bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU146 Triglyceride Glucose Index Is Superior To The Homeostasis Model Assessment Of Insulin Resistance For Predicting Severity Of Nonalcoholic Fatty Liver Disease In Korean Children And Adolescents
Authors: Yoon Jong Seo , Kim Eun Young 
Published: October 2023

Abstract
Disclosure: J. Yoon: None. E. Kim: None.
Background: Triglyceride glucose (TyG) index is known as a reliable insulin resistance surrogate marker to identify non-alcoholic fatty liver disease (NAFLD). Ultrasonographic fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting hepatitis in patients with NAFLD and accurately identifies histological severity. Few studies have compared the TyG index to homeostasis model assessment of insulin resistance (HOMA-IR) in the detection of NAFLD in children and adolescents. Additionally, there were no studies comparing the ability of TyG index and HOMA-IR to assess the severity of NAFLD. Objects: Therefore, we investigated the relationship between TyG index and NAFLD compared to HOMA-IR in identifying and assessing the severity of NAFLD in children and adolescents. Methods: Alanine aminotransferase (ALT) was used as the screening method for NAFLD (&gt;26IU/L in boys and &gt;22IU/L in girls), and US-FLI was performed on children who met these criteria. The US-FLI is a scoring system ranging 2-8 that evaluates based on intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. TyG index was calculated as ln(fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2). Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. The US-FLI was significantly correlated with TyG index (r=0.264, p=0.003) but not with HOMA-IR after controlling for sex, age, and BMI. Multiple linear regression analysis showed that TyG index were significantly associated with US-FLI (β=0.202, p=0.002) not with HOMA-IR after controlling for sex, age, and BMI. The TyG index was superior to HOMA-IR in its ability to detect the severity of NAFLD in US-FLI ≥4, ≥5, and ≥6. Conclusions: Both TyG index and HOMA-IR were useful for detecting pediatric NAFLD. However, the TyG index was useful for detecting the severity of NAFLD, whereas HOMA-IR was not. Therefore, we propose to use the TyG index to predict and evaluate the severity of NAFLD in children.
Presentation: Thursday, June 15, 2023
THU153 Deep Vein Thrombosis As The Presenting Symptom In An Adolescent With New-Onset Type 2 Diabetes
Authors: Cooper Felicia Ilyssa , Gurnurkar Shilpa , Carakushansky Mauri 
Published: October 2023

Abstract
Disclosure: F.I. Cooper: None. S. Gurnurkar: None. M. Carakushansky: None.
Introduction The prothrombin G20210A mutation occurs in a small portion of the population, but usually does not become apparent unless the individual exhibits another risk factor for clotting (such as diabetes in adulthood). In this case report, we discuss a 15-year-old male with extensive deep vein thrombosis (DVT) in the setting of hyperglycemia and a newly-discovered prothrombin G20210A mutation. Case Presentation A previously healthy, obese 15-year-old male presented to the emergency department with two days of left hip pain radiating down to the left calf, and one day of left calf swelling. The patient denied prolonged immobility, recent infections, or recent vaccinations. There was strong maternal family history of diabetes but no history of thrombosis. D-dimer was 2013 ng/mL (0-500 ng/mL). A Computed Tomography of the abdomen and pelvis with contrast revealed thrombi in the inferior vena cava, left common iliac, left external iliac, left internal iliac and left common femoral veins. Initial labs were remarkable for unexpected significant hyperglycemia-- random serum glucose 317 mg/dl (&lt;140 mg/dl).He was started on unfractionated heparin infusion as well as Lantus and Humalog insulins. An echocardiogram did not reveal pulmonary embolism or right heart strain. Hemoglobin A1C was 11.8% (3.4-5.6%) and C-peptide was detectable at 1.2 ng/mL (1.1-4.4 ng/mL), suggesting type 2 diabetes (in addition to negative anti-GAD 65 and islet cell antibody titers, in this child with a BMI of 34 kg/m2). The patient underwent image-guided thrombolysis and thrombectomy from the popliteal vein to the left iliac vessels and received continuous infusion of heparin and tissue plasminogen activator (TPA). As the clot improved over the subsequent days, he underwent image-guided angioplasty and removal of the popliteal sheath. He was then transitioned to enoxaparin and discharged on day 10 of hospitalization. His blood sugars responded well to insulin therapy (85-308 mg/dl). The patient received a staged thrombophilia workup. A heterozygous mutation was found in factor II (prothrombin G20210A) gene which is associated with a 2-4 fold increased risk of venous thromboembolism. The patient was discharged on enoxaparin, as well as Lantus and Humalog. He is followed by the Hematology and Endocrinology departments. Conclusion In this case, we presented the first written occurrence of DVT in a pediatric patient with type 2 diabetes. Our patient’s hyperglycemia caused by his new onset type 2 diabetes may have led to onset of an extensive DVT thrombosis at an usually young age, since he had an underlying prothrombin G20210A mutation. Our case also illustrates the need for a multidisciplinary approach (involving endocrinology, hematology, pediatric intensive care, and interventional radiology) for successful outcomes in these patients.
