bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-039 Prenatal Anti-Mullerian Hormone (pAMH) Exposure in Mice Induces Changes in Pubertal Onset, Fertility, and Stress Response in Both Male and Female Offspring
Authors: Ho Emily V , Shi Chengxian , Mellon Pamela L 
Published: May 2020

Abstract
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, classically presenting with disrupted ovulation, polycystic ovaries, and androgen excess, as well as many non-reproductive comorbidities. For instance, PCOS patients exhibit increased stress reactivity and higher rates of depression and anxiety compared to the general population. The prenatal anti-Mullerian hormone (pAMH)-induced model of PCOS was recently shown to recapitulate reproductive phenotypes in female mice, however little remains known about the consequences of pAMH exposure. We first aimed to expand upon this model by investigating pAMH-induced effects on offspring of both sexes. Pregnant dams on a C57Bl/6 background received daily i.p. injections of either AMH (0.12 mg/kg/d) or VEH late in gestation. Offspring were born into 4 groups (pAMH vs. VEH females, pAMH vs. VEH males) and assessed starting at weaning for changes in body weight, anogenital distance, pubertal onset, estrous cyclicity, fertility, and reproductive senescence. Statistical differences were determined by t-test or 2-way ANOVA when applicable, and significance set at p&lt;0.05. As expected, pAMH increased anogenital distance in females but not males. Pubertal onset was delayed not only in females as previously reported, but also in males. Additionally, pAMH adult females showed significant disruptions in estrous cycling at P60 (increased time spent in diestrus, decreased number of cycles, increased cycle length), only mild disruptions by P90, then robust disruptions at 8 mo, 10 mo, and 12 mo of age that were distinct from reproductive senescence. When paired with wildtype untreated mates for a fertility assay starting at 3 mo of age, pAMH females had smaller and fewer number of litters, while pAMH males showed only delayed plugging behavior. Although pAMH males showed no difference in testis weight, pAMH females also had significantly reduced ovarian and uterine weights in diestrus. Interestingly, during the fertility assay, we found increased fetal death from both the pAMH females and males, even though pAMH males were paired with wildtype untreated females. We hypothesized that the increased fetal death could be the result of an pAMH-induced stress phenotype in both sexes. Using a simple stress response test measuring defecation and urination during exposure to a novel environment, we found that pAMH robustly increased stress response in both sexes at multiple timepoints. We also assessed glucocorticoid response to a restraint stress paradigm in adult females. While we observed no differences in baseline serum corticosterone levels, the pAMH group showed increased peak levels followed by a prolonged elevation levels after 2 hr. Together, these results enhance existing knowledge of the effects of pAMH exposure by demonstrating alterations in both male and female mice on both reproductive and non-reproductive measures.
OR21-05 Primary Thyroid Lymphoma Developing from a Background of Lymphocytic Thyroiditis: First Report in Mice
Authors: Yasuda Yoshinori , Pani Fabiana , Caturegli Patrizio 
Published: May 2020

Abstract
Primary thyroid lymphoma is rare, accounting for less than 5% of all thyroid malignancies. It typically develops in patients with Hashimoto thyroiditis who have approximately a 70 fold higher risk than other patients. The mechanisms underlying the development of thyroid lymphoma remain unclear, and no mouse model has been described. For our studies of papillary thyroid cancer and lymphocytic thyroiditis, we crossed TPO-Cre-ER transgenic mice and hBRAFV600E knock-in mice onto the NOD.H2h4 background to establish TPO-Cre-ER_ hBRAFV600E NOD.H2h4 strain where papillary thyroid cancer is induced by the injection of tamoxifen and thyroiditis by the administration of iodine in the drinking water. Mice injected with corn oil or drinking regular water served as control. In 3 of 121 mice, TPO-Cre-ER_ hBRAFV600E NOD.H2h4 mice injected with corn oil and drinking iodinated water we observed the development of thyroid lymphoma. At about 6 months after the injection of corn oil, these mice developed a marked increase in the size of the thyroid gland, which appeared hypoechoic on thyroid ultrasound. Fine needle aspiration on the thyroid gland under ultrasound was performed, along with measurement of TPO antibodies, H&E thyroid histology, immunohistochemistry, and flow cytometry at the time of sacrifice. Histology established a diagnosis of Hodgkin lymphoma with the typical Reed Sternberg cells. Flow cytometry identified an increased frequency of CD8+ effector memory T cells in the thyroid lymphoma. TPO antibodies were significantly higher in mice with thyroid lymphoma than in those without, perhaps suggesting their utility as predictive biomarkers. In summary, we report a mouse model of thyroid lymphoma that evolves from a background of lymphocytic thyroiditis with a predictable natural course that can be monitored by thyroid ultrasound and TPO antibodies. This model can be used to study the mechanisms and development of thyroid lymphoma in patients.
