 51.2 years2. Here we present a case of a female from a medically underserved city in Mexico who was not diagnosed until the age of 16, three years after immigration to the United States. Case Presentation: The patient lived in Mexico and had little medical care. After she immigrated, she was referred to Pediatric Endocrinology due to an elevated hemoglobin A1c, hypertriglyceridemia, and elevated liver enzymes. At birth and in adolescence, the patient did not resemble any of her five fully biological siblings, had little adipose tissue, and had well-defined musculature. Physical exam findings included generalized absence of adipose tissue and prominent musculature, large hands and feet, acromegaloid features, acanthosis nigricans, hirsutism, and phlebomegaly. Breast development was Tanner Stage IV, and genitalia was Tanner Stage V, without clitoromegaly. Patient is currently being treated by psychiatry for Major Depressive Disorder and suicidal ideation. Results: She was diagnosed with diabetes mellitus due to elevated glucose on OGGT and hypertriglyceridemia. She was then started on a low carbohydrate diet, Metformin, and Atorvastatin. After treatment a significant improvement in labs were observed. Triglyceride levels decreased from 1112 mg/dL to 392 mg/dL(35-150 mg/dL), A1c from 8.5% to 5.8%(<5.8%), AST from 36 U/L to 16 U/L(12-32U/L), and ALT from 51 U/L to 20 U/L(5-32U/L). OGGT levels measured after treatment began were as follows: fasting: 95 mg/dL (70-100mg/dL), 1 hour: 242 mg/dL (130-140 mg/dL), and 2 hours: 229 mg/dL(<155 mg/dL). A liver ultrasound was normal. Genetic testing, Echocardiogram, EKG, and Leptin levels are all pending. Discussion/Conclusion: This case of an adolescent with CGL, who was not diagnosed until 16 years of age, demonstrates not only the health disparities and challenges faced by patients in border communities, but it also demonstrates the lack of knowledge of CGL in healthcare. By presenting this case, we hope to increase awareness of CGL within the medical community at large, and to improve the quality of life of our patients. References: 1. Garg, A. N Engl J Med 2004;350:1220-34 2.Akinci, B. et al., J Clin Endocrinol Metab 88:5433-5437, 2003

Presentation: 6/2/2024
9205 Copy Number Variation (CNV) in Self-Limited Delayed Puberty (SLDP)
Authors: Al-Sayed Yasmin , Ishida Miho , Hall Charlotte Louise , Howard Sasha R
Published: October 2024

Disclosure: Y. Al-Sayed: None. M. Ishida: None. C.L. Hall: None. S.R. 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
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

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

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<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

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

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 < 25, BMI 25-35, BMI > 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 > 35. For offspring, there was no difference in the birth weight, proportion of SGA was higher (6.6% vs 2.5-2.7%, p < 0.01), LGA was lower (2.0% vs 3.6-5.6%, p < 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 < 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 < 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

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<0.05, 2.56 ± 0.95 vs 3.16 ± 1.14 μg/kg/day, p<0.01 and 2.07 ± 0.57 vs 3.01 ± 1.14 μg/kg/day, p<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

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 <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<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

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<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<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

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<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<0.001), older age (p<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

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
8768 Initiation of Exogenous Sex Hormones in a Pediatric Gender Clinic
Authors: Roberts Christina M , Knoll Michelle M , Robertson Gail , Egan Anna , Moser Christine
Published: October 2024

Disclosure: C.M. Roberts: None. M.M. Knoll: None. G. Robertson: None. A. Egan: None. C. Moser: None.

