bluuebunny/crossref_metadata_2025_split huggingface dataset:
7335 Myxedema Coma in an Adolescent Patient: A rare, lethal manifestation of profound hypothyroidism
Authors: Rodriguez Christian , Mejias Exa M , Berrios Luis R , Currais Carolina 
Published: October 2024

Abstract
Disclosure: C. Rodriguez: None. E.M. Mejias: None. L.R. Berrios: None. C. Currais: None.
Myxedema coma is a rare, life-threatening condition that represents the most severe manifestation of profound hypothyroidism. It is characterized by extensive end-organ dysfunction. Therefore, it is crucial to have a high index of suspicion in order to identify it promptly and initiate treatment. We report a case of an adolescent patient with past medical history of Type 1 Diabetes Mellitus and hypothyroidism who was initially admitted to pediatric wards due to hypertension, constipation and acute kidney injury (AKI). The patient was transferred to the pediatric intensive care unit (PICU) after he developed multi-organ failure secondary to myxedema coma. His laboratory work up was remarkable for severe hypothyroidism with a thyroid-stimulating hormone (TSH) &gt; 679, uncontrolled diabetes mellitus (Glycosylated Hemoglobin 13.1%) and chronic kidney disease (Creatinine 2.56). During his hospital course, he required long term hemodialysis, mechanical ventilation and underwent cardiorespiratory resuscitation multiple times. Since myxedema coma is an uncommon manifestation of pediatric hypothyroidism, pediatric guidelines are not available. We aim to reinforce the awareness of myxedema coma and encourage physicians to have a high index of suspicion as the widespread availability of TSH assays and its use can aid in the diagnosis and treatment of these patients. Furthermore, we emphasize an interdisciplinary approach to avoid mortality and long-term complications.
Presentation: 6/1/2024
7537 Composite Pheochromocytoma-Ganglioneuroma Secreting Vasoactive Intestinal Peptide: A Case Report
Authors: Brochu Benjamin , Collin Yves , Temmar Rabia , Bernier Frederic , Dandurand Karel , St-Jean Matthieu , Massicotte Marie-Hélène 
Published: October 2024

Abstract
Disclosure: B. Brochu: None. Y. Collin: None. R. Temmar: None. F. Bernier: None. K. Dandurand: None. M. St-Jean: None. M. Massicotte: None.
Background: Composite pheochromocytoma-ganglioneuroma is a rare tumor combining features of both pheochromocytoma/paraganglioma (PPGL) and neurogenic tumors. Cosecretion of vasoactive intestinal peptide (VIP) is even less common and highlights the diverse secretory potential of these tumors. Clinical Case: An 80-year-old woman presented with severe chronic diarrhea that had been progressively worsening over the past 10 years. The diarrhea was associated with chronic hyponatremia between 128 and 132 mmol/L. She also had mild hypertension, with a mean blood pressure of 145/90 mm Hg. An abdominal CT scan revealed a right adrenal mass of 68 mm x 44 mm x 50 mm with a density of 19 HU without contrast. A 24-hour urinary collection demonstrated normetanephrines (NM) levels at 3.5 times the upper limit of normal. A 68Ga-DOTATATE PET/CT demonstrated significant uptake only in the adrenal mass. Because of the ongoing severe diarrhea, that is unusual in the context of NM secreting PPGL, serum VIP level was measured and came back at nearly three times the upper limit of normal. A provisional diagnosis of pheochromocytoma with VIP and catecholamines cosecretion was made and surgical resection by laparotomy was performed without complication. Pathology demonstrated a composite tumor combining a pheochromocytoma and a ganglioneuroma, with a Pheochromocytoma of the Adrenal gland Scaled Score (PASS) score of 3. Tumor immunohistochemical staining was positive for VIP in both pheochromocytoma and ganglioneuroma cells. After surgery, diarrhea and hyponatremia resolved and blood pressure normalized. Conclusion: This is one of the very rare cases described in the current literature of a composite pheochromocytoma coproducing catecholamines and VIP. While the two tumors might have developed synchronously, the finding of VIP secretion in the pheochromocytoma and the ganglioneuroma suggest that both tumors might originate from the same cell.
