bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-679 Early Onset Diabetes Mellitus in a Young Woman with Ring Chromosome 13 Syndrome
Authors: Buehler Lauren Anne , Mikhael Alexandra , Zimmerman Robert S 
Published: May 2020

Abstract
Background: Ring chromosome 13 is a rare genetic disorder in which the two ends of chromosome 13 are fused together to form a ring shape. Ring formation subsequently leads to gene deletions on both the long and short arms of the chromosome. Observed phenotypes among these patients are variable due to differences in the number of genetic deletions that occur with fusion. Common clinical features seen in ring chromosome 13 include micro- or anencephaly, severe mental retardation (MR), ambiguous genitalia, growth retardation, and facial dysmorphism. To our knowledge, diabetes mellitus (DM) has only been reported in two published case reports of patients with ring chromosome 13. It has been proposed that development of DM in this syndrome may be due to deletion of the IRS2 gene on the long arm of chromosome 13. This hypothesis is based on evidence from knockout mice studies and genetic comparisons of ring chromosome 13 patients with and without DM.
Clinical Case: We present a case of a 23-year-old woman with a known history of mosaic ring chromosome 13 abnormality who was diagnosed with DM at age 21. Diagnosis was made incidentally based on laboratory data obtained at a routine outpatient visit. Hemoglobin A1c at that time was 13.1%. Glutamic acid decarboxylase and insulin antibodies were negative. She has been on a basal-bolus insulin regimen since diagnosis with overall good glycemic control (average hemoglobin A1c 6.5%). She has no known micro- or macrovascular complications of DM. She has no family history of chromosome 13 syndrome or DM. Other notable clinical features associated with her ring chromosome 13 disorder include MR, spastic encephalopathy, delayed puberty (menarche at age 18), scoliosis, facial dysmorphism, and deficiencies in clotting factors 7 and 10.
Conclusion: DM is a common disorder that is typically multifactorial in etiology. In rare cases, DM can be the result of monogenic mutations or deletions. We present a case of a young woman with early-onset antibody-negative DM thought to be related to gene deletions resulting from her underlying ring chromosome 13 abnormality. There is some evidence from prior case reports and rodent studies to suggest that DM in patients with this disorder may be the result of IRS2 deletion from the long arm of chromosome 13. Although DM is a rare complication of ring chromosome 13 disorder, early screening should be considered in these patients to prevent development of downstream complications.
References:
1. Babaya N, Noso S, Hiromine Y, Ito H, Taketomo Y, Yamamoto T, Kawabata Y, Ikegami H. Early-Onset Diabetes Mellitus in a Patient With a Chromosome 13q34qter Microdeletion Including IRS2. J Endocr Soc. 2018 Sep 11;2(10):1207-1213.
2. Lagergren M, Börjeson M, Mitelman F. Prophase analysis of ring chromosome 13--an attempt at phenotype-karyotype correlation. Hereditas. 1980;93(2):231-3.
MON-625 Utility of Continuous Glucose Monitoring in Children with Type 1 Diabetes: Is HbA1c Enough?
Authors: Owens Lindsey L , Chalise Sweta , Vyas Neha , Gurnurkar Shilpa 
Published: May 2020

Abstract
Introduction: Type 1 diabetes is an autoimmune condition resulting in insulin deficiency that requires daily insulin therapy and self-monitoring of blood glucose. Continuous glucose monitoring (CGM) systems allow for measurement of interstitial fluid glucose levels in a continuous fashion to identify variations and trends that are not feasible with conventional self-monitoring. Hemoglobin A1C (HbA1C) is the method used to assess adequate glycemic control and relates to future risk of developing complications. Current evidence has shown improvement in HbA1C with concomitant use of CGM in adults over 25 years of age with Type 1 diabetes, whereas studies in children and adolescents have failed to show this. However, it is important to note the limitations in HbA1C use as it is a marker of average blood glucose over 3 months but does not reflect glycemic variability. More recent data has suggested that factors such as time in range (TIR), which can be determined with CGM use, are also associated with decrease risk of diabetes complications.
Methods: The goal of our study was to analyze the change in HbA1C levels after using a CGM (DEXCOM G4, G5, G6) over a 6-month period in pediatric patients with Type I diabetes. Two HBA1c levels 3 months apart from 92 patients were collected before using a CGM and two while using a CGM. Results were compared by using a dependent samples t-test. IBM SPSS 25.0 was used for data analysis.
