bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-688 Emphysematous Gastritis and Diabetes
Authors: Singh Abhilasha , German Massiell , Grotzke Marissa Paige 
Published: May 2020

Abstract
Background: Emphysematous gastritis (EG) is a rare and severe form of gastritis of infectious origin. Diabetes is an important underlying risk factor as it leads to a systemic predisposition to infections. Other risk factors include long term steroid use, nonsteroidal anti-inflammatory (NSAID) use, alcohol use, corrosive ingestion, and pancreatitis, all of which disrupt gastric mucosa. First described in the 1800s, it is characterized by the presence of air in the stomach wall and differentials for these cases include gastric emphysema and cystic pneumatosis both of which are non-infectious in origin.
Clinical Case: A 57-year-old male with type 2 diabetes presented with a one-day history of abdominal pain, non-bloody diarrhea, and vomiting. One day prior to presentation, he developed diarrhea which was followed by episodes of projectile vomiting reported as orange-tinged with mucus. On the day of admission, he was afebrile, tachycardic in 120s with stable blood pressure. Laboratory evaluation was significant for leukocytosis at 18.8 k/uL (4.3–11.3 k/uL) and lactic acidosis 2.37 mmol/L (0.7–2.1 mmol/L). Abdominal examination was notable for soft abdomen with diffuse tenderness to deep palpation without rebound or guarding. Further workup with Computed Tomography (CT) was concerning for emphysematous gastritis with air in the gastric vein, splenic vein, and portal vein. Given hemodynamic stability and benign abdominal examination, medical management was initiated. He was started on ceftriaxone and metronidazole which were continued for a total of 10 days with clinical improvement. Discussion: EG results from disruption in gastric mucosa which facilitates translocation of gas-producing bacteria commonly Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa, and Enterobacter subspecies. Immunosuppression with diabetes is an important underlying factor and patients are at risk even with controlled diabetes. Additionally, patients with diabetic complications like gastroparesis with frequent retching are at increased risk. Considering variable and non-specific symptoms of presentation, a high index of clinical suspicion is required for recognition as it may have a fulminant course with high mortality risk. CT scan is the imaging of choice for diagnosis. Management primarily consists of bowel rest, antibiotics and monitoring for signs of peritonitis. In the absence of complications including rupture or stricture formation, surgery is not recommended. In our case, possible gastroenteritis with subsequent vomiting and retching in the setting of underlying diabetes predisposed to the development of emphysematous gastritis. Although air in the portal venous system is associated with higher mortality, our patient was successfully managed conservatively. As the diagnosis carries a high mortality risk, early recognition is imperative for a successful outcome.
SUN-308 Central Adrenal Insufficiency Is Rare in Adults with Prader-Willi Syndrome
Authors: Rosenberg Anna G W , Pellikaan Karlijn , Poitou Christine , Goldstone Anthony P , Hoybye Charlotte , Markovic Tania , Grugni Graziano , Crinò Antonino , Caixàs Assumpta , Coupaye Muriel , van den Berg Sjoerd A A , van der Lely Aart Jan , de Graaff-Herder Laura C G 
Published: May 2020

Abstract
Introduction: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. This is partly due to the variable results of the synacthen test, compared with the more robust metyrapone test (MTP) and insulin tolerance test (ITT). In some countries, patients with PWS receive stress-dose corticosteroids during physical or psychological stress. Side effects of frequent corticosteroids use are weight gain, osteoporosis, diabetes mellitus and hypertension, already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity or even mortality. To prevent over- and undertreatment with corticosteroids, we assessed the prevalence of CAI in a large international cohort of adults with this rare disorder.
Methods: The hypothalamic-pituitary-adrenal axis was tested in 81 adult subjects (55 Dutch, 10 British, 10 French, 6 Swedish) with genetically confirmed PWS. For multiple-dose MTP, 11-deoxycortisol &gt;230 nmol/L (7.6 g/dL) was considered sufficient. For Dutch, French and Swedish patients who underwent ITT, cortisol &gt;500 nmol/L (18.1 μg/dL) was considered sufficient. For British patients cortisol &gt;450 nmol/L (16.3 μg/dL) was considered sufficient, as this center used a different assay. Additionally, we reviewed medical files of 645 adults with PWS from Italy (240), France (110), the Netherlands (110), Australia (60), Spain (45), Sweden (38) and the United Kingdom (42) for symptoms of hypocortisolism/adrenal crisis during surgery.
Results: Data on 81 adult subjects (46 males and 35 females), median age (range) 25.2 yr (18.0 – 55.5), median BMI (range) 29.1 kg/m2 (20.0 – 62.0), with genetically confirmed PWS were collected. 33 subjects (41%) were using GH treatment since childhood. Multiple-dose MTP was performed in 45 subjects and ITT in 36 subjects. Both tests were well tolerated by all individuals. CAI was excluded in 80 of 81 patients. One patient with a peak cortisol level of 494 nmol/L (just below cut-off level of 500 nmol/L) was prescribed hydrocortisone for use during physical stress. There was no relation between baseline cortisol and ITT/multiple-dose MTP results. Even patients with a low baseline cortisol level (lowest: 102.0 nmol/L) had normal responses. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative corticosteroids treatment. None of them displayed any features of hypocortisolism/adrenal crisis.
Conclusions: CAI is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing corticosteroids stress-doses in adults with PWS.
Funding: CZ foundation.
SUN-069 A 14 Year Old Female with Primary Amenorrhea
Authors: Chakravarthy Varshini , Ejaz Sehar 
Published: May 2020