Presentation: 6/1/2024
7644 Novel Candidate Genes for SRY-Negative 46,XX Differences of Sex Development with Testicular Differentiation
Authors: Ferrari Maria Tereza Martins , Nishi Mirian Yumie , Jorge Alexander Augusto Lima , Benedetti Anna Flavia Figueiredo , Batista Rafael Loch , Silva Elinaelma Suelane do Nascimento , Martinez Alejandro , Mericq Veronica , Carvalho Filomena Marino , Mendonca Berenice Bilharinho , Domenice Sorahia 
Published: October 2024

Abstract
Disclosure: M.M. Ferrari: None. M.Y. Nishi: None. A.A. Jorge: None. A.F. Benedetti,: None. R.L. Batista: None. E.S. Silva: None. A. Martinez: None. V. Mericq: None. F.M. Carvalho: None. B.B. Mendonca: None. S. Domenice: None.
Introduction: Gonadal development in mammals is a dynamic and complex process, which requires the interaction of multiple factors in a meticulous feedback control and self-regulation system. Defects in genes involved in this process may cause differences of sex development (DSD). In rare cases, the gonads of 46,XX individuals differentiate completely into testes (46,XX testicular DSD, 46,XX TDSD), or with the coexistence of testicular and ovarian tissues in the same individual (46,XX ovotesticular DSD, 46,XX OTDSD). Strategies of large-scale parallel sequencing have enabled the simultaneous analysis of known genes, as well as the identification of novel candidate genes contributing to molecular diagnosis of these conditions. Objective: To establish the molecular diagnosis of a cohort of SRY-negative 46,XX T/OTDSD patients using the whole exome sequencing (WES) technique. Patients and Methods: Twenty-three families (24 patients) were evaluated, 22 patients with sporadic disease, and one family with two affected siblings. Histological diagnosis of OTDSD was confirmed in all patients, except in two with the presumptive (non-histological) diagnosis of TDSD. WES was performed using the Illumina platform. The variants were classified according to ACMG criteria. Results: Six different candidate genes associated with the 46,XX DSD phenotype were identified in the 23 families (26%) studied; all in patients with OTDSD diagnosis. Two variants were classified as likely pathogenic in FLNB and SOX10 genes, and four as VUS in IMMP2L, SOX8, PRKACG, and CLASP1 genes. The unavailability of analysis of case-parent trio samples hampered the classification of some of the novel candidate allelic variants. All these candidate genes were selected as potential causes of OTDSD, based on evidence of direct or indirect interactions of these proteins with SOX9. In the two siblings with 46,XX OTDSD, the allelic variant c.397delT (p.Ser133Leufs*7) in IMMP2L was identified in a heterozygous state and was absent in the unaffected family members (mother and third XY sibling). A potential role of Immp2l had been previously associated with the etiology of XX female-to-male sex reversal in sheep lineage. Conclusion: Although establishing the genetic etiology of gonadal development abnormalities in individuals with 46,XX TDSD/OTDSD remains a challenge, the results of this study generated new information and perspectives on the mechanisms involved in gonadal development.
Presentation: 6/3/2024
9356 Occurrence Of Dyslipidemia During Modified Atkins Diet In Children With Intractable Epilepsy And Effect Of Lipid-Lowering Agents On Dyslipidemia
Authors: Yoo Ji Eun , Kim Seo Jung , Chae Hyun Wook 
Published: October 2024

Abstract
Disclosure: J. Yoo: None. S. Kim: None. H. Chae: None.
