bluuebunny/crossref_metadata_2025_split huggingface dataset:
7548 Final adult height in children with idiopathic growth hormone deficiency after growth hormone treatment
Authors: Lee Hae Sang , An Se Jin , Cho Min Hyung , Nam Hyo-Kyung 
Published: October 2024

Abstract
Disclosure: H. Lee: None. S. An: None. M. Cho: None. H. Nam: None.
Objective: The aim of this study was to assess the final adult height (FAH) achieved through recombinant human growth hormone (GH) treatment and the factors influencing FAH. Methods: We retrospectively reviewed the charts of all patients diagnosed with IGHD who were prepubertal when they began GH treatment since August 2007. FAH was determined in 41 patients (28 males and 13 females) by July 2023. Results: 41 patients started treatment at an average age of 9.1 years and continued for 6.5 years. The mean initial height was -2.6 standard deviation scores (SDS) and the mean FAH was -0.6 SDS. GH treatment was initiated at a significantly younger age in females than in males (7.2±1.9 vs 10.0±3.2; p=0.01). The mean FAH was 169.9±4.5cm for males and 156.1±3.2cm for females. Differences between initial height and final height SDS were not significant between males and females. The mean of FAH SDS was higher compared to their mid-parental height -1.0 SDS (p=0.017). In multiple regression analysis, FAH showed a positive correlation with initial height, duration of treatment, and growth rate in the first year of treatment, and a negative correlation with BMI SDS at the start of GH (r2=0.59; p=0.000). FAH SDS was positively related to initial height SDS and growth rate in the first year of treatment. (r2=0.3; p=0.001) Conclusions: The mean FAH SDS after GH treatment was significantly higher than the mean MPH SDS in IGHD patients. Moreover, the good response of GH treatment was associated with longer treatment duration, greater height at the start of treatment, better treatment response at 1 year, and lower initial BMI SDS.
Presentation: 6/3/2024
7673 Genetic Analysis and Clinical Characterization of Patients with Congenital Hypopituitarism Due to Gene Defects
Authors: Sasson T M , Arnhold I J , Mendonca B B , Carvalho L R 
Published: October 2024

Abstract
Disclosure: T.M. Sasson: None. I.J. Arnhold: None. B.B. Mendonca: None. L.R. Carvalho: None.
Introduction: Congenital hypopituitarism is characterized by the deficiency of one or more hormones secreted by the anterior pituitary gland. The genetics of this pathology is complex, and the molecular diagnosis is established in approximately 13% of cases. Objectives: The aim of the present study is to characterize the phenotype harboring pathogenic variants causing congenital hypopituitarism. Methods: Among 393 subjects with congenital hypopituitarism followed up at a tertiary health center, 57 subjects (14,5%) were selected due to a confirmed molecular diagnosis by exome in 9 subjects or by gene panel or Sanger sequencing in 48 subjects. This was a retrospective study where data from medical records, clinical, laboratory and radiological characteristics were analyzed. Results: The most frequent variants identified by sequencing analyzes were in the following genes: PROP1 (29.8%), GH1 (22.8%), GHRHR (15.7%), followed by GLI2, OTX2, HESX1, POU1F1, TGIF1, GHRS, CDH2, SATB1, SOX3 e LZTR1. Consanguinity was reported in 50% of cases, and there was the presence of familial cases of short stature in 60%. The average age at the start of follow-up was 11.1 years (11 SD), 40% of them were male and 52.3% had physical stigmata typical of GH deficiency. Regarding hormonal deficiencies, 27 (47%) had isolated Growth Hormone Deficiency (DGHI) and the others, multiple deficiencies. MRI study of the pituitary gland showed some alteration in 66%, 54% of whom had adenohypophysis hypoplasia and 31% had an ectopic or non-visualized neurohypophysis. From 29 patients with IGF-1 levels available, 28 were below the reference range for sex and age. The serum GH peak after the stimulus test was on average 1.28 ng/mL (1.4SD), of these, only 4 cases had GH peak between 3.3 and 5.0 ng/mL and 1 patient with low IGF-1 and an ectopic neurohypophysis had GH peak of 6.0 ng/mL in a glucagon test. Regarding growth, the initial height in z-score was -4.8 and the average growth at the end of the first year of treatment was 10.7cm, with the average height after this period of Z-3.35. The average of final delta target height (final height Z-score minus the target height Z-score) of patients who underwent hormonal treatment was -0,53 (good response = delta &lt;-1.5). Conclusion: In subjects with congenital hypopituitarism and an established molecular diagnosis, the most frequently affected genes were PROP1 and GH1, the great majority presented a stimulated GH peak &lt; 3.3 ng/mL (only one patient had GH &gt; 5), low basal serum IGF-1 and good increase in growth speed at the end of the first year of treatment with recovery of final height at the end of GH therapy.
Presentation: 6/3/2024
8244 Genetic Evaluation Using Next-Generation Sequencing of Children with Short Stature &lt; A Single Tertiary Center Experience
Authors: Park J , Kim S , Joo E , Lee J E 
Published: October 2024