Introduction: The demographics of patients seeking care for gender dysphoria have changed significantly since care was started in 1987. The criteria for prescribing sex hormones have also evolved to allow a greater range of patients to receive gender-affirming hormones. We examined factors associated with prescription of gender-affirming hormones to patients presenting for gender-affirming care our clinic. Methods: Secondary analysis of sex hormone initiation as a minor among 14-17-year-old adolescents diagnosed with gender dysphoria, seen in the pediatric gender clinic between 2/19/2018 and 7/20/2022. We extracted demographic variables, appointment dates, and sex hormone prescription data from our electronic medical record. We collected patient reports of gender identity and suicidal behavior, and parent and adolescent reports of general adolescent well-being, months of gender dysphoria and social transition, and parental support for the adolescent’s gender identity from electronic clinic surveys. Results: We identified 273 adolescent-parent dyads with complete data. Most of our sample were assigned female at birth (74.4%), transgender male (59.3%), and white (83.5%) adolescents who lived in urban (86.4%) and lower-middle-income (64.5%) areas. The average age was 15.9+/-1.1 years. A minority of adolescents reported recent suicidal ideation 60/273 (22%), and prior suicide attempts 20/273 (7%). Parents reported a shorter duration of gender dysphoria (-16.7 months (95%CI: -22.0, -11.5)) and social transition (-4.7: -6.5, -3.0), and higher levels of parental support than adolescents. Approximately half, 146/273 (53.5%), of adolescents started sex hormones. The average age at initiation was 16.5 years +/- 0.9. Age at presentation, length of gender dysphoria or social transition, and the presence of suicidal ideation or attempts were not associated with initiation of sex hormones. Assigned males (OR:1.82:95%CI 1.04, 3.19), adolescents with higher parent-reported parental support for the adolescent’s identity (1.03:1.01, 1.04), and adolescents with private insurance rather than Medicaid (Blue Cross- 5.39:2.73, 10.64) were more likely to start sex hormones as a minor. Conclusion: Published criteria for the initiation of sex hormones among adolescents with gender dysphoria, including age, persistence of dysphoria, and the presence of suicidality, did not predict the prescription of sex hormones to minors in our clinic. Parent-reported support for the adolescent’s gender identity played a small role in predicting the prescription of hormones, but male sex assigned at birth and having private health insurance played larger roles. Further exploration of these findings is needed to ensure equity in the treatment of gender dysphoria.

Presentation: 6/3/2024
7269 Interim Analysis of Gonadotropin-Releasing Hormone Agonist (GnRHa) Treatment in Children with Central Precocious Puberty: Focus on FMV Urinary LH Levels and Clinical Outcomes
Authors: Luo Xiaoping , Hou Ling , Li Yanhong , Sun Yan , Jin Xin Kinson
Published: October 2024

Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda.

Background: Central precocious puberty (CPP) refers to early activation of the hypothalamic–pituitary–gonadal (HPG) axis in children. There is an urgent need to understand the treatment pattern and clinical outcomes among children suffering from CPP. Studies have reported that first morning voided (FMV) urinary Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) have substantial association with CPP tested in GnRH stimulation test and can be useful in diagnosis and management of CPP in children. Gonadotropin-releasing hormone agonists (GnRHa) such as Leuprolide acetate (LA) are the recommended treatment for children suffering from CPP. The current study aimed to provide the information on level of LH and FSH in FMV urine when CPP diagnosis at baseline and the present results may also revealed trend of FMV-LH and FMV-FSH change during LA intervention in children with CPP. Here we present interim results from this study. Methods: This is an open-label, multicentre, single arm, prospective study that enrolled 31 subjects with CPP. Individuals were administered LA depot 11.25 mg, subcutaneously every 12 weeks. The study comprises a screening period; a 6-month treatment period: 24 weeks; and a post-treatment follow-up period: 12 weeks. The FMV urinary LH and FSH were diagnosed by Clopper-Pearson method with a 95% confidence interval. Results: Due to the data collection time point for the interim analysis, only 8 female subjects reached the 12-week visit time point and had a 12-week visit for FMV urinary Gn testing. Therefore, for this interim analysis, only FMV Gn decline at week 12 of the 8 subjects who had a 12-week visit will be presented. At baseline, the mean value of FMV urinary LH and FSH is 0.58 IU/L and 2.27 IU/L respectively. The FMV Gn urinary LH was demonstrated a decrease in 87.5% (95% CI: 47.35,99.68) of the children after LA intervention. Additionally, urinary FSH value of FMV urinary Gn was found to decrease in 75.00% of the children (95% CI: 34.91,96.81) compared to baseline FSH value. Conclusion: The present study reveals a decreasing trend in FMV Gn urinary LH and FSH levels in CPP children treated with LA during interim analysis. LA was shown to be safe and effective in ameliorating the level of LH and FSH in children suffering from CPP. From the study, it can be concluded that urinary LH and FSH may act as a potential biomarker for diagnosis and management of CPP.

Presentation: 6/3/2024