Introduction: The Modified Atkins Diet (MAD), as a type of Ketogenic diet (KD) therapy, is utilized as a treatment for intractable epilepsy. Compared to the classic KD, it has a lower ratio of fat to carbohydrate plus protein, resulting in higher compliance among patients. Dyslipidemia is known as a major complication of KD, but when it comes to MAD, there is a scarcity of long-term studies investigating lipid level alterations in children.In this study, our objective is to examine the impact of the MAD on serum lipid levels in children and adolescents with intractable epilepsy. Method: A total of 106 patients with intractable epilepsy aged under 19 who initiated MAD from January 2016 to December 2021 and maintained MAD for a minimum of 12 months were enrolled. Laboratory test for lipid level were conducted at baseline, 1 month, 3 months, 6 months, and subsequently at 6-month intervals after initiation of MAD. The prevalence rate of dyslipidemia and lipid levles by period after MAD was analyzed. Dyslipidemia is defined as having any one of the following criteria: total cholesterol ≥200 mg/dL, LDL (Low-density lipoprotein) ≥130 mg/dL, HDL (High-density lipoprotein) &lt;40 mg/dL, and triglyceride ≥100 mg/dL for children aged 0-9 and ≥130 mg/dL for adolescents aged 10-18.3. Result: The prevalence rate of total dyslipidemia observed at baseline, 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months, were 31.1%, 67.6%, 69.5%, 68.2%, 59.5%, 60.5%, 53.7%, 47.1%, and 31.3%, respectively. When the average value and prevalence rate for each type of dyslipidemia were analyzed, total cholesterol and LDL levels showed an increase from the 1-month period compared to the baseline, peaked at the 3-month period, and gradually decreased from the 6th month with statistical significance. In the case of triglycerides, the prevalence rate of hypertriglyceridemia was highest at 3 months, but the average value was highest at 1 month with statistical significance. However, in HDL, both the average value and the prevalence rate of hypo-HDL cholesterolemia did not exhibit a significant difference over the entire period. Conclusion: MAD increases the incidence of dyslipidemia until three months after initiation, but in most cases, it tends to decrease even without treatment after six months.
Presentation: 6/1/2024
8234 Composite Pheochromocytoma-Ganglioneuroma: Two Clinical Cases Presenting To St. Elizabeth’s Medical Center
Authors: El Najjar Mayssam , Naous Elie , Blake Caroline , Teresa Sweeney Ann 
Published: October 2024

Abstract
Disclosure: M. El Najjar: None. E. Naous: None. C. Blake: None. A.T. Sweeney: None.
Introduction: Pheochromocytomas (PCCS) are rare catecholamine producing tumors that originate from the chromaffin cells of the adrenal medulla. In 3-9% of cases, they may be accompanied by other tumors. Ganglioneuromas are the most encountered tumor type that occur with PCC and are termed composite PCC-GN. The entity is very rare with &lt; 35 cases reported. Herein, we present 2 cases of composite PCC-GN. Case Presentation: Patient 1 (Pt1) & Patient 2 (Pt2): were 35- & 54-year-old obese females. Pt1 had controlled hypertension and symptoms of anxiety along with palpitations, diaphoresis and flushing. Pt2 had type 2 diabetes and complained of abdominal pain. Metabolic studies showed elevated total plasma fractionated metanephrines(MNs). MNs in Pt1 and Pt2 were: 76 and 61pg/ml respectively (normal &lt;57 pg/ml) and normetaneprines levels were 161 and 116pg/ml respectively (normal &lt;148 pg/ml). Abdominal computed tomography (CT) scans demonstrated right adrenal masses in both cases with Pt1 having a 2.3 x 2.3 x 2.6 cm mass (Figure1) with smooth margins measuring 36 Hounsfield units (HU) on non-contrast(NC) CT imaging with 0% washout on delayed imaging after IV contrast. Pt2 on NCCT had a 4.5 x 3.5 cm right adrenal mass measuring 73 HU and a subsequent abdominal MRI(Figure2) demonstrated the mass to have heterogenous signal intensity. Both patients were prepared with pre-operative a and b blockade and underwent laparoscopic robotic adrenalectomies without complications. Pathological analyses in both cases revealed composite PCC-GN. Pt2 underwent genetic testing which did not reveal any known mutations. Surveillance in both patients demonstrated no recurrence. Clinical lesson: The clinical presentation of PCC-GNs is indistinguishable from isolated PCCs. The definitive diagnosis is through histopathological analysis. Histologically the composite tumor is composed of two distinct patterns with PCC showing angular cells with granular, basophilic cytoplasm, arranged in nests, while GNs show ganglion cells in fibrous stroma. Immunohistochemistry show the PCCs staining for chromogranin A and synaptophysin while GNs stain for S-100 protein and neurofilament antibody. Most cases occur in patients between 40 - 60 years old. Most PCC-GNs are functional, with increased MNs. PCC-GN composite tumors may occur sporadically but have also been described as part of syndromes such as MEN2A and NF1. The definitive treatment for PCC-GN is complete surgical excision which is associated with an excellent prognosis. The probability of recurrence is low though distant metastases have rarely been reported. Therefore, lifetime surveillance is critical.