Abstract
Disclosure: J. Park: None. S. Kim: None. E. Joo: None. J. Lee: None.
Purpose: We aimed to investigate the genetic causes of suspected genetic short stature in 37 patients using next-generation sequencing (NGS) and describe their phenotypes and various genetic spectra. Methods: We reviewed the medical records of 50 patients who underwent genetic testing using NGS for suspected genetic short stature from June 2019 to December 2022. Patients with short stature caused by non-genetic factors or common chromosomal abnormalities were excluded. Thirty-seven patients from 35 families were enrolled in this study. We administered one of three genetic tests (targeted panel sequencing using two different panels or whole exome sequencing) to patients according to their phenotypes. Results: Clinical and molecular diagnoses were confirmed in 15 of the 37 patients, and the overall diagnostic yield was 40.5 %. Fifteen pathogenic/likely pathogenic variants were identified in 13 genes (ACAN, ANKRD11, ARID1B, CEP152, COL10A1, COL1A2, EXT1, FGFR3, NIPBL, NRAS, PTPN11, SHOX, SLC16A2). The diagnostic rate was high in the patients with small for gestational age (7/11, 63.6 %). Conclusions: Genetic evaluation using NGS can be helpful in patients with suspected genetic short stature who have clinical and genetic heterogeneity. Further studies are needed to develop patient selection algorithms and panels containing growth-related genes. Keywords: Dwarfism, Growth Hormone, Next-Generation Sequencing
Presentation: 6/2/2024
8576 Genomic and Transcriptomic Characterization of Pediatric Thyroid Cancers
Authors: Ricarte-Filho J C , Reichenberger E R , Hinkle K , Isaza A R , Bauer A J , Franco A T 
Published: October 2024

Abstract
Disclosure: J.C. Ricarte-Filho: None. E.R. Reichenberger: None. K. Hinkle: None. A.R. Isaza: None. A.J. Bauer: None. A.T. Franco: None.
Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in both pediatric and adult populations. Recent genomic profiling of papillary thyroid cancers, including that of the Cancer Genome Atlas, has uncovered the genetic alterations and molecular mechanisms driving thyroid cancer. However, these studies were primarily focused on adult patients. Despite their favorable prognosis, pediatric PTCs have higher rates of metastasis and recurrence than adult PTCs, but the molecular characterization of these tumors have been comparatively lacking. Methods: Here we explore the genomic and transcriptomic landscape of pediatric PTCs from 126 patients, including 107 primary tumors and 19 lymph node metastases (non-paired) using whole-exome sequencing and RNA sequencing. Thirteen primary tumors also had a paired lymph node metastasis analyzed. Results: We found driver alterations in 113 of 126 (90%) of the PTCs investigated, including the identification of a novel receptor tyrosine kinase (RTK) fusion not previously reported in thyroid cancer. Genetic drivers were predominantly kinase fusions (48%), most commonly fusions of RET (22%), NTRK3 (10%), ALK (5%) and NTRK1 (5%). The most common point mutations were BRAF p.V600E (21%), NRAS p.Q61R/K (9%) and hotspot mutations in DICER1 (4%). We found genetic alterations in 12 of the 13 paired lymph node metastasis. In all 12 cases the metastatic tissue harbored the same alterations found in the primary tumor. Eight out of 12 cases had fusions (3 RET, 3 NTRK3 and 2 NTRK1), and the additional 4 cases had point mutations (3 BRAFV600E and 1 TSHRM543T). Fourteen patients (11%) had widely invasive disease with lateral lymph node and distant metastases (N1bM1). Most of these N1bM1 tumors (13/14; 93%) were driven by RTK fusions (5 NTRK3, 3 RET, 3 NTRK1 and 2 ALK). The one case lacking a kinase fusion had a CHEK2 mutation. Conclusion: Our genomic and transcriptomic analysis allowed the detection of driver alterations in ∼90% of the cases, reducing the so-called “dark matter” in our cohort. Our data support that kinase fusions are associated with metastatic disease in pediatric PTC. Patients with RET/NTRK/ALK fusions have worse outcomes than those with BRAF p.V600E mutation and RAS-like alterations (NRAS, DICER1, non-V600 BRAF, PTEN). By using the transcriptional profiling generated in this study, we are currently investigating the molecular mechanisms underlying the metastatic behavior of pediatric PTCs harboring oncogenic fusions, including changes in MAPK transcriptional output, differentiation score and recruitment of signaling pathways potentially associated with the metastatic behavior of these tumors.
Presentation: 6/3/2024
7819 Hypoglycemia with Hereditary Hemorrhagic Telangiextsia in a Boy After Liver Transplantation
Authors: Miyagi Hajime , Igarashi Mizuho , Tanimoto Eri , Horikawa Reiko 
Published: October 2024