Presentation: Thursday, June 15, 2023
THU154 The Effects Of Combined Arginine And Sinemet Stimulation On Copeptin Levels In The Pediatric Population
Authors: Sastry Shruti , March Christine , Garibaldi Luigi , McPhaul Michael John , Wheeler Sarah 
Published: October 2023

Abstract
Disclosure: S. Sastry: None. C. March: None. L. Garibaldi: None. M.J. McPhaul: None. S. Wheeler: None.
Introduction: Most agents that stimulate the secretion of growth hormone (GH) also induce secretion of copeptin (COP), a stable surrogate of AVP. For the evaluation of the polyuria-polydipsia syndrome (PPS), COP stimulation by intravenous (IV) arginine (ARG) has been proposed as a less invasive test than those based on osmotic stimulation of the posterior pituitary, though it provides a weaker stimulus in children than in adults (∼30% vs. 50% increase). After having observed a robust COP response to combined ARG and insulin stimulation (March C, Horm Res Pediatr 2023, PMID: 36513057), we explored the effect of combined IV ARG and oral L-Dopa/carbidopa (LDc, 10:1 ratio), another known stimulus for GH secretion, on COP secretion in non-AVP deficient children. Subjects and Methods: We enrolled 30 healthy subjects with short stature (73% male, mean age ± SD 10.5±3.0 years) undergoing fasting GH stimulation testing in a prospective, single-arm study to assess their COP response. At 0 minutes (min), ARG (500 mg/kg) was infused over 30 min IV and LDc (200 mg/m2 BSA of L-Dopa) was given orally. Serum COP (B.R.A.H.M.S Kryptor assay, Quest Diagnostics) was measured at 0, 60, 90 and 120 min. Results: Median (interquartile range (IQR)) COP values (pmol/L) were 8 (5-10) at 0 min, 17 (13-44) at 60 min, 24 (13-41) at 90 min, and 30 (16-56) at 120 min. Peak COP concentrations at 60, 90, and 120 min all increased significantly from baseline (p&lt;0.001, Wilcoxon sign rank test), but were highly variable in both value (range 10-449) and the timing of the peak (60 min in 33%, 90 min in 17%, 120 min in 50%). Except for 1 subject whose COP values did not change, all subjects had a robust COP peak, ranging from 1.6 to ∼90x the baseline value. The median (IQR) copeptin peak value [50 (41-129) pmol/L] was higher in subjects experiencing nausea/vomiting than in those who did not show this known side effect of LDc [25 (16-44), p=0.03 by Wilcoxon test]. Conclusions: Combined ARG and LDc appear to induce intense stimulation of COP secretion, with widely variable stimulated COP responses. The lowest COP peak value and the median response in this series were much greater than those previously reported to ARG alone in our previous study and the literature. Side effects were well tolerated. The data suggest that this test should be piloted for the differential diagnosis PPS as an alternative to ARG stimulation alone and/or the water deprivation test.
Presentation: Thursday, June 15, 2023
THU168 PRMT7 Gene Mutation—A Rare Genetic Syndrome With Novel Endocrine Associations
Authors: Nutakki Krishna Veni , Nalla Smitha , Deb Prasun , Vulpala Alekya 
Published: October 2023

Abstract
Disclosure: K. Nutakki: None. S. Nalla: None. P. Deb: None. A. Vulpala: None.