Presentation: 6/3/2024
7447 Rare KSR2 Variants: The Effect of Glycine and N-acetylcysteine (GlyNAC) Supplementation
Authors: Youn Ji Youn , Carcamo-Bahena Yareli , Lartigue Elecia , Sisley Stephanie 
Published: October 2024

Abstract
Disclosure: J. Youn: None. Y. Carcamo-Bahena: None. E. Lartigue: None. S. Sisley: None.
Kinase suppressor of ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Of note, disruption of the kinase domain of KSR2 in humans and mice causes obesity by reducing metabolic rate, suggesting its important role in energy homeostasis. In the present study, we identified two variants (P189L, T290A) with mutations located in the proximal CA2 region from children with severe, early-onset obesity. Since variants in this region have not been confirmed to cause obesity, we generated plasmid constructs containing these KSR2 mutations by site directed mutagenesis. The HEK293 cells transfected with KSR2 plasmid construct containing P189L or T290A had reduced binding affinity with AMPK and phosphorylation of AMPK without affecting KSR2 protein integrity. These variants also significantly reduced cellular metabolic rates measured by Seahorse analysis in C2C12 cells, suggesting that KSR2 variants in the proximal CA2 region can result in impaired KSR2 function, subsequently leading to a decrease in cellular metabolic rate. In addition, these KSR2 variants decreased protein levels of NRF-2, a transcription factor of cytoprotective genes regulating the antioxidant glutathione (GSH) pathway compared to wild type KSR2 which augmented NRF2 levels. We also observed lower levels of total GSH and GSH/Glutathione disulfide (GSSG) ratio and higher levels of thiobarbituric acid reactive substances (TBARS), an indicator of oxidative stress, indicating an imbalance of antioxidant and oxidant with proximal KSR2 variants. However, treatment of cells with Glycine and N-acetylcysteine (GlyNAC) reversed the detrimental effects of KSR2 variants by normalizing protein expression levels of NRF-2, GSH/GSSG ratios and TBARS levels. Taken together, we show strong evidence that two new KSR2 variants, P189L and T290A, cause disruption of KSR2 function. Additionally, we also report a novel role of KSR2 in maintaining redox homeostasis suggesting that increased oxidative stress following GSH deficiency may play an important role in the development of obesity from KSR2 variants.
Presentation: 6/1/2024
6866 Real-world implications and limitations of GLP-1 prescriptions in adolescents
Authors: Castano Gabriel , Sisley Stephanie 
Published: October 2024

Abstract
Disclosure: G. Castano: None. S. Sisley: None.
Background: Glucagon-like-peptide-1 agonists (GLP1), approved for adolescents ≥ 10 years in 2019 for type 2 diabetes (T2D) and ≥ 12 years in 2020 for obesity, require adequate dose titration and have known side effects. There is little information on insurance approval, adherence to titration regimens, or the side effects of liraglutide in clinical practice. Methodology: We performed a retrospective review of all patients &lt;18 years old who were prescribed GLP-1 at a large children’s hospital. We collected demographic information, prescription orders, insurance approval, and drug initiation dates. For individuals who completed at least 26±8 weeks of treatment, we also collected dose titration, side effects, and insulin doses. Results:599 patients were prescribed GLP-1 from 2019 to 2023, with a mean age of 14.99±2.1 years, 58% female, 58% public insurance, and 74% (n=442) with T2D. The cohort was comprised of 63% White, 30% Black, and 2.3% Asian individuals, with 52% of Hispanic ethnicity. 