MON-137 Evaluation of the Timeliness of Serial Denosumab Administrations at the University of Colorado Hospital
Authors: Zaman Adnin , Billups Sarah J , Rothman Micol S 
Published: May 2020

Abstract
BACKGROUND:
Denosumab is an antiresorptive medication commonly used in the treatment of osteoporosis that works by slowing bone loss. This medication should not be delayed or interrupted without initiation of an alternative treatment (i.e. bisphosphonates) as studies have shown that this can lead to rapid bone loss, very high markers of bone turnover, and increased vertebral fracture (VF) risk. It is unknown how frequently dosing is delayed in practice settings and how best practices can ensure timely dosing. Our study aimed to (1) evaluate the frequency and causes of delayed denosumab doses at our institution and (2) compare the incidence of delayed doses before and after implementation of a new electronic ordering process.
METHODS:
We performed a retrospective chart audit for all patients receiving two or more denosumab doses at our institution between 1/1/16-8/11/18 and categorized those whose doses were &gt;/=214 days (7 months) as delayed. We reviewed notes, imaging, and labs in a subset of this population to assess reasons for the delay. On 8/11/18, a new outpatient infusion center (OIC) therapy plan went into place. This plan bundled a one-year denosumab order (2 doses) with an automatic referral to the OIC along with physician reminders for renewal. We compared rates of delayed denosumab dosing before and after implementation of this new order process.
RESULTS:
Between 1/1/16-8/11/18, 385 patients received 1295 doses of denosumab, with 160 (41.6%) receiving 193 instances of delayed doses. We reviewed the charts of 98 individuals who received 111 instances of late doses between 7/6/16-8/11/18. The most prevalent reasons for delays were: delays in follow-up by the patient (27.9%), delays in the provider placing an order for the drug and OIC referral simultaneously (27.9%), and delays in OIC scheduling (18%). During the 14 months after implementation of the new ordering process, 347 patients received 614 instances of denosumab, of which 123 (35.4%) received 128 instances of delayed dosing. This is a relative decrease of 17.5% (p=0.09) for the proportion of patients with a late dose.
CONCLUSIONS AND FUTURE DIRECTIONS:
Nearly half of the patients on denosumab in our hospital received delayed denosumab dosing. Delays were often due to a lack of coordination between subsequent dose order placement and referral to the OIC. Our institution successfully implemented a bundled therapy plan to improve timely dosing. By March 2020, we expect to reassess the post-intervention group to further describe reasons for dosing delays. We also will compare rates of VFs associated with delayed denosumab dosing pre- and post-intervention periods.