Background: Causes of short stature in children include pathologic causes (genetic diseases, underlying systemic disease, or growth hormone deficiency) and non-pathological variants such as familial and constitutional short stature. Genetic causes include Turner’s syndrome, SHOX mutations, Noonan’s syndrome and Silver- Russel syndrome besides others. Homozygous/compound heterozygous mutations in Protein Arginine Methyltransferase 7 (PRMT7) can result in Short Stature, Brachydactyly, Intellectual Developmental Disability and Seizures syndrome (SBIDDS) . Here, we report a child with SBIDDS syndrome who has associated endocrine manifestations of growth hormone deficiency and primary hypothyroidism. Case report: A 9-year-old male child, twin A of dichorionic diamniotic gestation, presented to the Endocrine OPD with short stature. There was a history of developmental delay, seizure disorder and mild intellectual deficit. Excessive weight gain was observed since 4 years of age. On examination, he was short with abdominal obesity, brachydactyly, simian crease and macroglossia. Height was below 3rd centile and weight at the 97th percentile. SMR was pre-pubertal. Investigations confirmed primary hypothyroidism.GH deficiency (peak GH after clonidine stimulation was less than 4 microgram/L) and reduced IGF-I levels were also found. Twin B was noted to have a normal height percentile. In both, skeletal maturation was consistent with chronological age. Twin A was treated with rGH and levothyroxine and responded well to rGH treatment. Whole exome sequencing revealed homozygosity for PRMT7 mutation in twin A with both parents heterozygous for the same gene mutation. His twin sibling, twin B was also found to be homozygous for the mutation, but he did not display any characteristics of the syndrome. Discussion: To the best of our knowledge, this is only the second reported case of SBIDDS syndrome (PRMT7 mutation) with documented growth hormone deficiency and only case with documented primary hypothyroidism. Height gain observed over the period of rGH treatment is suggestive of a possible role of GH/IGF-I axis alterations as contributors of growth impairment in these children. PRMT7 encodes for an arginine methyltransferase, involved in several biological processes, such as DNA transcription and repairing, RNA splicing, cell differentiation. We would like to propose that children with SBIDDS syndrome may be tested for GH deficiency as part of their overall assessment. Likewise, it should be further explored if PRMT7 gene mutation testing should be recommended in a child presenting with short stature and one or more manifestations of SBIDDS syndrome.
Presentation: Thursday, June 15, 2023
THU612 SDHx Pheochromocytoma/Paraganglioma Has Elevation Of Arginine And Lysine Metabolites
Authors: Ghayee Hans Kumar , Richter Susan , Bechmann Nicole , Kalavalapalli Srilaxmi , Joy Guingab-Cagmat , Xu Yiling , Cusi Kenneth , Tischler Arthur , Powers James F , Beuschlein Felix , Robledo Mercedes , Fliedner Steffi , Quinkler Marcus , Fassnacht Martin , Timmers Henri , Pacak Karel , Eisenhofer Graeme , Garrett Timothy J 
Published: October 2023

Abstract
Disclosure: H.K. Ghayee: None. S. Richter: None. N. Bechmann: None. S. Kalavalapalli: None. G. Joy: None. Y. Xu: None. K. Cusi: None. A. Tischler: None. J.F. Powers: None. F. Beuschlein: None. M. Robledo: None. S. Fliedner: None. M. Quinkler: None. M. Fassnacht: None. H. Timmers: None. K. Pacak: None. G. Eisenhofer: None. T.J. Garrett: None.
Background: Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that arise from the chromaffin cells of the adrenal medulla or sympathetic/parasympathetic paraganglia respectively. There are more than 25 genetic drivers identified in these tumors. These genetic mutations are categorized into the three main clusters. However, cluster 1 and cluster 2 comprise most of the known genes. Within cluster 1, SDHx mutations are associated with aggressive disease. To better understand the metabolic signature of these tumors, our group performed untargeted metabolomics of over 200 pheochromocytomas and paraganglioma tissue samples. Methods: Frozen tissues were processed and sent to the University of Florida and analyzed in 2 batches. Analysis was conducted using liquid chromatography high-resolution mass spectrometry with full blinding and randomization. Raw data were converted to mzXML and then processed using MZmine to identify features. Blank feature filtering was conducted to filter noise and very low abundant features. Metabolite identification was first conducted with reference to an in-house retention time library of 1200 metabolites and further identification was conducted by searching the human metabolome database. Statistical analysis was performed in R. Results: Comparing cluster 1 vs cluster 2, we observed an overall increase in purine metabolites specifically adenine, AMP, GMP, UMP, CMP, cytidine, and dihydrothymine in cluster 2. Arginine metabolism was lower in cluster 2, specifically dimethylarginine, citrulline, and N-methyl-L-arginine. Comparing SDHx vs cluster 1, we observed an overall increase in arginine metabolism with ornithine, citrulline, N-acetyl-ornithine, proline and hydroxy-proline. We also observed an increase in lysine metabolism in SDHx vs cluster 1 with lysine, N-acetyl-lysine, cadaverine, glutarate, 2-hydroxyglutarte, 2-oxoglutarate, succinate and trimethyllysine all being elevated. A decrease in serotonin in SDHx compared to cluster 1 was seen. Conclusion: Global metabolomic analysis of pheochromocytomas and paragangliomas has uncovered important pathways that drive the metabolic functions depending on the gene cluster. Most notably, arginine and lysine metabolites were increased in SDHx tumors.