Results: Preliminary analysis indicates the average change in HBA1C among the patients (N=92) before (-0.08 ± 1.16) and while using the CGM (0.12 ± 1.00) was not significantly different (t (79) = -1.27, p = 0.21). The average change in HBA1C was also not significantly different (p&gt;0.05) among the patients before and while using the CGM for gender (males and females), age groups (0-7 years, 8-14 years, and 15-24 years), and generations of DEXCOM used (G4, G5, and G6).
Conclusion: As has been shown in other studies, we did not find a significant change in HbA1c after CGM use for 6 months in our patients. While HbA1C is a reflection of blood sugars over a 3-month period, it does not provide information about glycemic excursions. Metrics derived from CGM use, such as TIR, can provide actionable information which we did not address in our study. There have been reports of the association between TIR and long-term complications of diabetes. Most data comes from studies in adults and pediatric data is lacking. We propose that future studies must look into CGM metrics such as TIR to better define glycemic control in pediatric patients with diabetes mellitus.
OR05-05 Lethal ERα-Dependent Hyperactivation of the Unfolded Protein Response Induces Complete Regression Without Recurrence of Primary and Metastatic Breast Cancer
Authors: Duraki Darjan , Boudreau Matthew W , Wang Lawrence , Mao Chengjian , Tang Bingtao , Ma Liqian , Roy Edward J , Fan Timothy M , Park Ben Ho , Nelson Erik R , Hergenrother Paul J , Shapiro David J 
Published: May 2020

Abstract
Metastatic estrogen receptor α (ERα) positive breast cancer is presently incurable and most patients die within 7 years. From a medicinal chemistry program, we identified a novel small molecule that acts through ERα to kill breast cancer cells and often induces complete regression without recurrence of large, therapy-resistant primary breast tumors and of lung, bone, and liver metastases. To target metastatic ERα positive breast cancer, we exploited our finding that estrogen-ERα activates an extranuclear tumor-protective, signaling pathway, the anticipatory unfolded protein response (UPR). We repurposed this tumor protective pathway by targeting it with the small molecule, ErSO. ErSO kills cancer cells by acting non-competitively through ERα to induce lethal hyperactivation of the anticipatory UPR, triggering rapid necrotic cell death. Using luciferase to image primary tumors and metastases containing lethal ERαD538G and ERαY537S mutations seen in metastatic breast cancer, oral and injected ErSO exhibited unprecedented antitumor activity. In mouse xenografts bearing large breast tumors, oral and injected ErSO induced complete regression (&gt;115,000 fold mean regression) in about 45% of mice (18/39). Although durable response for 4-6 months without additional treatment was common, tumors that did recur remained fully sensitive to ErSO re-treatment. Consistent with the essential nature of the UPR pathway targeted by ErSO, in more than 100 tumor-bearing mice, we have never seen an ErSO-resistant tumor. In just 7 days, oral ErSO induced complete regression of most lung, bone, and liver metastases. ErSO is well-tolerated in mice and blood-brain-barrier penetrant. Injected ErSO induced profound regression of challenging brain tumors. On average, ErSO-treated tumors were &gt;180-fold smaller than vehicle-treated tumors. These xenograft studies used human cancer cells in mice that lack a functional immune system and therefore did not exploit the known ability of inducers of necrotic cell death to activate immune cells and induce immunogenic cell death. Notably, medium from breast cancer cells killed by ErSO contained high levels of immune cell activators, robustly activated mouse and human macrophages and increased macrophage migration. Moreover, use of ErSO is not limited to breast cancer. ErSO rapidly kills ERα positive ovarian and endometrial cancer cells that do not require estrogen for growth. ErSO’s potent activity against advanced primary and metastatic ERα-positive breast cancers represents a paradigm shift in leveraging ERα for anticancer efficacy.
SAT-013 Segesterone Acetate (SA) Serum Levels with a Statistical Model of Continued Use of the SA/Ethinyl Estradiol (EE) Contraceptive Vaginal System
Authors: Liu James H , Archer David F , Simon James A , Kaunitz Andrew M , Plagianos Marlena , Bernick Brian , Mirkin Sebastian 
Published: May 2020

Abstract
The novel, ring-shaped, contraceptive vaginal system (CVS; Annovera™), contains 103 mg of SA and 17.4 mg of EE, and delivers a mean dose of SA 0.15/EE 0.013 mg/day. The CVS was designed to last thirteen cycles in a 21 day-in/7 day-out regimen. Objectives of these analyses were to determine the amount of SA/EE remaining in the CVS after 13 cycles of use and to estimate the SA level in serum after 1 year of continuous use.
