bluuebunny/crossref_metadata_2025_split huggingface dataset:
6825 α-Klotho Levels in Girls with Central Precocious Puberty
Authors: Hwang I , Kim E 
Published: October 2024

Abstract
Disclosure: I. Hwang: None. E. Kim: None.
Background: The exact mechanisms that trigger the onset of puberty are not fully understood. While it is known that elevated estradiol during puberty induces an increase in IGF-1, which subsequently promotes a rise in α-klotho levels, the relevance of these elevated α-klotho levels in children with Central Precocious Puberty (CPP) remains to be established. Given the potential significance of α-klotho in pubertal development, we initiated this study to determine whether increased α-klotho levels in CPP children are meaningfully pronounced and if these levels could serve as a reliable marker for CPP diagnosis and monitoring. Methods: A total of 139 girls were enrolled in the study, comprised of 82 diagnosed with CPP and 57 who were healthy prepubertal controls. From March 2020 to May 2023, we assessed both α-klotho levels and clinical parameters. α-klotho concentrations were measured using an α-klotho ELISA kit. For the girls with CPP, we additionally analyzed samples taken 6 months after GnRH agonist treatment. Result: α-Klotho levels were higher in the CPP group compared with the controls (CPP group: 2529 ± 999 ng/mL; control group: 1802 ± 675 pg/mL) (P &lt; 0.001). α-Klotho significantly decreased after 6 months on GnRH agonist treatment.(2147± 789 pg/mL) (P &lt; 0.001). α-Klotho levels were positively correlated with height-SDS, weight-SDS, bone age, ALP, IGF-1 SDS, baseline FSH and LH. α-Klotho relationship with IGF-1 SDS, baseline LH studied by partial correlation with adjustment for age, height and weight SDS (r= 0.275, p= 0.003; r= -0.229, p= 0.014). A ROC curve analysis identified an α-klotho cut-off differentiating CPP from controls, with a cut-off of 1914 pg/mL distinguishing CPP girls from controls with a sensitivity of 69.5% and specificity of 70.2%; the area under the curve was 0.723. Conclusion: Our study indicates a notable association between elevated α-klotho levels and CPP, especially as these levels adjust following GnRH agonist treatment. Based on our findings, considering α-klotho concentrations might offer a way to distinguish CPP from controls. Further studies could elucidate the potential of α-klotho as a biomarker for CPP diagnosis and monitoring.
Presentation: 6/1/2024
12431 14-year-old Presenting With Thrombocytopenia-Associated Multi-Organ Failure In The Setting Of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome
Authors: Gunaratne-Breaux Naiomi C , Deplewski Dianne 
Published: October 2024

Abstract
Disclosure: N.C. Gunaratne-Breaux: None. D. Deplewski: None.
Title: 14-Year-Old Presenting with Thrombocytopenia Associated Multi-Organ Failure in the setting of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome Background: Coagulation complications are rare in hyperglycemia emergencies in children and adolescents. In patients presenting with severe and atypical hyperglycemia emergencies, special considerations need to be made to rule out life-threatening coagulopathy. Clinical Case: A 14-year-old male with history of Type 1 Diabetes presented in severe Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome overlap. Initially had severe hypotension and altered mental status concerning for cerebral edema. Initial venous blood gas showed pH of 6.82, pCO2 17.1, and HCO3 2.8, serum glucose was 1375 mg/dL, serum ketones &gt;7.00 mmol/L, and serum osmolality was 384 mOsm/kg. Once insulin drip was started, glucose, ketones, and serum osmolality improved, but patient continued to be encephalopathic and had worsening tachypnea and desaturations. Patient was eventually intubated. After intubation, patient’s acidosis improved, but patient developed kidney failure (prompting initiation of dialysis), liver injury, decreased cardiac function, and high inflammatory state. A comprehensive multi-specialty team including pediatric intensive care, infectious diseases, rheumatology, neurology, and cardiology were involved in the care. On day three of admission, patient had multiple areas of ischemia on fingertips and ear and clotting of multiple IV and dialysis catheters, prompting a coagulopathy evaluation. Labs showed microcytic anemia (hemoglobin 10.0 g/dL; mean corpuscular volume 75fL), thrombocytopenia (platelet count 17 10e3/uL), coagulopathy (prothrombin time 16.8 sec, INR 1.3, prolonged thrombin time 48.8 sec), and elevated ferritin (507 ng/mL). Given labs and multi-organ involvement, determined by hematology to be Thrombocytopenia Associated Multi-Organ Failure (TAMOF). Patient was started on plasmapheresis and had dramatic improvement – was eventually extubated and returned to neurologic baseline without any notable deficits. Multi-specialty team ruled out all other possible causes of TAMOF; determination that the TAMOF developed secondary to DKA/HHS. Conclusion: Hyperglycemia emergencies can lead to a hyperinflammatory state that can lead to disruption of the coagulation cascade, including disseminated intravascular coagulopathy or thrombotic thrombocytopenia purpura. There have been rare reports of thrombocytopenia associated multi-organ failure provoked by DKA, thought secondary to critical illness mediated low ADAMST13 levels. This is a novel case of TAMOF caused by DKA/HHS overlap syndrome. It is important to screen for coagulopathy in cases of patients with DKA or DKA/HHS who do not show clinical improvement with resolution of ketosis and hyperosmolarity.