Presentation: Thursday, June 15, 2023
THU184 Varying Presentations Of 46XX OTD
Authors: Mishra Ipsita , Sahoo Subhendu Kumar , Baliarsinha Anoj Kumar 
Published: October 2023

Abstract
Disclosure: I. Mishra: None. S.K. Sahoo: None. A.K. Baliarsinha: None.
Ovotesticular disorder of sex development (OT-DSD) is a condition associated with presence of both testicular and ovarian tissue in same individual, in which these tissues may co-exist either in the same gonad or independently. 46 XXOTD are most common. We describe 3 cases of 46 XXOTD presenting in their post pubertal years with varied presentation. Case 1: 19 year old reared as male presented with peripubertal gynaecomastia and cyclical pain abdomen. On examination there was symmetrical genitalia, non palpable gonads, microphallus, single genital opening below phallus (Prader 3), pubic hair stage 4, axillary hair stage 3 and breast stage 5. Biochemical evaluation revealed serum testosterone (19 ng/dl), 17-hydroxy progesterone (1.7ng/ml), LH (2.6IU/L), FSH (8.6IU/L) and E2(112pg/ml). Karyotype 46XX, FISH SRY negative. USG abdomen s/o uterus like structure with absent wollfian remnants. Post laproscopy histopathology s/o bilateral ovotestis, normal ovarian stroma with hyalinized seminiferous tubule, sertoli cells and leydig cells. Case 2: 18 year old reared as male presented with peripubertal gynaecomastia and genital ambiguity. On examination there was asymmetrical genitalia, palpable right scrotal gonads, phallus, single genital opening at base of phallus, pubic hair stage 4, axillary hair stage 3 and breast stage 5. Biochemical evaluation revealed serum testosterone (110ng/dl), LH (4.6IU/L), FSH (11.2IU/L) and E2(46pg/ml). Karyotype 46XX.USG abdomen s/o hypoplastic uterus like structure with possible ovary in left side of pelvis, hypoplastic testis in right scrotal sac. Post laproscopy histopathology was s/o left dysgenetic ovary, and hypoplastic uterus. Case 3: 17 year old reared as male presented with peripubertal gynaecomastia. On examination there was symmetrical genitalia, non palpable gonads, microphallus, single genital opening at the base of phallus (Prader 4), pubic hair stage 4, axillary hair stage 2 and breast stage 4. Biochemical evaluation revealed serum testosterone (98ng/dl), 17-hydroxyprogesterone (0.58ng/ml), LH (4.05IU/L), FSH (7.12IU/L) and E2 (96 pg/ml). Karyotype 46XX, FISH SRY positive. USG abdomen s/o uterus like structure with apparent left ovary and non visualization of right gonads. Post laproscopy histopathology s/o rudimentary uterus, left ovary with follicles and right gonads showing semineferous tubules with sertoli cells and few hyperplastic leydig cells. 46 XX OTDSD presents with wide phenotypic variability, which influences decisions about gender assignment and need of surgery. Conservative therapy, whenever feasible, is desirable to achieve fertility. Multidisciplinary team approach is required for healthy physical and psychological well-beings of these individuals.
Presentation: Thursday, June 15, 2023
THU185 Molecular Etiologic Spectrum Of Patients With 46,XY And 46,XX Disorders Of Sex Development
Authors: Kim Ja Hye , Park Soyoung , Hwang Soojin , Yoon Ji-Hee , Kim Gu-Hwan , Yoo Han-Wook , Choi Jin-Ho 
Published: October 2023

Abstract
Disclosure: J. Kim: None. S. Park: None. S. Hwang: None. J. Yoon: None. G. Kim: None. H. Yoo: None. J. Choi: None.