Abstract
Disclosure: H. Miyagi: None. M. Igarashi: None. E. Tanimoto: None. R. Horikawa: None.
Introduction: Hereditary hemorrhagic telangiectasia (HHT) causes arteriovenous malformation (AVM) in liver, lung, and brain. It is not clear whether it also causes hypoglycemia. We show a case of HHT combined with hypoglycemia after liver transplantation, improved by nutrition management and growth hormone treatment. Case: 11 months old boy born from a mother with HHT was diagnosed as having with AVM prenatally. He was once operated for the liver AVM but developed a new collateral circulation which caused severe heart failure and lead to liver transplantation. He showed severe growth retardation and malnutrition. His body weight was 4.6 kg and height were 60 cm (-5.8 SD) when he was 1 year old, and blood test showed low albumin for 3 g/dL (3.4 - 4.7 g/dL), and total protein for 4 g/dL (5.7 - 7.5 g/dL). Hypoglycemia was found while switching his nutrition from parenteral to enteral nutrition after operation. His insulin was under 0.3 µU/mL when his blood glucose was 49 mg/dL IGF1 was 17 ng/mL (ref.11 - 149 ng/mL), suggested growth hormone (GH) deficiency. GH stimulation test showed blunted response. GH treatment was started. Other pituitary hormones were within normal range. Nutritional support was added using high-calory milk. After GH treatment, IGF1 level increased to 87 ng/mL. GH and nutritional management improved not only his weight and height gain but also his glycemic control. Discussion: Hypoglycemia may be caused by both GHD and malnutrition. GHD and low IGF1 might be caused by malnutrition. Retesting GH secretion after improvement of nutrition is planned to clarify his pituitary function.
Presentation: 6/2/2024
8706 Hypoparathyroidism and Hypercalcemia in Premature Secondary to Excessive Vitamin D: Everything in Excess is Opposed
Authors: Bastos Dyrlanne Marcia Lopes , Bastos Ana Clara Freire da Cunha 
Published: October 2024

Abstract
Disclosure: D.M. Bastos: None. A. Bastos: None.
Introduction: Vitamin D intoxication in children is rare but its incidence is increasing as vitamin D is supplemented more often and in higher doses. Coma, ventricular fibrillation, and acute renal insufficiency are possible life-threatening presentations of vitamin D-induced hypercalcemia. Nephrocalcinosis, renal lithiasis, vascular calcifications, and arterial hypertension are known late complications of severe or longstanding hypercalcemia. The most common causes of vitamin D intoxication in children are manufacturing errors, parental dosing errors, and erroneous medical prescriptions. Case Presentation: A premature girl admitted to the neonatal ICU 3 months ago due to poor weight gain and was taking vitamin D and infant formulas and developed tachycardic heart rhythm with irregular rhythm and kidney changes. The investigation of the condition was re-evaluated, and the patient was seen with hypercalcemia, an increase of more than 100x in the dosage of 25(OH)vitamin D, an increase in the dosage of 1.25(OH)vitamin D, suppressed PTH, an increase in creatinine and urea. In addition, an ultrasound was performed showing the presence of small kidney stones, none of which were obstructive. After discontinuing vitamin D supplementation, the patient progressed satisfactorily with a reduction in cardiac and renal changes. Discussion: Currently, vitamin D supplementation has been carried out more frequently, as, in addition to increasing the absorption of calcium in the body, it reduces the risk of diseases, such as rickets and osteopenia of prematurity. The body is only able to produce vitamin D after exposure to sunlight. In the absence of regular exposure, dietary sources alone are not sufficient to maintain adequate levels. Cases of hypervitamin D generally occur in situations of excessive supplementation. In the present report, the dose used was 40 times higher than recommended. Initial tests revealed elevated calcium and undetectable PTH levels. The diagnosis of vitamin D intoxication is not common in cases of hypercalcemia, as it is infrequent, especially before the advent of vitamin D supplementation. Vitamin D toxicity is usually iatrogenic, or due to accidental overdose. These factors, along with a lack of public education about safe dosing, have likely contributed to the increase in reported cases of vitamin D toxicity. Conclusion: Vitamin D supplementation, especially when using compounded medications, must be adequately monitored due to the potential risk of poisoning. Vitamin D toxicity remains a pressing issue and its incidence will likely continue to grow, primarily because of the widespread availability of over-the-counter formulations and public interest.
Presentation: 6/3/2024
6513 Identification of pathogenic ACAN variants in healthy children with normal height and advanced bone age
Authors: Hernandez M , Unanue N , Gallardo V , Van duyvenvoorde H , Mericq M V 
Published: October 2024