Presentation: 6/2/2024
8721 A Case of Congenital Hyperinsulinism Manifesting as Transient Hypoglycemia During Illness Due to Mosaic Variant of Unknown Significance in ABCC8
Authors: Bell-Sambataro Esther Eunice , Mamilly Leena 
Published: October 2024

Abstract
Disclosure: E.E. Bell-Sambataro: None. L. Mamilly: None.
Background: Congenital hyperinsulinism (CHI) is characterized by inappropriate secretion of insulin during periods of low blood glucose. CHI can lead to significant complications such as seizures, developmental delays and neurologic damage. CHI can be caused by multiple genetic variants. The most common genetic etiologies are loss of function mutations in the genes ABCC8 and KCNJ11 encoding the pancreatic Beta (β)-cell ATP-sensitive potassium channel causing over secretion of insulin from the β-cells. We report a challenging pediatric case with a clinical presentation of CHI in an infant with a de novo mosaic ABCC8 gene variant of unknown significance manifesting only during times of illness. Clinical Case: A male infant born at 36 weeks gestational age was transferred to a tertiary center NICU secondary to seizure activity and hypoglycemia after the 24 hours of life with glucose levels as low as 32 mg/dL. His birth weight was normal and there was not maternal history of diabetes mellitus. The hypoglycemia persisted throughout the first week of life and required a glucose infusion rate of 11 mg/kg/min, without success in obtaining a critical sample. He had multiple seizures and MRI brain showed signs of hypoglycemic encephalopathy. Subsequently, he was weaned off IV dextrose and completed a 6 hour safety fast prior to discharge. Rapid genome testing resulted in a de novo, mosaic variant of unknown significance in ABCC8 (C.3622G&gt;A resulting in amino acid substitution p.Glu1208Lys). His family reported significant but transient hypoglycemia during times of illness. At the age of 11 months, he was hospitalized for significant hypoglycemia during an episode of acute gastroenteritis and was treated with dextrose-containing fluids for 36 hours. A subsequent diagnostic fasting study resulted in hypoglycemia within 5.5 hours with capillary glucose of 49 mg/dL. At the time of hypoglycemia, beta hydroxybutyrate was inappropriately low at 0.78 mm, insulin level was suppressed &lt;2 mcIU/mL. Glucagon (30 mcg/Kg) was administered after the initial sample was drawn with a significant increase in glucose from 49 mg/dL to 103 mg/dL. Based on the positive glucagon response and low serum ketone, the clinical diagnosis of CHI was made and diazoxide was initiated while awaiting other results. After the second dose of diazoxide, all glucose levels remained above 80 mg/dL. He was sent home on a continuous glucose monitor and diazoxide. Conclusion: CHI can occur due to autosomal recessive or autosomal dominant ABCC8 loss-of-function mutations of which more than half are not responsive to diazoxide. In this case report, we describe the diagnosis of hyperinsulinemic hypoglycemia in an infant with an ABCC8 variant classified with unknown significance. We describe a good initial response to diazoxide in normalizing blood glucose levels in this infant.
Presentation: 6/2/2024
5174 A longitudinal retrospective cohort study on the application of the Superimposition by translation and rotation (SITAR) model to estimate body composition growth trajectory in Korean children and adolescents during puberty
Authors: Kim Seo Jung , Kim Sujin , Suh Junghwan 
Published: October 2024

Abstract
Disclosure: S. Kim: None. S. Kim: None. J. Suh: None.