Background: Disorders of sexual development (DSDs) is a group of congenital conditions associated with discordant development of chromosomal, gonadal, and anatomical sex. Sex development is a complex process with a precise synergistic temporal-spatial transcriptional regulation of multiple genes. Advances in next-generation sequencing (NGS) techniques have achieved genetic diagnosis for up to 40 % of 46,XY DSDs. This study investigated the etiological distribution of DSDs identified by NGS. Methods: This study included 70 patients with DSDs (56 patients with 46,XY DSD and 14 patients with 46,XX DSD). Molecular genetic analysis was performed using targeted gene panel sequencing (n = 43) and whole-exome sequencing (WES, n = 26), including 25 patients for the first-line test and one without sequence variants by targeted gene panel sequencing. Whole-genome sequencing (WGS) was performed on 7 patients, including two patients for the first-line test and five patients without sequence variants by targeted gene panel sequencing or WES. Results: Patients with DSDs presented in infancy with ambiguous genitalia and at older children with aberrant pubertal development or discordance between karyotype and external genitalia. Twenty-four of 56 patients (42.9%) with 46,XY DSD were reared female, and 5 of 14 patients (35.7%) with 46,XX DSD were raised as a male. Pathogenic or likely pathogenic variants were identified in 21 of 56 patients with 46,XY DSD (37.5%); however, no rare sequence variants were found in patients with 46,XX DSD. The AR variants were the most common (8/70, 11.4%), followed by CYP17A1 (4/70, 5.7%), SRD5A2 (4/70, 5.7%), NR5A1 (2/70, 2.8%), GATA4 (1/70, 1.4%), MYRF (1/70, 1.4%), and deletion of DMRT1/2 (1/70, 1.4%). Mutation-positive patients with 46, XY DSD were assigned as female more frequently than mutation-negative patients (19/21 vs. 6/35, P-value &lt;0.001). The lower diagnostic yield was observed in patients with a less severe phenotype, such as hypospadias or micropenis. Conclusions: This study demonstrated that genetic etiologies could be identified in 37.5% of patients with 46,XY DSD, whereas there were no genetic variants in patients with 46,XX DSD. Patients with a more severe phenotype were more likely to have a conclusive genetic diagnosis. NGS is a helpful technique to improve diagnostic efficiency in patients with DSD because of phenotypic and genetic heterogeneity.
Presentation: Thursday, June 15, 2023
THU188 Clinical Conundrum: Salt Wasting Congenital Adrenal Hyperplasia With Paradoxical High Cortisol
Authors: Pillai Chanthu 
Published: October 2023

Abstract
Disclosure: C. Pillai: None.
Background: Salt wasting congenital adrenal hyperplasia (CAH) is a severe life-threatening condition and thus a cannot miss diagnosis. In salt wasting CAH, cortisol is generally very low. An ACTH stimulation test is often used to diagnose adrenal insufficiency and initiate life-saving hydrocortisone therapy. Clinical Case: I present a case of a male infant who was found to have salt-wasting CAH crisis despite a paradoxically high serum cortisol. He had an abnormal newborn screen for CAH. He was sent to the ER for reportedly high 17-hydroxyprogesterone (17-OHP). Endocrine was consulted and a serum 17-OHP, ACTH and cortisol level was requested. He was an incredibly difficult patient to collect blood work and after multiple attempts only a serum cortisol was collected. He was admitted for an ACTH stimulation test to rule out salt wasting CAH. His physical exam was unremarkable with male external genitalia with descended prepubertal testes. His cortisol from the ER resulted at 36.5 mcg/dL without any steroid administration in the morning. Family refused to do any additional blood work in the morning. Even anesthesiology was not able to collect the requested labs. The ACTH stimulation test was canceled, and he was discharged with close follow-up in 1 week. The state newborn screen department called and reported his initial 17-OHP was undetectably high. He was seen the same day and his BMP showed clear signs of salt wasting. His serum sodium was 131 mmol/L and potassium was 7.2 mmol/L. He was admitted for a salt wasting crisis and responded well to hydrocortisone and fludrocortisone. Serum sodium and potassium normalized. Blood draw issues continued and only BMP were collected during the hospitalization. 17-OHP after several days of therapy was 3270 ng/dl. 17-OHP, sodium and potassium have normalized on therapy. Genetic testing is pending. Conclusions: By reporting this case, I draw attention to the possibility that high levels of cortisol do not definitely rule out salt-wasting CAH.
Reference Ranges: NA 132 - 145 mmol/L K 3.0 - 6.0 mmol/L Cortisol: 1.7 - 14.0 ug/dL 17 OHP:INTERPRETIVE INFORMATION for 17-Hydroxyprogesterone in premature and normal male infants: Premature (26 to 28 weeks) 124 to 841 ng/dL Premature (29 to 35 weeks) 26 to 568 ng/dL Full term Day 3 7 to 77 ng/dL 4 days to 2 months Less than 200 ng/dL.
Presentation: Thursday, June 15, 2023