MON-490 Calcitonin-Based Thyroidectomy Is a Safe Approach in Patients with Germline RET Mutation and Permits to Delay Surgery in Children
Authors: Prete Alessandro , Romei Cristina , Tacito Alessia , Ramone Teresa , Bottici Valeria , cappagli virginia , Viola David , Matrone Antonio , Agate Laura , Lorusso Loredana , Valerio Laura , Giani Carlotta , Puleo Luciana , Molinaro Eleonora , Elisei Rossella 
Published: May 2020

Abstract
Introduction: Medullary thyroid cancer (MTC) arises from C cells secreting calcitonin. In familial MTC cases, a germline RET mutation is discovered in 98% of cases. Nowadays, an early diagnosis and radical surgery are the only curative approach. However, thyroidectomy in children is associated with a higher rate of surgical adverse events, compared to surgery in adults. The best clinical approach in patient harboring germline RET mutation (gene carriers, GC) is still undefined. Methods and materials: since 1994 to 2018 we identified 174 GC by RET screening. 56 GC underwent total thyroidectomy and lymph node dissection for the evidence of high calcitonin levels at the first clinical evaluation, whereas 27 GC underwent surgery for high stimulated calcitonin levels during the active surveillance (median 16 months, range 13-118). 90 GC are still in follow up. Results: In the group of 27 GC patients who underwent surgery during the active surveillance, 15 GC had only C cells hyperplasia (CCH) foci and 12 were affected by MTC. These carcinomas were all confined to the thyroid, without any lymph node and distant metastasis. All these patients are still in clinical remission, after a median follow-up of 4 years (range 1-11). At time of the surgery, the patients affected by MTC were significantly older than patients harboring only CCH (median 49 vs 30 years old, respectively). Among these 27 GC, 7 were diagnosed as GC when they were younger than 18 years (median 7 years old, range 2-18) and they underwent surgery after a median period of 3 years (range 1-10 years), when they were all older than 7 years. In this group, 6 of 7 were affected by CCH and only one case by a microMTC. There were not any persistent surgical adverse events and all of them are still in clinical remission. 41 of 90 GC, who are still in active surveillance, were younger than 18 years at time of RET screening: nowadays, 10/41 are older than 18 years and 15/41 are older than 14 years, all with calcitonin still in the normal range. Conclusions: we demonstrated that the calcitonin-based thyroidectomy is a safe approach in GC. Intriguingly, this approach seems to be interesting especially in children in order to perform still an early and safe surgery but when they are older, possibly adults.
MON-642 Genetic Knockout of Intestinal Hexokinase Domain-Containing Protein 1 Affects Whole-Body Glycemic Control and Triglyceride Metabolism
Authors: Zapater Joseph Louis , Khan Wasim , Layden Brian T 
Published: May 2020

Abstract
Hexokinase domain-containing protein 1 (HKDC1) is a recently discovered putative fifth hexokinase that is widely expressed in a variety of human and mouse tissues. Previous work indicate that HKDC1 is important for whole-body glucose homeostasis and utilization in pregnancy and aging, and suggest roles for HKDC1 in nonalcoholic fatty liver disease development and progression of hepatocellular carcinoma. Prior work in the lab further showed that global heterozygous-deleted HKDC1 mice exhibit blunted uptake of triglycerides following an olive oil bolus compared to wild-type mice, suggesting a role for intestinal HKDC1 expression in intestinal lipid metabolism (unpublished results). To specifically study the significance of intestinal HKDC1 on whole-body glucose and lipid homeostasis, we utilized Cre-mediated recombination of HKDC1 in which Cre was expressed under the control of the villin gene promoter, creating a mouse model in which HKDC1 expression is specifically deleted in the intestinal epithelium. Quantitative RT-PCR data confirmed the knockout of HKDC1 within the mouse intestine in young and aged mice, while HKDC1 expression in other tissues was comparable to wild-type mice. Next, intestinal HKDC1 knockout mice and their wild-type littermate controls were either maintained on a normal diet or were switched to a high fat diet at 6 weeks of age to simulate the state of impaired glucose tolerance, and the effects of intestinal HKDC1 on glucose and lipid homeostasis were analyzed between 28-34 weeks of age. Mice fed a normal diet did not exhibit any differences in serum glucose or triglyceride during oral/intraperitoneal glucose tolerance tests or oral olive oil bolus, respectively, regardless of intestinal HKDC1 status. Interestingly, mice lacking intestinal HKDC1 that were on a high fat diet demonstrated improved overall glycemic control compared to wild-type mice after the administration of an oral glucose load, all while there were no changes in insulin levels, gluconeogenesis or insulin tolerance related to HKDC1 status. Additionally, introduction of an intraperitoneal glucose load to mice fed a high fat diet did not alter glucose control in the presence or absence of intestinal HKDC1. However, high fat diet-fed mice lacking intestinal HKDC1 did not have a significant increase in serum triglyceride following an oral olive oil bolus, while their stool fat and triglyceride content were comparable to wild-type. Collectively, these data indicate that intestinal HKDC1 has important roles in glucose and triglyceride metabolism within the intestinal epithelium, and further suggest a role in whole-body glucose homeostasis and in the development of insulin resistance and diabetes.
