bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-185 Primary Adrenal Lymphoma Presenting with Symptomatic Hypercalcaemia
Authors: Forde Hannah Elizabeth , Noble Jane , Gibbons David , Holian John , Gerard Connaghan Daniel , Crowley Rachel K 
Published: May 2020

Abstract
Introduction: Primary adrenal lymphoma (PAL) is a rare cause of adrenal enlargement with approximately 200 cases reported in the literature to date. It tends to affect elderly men and has a high incidence of bilateral involvement at diagnosis. We report the case of a 66 year old man, whose PAL manifested with symptomatic hypercalcaemia.
A 66 year old male, originally from the Philippines, was referred to the emergency department with nausea, vomiting, weight loss and right flank pain. His past medical history was significant for hypertension, gout and stage 3b chronic kidney disease. His medications were amlodipine, losartan and febuxostat. His family history was significant for hypertension. On examination he was hypertensive (blood pressure, 160/100 mmHg) and hyperpigmented. His laboratory investigations revealed; corrected calcium of 3.79 mmol/l, undetectable PTH, vitamin D 49 nmol/l. He was treated with intravenous (IV) 0.9% saline and IV zoledronic acid and his calcium levels improved.
To investigate causes of non-PTH mediated hypercalcaemia, computerised tomography of the thorax, abdomen and pelvis (CT TAP) as well as a positron emission tomography (PET) scan were performed. These demonstrated bilateral, large, metabolically active adrenal masses with no evidence of extra-adrenal disease. Differential diagnosis at this point included bilateral adrenal hyperplasia, metastases, lymphoma or adrenal TB. There were no radiological features of adrenocortical carcinoma (ACC) or phaeochromocytoma and subsequent biochemical investigations confirmed no evidence of cortisol, androgen or catecholamine excess. Adrenocorticotrophic hormone (ACTH) levels were elevated however, and a synacthen test revealed inadequate adrenal reserve (peak cortisol 214 nmol/l). The patient was commenced on maintenance steroids and with stress dose steroid cover, proceeded to adrenal biopsy. Histology confirmed diffuse large B cell non-Hodgkin’s lymphoma. Haematology became involved in his care and he commenced polychemotherapy in the form of R-CHOP, 1 week post confirmation of the diagnosis. His treatment is ongoing and he has tolerated it well with minimal side effects, except a flare of gout.
Learning points: PAL should be considered in the differential diagnosis in patients with bilateral adrenal masses. Image guided adrenal biopsy is the gold standard for diagnosis, though caution must be exercised and an ACC or phaeochromocytoma should be excluded prior to biopsy. The prognosis of PAL is poor and therefore early diagnosis and prompt initiation of treatment are required to improve outcomes.
SUN-141 Altitude as the Second Hit on the Appearance of Paragangliomas
Authors: Arcos Oscar , Zambrano Maria , Valenzuela Alex , Omehara Miguel , Muniere Jaqueline , Sanchez Gabriel , Lizcano Fernando 
Published: May 2020

Abstract
Paragangliomas are rare neuroendocrine tumors with a high degree of inheritance. These neoplasms arise from the extra-adrenal autonomic paraganglion and can secrete catecholamines. Many patients debut with symptoms of hypertensive crisis, tachycardia, dyspnea, headache and intense sweating. However, many tumors that are derived from the parasympathetic system are asymptomatic. Supported on the genetic basis are classified into two conglomerates: conglomerate I are those that have mutations and alter the response to hypoxia. Cluster II has a more syndromatic component, with alteration in the function of complex signaling pathways. A study based on histopathological diagnoses was carried out between 2007 and 2017 at a hospital in Bogotá (Colombia) 2600 meters above sea level, which documented 108 cases of paragangliomas that were predominantly located at the carotid level (76%), with a 4.7:1 ratio between women and men. 93.2% of the patients came from geographical locations with heights above 2,500m above sea level. Most of the tumors were asymptomatic. We draw attention to the fact that paragangliomas are probably more frequent than clinically diagnosed and the influence of the environment on the development of these tumors is highlighted, with a special contribution of oxygen pressure as a second event that contributes to the formation of the tumor.
SUN-926 Malignant Transformation of a Benign Glucagonoma After 13 Years
Authors: Shakir Mohamed K M , Usman Aqueel , Bauer Elizabeth M , Hoang Thanh Duc 
Published: May 2020