Abstract
Disclosure: M. Hernandez: None. N. Unanue: None. V. Gallardo: None. H. Van duyvenvoorde: None. M.V. Mericq: None.
Background/rationale: Linear growth is determined by proliferation and differentiation of growth plate (GP) chondrocytes. The main proteoglycan component of the extracellular matrix of GP is ​​aggrecan, encoded by the ACAN gene. Homozygous pathogenic variants have been reported in patients with spondylo-metaphysial dysplasia. Heterozygous pathogenic variants are associated with non-syndromic short stature of pre or postnatal onset, in most cases with advanced bone age, early-onset dissecting osteoarthritis, and some other dysmorphic features. Hypothesis Children with normal height and significant advanced bone age can present pathogenic variants in the ACAN gene. Patients and methods: Healthy prepubertal children referred for height evaluation because of advanced bone age (≥ 2 SDS using Bayley Pineau, validated using Bonexpert) in combination with normal height (± 2 SDS) and BMI (15th-85th centile ) were included, after signing informed consent. We excluded puberty by clinical Tanner staging, CAH or premature adrenarche (DHEAS &gt; 40 micr/dl RIA), GH excess or thyroid disorders and medications that could advance bone age. Genomic DNA was isolated from peripheral blood using QIAamp DNA Mini kit (Qiagen, Germany). Sequencing was performed on an Illumina platform using the Agilent enrichment kit SureSelectXT Clearseq Inherited Disease Panel (IDP). SNV (single nucleotide variant and CNV (copy number variant) data analysis of all coding exons of the ACAN gene including +/- 20 nucleotides of flanking intron sequences was performed, with exception of the complex Variable Number of Tandem Repeats (VNTR) structure in exon 12. Results : 17 prepubertal Caucasian children (2 females) were genotyped at a mean age 7.7 ±1.8 years, a height of -0.47±0.89 SDS, a BMI of -0.05 ±1.19 SDS, a mid-parental height of -0.34 ±0.59 SDS and mean difference between height and MPH 0.28±0.77 SDS . None of these children had a pathogenic ACAN variant. Conclusion: this study suggests that pathogenic ACAN varians appear not to be a prevalent cause of advanced bone age in healthy prepubertal children. Follow-up of this group of patients will provide us with more information on the impact of the advanced bone age on final height. Dependent on the final height outcome, additional genetic investigations can be considered.
Presentation: 6/3/2024
6805 Impact of Feeding Types on Catch-Up Growth in Early Infancy Among Small-for-Gestational-Age Infants: A Nationwide Korean Study
Authors: Choi Jinjoo , Choe Yunsoo , Yang Seung 
Published: October 2024