Abstract
Background: Swyer Syndrome is an extremely rare disorder of sexual development. These patients often present with primary amenorrhea during adolescence and are phenotypically female with 46 XY chromosomes. Given the association of invasive gonadal malignancies with this disorder, suspicion should be high in patients who present with a stagnant or decreased rate of pubertal progression. We present a case of Swyer Syndrome in a 14-year-old female with primary amenorrhea in the setting of decreased pubertal progression. Case: A 14-year-old female presents with a chief complaint of primary amenorrhea. She first noticed breast budding 2 years prior but reports no significant increase in breast tissue over the last 2 years. She does not appreciate any other signs of puberty. She denies any acne, body odor, hirsutism, hair loss, or abdominal/pelvic pain. She denies any changes in her diet or physical activity and is not on any medication. No history of cancer, surgeries, or radiation exposure. There is no family history of infertility or delayed puberty. Her vitals on presentation are within normal limits. Her growth parameters are the following: weight-69.9 kilos, height-163 cm, and BMI-26.3. Physical exam shows a well-appearing adolescent with grossly female external genitalia and the breast exam is SMR II. No pubic or axillary hair appreciated on the exam. Although our patient did not meet the traditional definition of primary amenorrhea, a workup was started due to the slow progression of puberty. Initial blood testing shows normal blood count, electrolytes and thyroid levels. DHEA-S androstenedione, free and total testosterone were all within normal limits. Further results such as LH (25.4 uIU/mL), FSH (56.5 mIU/mL) and estradiol (22 pg/mL) along with low levels of AMH (0.52 ng/mL) and inhibin A (1pg/mL) confirms suspicion for ovarian insufficiency. Chromosomal analysis and pelvic ultrasound findings of a small uterus and ovaries led to our diagnosis of Swyer syndrome. Our patient had surgical resection of both ovaries and fallopian tubes and the ovarian pathology showed gonadoblastoma with invasive dysgerminoma in both gonads. She was started on hormone replacement after gonadectomy. Conclusion: Although Swyer syndrome is uncommon with an incidence of 1 in 80,000, this case illustrates that suspicion for Swyer Syndrome should be high in patients with slow progression of puberty and primary amenorrhea (1). Early diagnosis is critical, as patients with gonadal dysgenesis are at great risk for germ cell cancers. Though most of these patients have an identifiable genetic mutation, we were unable to elicit the exact mutation in our patient despite whole-genome sequencing. References: Jaideep Khare, Prasun Deb, Prachi Srivastava & Babul H. Reddy (2017) Swyer syndrome: The gender swayer?, Alexandria Journal of Medicine, 53:2, 197–200, DOI: 10.1016/j.ajme.2016.05.006 Varshini Chakravarthy, Sehar Ejaz. A 16-Year-Old With Amenorrhea and Delayed Breast Development - Medscape - Jan 14, 2020
SUN-922 An Indolent Recurrent Parathyroid Carcinoma - A Case Report
Authors: Murthi Swetha , Abdulla Maha B , Har-El Gady , Opher-Iosifescu Elana , Merker Edward 
Published: May 2020