Abstract
Glucagonoma are rare neuroendocrine tumors arising solely in the pancreas and approximately 25 % of glucagonoma cases start in a benign form. We hereby report a 76 -year-old male who was initially diagnosed with asymptomatic benign glucagonoma. Follow-up surveillance 13 years later shows that the tumor has undergone differentiation into a malignant form. Case Report: A 63-year-old man was referred for evaluation of an enhancing lesion (2.7 cm) at the pancreatic tail. He was completely asymptomatic with normal physical exam. Initial labs: normal except for elevated serum glucagon level (206 pg/mL, ref 0–60). A 2-hour oral GTT confirmed the autonomy of glucagon secretion by the tumor. Somatostatin and other tumor markers were normal. PET scan showed abnormal uptake at the distal pancreatic tail, correlating with the CT scan findings. The patient underwent laparoscopic distal pancreatectomy, with removal of a 2.8cm mass which predominantly expressed glucagon. Plasma glucagon level in the peripheral venous blood and intraoperative splenic vein dropped to &lt;50 pg/mL immediately after the surgical resection. Following surgery patient remained completely asymptomatic for the next 13 years with normal blood glucose, glucagon, insulin, chromogranin levels, complete blood count and liver functions. Additionally patient continued to have normal surveillance MRIs of the abdomen. 13 years following removal of pancreatic mass, an elevated glucagon serum level (230 pg/mL) was noted on routine surveillance screening. At this time patient also remained asymptomatic. Abdominal MRI and PET scan revealed a 4-cm pancreatic mass with hepatic metastases. Biopsy of the hepatic lesion confirmed glucagonoma. Patient was treated with Lanreotide which has normalized the serum glucagon levels and the tumor size remained stable for the 12 months of follow up. Discussion: In our patient the glucagon secreting tumor without any classic presenting symptoms was found incidentally and the asymptomatic glucagonoma treated surgically presumably at an earlier stage. It is known that some glucagonomas are associated with serum levels of the peptide in the “physiologically elevated” range, even in the presence of necrolytic migratory erythema. The complete remission without any treatment lasting for more than 13 years confirmed the benign nature of the tumor. It is also reported that gluconomas less than 2 cm in size has less potential for metastasis. The usual recommendation is to monitor these patients post-resection to a maximum of 10 years although in our patient the malignant nature of the tumor was expressed 13 years after initial resection. The reason for malignant transformation after this prolonged period remains unknown. This case highlights the importance of continuous monitoring neuroendocrine tumors even beyond 10 years after surgery.
SUN-255 The Synthetic Progestin, 17-alpha-hydroxyprogesterone Caproate, Used in Human Pregnancy Alters Prefrontal Cortical Development in Rats
Authors: Lolier Melanie L , Wagner Christine K 
Published: May 2020

Abstract
17-alpha-hydroxyprogesterone caproate (17-OHPC) is a synthetic progestin commonly prescribed for the prevention of recurrent preterm birth. Treatment with 17-OHPC in high-risk pregnant women begins between gestational weeks 16-20, and continues through week 36 1. Recent studies suggest that 17-OHPC is not an effective treatment for reducing rates of preterm delivery 2,3. Most concerning is the timing of 17-OHPC administration, which coincides with critical periods of mesocortical dopamine pathway development in the fetus 4. Regulating behaviors of executive function, the mesocortical pathway originates in dopaminergic neurons of the ventral tegmental area (VTA) that innervate the medial prefrontal cortex (mPFC). Disruptions in mesocortical dopamine pathway development are believed to underlie deficits in cognitive functioning 5,6.
In rodent models of cortical development, the developing mesocortical dopamine pathway is sensitive to progestins. There is transient expression of nuclear progesterone receptors (PR) in both the VTA and mPFC 7. PR are powerful transcription factors that can alter gene expression and fundamentally alter neural development 8,9. When rodents are treated with 17-OHPC during mesocortical dopamine pathway development, there are significant sex-specific alterations in dopaminergic innervation of the mPFC and deficits in cognitive behaviors in adulthood 10. Microglia, the resident immune cells of the central nervous system, play a critical role in establishing dopaminergic circuitry of the forebrain 11. The following experiment tested the hypothesis that 17-OHPC alters microglia activity in a sex-specific manner. Our results reveal that there is an innate sex difference in the number of reactive microglia, where control group females had significantly more than males. Treatment with 17-OHPC abolishes this sex difference by reducing the number of reactive microglia in 17-OHPC treated females to male-like levels in both the prelimbic (PL) and infralimbic (IL) mPFC. There is also a significant reduction in the percentage of reactive microglia in 17-OHPC treated animals compared to controls. These results suggest that early 17-OHPC exposure may decrease functional microglial activity during critical periods of cortical development, and that females are more vulnerable than males. Consideration should be given to the potential effects of 17-OHPC on neural and cognitive development in children.
SUN-739 Next Generation AR Antagonists Increase Systemic Active Glucocorticoid Exposure by Altering Glucocorticoid Metabolism
Authors: Alyamani Mohammad , Sharifi Nima , Li Jianbo , Patel Mona , Berk Michael , Taylor Susan , Przybycin Christopher , Posadas Edwin M , Madan Ravi , Gulley James L , Rini Brian I , Garcia Jorgi A , Klein Eric A 
Published: May 2020