MON-595 Severe Copper Deficiency Post-Bariatric Surgery with Serious Preventable Complications
Authors: Aljaberi Asma Khaled , Boharoon Hessa 
Published: May 2020

Abstract
Copper is an essential cofactor in many enzymatic reactions vital to the normal function of the hematologic, vascular, skeletal, antioxidant, and neurologic systems. Parenteral nutrition and chronic tube feeding are used in various mal-absorptive syndromes, including following gastrectomy and gastric bypass surgery. Features of copper deficiency include hematologic abnormalities (anemia, neutropenia, and leukopenia) and myeloneuropathy; the latter is a rarer and often unrecognized complication of copper deficiency.
We describe a 36 -year-old Emirati woman who was referred to endocrinology service because of generalized body weakness and fatigue post bariatric surgery. The patient initially noted a lower extremity swelling in feet bilaterally that worsened in severity over time and progressed up to knees. Over a 3 month period, her ability to ambulate gradually deteriorated. She also noticed maculopapular skin rash over both shins. Patient had Sleeve Gastrectomy in 2011. Followed by conversion of sleeve to RYGB surgery in 2018 due weight loss failure. Patient is known to have well controlled hypothyroidism on thyroxine. She was prescribed vitamin D, neurobion, iron and multivitamins tablets post surgery but never been compliant. The patient was admitted with severe malnutrition due to poor oral intake over the last 5 months prior to admission. Her total weight loss was 34.5 kg (32% weight change, BMI 28 .52kg/m2) in less than 9 months post surgery. Initial labs revealed severe hypoalbuminemia, normochromic anemia and neutropenia. Iron, folate, thiamine, and vitamin B12 levels were normal. Vitamin B6 level was normal at 11 mcg/L (normal = 5-50 mcg/L). The serum copper level was low at 310 µg/l (normal = 794-2023µg/l). Zinc level was low at 447 µg/l (normal = 551-925µg/l). Nutritional needs were estimated using the following formulas; 22-25 kcal/kg ideal body weight (IBW)/d and 1.5-2.0 g protein/kg IBW/d, 30-35 ml IVF/kg /d. The patient’s input/output, body weight, and clinical status were monitored. Parenteral nutrition additive copper 0.3 mg/day and oral copper 8 mg daily, resulted in the rapid correction of hematologic indices over one week. Combined multivitamins supplementation and oral copper supplements alone normalized serum copper levels over 4 weeks and resulted in resolution of weakness and body edema.
This report serves to alert physicians of the association between bariatric surgeries and subsequent severe copper deficiency in order to avoid diagnostic delays and to improve treatment outcomes.
SUN-013 Cardiometabolic Profile of Brazilian Women with Polycystic Ovary Syndrome (PCOS): A Systematic Review and Meta-Analysis
Authors: Marchesan Lucas Bandeira , Ramos Ramon Bossardi , Oliveira Monica , Spritzer Poli Mara 
Published: May 2020

Abstract
Introduction. PCOS is a frequent endocrine disease and its clinical expression may be influenced by ethnicity and sociocultural backgrounds. Despite its high prevalence, few studies are available regarding clinical characteristics of Brazilian women with PCOS. The aim of this study was to summarize the available evidence regarding metabolic risks in PCOS population in Brazil trough a systematic review and meta-analysis. Materials and Methods. We systematically searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials for studies published until July 31, 2019. Results. Eleven cross-sectional and case-control studies were selected for the present meta-analysis, including 898 women diagnosed with PCOS and 2176 controls. All used the Rotterdam criteria for the diagnosis of PCOS. Compared to controls, BMI was higher in PCOS [standardized mean difference (SMD) 0.67 (95% CI 0.29, 1.05) I²=91%], as well as waist circumference [SMD 0.88 (0.40, 1.37) I²=93%]. Systolic and diastolic blood pressure were higher in PCOS, SMD 0.66 (0.30, 1.01) I²=83%, SMD 0.55 (0.24, 0.87) I²=81%, respectively. Glucose and HOMA-IR were higher in PCOS, SMD 0.22 (0.02, 0.41) I²= 57%, SMD 0.78 (0.52, 1.04) I² =26% respectively. Regarding lipid profile, PCOS had higher values for triglyceride [SMD= 0.39 (0.14, 0.64, I² =63%)], total cholesterol [SMD 0.36 (0.15, 0.57, I²=57%)] and LDL [SMD 0.44 (0.11, 0.78, I²=82%)] and lower values for HDL [SMD -0.56 (-0.78, -0.34) I²=68%]. Conclusions. Even though the studies considered were observational, including mostly small samples, the evidence from this meta-analysis indicates women with PCOS from different regions of Brazil present worse cardiometabolic profile than women without PCOS. This systematic review and meta-analysis is registered in PROSPERO (CRD42016038537).