Introduction: In addition to adulthood, pediatricians have noted a growing emphasis on research concerning sarcopenic obesity. Studies in this field have expanded beyond basic BMI-related inquiries, actively delving into investigations based on body fat mass (BFM) and fat-free mass (FFM). However, limited research has systematically analyzed the acquisition of body composition during children and adolescence based on longitudinal data. Objective: This study aims to assess the acquisition of weight, FFM, and BFM during the pubertal growth of Korean children and adolescents. Methods: This study utilized mixed longitudinal body measurement and body composition data, employing bioelectrical impedance analysis, from 4,641 height measurements (2,204 for boys and 2,437 for girls) obtained from 361 individuals (170 boys and 191 girls) among Korean children and adolescents aged 7 to 18. The SITAR (the Superimposition by Translation and Rotation) model, a shape-invariant growth curve model, was used to estimate a reference height velocity curve during pubertal growth. Results: The SITAR methodology allowed us to investigate the timing, magnitude, and intensity of adolescent weight, FFM, and BFM gain. The results revealed significant differences in growth trajectories between boys and girls, with boys exhibiting a persistent elevation in FFM and a pattern of ascent followed by a decline in BFM, while girls show an increase in BFM and a deceleration in FFM growth. In Korean boys, the peak weight velocity (PWV) occurred at a mean age of 12.41 years, with a rate of 8.19 kg/year. Peak fat-free mass velocity (PFV) was observed at a mean age of 9.69 years, with a rate of 7.60 kg/year, and peak body fat mass velocity (PBV) at a mean age of 12.70 years, with a rate of 2.67 kg/year. In Korean girls, the mean age of PWV was 11.28 years, with a velocity of 6.33 kg/year. PFV occurred at a mean age of 12.33 years, with a rate of 4.86 kg/year, and PBV at a mean age of 11.13 years, with a rate of 2.72 kg/year. The ages of peak velocities of height (PHV), PWV, PFV, and PBW positively correlated. Conclusions: This study is the first to apply the SITAR model to examine the acquisition of body composition in Korean children and adolescents. Future research should delve into exploring the connections between various disease groups during childhood and adolescence and the patterns of change in body composition.
Presentation: 6/1/2024
7772 A Study on Role of Anti-Mullerian Hormone and Inhibin B in 46,XY Disorders Of Sexual Development
Authors: Kudugunti Neelaveni , Bangaru Sai kiran , Sahay Rakesh Kumar 
Published: October 2024

Abstract
Disclosure: N. Kudugunti: None. S. Bangaru: None. R.K. Sahay: None.
Background: In pre-pubertal period, a major part of the testicular tissue is constituted by Sertoli cells for which AMH, Inhibin B are specific biomarkersHigh AMH, Inhibin B levels in the prepubertal period is via FSH stimulation, which is mistakenly considered to be silent due to its reduced activity Aim & Objectives: To assess AMH and Inhibin B measurements in the diagnostic workup of prepubertal children with different subtypes of 46,XY DSD and comparing with normal controls To assess Sertoli cell function with AMH and Inhibin B and to assess correlation between testosterone elevation after hCG stimulation, basal AMH and Inhibin B Patients and methods: Pilot study-Single centered, Cross-sectional Observational study. After ethical committee approval, 40 children with 46,XY DSD & 40 healthy age matched, boys as controls recruited after taking assent. All children with DSD underwent karyotyping, assessment of hCG stimulated testosterone, DHT and androstenedione. Basal AMH and inhibin B were measured in both cases and controls. Data were analysed using IBM SPSS version 25. Results: The mean age at presentation was 4.09 years.The diagnosis was made clinically and biochemically, genetic analysis done in few patients. Out of 40 cases, 26 had normal hCG stimulated testosterone of &gt;100 ng/dl (17 cases were 5 alpha reductase type 2 deficiency [5αR2D], 9 cases were PAIS) & 14 had low hCG stimulated testosterone of &lt;100 ng/dl (8 cases were 17βHSD3 deficiency, 4 cases were Partial gonadal dysgenesis [PGD], 2 cases were Vanishing testis syndrome). In the low testosterone group, mean AMH in 17βHSD3 deficiency-279.95 ng/ml, in PGD-31.16 ng/ml which is statistically significant in differentiating these disorders(p-0.002)& mean Inhibin B in 17βHSD3 deficiency-186.41 pg/ml, in PGD-35.95 pg/ml which is statistically significant in differentiating these disorders (p-0.007). In vanishing testis syndrome, AMH & Inhibin B were helpful in confirming the absent functioning testicular tissue Whereas in normal testosterone group, mean AMH in PAIS-235.65 ng/ml, in 5αR2D-289.08 ng/ml difference is not statistically significant(p-0.36)& mean Inhibin B in PAIS-204.50 pg/ml, in 5αR2D-190.91 pg/ml difference is not statistically significant(p-0.72) There was significant correlation between basal AMH and hCG stimulated testosterone (r=0.434; p-0.002), Inhibin B and hCG stimulated testosterone(r=0.438; p-0.001), AMH and Inhibin B(r=0.770; p&lt;0.001). Conclusion: AMH and Inhibin B are valuable in differentiating PGD, 17βHSD3 deficiency in low hCG stimulated testosterone patients, but not helpful in differentiating PAIS, 5αR2D in normal hCG stimulated testosterone patients. Especially in PGD they may have a role with respect to fertility prospects and malignancy risk assessment.