Abstract
Enzalutamide and apalutamide are potent next-generation androgen receptor (AR) antagonists used in metastatic and non-metastatic prostate cancer. Despite the increased survival benefits of these agents, resistance normally occurs and the disease transitions to its lethal form. We hypothesized that enzalutamide and apalutamide suppress 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which normally converts cortisol to cortisone, leading to elevated cortisol concentrations and increased ratio of active to inactive glucocorticoids. We measured cortisol and cortisol/cortisone ratio (substrate/product of 11β-HSD2) in serum using mass spectrometry before and 1 month on-treatment in 3 clinical trials: 1) neoadjuvant apalutamide + leuprolide (n=25) 2) enzalutamide +/- PROSTVAC for metastatic castration-resistant prostate cancer (n=54) and 3) enzalutamide +/- PROSTVAC for non-metastatic castration-sensitive prostate cancer (n=38 patients). Progression-free survival (PFS) was determined in the metastatic CRPC study of enzalutamide +/- PROSTVAC for those with glucocorticoid changes above and below the median. A statistically significant rise in cortisol concentration and cortisol/cortisone ratio with AR antagonist treatment occurred uniformly across all 3 clinical trials. For example, a rise in cortisol/cortisone ratio occurred in 23/25 (92%) patients (p &lt; 0.001), 36/54 (67%) patients (p &lt; 0.001), and 30/38 (79%) patients (p = 0.051), in the 3 respective trials. In the trial of enzalutamide +/- PROSTVAC for metastatic CRPC, high cortisol/cortisone ratio in the enzalutamide arm was associated with significantly improved PSA progression-free survival and radiographic progression-free survival. However, in the enzalutamide + PROSTVAC arm, the opposite trend was observed. In conclusion, treatment with enzalutamide or apalutamide increases systemic exposure to active glucocorticoids. These findings have potential consequences for immune suppression and the efficacy of treatment combinations using next-generation AR antagonists. On-treatment, glucocorticoid changes might serve as a pharmacodynamic biomarker.
MON-663 Prandial Insulin Dosing Based on Carbohydrate Content Does Not Significantly Improve Glycemic Control in Hospitalized Patients with Diabetes
Authors: Goel Heenam , Dojki Farheen K , Davis Dawn Belt 
Published: May 2020