SUN-916 Novel Germline p.Gly42Arg MEN1 Missense Mutation in a Family Harboring Very Aggressive Pancreatic Tumor, Hyperparathyroidism and Pituitary Tumor
Authors: Naves Luciana Ansaneli , Santana Lidiana B , Miranda Isabella Santiago M , Rosa Isabella Naves , Mesquita Pedro G , Santa Rita Ticiane H , Sousa Claudia F , Barra Gustavo Barcelos 
Published: May 2020

Abstract
Background.Pancreatic neuroendocrine tumors ocurs in 30-80% of patients with MEN-1, and may be non-functioning and hormone secreting tumors. Non-functioning GEP-NETs are increasingly recognised due to advanced imaging modalities such as endoscopic ultrasound thus became the most common type in MEN1 patients. Several mutations MENIN gene were described, although patients with missense mutations are considered as low-impact mutation carriers.Case report.Index case, female, 47 years old, menarche at age of 16yo, amenorrhea until 23yo, when started continuous oral contraceptives. At age of 45 presented dizziness, paresthesia, cramps, had the diagnosis of Hyperparathyroidism related to multinodular parathyroid hyperplasia (Calcium 14mg/dL, PTH 117 pg/mL) and macroprolactinoma (prolactin 235 ng/mL; pituitary tumor 1.2 X 1.0 cm). All siblings and her mother were recruited and one brother, aged 45 years confirmed the diagnosis of hyperparathyroidism and nephrocalcinosis. Their mother, aged 77 years old, presented abdominal pain, and had the diagnosis of aggressivepancreatic tumor compressing bile duct causing intra and extra-pancreatic dilation, associated with metastatic lymph nodes. She was sunmitted to total pancreato-gastrectomy with esophagus jejunum anastomosis. Genetic screening:MEN1genetic screening for mutations was performed in all patients. In these probands, MLPA analysis was performed to detect large deletions of the MEN1gene, using SALSA MLPA probemix kit P017-D1 according to the manufacturer’s instructions (MRC-Holland, Amsterdam, The Netherlands).DNA was extracted from EDTA-Whole blood using MagNA Pure 24 (Roche). Sequencing libraries were qualified/quantified using TapeStation4200 (Agilent). Test method included coding regions ±10bp flanking intronic sequences of 3921 genes enriched using Kappa HyperPlus Library Preparation Kit (Roche) and SeqCap EZ inherited disease panel (Roche) and sequenced (2x75-bp Mid Output V2 Reagent) using NextSeq-500 (Illumina) (estimated mean coverage-100X). Read alignment, variant calling, variant filtration and annotation were performed with Varstation. SNVs and small indels (20bp) with total-read-depth,10X and variant-read-frequency more than20% found on AIP, APC, CDC73, CDKN1B, DICER1, FH, MAX, MEN1, MET, NF1, PRKAR1A, PTEN, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53, VHL, WRN genes were analyzed.A missense mutation in exon 2, MEN1:c.124G.C:p.(GLY42Arg) was detected. Discussion and conclusion:MEN1-associated GEP-NETs seem to have a low proliferation rate and long survival has been reported, they should be of particular attention, since they are still the principal cause of death in MEN1 patients.Early screening and diagnosis are crucial for MEN-1 phenotypes.