Presentation: 6/3/2024
7316 A Unique Presentation of Diabetes Mellitus in an 8-Year-Old Male Positive For 3 Different Mutations Related to MODY
Authors: Senguttuvan R , Pamfil A 
Published: October 2024

Abstract
Disclosure: R. Senguttuvan: None. A. Pamfil: None.
Background: Maturity-Onset Diabetes of the Young (MODY) is the most common form of inherited non-autoimmune diabetes mellitus, characterized by autosomal dominant inheritance, young age at onset and beta cell dysfunction. There are at least 14 MODY mutations and we present a pediatric case not meeting criteria for type 1[T1DM] or type 2 diabetes mellitus[T2DM], who tested positive for mutations in 3 different genes known to cause MODY. Case: An 8-year-old male, born full term, 2776 grams and 48.3 cm, without history of neonatal hypoglycemia or hyperglycemia, was referred for new onset diabetes mellitus management. While undergoing evaluation for abdominal pain and constipation, he was found to have a fasting glucose of 126 mg/dL (7 mmol/L) and hemoglobin A1C of 6.5%. He endorsed polyuria, but no polydipsia. He had no clinical signs of insulin resistance (e.g., acanthosis nigricans) and a BMI of 23.65 kg/m2, at the 97th percentile. Family history is positive for diabetes mellitus requiring insulin, in father (diagnosed at 11 years) and paternal grandmother and T2DM in paternal aunt. Laboratory evaluation was negative for all 5 antibodies (GAD, IA-2, Anti-islet cell antibody, Zinc Transporter 8 and Insulin antibodies) and revealed an insulin level of 15.9 uIU/mL (RR: &lt;2.0-13.0) and C peptide: 2.3 ng/mL (RR: 1.1-4.4). Lacking diagnostic criteria for T1DM or T2DM, genetic testing was performed. Patient tested heterozygous for mutations in 3 genes known to cause MODY: GCK [(c.350 G&gt;T p. (G117V)], ABCC8 [(c.2270 C&gt;G p.(T757R)], and HNF1B [(c.68A&gt;G p.(K23R)], all variant of uncertain significance. Over an 8-month period, patient's weight decreased from 98 lbs. (44.9 kg) to 90 lbs. (41.1 kg) after meeting with our dietician and implementing healthy dietary changes, and his beta cell function markers improved from diagnosis: Fasting insulin (4.5 uIU/mL), C peptide (1.3 ng/mL), and glucose 119 mg/dL; Hemoglobin A1C remained relatively stable at 6.1%. A kidney ultrasound was normal. No medical intervention were started yet, and patient is being monitored clinically and biochemically every 3-4 months. Discussion: Clinical monitoring over time, genetic testing in the parents, are critical in this patient’s long-term treatment plan and prognosis. To our knowledge, this may be the first case of diabetes mellitus in a pediatric patient, positive for mutations in 3 different genes known to cause MODY. South Texas has one of the highest incidences of T2DM in the USA. In addition to screening for genetic forms of diabetes, in patients with negative T1DM antibodies and atypical phenotype for T2DM, we should consider genetic screening in mildly obese pediatric and young adult patients without significant acanthosis nigricans, who were already diagnosed as T2DM.
Presentation: 6/1/2024
6471 Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone
Authors: Pollock Netanya I , Song Minkeun , Wolf Alexander , Li Yimei , Hawkes Colin , Motamedi Niloofaralsadat , Denburg Michelle R , Mostoufi-Moab Sogol 
Published: October 2024

Abstract
Disclosure: N.I. Pollock: None. M. Song: None. A. Wolf: None. Y. Li: None. C. Hawkes: None. N. Motamedi: None. M.R. Denburg: None. S. Mostoufi-Moab: None.