Abstract
Introduction: Diabetes mellitus (DM) is a highly prevalent concern in hospital medicine. In-hospital hyperglycemia and hypoglycemia are common. Hospitalized patients have variable and unpredictable amounts of carbohydrate content in their meals. We hypothesized that order sets that allow for flexible dosing of prandial insulin using an insulin to carbohydrate ratio (ICR) would provide superior blood glucose control in the complex hospital environment. Methods: We performed a retrospective review of electronic medical records from a single university hospital. The hospital implemented new order sets allowing prandial insulin dosing based on an ICR and inpatient nursing staff received necessary training. We compared glucose levels over the first three days after admission in hospitalized patients prescribed prandial insulin either as a fixed dose or based on an ICR. Patients on fixed dose insulin were selected from a time 3 months prior to the implementation of ICR order sets, to avoid any bias in patient selection. Patients on ICR dosing were selected from 3 months after implementation of ICR order sets, to allow adequate time for initial implementation. Our inclusion criteria included patients admitted to both medicine and surgery services, with Type 1 or Type 2 DM, age between 18-80. Exclusion criteria included transplant patients, patients on insulin infusion, pregnancy, steroid use and dialysis. 65 patients were included in each group. Outcome measures included average blood glucose over 72 hours, fasting and postprandial hypoglycemia (&lt;70 mg/dL) and hyperglycemia incidence (&gt;180 mg/dL). Results: Average glucose over 3 days was 167 +/- 39 mg/dL and 162 +/- 33 mg/dL and did not differ between groups. However, a higher percentage of glucose values were in target range (70-180 mg/dL) in the fixed dosing group (67.9%) compared to ICR (62.5%, p=0.018). The incidence of hypoglycemia was low and did not differ between groups (1.2% in both). However, patients had more overall hyperglycemia with ICR dosing (36% vs 31%, p=0.018), particularly pre-lunch hyperglycemia (52% vs. 38%, p=0.007). Fasting glucose was similar between groups.
Conclusions: In conclusion, our study demonstrated that prandial insulin administered based on ICR did not improve overall glycemic control or reduce incidence of hypoglycemia in hospitalized patients with diabetes. In fact, overall and post-meal rates of hyperglycemia were generally higher with ICR dosing. This could be related to inaccurate counting of carbohydrates or delayed timing of insulin administration as it was given after the food was consumed. Additional studies are needed to further evaluate the effectiveness of flexible meal dosing and the impact on patient satisfaction and staff workload.
SUN-639 Secretagogin Levels Are Unrelated to Gestational Diabetes Mellitus in a Cohort of Pregnant Women
Authors: Deischinger Carola , Harreiter Jürgen , Wagner Ludwig , Baumgartner-Parzer Sabina , Kautzky-Willer Alexandra 
Published: May 2020

Abstract
Introduction
Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients.1,2,3 Up to this day, no study on SCGN levels in patients with gestational diabetes mellitus (GDM) has been published.
Patients and Methods
In 138 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of GDM patients were compared to women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with an oral glucose tolerance test (oGTT) performed before 20 weeks gestation. The women with GDM (39.1%) were further divided into GDM types depending on insulin sensitivity or secretion defects defined as below the 25th percentile in the oGTT of the NGT controls.
Results
Compared to women with NGT (mean SCGN= 52.7 ng/dl), there was no statistically significant difference in SCGN in patients with GDM (mean value 53.9 ng/dl, p=0.857). After splitting into secretion defect and insulin resistance subtypes, SCGN remained unrelated to GDM in our study population. However, Secretagogin was found to be significantly higher in postpartum visits (mean= 62.9 ng/dl) than during pregnancy (mean value= 48.5 ng/dl; p= 0.047). Furthermore, SCGN was positively correlated with BMI (p=0.006) in the present analysis.
Conclusion
Unlike in studies conducted on type 2 diabetes,1,2,3 a relationship between GDM and Secretagogin levels could not be demonstrated in this study. However, lower levels during pregnancy point towards physiological changes in SCGN levels unrelated to (gestational) diabetes mellitus. Further research, ideally including before-pregnancy levels, is paramount to assess possible roles of SCGN during pregnancy.
1. Maj M, Wagner L, Tretter V, et al. A TRPV1-to-secretagogin regulatory axis controls pancreatic β-cell survival by modulating protein turnover. EMBO J. 2017;36(14):2107-2125. doi:10.15252/embj.201695347
2. Yang C, Qu H, Zhao X, et al. Plasma Secretagogin is Increased in Individuals with Glucose Dysregulation. Exp Clin Endocrinol Diabetes. 2019:0-4. doi:10.1055/a-1001-2244
3. Maj M, Wagner L, Tretter V. 20 Years of Secretagogin: Exocytosis and Beyond. Front Mol Neurosci. 2019;12(February):1-10. doi:10.3389/fnmol.2019.00029
SUN-266 Protein Induced Pancreatic Hormone Secretion Is Modulated by Vagal CaSR
Authors: Norton Mariana , Cork Simon C , Alonso Aldara Martin , Roberts Anna G , Patel Yateen S , Cheng Sijing , Hansford Robert , Cao Ye , Salem Victoria , Hanyaloglu Aylin Carla , Chang Wenhan , Murphy Kevin Graeme 
Published: May 2020