Residual SA/EE levels from CVS used by women (n=18) for 13 cycles of 21/7 regimen in a phase 3 clinical trial were further analyzed in vitro. Hypothetical SA level in serum after 1 year of continuous use was estimated using data from 39 women who participated in a 13-cycle pharmacokinetic study of the 21/7 CVS regimen. The serum data were used to construct a statistical model for the change in serum SA concentrations from cycle 1 to cycle 13. The data from each individual subject was modeled to estimate the serum SA level based on days of use. Each subject’s model was then used to estimate the serum SA level after 364 days of continuous CVS use. The average of all 364-day values from valid models was then calculated.
After 13 cycles of a 21/7 regimen, the amount of SA/EE remaining in the CVS was 61.7 mg/14.0 mg (60%/80% of the original SA/EE load), which established the release of 0.15 mg SA and 0.013 mg EE per day for a total of 273 days. The model predicted that the mean serum SA level after 364 days of continuous use was 71 pmol/L with a lower limit of the 90% CI of 52 pmol/L.
A high percentage of SA/EE remained in the CVS after 13 cycles of use. Serum SA levels predicted by the model following 1 year of continuous use were similar to those previously observed (mean 73 pmol/L) at 1 year in a SA silicone implant trial in which there were no reported pregnancies at 1 year (Sivin et al, Contraception. 2004;69:137-144). No pregnancy or PK data with continuous use of the CVS is available at this time. Further study on the continuous use of the CVS is warranted.
SUN-124 Are Venous Thromboembolic Events Increased in MEN1 Patients?
Authors: Lee Maya E , Sustache Yashira M Ortega , Agarwal Sunita Kishore , Tepede Aisha , Mandl Adel , Bansal Rashika , Tirosh Amit , Piaggi Paolo , Weinstein Lee Scott , Simonds William F , Blau Jenny 
Published: May 2020

Abstract
Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder in which patients develop multiple simultaneous hormone-secreting tumors. Most common tumors include: anterior pituitary adenomas (50%), multi-gland parathyroid adenomas (95%), and gastroenteropancreatic neuroendocrine tumors (40-80%). Only rare MEN1 associated glucagonomas (&lt;1%), and ACTH-producing neuroendocrine tumors (&lt;5%) are known to increase risk of hypercoagulability. It is unknown if patients with MEN1 syndrome have increased risk of venous thrombolytic events (VTE), defined as a deep-vein thrombosis and/or pulmonary embolism.
Methods: We queried a prospective natural history study of MEN1 patients who tested positive for germline MEN1 mutations (n=287) between 1991-2019 (54 patients on our current protocol were followed before 1991; the earliest was 1971). All lifetime events of VTE were included. Search terms included: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban and apixaban. After initial screening, 10 patients were removed due to insufficient clinical data. Kaplan-Meier analysis was performed to compare age of death between the two cohorts. Results were expressed as mean ± standard deviation.
Results: Thirty-four subjects (mean 57.5 years-old, 17 women) were identified with any VTE, yielding a prevalence rate of 13.4%. The incidence of VTE corresponded to 264 events per 100,000 patient-years, which was ~2-fold higher than the estimated annual incidence rate in the general population (104-183/100,000 patient years).1 Kaplan-Meier analysis revealed no significant difference in survival between the two groups (non-VTE cohort mean 81.1 years ± 2.23; VTE cohort mean 77.4 years ± 3.45; p = 0.96). Thirty-two events occurred during the surveillance period at our institution; 9 individuals had more than one VTE. At the time of VTE, 80% had hyperparathyroidism (mean PTH ± SD; 97.56 pg/mL ± 90.76), 21% had hyperprolactinemia (prolactin 25.7μg/L ± 43.41), 62.5% had hypergastrinemia (mean gastrin 1100.9 pg/mL ± 3127.8), and 84.6% had non-functional pancreatic neuroendocrine tumors. One patient was identified to have a Factor V Leiden mutation, 3 patients had lupus anti-coagulant. Eleven patients experienced events within a post-surgical period of 3 months.