90% of prescriptions were for liraglutide, and 10% for other GLP1 analogs, including exenatide, dulaglutide, and semaglutide. Insurance denied 41% (n=244) of prescriptions, with more denials in those without T2D, 64% vs 32% in patients with T2D.Whereas private insurance denied more prescriptions than Medicaid in patients with T2D (54% vs 27%), the reverse was true for patients without T2D ( 55% private vs 69% Medicaid). Patients lost to follow-up in the first 3 months accounted for 22% (n=135) of the cohort, even though 48% (n=66) of those patients had insurance approval.Those who had insurance approval and took liraglutide for at least 26 weeks accounted for 34% (n=204) of the cohort. Of the patients with T2D, 50% (n=95) titrated to 1.8mg by their first follow-up appointment (1-3 months after prescription start), 33% (n=62) by 6 months, and 17% (n=32) never reached 1.8mg. In patients prescribed a higher dose of liraglutide (3.0 mg daily), 42% (n=8) titrated to 3mg over 5 weeks as prescribed, and 52% (n=10) never reached 3mg, with only one of them not reaching 1.8 mg.Most patients (82%, n=169) had no side effects documented in their charts. From those with side effects reported, GI problems (nausea, vomiting, diarrhea) were noted in 12% (n=25), and 2% (n=4) reported injection site reactions. Side effects that required medication discontinuation included hypoglycemia (n=1), mild pancreatitis (n=1), and severe pancreatitis (n=2). Conclusion: In clinical practice, despite FDA approval, insurance coverage of liraglutide is limited. Almost half of the patients require extra time to reach full doses of liraglutide, with one-third never reaching full treatment doses. Severe pancreatitis may be a previously unpublished side effect. More research is needed to understand how real-world adherence and side effects of liraglutide affect clinical outcomes.
Presentation: 6/1/2024
8488 Sex-Specific Differences in an Alstrom Syndrome Mouse Model
Authors: Carcamo-Bahena Y , Youn J , Lartigue E , Sisley S 
Published: October 2024

Abstract
Disclosure: Y. Carcamo-Bahena: None. J. Youn: None. E. Lartigue: None. S. Sisley: None.
Background: Alström syndrome is a monogenic autosomal recessive disorder caused by loss of the ALMS1 gene that affects 1 in 1 million. Loss of a functional ALMS1 protein leads to global disorganization of microtubules. Patients are affected by progressive vision and hearing loss and are at risk of developing obesity and type 2 diabetes. Aside from reproductive system anomalies, no clinical reports have identified sex-specific difference in patients with Alström syndrome. Methods: Male and female Alms1tvrm[1]02/tvrm[1]02 (null), Alms1tvrm[1]02/+ (heterozygous) and wildtype littermate mice were weaned onto standard chow diet. At 16 weeks of age, they were changed to a 45% high fat diet (HFD). Weekly body weights were collected and intraperitoneal glucose tolerance tests (GTTs, 1.5 g/kg D20W) were performed at three different time points (11, 16, 25 weeks of age). Results:Alms1 null mice were heavier than wildtype and heterozygous mice on standard chow diet. In males, significant changes in weight gain in null mice occurred by 10 weeks compared to wildtype and heterozygous mice (p&lt;0.05). In females, compared to null, this change was observed by 13 weeks (p&lt;0.05). Although female mice are typically protected from diet-induced obesity, the null females weighed the same as the null males (65.0 ± 2.0 vs 67.7 ± 2.8 g) after 9 weeks on HFD. We observed sex and diet specific differences in GTT outcomes. On chow diet, Alms1 deficiency did not affect glucose levels during a GTT in female mice. However, after 9 weeks of HFD (25 weeks of age), baseline fasting glucose levels were higher in the null females compared to wildtype (p&lt;0.05) and heterozygotes (p&lt;0.01). Additionally, the GTT curve was monophasic, indicating onset of diabetes whereas wildtype and heterozygotes (p&lt;0.0001) had normal curves. Null male mice showed an impaired glucose response at 11 weeks of age on chow diet compared to wildtype and heterozygous males (p&lt;0.001) and by 16 weeks, the GTT glucose curve for Alms1 null mice was monophasic. After 9 weeks of HFD, no differences were observed in glucose levels during a GTT. Conclusions: We observed sex-specific differences in this Alms1 null mouse model related to body weight and glucose tolerance with male null mice exhibiting earlier obesity and impaired glucose tolerance and female mice showing more pronounced effects on a HFD. Future research should investigate if these sex-specific effects alter responses to dietary or pharmaceutical interventions.
Presentation: 6/1/2024