Abstract
The existence of a vago-vagal entero-pancreatic pathway, where sensory information from the gut can signal via vagal afferents to the brain to mediate changes in pancreatic function, has been recognised for over a century, and investigated extensively with regards to pancreatic exocrine secretions. However, the role of such pathways in pancreatic endocrine secretions has received less attention.
The secretion of insulin and glucagon in response to protein and amino acids is conserved across species. This effect is thought to promote amino acid uptake into tissues without concomitant hypoglycaemia. We found that the essential amino acid L-Phenylalanine potently stimulates glucagon secretion, even when administered directly into the gut at small doses unlikely to significantly raise systematic levels. Administration of L-Phenylalanine also increased neuronal activation in the rat and mouse dorsal vagal complex, the central nervous system region directly innervated by vagal afferents.
L-Phenylalanine modulates the activity of the calcium sensing receptor (CaSR), a nutrient sensor more commonly known for its role in calcium homeostasis, but which is thought to also act as a sensor of aromatic amino acids. Interestingly, the CaSR is one of the few nutrient sensors expressed in vagal afferents and in vitro calcium imaging revealed CaSR synthetic agonists activate subpopulations of vagal afferents.
The role of CaSR in vivo was investigated further by selectively knocking down the CaSR in vagal afferents. Briefly, CaSR floxed mice were bilaterally injected directly into the nodose ganglion, where the cell bodies of vagal afferents are located, with a cre expressing adeno-associated virus. CaSR knockdown did not interfere with normal food intake, nor the vagal-dependent anorectic effects of cholecystokinin, or of L-Phenylalanine. However, it did blunt protein-induced glucagon secretion, suggesting involvement of the CaSR in the vagus nerve in protein sensing and glucose homeostasis.
Future studies are required to determine the importance of vagal CaSR in protein induced pancreatic endocrine secretions, and the possibility of exploiting this circuit to develop new anti-diabetic therapies.
MON-705 Islet Auto-Transplantation Following Partial Pancreatectomy Improves Glycemic Outcomes and Reduces Length of Hospital Stay: Multi-Center, Case-Control Study
Authors: Chaidarun Sushela S , elmunzer Joe B , kerrington Smith D , Gardner Timothy B 
Published: May 2020

Abstract
Introduction: Islet auto-transplantation (IAT) is increasingly being performed to prevent brittle diabetes following pancreatic resection in patients with benign pancreatic diseases. While patients undergoing total or completion pancreatectomy clearly benefit from IAT, the glycemic benefit of IAT in patients undergoing partial pancreatic resection is not known. We aimed to determine if IAT improved glycemic outcomes in patients undergoing partial pancreatectomy for benign pancreatic diseases. Methods: We performed a multicenter, retrospective case-control study of patients who underwent partial pancreatic resection with IAT at two tertiary care centers. Case patients were compared to controls who underwent partial pancreatic resection without IAT at one center prior to offering IAT. The primary outcome was the mean change in pre vs. post-operative HgA1c following transplant as well as the development of new post-operative diabetes. Results: 9 patients requiring partial pancreatectomy for benign disease underwent IAT and were compared to 13 historical controls without IAT. Baseline characteristics were similar between groups including age, etiology of pancreatitis, the presence of diabetes and pre-operative HgA1c (5.7 vs. 5.2, p=0.448). With a median follow-up of 22 months, those who received an IAT had a smaller increase in their pre- vs. post-operative HgA1c (0.42 vs 2.83, p=0.004) and one case patient (14.3%) vs. three control patients (23.1%) developed new post-operative diabetes (p=0.581). Patients who underwent IAT had a shorter length of stay (6 days vs 11 days, p=0.039) compared to control patients. Conclusions: Patients undergoing partial pancreatic resection for benign pancreatic disease should be considered for IAT, as long-term glycemic outcomes are improved in those undergoing transplant. The shorter length of hospital stay is likely related to less brittle glucose control after the surgery with some endogenous insulin production by auto-islet graft function.