Title: Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone Objectives: Aromatase inhibitor (AI) therapy in combination with growth hormone (GH), or as monotherapy, may have a role in improving height outcomes in male pediatric patients with GH deficiency (GHD). The effectiveness of AI therapy in the childhood cancer survivors is not known. In this retrospective study, we assess adult height (AH) in childhood cancer survivors treated with AI combined with GH therapy compared to those treated with GH alone. Methods: This was a single center retrospective cohort study of male survivors of childhood cancer treated with GH for diagnosis of GHD between 2007 and 2023. We compared AH outcomes in males treated with GH alone or in combination with off-label use of AI. Demographic and clinical characteristics, including anthropometric measurements, endocrinopathies, and cancer history, were obtained from the medical record. AH was noted as height documented at fusion of growth plates or following 18 years of age. Differences in demographic, clinical, and treatment characteristics were assessed using univariate tests of association. Multivariable regression with stepwise selection was used to examine risk factors associated with AH. All statistical analyses were performed using Stata 18.0. Results: Ninety-two patients were included; 70 were treated with GH monotherapy and 22 with combination AI/GH. Median age at AI initiation was 13.6 years (IQR 12.3-14.3) versus 11.2 years (IQR 8.6-12.9) for GH (unpaired t-test p-value &lt;0.01; 95% CI -4.01, -1.91). A greater proportion of patients in the AI/GH group had been treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (Fisher’s exact p-value &lt;0.01). There was no statistically significant difference in AH or AH Z-score between treatment groups, with the median AH Z-score in the AI/GH group -1.95 (IQR -3.11, -0.75) versus -1.39 (IQR -2.65, 0.11) in the GH group. In multivariable linear regression, history of radiation to the spine (β= -5.9, 95% CI -11.2, -0.6), height Z-score (β= 0.3, 95% CI 0.11, 0.46), BMI Z-score (β= 3.2, 95% CI 0.95, 5.5), and advanced bone age at GH or AI treatment initiation (β= -10.1, 95% CI -17.3, -2.9) were significantly associated with AH. Conclusions: Adjunctive treatment with AI and GH was not associated with increased AH outcomes in male survivors of childhood cancer compared to GH monotherapy. Future work is needed to determine optimal adjunctive medical therapy to maximize FAH impacted by cancer therapy for this patient population.
Presentation: 6/3/2024
8076 Advancing Career Development of Physician-Scientists Engaged in Diabetes Research: Insights into the National K12 DiabDocs Program
Authors: Dasani Komal D , Bishop Franziska K , Golden Sherita H , Laffel Lori M , Mirmira Raghavendra G , Steck Andrea K , Willi Steven M , Maahs David M , DiMeglio Linda A 
Published: October 2024

Abstract
Disclosure: K.D. Dasani: None. F.K. Bishop: None. S.H. Golden: None. L.M. Laffel: None. R.G. Mirmira: None. A.K. Steck: None. S.M. Willi: None. D.M. Maahs: None. L.A. DiMeglio: None.
Background: In July 2022 the NIH established a multi-center National K12 “Diabetes-Docs: Physician-Scientist Career Development Program” (DiabDocs) to support mentored research experiences and tailored career development training for cohorts of physician scientists focused on diabetes research. DiabDocs scholars are board-certified or board-eligible physicians with training in pediatric or adult endocrinology or in another area tied to diabetes research and care. The program addresses the shortage of physicians engaged in diabetes research and is open to scholars at any eligible institution in the United States. Methods: The DiabDocs program was implemented by two multi-center Program Directors (MPD), in collaboration with an Executive Leadership Committee (ELC) comprised of experienced basic science and clinical/translational physician-scientists. Additional faculty from 19 different institutions have engaged in advisory and reviewer roles. The program solicits Letters of Intent (LOIs) annually from interested candidates followed by invitations for full applications; a program retreat features educational workshops and diversity training; and a Study Section selects Scholars. Currently, the program is in its third recruitment cycle for additional scholars to start Summer 2024. Additional career development programming is available through a series of interactive webinars. The program also has a strong commitment to diversity, equity, and inclusion, including a “DiabDiversity” program to support in-person engagement in DiabDocs experiences by under-represented in medicine trainees. Results: After two successful recruitment cycles in 2022-2023 that reviewed 24 LOIs, 11 scholars were selected. The funded scholars (6 Adult and 5 Pediatric Endocrinologists) include 3 individuals self-identifying as underrepresented in medicine and 7 females. For the 2023 application cycle, 24 LOIs were received (11 from Adult and 9 from Pediatric Endocrinology, 2 in combined Pediatric/Adult Endocrinology, and 2 from other specialties). Conclusions: The DiabDocs program aims to identify, recruit, and support outstanding early career physician scientists. The program provides a national network with resources for protected research time, career development programs, and national mentorship to develop cohorts of skilled professionals contributing to the advancement of diabetes research.
Presentation: 6/2/2024