Conclusions: Hypercoagulability in MEN1 has been previously unidentified. Our cohort data suggests a two-fold increase in the incidence of VTE as compared to the general population, with a high risk occurring within the perioperative period. Further mechanistic investigation and validation from other cohorts are needed to confirm the increased prevalence of VTE in this population.
1Heit, John A., et al. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015 Aug;12(8): 464-474.
SAT-382 Pyridoxal 5’-Phosphate Cerebrospinal Fluid Abnormalities in Hyopophosphatasia Before and After Enzyme Replacement Therapy
Authors: Wright Jordan J , Hu Jiun-Ruey , Yi Zahra Shajani , Dahir Kathryn McCrystal 
Published: May 2020

Abstract
Introduction: Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP), characterized by a wide range of skeletal and neurological symptoms. Little is known about the mechanism of neurologic involvement, but it may result from inefficient hydrolysis of vitamin B6 (pyridoxal 5’-phosphate, PLP), which is involved in neurotransmitter synthesis and is markedly elevated in HPP. However, it remains unknown what PLP levels are in the cerebrospinal fluid (CSF) of patients with HPP. We report two cases: (1) one with pre- and post-treatment CSF PLP levels and (2) one with pre-treatment CSF PLP and neurotransmitter levels.
Case 1: A 30-year-old woman with extensive fracture history presented with seizure-like activity. Laboratory evaluation while on no B6 supplementation was notable for low ALP (14 U/L, ref: 40-150), high plasma PLP (362 mcg/L, ref: 5-50), and high CSF PLP (16 mcg/L), with a low CSF/plasma PLP ratio (0.04, ref: 0.1-0.7[1]). Genetic testing showed a pathogenic variant of TNSALP (Het c.1133A&gt;T, p.Asp378Val, rs 121918008). After initiation of enzyme replacement therapy (ERT), her plasma and CSF PLP levels normalized to 6.3 and 1.4 mcg/L, respectively, with a ratio of 0.23. She reported improvement in energy level and seizure-like activity after several months of ERT.
Case 2: A 34-year-old man with no history of skeletal pathology presented with diffuse musculoskeletal pain, weakness, and loss of sensory function attributed to generalized peripheral neuropathy. Laboratory evaluation while on no B6 supplementation was notable for low ALP (23 U/L), high plasma PLP (496 mcg/L), and high CSF PLP (17 mcg/L) with a low CSF/plasma ratio (0.03). CSF neurotransmitter levels were also low, including 5-hydroxyindoleacetic acid (40 nmol/L, ref: 67-140) and homovanillic acid (115 nmol/L, ref: 145-324). Genetic testing showed heterozygous expression of a catastrophic frameshift mutation of TNSALP (c.662del, p.Gly221Valfs*56). ERT is being considered at this time.
Conclusions: We report the novel findings that in these patients with HPP:
1. CSF PLP levels are markedly elevated, though to a much lesser extent than plasma levels. Elevated CSF/plasma ratios suggest that transport of PLP and its metabolites across the blood brain barrier may be impaired in HPP.
2. Decreased CSF neurotransmitter levels, as seen in our patient, may contribute to neurologic symptoms of HPP.
3. Enzyme replacement therapy normalized both CSF and plasma PLP in case 1. Further studies are needed to understand how these changes affect patient symptoms and prognosis.
Citation:
1. Albersen, M., et al., Vitamin B-6 vitamers in human plasma and cerebrospinal fluid. Am J Clin Nutr, 2014. 100(2): p. 587-92
SUN-630 Insulin Pumps Versus Multiple Daily Injections in Type 1 Diabetic Pregnancies
Authors: Albanese Isabella , Garfield Natasha 
Published: May 2020

Abstract
Background: Pregnancy is associated with physiological increased resistance to insulin, leading to increased insulin requirements for diabetic women. Poor glycemic control in pregnancy is associated with neonatal and maternal complications. Insulin has been traditionally administered subcutaneously through multi daily injections (MDIs) however, use of insulin pumps or continuous subcutaneous insulin infusion (CSII) has become more widespread. As glycemic control has direct influence on perinatal and maternal outcomes, comparing MDIs and CSII in pregnant women with Type 1 Diabetes Mellitus (DM1) is of interest.