Abstract
Disclosure: J. Choi: None. Y. Choe: None. S. Yang: None.
Purpose: The study aimed to compare growth patterns and catch-up growth (CUG) in small-for-gestational-age (SGA) infants up to age four, based on feeding type during the first 4-6 months, using nationwide data. Methods: A total of 42,295 children born SGA (21,917 boys, 52.%) who underwent the first (4-6 month), 2nd (9-12 month), 3rd (18-24 month) and 5th (42-48 month) National Health Screening Program for Infants and Children (NHSPIC) under the National Health Insurance Service from 2007 to 2014 were included. The study population was categorized into two groups based on the primary milk feeding type recorded in the self-reported questionnaire during the first round of NHSPIC: the ”Breastfed”group, and the "Formula-fed" group. Catch-up growth (CUG) was defined as a Height Standard Deviation Score (Ht SDS) of 3rd percentile or above at the 5th NHSPIC visits. We used propensity scores to 1:1 match breastfed and formula-fed group based on sex, birth weight, cesarean section, socioeconomic status, residance. Multivariate logistic regression analysis was performed to evaluate the effect of milk feeding type on CUG at 4 years of age. Results: 49.1% of infants (n = 20,774) were breastfed and 50.9% (n = 21,521) were formula-fed. The median birth weight was 2.7 kg (interquartile range: 2.5-2.9 kg), and 98.7% of the children (n = 41,752) achieved CUG by the 5th NHSPIC round. Following propensity score matching, both groups included 19,308 infants. At four years of age, the breastfed group showed a lower likelihood of achieving CUG compared to the formula-fed group (aOR 0.794, 95% CI 0.665-0.948). During the 1st NHSPIC round, the breastfed group had a significantly lower weight Z-score (mean: -0.05, range: -0.64 to 0.41) than the formula-fed group (mean: 0.14, range: -0.42 to 0.78, p &lt; 0.001). This trend was more pronounced from the 1st to 2nd round, with greater decreases in both weight and height Z-scores for the breastfed group (weight difference: -0.36, range: -0.74 to 0.02; height difference: -0.21, range: -0.62 to 0.20) compared to the formula-fed group (weight difference: -0.17, range: -0.53 to 0.20; height difference: -0.13, range: -0.53 to 0.28, p &lt; 0.001). However, from the 2nd round, the breastfed group demonstrated faster gains in both weight and height (p &lt; 0.001). Conclusion : In a study of Korean SGA infants, those breastfed during the first 4-6 months post-birth had lower CUG rates at four years compared to formula-fed infants. The breastfed group exhibited less weight and height gain, especially between the 1st and 2nd NHSPIC rounds, aligning with the initial phase of solid food introduction. These findings may suggest the need for enhanced nutritional supplementation for breastfed SGA infants. Further research is necessary to explore other factors that may impact growth during this critical developmental period.
Presentation: 6/3/2024
6394 Prevalence of Diabetes Insipidus in Pediatric Patients Who Have Been Declared Dead by Neurologic Criteria
Authors: Larancuent Cesar Esteban , Merilan Valandrea , Leoncio Michael , Lozano Juan M , Totapally Balagangadhar R 
Published: October 2024

Abstract
Disclosure: C.E. Larancuent: None. V. Merilan: None. M. Leoncio: None. J.M. Lozano: None. B.R. Totapally: None.
Introduction: Death by neurological criteria (DNC) or brain death (BD), occurs in individuals who have sustained catastrophic brain injury and are in permanent coma with loss of all brainstem function, coupled with the inability to breathe in the setting of hypercarbia and acidosis. Diabetes insipidus (DI) occurs in many but not all patients with DNC. Several studies indicate varying prevalence rates of DI among pediatric patients with DNC. Objective: Our objective was to determine the prevalence of DI in children who have been declared DNC, and the frequency of DI in these children according to the mechanism of brain injury. Methods: A retrospective analysis of 57 pediatric inpatients 0-21 years subsequently declared BD at Nicklaus Children’s Hospital from January 2013 to June 2023. Data was gathered from the hospital's electronic medical records and the VPS database. The primary exposure is brain death, while the secondary exposure is the mechanism of brain injury. These injuries were categorized into anoxic, traumatic brain injury (TBI), and brain tumors/space-occupying lesions (malignancy). The prevalence of DI was assessed as the primary outcome, and it was compared between three etiologies for brain death using Pearson Chi-square. Due to the study's small sample size, the association between the cause of BD and DI was not adjusted by covariates, such as sex and age. This study was exempted by the IRB. Results: Of the 53 patients declared BD, 47 (88.7%, 95% CI 77.9% to 95.3%) were diagnosed with DI. The prevalence of DI did not change significantly according to the etiology of brain injury leading to BD (84.4%, 100.0%, and 92.3% for anoxic brain injury, TBI, and malignancy, respectively; p = 0.410). The characteristics of children according to the etiology of brain death are presented in Table 1. The characteristics of children according to the development of DI are presented in Table 2. ICU length of stay, the duration to brain death declaration, and eligibility for organ donation varied with the etiology of brain death (Table 1). Conclusions: The prevalence of DI is high in pediatric patients declared BD, and it is not significantly different based on the etiology of brain death. Given this high prevalence, diligent DI management is needed to improve organ donation outcomes.
Presentation: 6/2/2024