Aim: To investigate whether there is a difference in birth weights in infants born from DM1 mothers who use CSII compared to MDIs.
Methods and Results: This is a retrospective cohort study of women diagnosed with DM1 on either MDIs or CSII whose pregnancies were followed at our institution. The following data was collected on chart review: age, years since DM1 diagnosis, BMI and weight gain at each trimester, total daily insulin dose at delivery, presence of retinopathy or nephropathy, gestational age at delivery, delivery method, presence of hypertension, pre-eclampsia or eclampsia, birth weight, sex of infant and neonatal complications. Preliminary analysis of our currently available data demonstrates that in age-matched groups of women on MDI (N=44) compared to CSII (N=8), there was no significant difference in infant birth weights (3491g ± 760 vs. 3554g ± 666, respectively). There was also no significant difference in neonatal complications (jaundice, hypoglycemia, shoulder dystocia, macrosomia, respiratory distress or prematurity). Women on CSII had been diagnosed with DMI for a significantly longer period of time (20 vs. 14 years) and were on higher total daily doses of insulin per body weight at time of delivery (p&lt;0.05). Despite this, there was no significant difference in weight gain during pregnancy between the groups. There was also no significant difference in the presence of hypertension, pre-eclampsia, eclampsia or in C-section rates.
Discussion: Given the paucity of studies and the increasing use of pump technology among diabetic women, there remains a need for further research comparing the effects of MDIs and pumps on birthweights as well as other neonatal and maternal outcomes.
SAT-058 A Rare Case of Primary Hyperparathyroidism in a Pediatric Patient
Authors: Salazar Natalia , Merz Jeff M , Burdea Liliana , Minutti Carla 
Published: May 2020

Abstract
Introduction: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder in adult patients, but it is rare in pediatric patients. It is usually diagnosed when patients present with symptomatic hypercalcemia or known complications. In children, atypical presentation often results in delayed diagnosis and increased morbidity. We report a 10-year-old boy presenting with abdominal pain and emesis, found to have hypercalcemia and, ultimately, PHPT. His genetic evaluation was notable for a mutation in the RET gene (3.2C&gt;A) of unknown clinical significance. Case presentation: A 10-year-old male with a history of constipation presented to the emergency department with five days of abdominal pain and emesis. Initial workup revealed high serum calcium (Ca) of 17.3 mg/dL (8.7-10.7) and ionized Ca (ICal) of 2.01 mmol/L (0.95-1.32). Further evaluations revealed low phosphorus level 3.5 mg/dL (4.5-6.5) and high parathyroid hormone level (iPTH) of 329.2 pg/mL (8.0-85.0). These findings were consistent with PHPT. Neck US demonstrated a cervical mass in the mid-right thyroid measuring 0.5 x0.3 x0.5cm, questionable for parathyroid adenoma, which was confirmed with 99mTc-MIBI scintigraphy and neck CT. His Ca level initially responded to fluid resuscitation and Lasix, with Ca level decreasing to 13.6. However, on hospital day two, his Ca level became refractory to all interventions, rising to 16 and prompting the use of bisphosphonates. The patient underwent neck exploration with partial parathyroidectomy and lymph node excision. Pathology revealed hypercellular parathyroid tissue consistent with parathyroid hyperplasia. Intraoperatively iPTH was reduced from 3,134.7 to 79.8 and remained within normal limits since. Postoperatively course was uncomplicated, and the patient was discharged home on oral Ca carbonate and vitamin D. A genetic evaluation was remarkable for a change in the RET gene (3.2C&gt;A), a finding of unknown clinical significance. This change has not been seen in association with an individual who fulfills the clinical diagnosis of MEN2A. To further determine if the variant identified in the RET gene is a benign variant, the mother was tested for MEN2A and was negative. Father could not be tested, but family history was significant for thyroid malignancies. The patient is currently doing well four months postoperatively. His Ca level remains normal. Due to the genetic finding and the concern of MEN2A syndrome, the patient is followed closely by pediatric endocrinology and genetics. Conclusion: PHPT is a common endocrine disorder in adults but rare in children. The diagnosis of pediatric PHPT is almost always delayed due to atypical presentation and rarity of the disease. As secondary organ damage is common, a multi-organ assessment is mandatory. Due to the association with other syndromes, a genetic evaluation should be performed.