Abstract
Introduction
Parathyroid carcinoma is a rare endocrine malignancy with reported incidence from 0.5 to 5% of primary hyperparathyroidism (1). Etiologies include prior neck irradiation, adenoma or hyperplastic parathyroid gland. Molecular pathogenesis includes RB gene overexpression, low P53, loss of APC and especially HRPT2 tumor suppressor gene. It has low malignant potential, but tends to recur locally or spread to contiguous areas. Here, we present a case of a recurrent parathyroid carcinoma that recurred after 17 years.
Clinical Case
The patient is a 56 YO female with Stage 1 breast cancer status post bilateral mastectomy who had underwent resection of a 2.5cm low-grade left lower parathyroid carcinoma in 1997 after 10 years of primary hyperparathyroidism. At that time of resection, iPTH was 2500 pg/ml and calcium level greater than 15 mg/dl. She presented with hypercalcemia (Calcium 11.5 mg/dl, PTH 67.1 pg/ml) again after 17 years. Work-up showed a 2.3 cm suspected parathyroid lesion in the left neck. She underwent removal of the left upper parathyroid gland along with a right enlarged parathyroid gland, as intra-operative PTH did not decline. Pathology confirmed parathyroid carcinoma with capsular invasion and muscle infiltration of the left gland and adenoma of the right gland. Repeat imaging in a month showed persistent parathyroid activity in the left neck. She had removal of the left upper parathyroid and a left paratracheal mass excision with pathology confirming recurrent parathyroid carcinoma. After 4 years, her PTH and calcium levels rose. Sestamibi imaging showed abnormal activity in a 1.1 cm soft tissue mass near the sternal notch. The patient underwent complete excision of the left suprasternal mass and the left sternohyoid muscle with pathology confirming recurrent parathyroid carcinoma with lympho-vascular and perineural invasion. Follow-up Sestamibi imaging after a month showed no abnormal activity with recent labs of calcium level 10mg/dl and PTH 25 pg/ml.
Conclusion
Recurrent parathyroid carcinoma remains a challenge. Complete resection of the lesion along with care to avoid capsule rupture to prevent local seeding remains the treatment strategy. The main cause of morbidity and mortality is the sequelae of uncontrolled hypercalcemia rather than tumor burden. Management of hypercalcemia includes hydration, bisphosphonates and cinacalcet. Even though it is not radiosensitive, neck radiation after surgery may be helpful in preventing tumor regrowth. Clinical trials using nivolumab and ipilimumab are being conducted to treat parathyroid carcinoma (2).
Reference
1. Givi, B., & Shah, J. P. (2010). Parathyroid carcinoma. Clinical oncology, 22(6), 498–507
2. Long, K. L., & Sippel, R. S. (2018). Current and future treatments for parathyroid carcinoma. International Journal of Endocrine Oncology, 5(01), IJE06
OR19-04 Glucocorticoid Production in the Nervous and Immune Systems: Evidence for a Local HPA Axis Homolog
Authors: Salehzadeh Melody , Hamden Jordan Edward , Li Michael X , Bajaj Hitasha , Ma Cathy , Soma Kiran K 
Published: May 2020

Abstract
Glucocorticoid Production in the Nervous and Immune Systems: Evidence for a Local HPA Axis Homolog
The hypothalamic-pituitary-adrenal (HPA) axis is a critical stress response system in vertebrates. The hypothalamus secretes corticotropin-releasing hormone (CRH), which binds its receptor (CRH-R1) in the anterior pituitary. The anterior pituitary then secretes adrenocorticotropic hormone (ACTH), which binds its receptor (MC2R) in the adrenal glands and stimulates secretion of glucocorticoids into the bloodstream. Glucocorticoids are critical modulators of neural and immune system development. During early development (postnatal day (PND) 2 to 12), mice show decreased adrenal glucocorticoid secretion at baseline and in response to stressors, termed the stress hyporesponsive period (SHRP) (1). Traditionally, glucocorticoids have been thought to be synthesized only in the adrenal glands. However, recent evidence demonstrates that glucocorticoids are also produced in extra-adrenal tissues, such as the brain and lymphoid organs (2). This may be of particular importance during the SHRP, as local production allows glucocorticoid modulation of specific tissues and cells, without general effects throughout the organism. Importantly, the factors that regulate local glucocorticoid production remain unknown. To study the regulation of local glucocorticoid production, we examined whether mediators of the HPA axis are locally expressed at baseline and in response to an immune stressor. We assessed systemic and local glucocorticoid levels in neonatal (PND5) C57BL/6J mice 4hr after an immune challenge with lipopolysaccharide (50µg/kg i.p.) or vehicle control. We examined blood, microdissected brain regions (prefrontal cortex, hippocampus, hypothalamus), and lymphoid organs (thymus, spleen, bone marrow). A panel of 7 steroids was measured via liquid chromatography tandem mass spectrometry (LC-MS/MS). Gene expression of Crh, Crh-R1, Pomc, and Mc2r was quantified via qPCR. Preliminary data indicate that corticosterone was 2-fold higher in tissues than in blood after an immune stressor. The thymus expressed all genes of interest, supporting the existence of a local HPA axis “homolog” in the thymus. Brain, spleen and bone marrow expressed a subset of the genes of interest. These exciting data demonstrate that all the mediators of the HPA axis are locally expressed within the thymus, likely to regulate thymocyte development and reactivity. Greater understanding of local glucocorticoid production will provide crucial insight into neural and immune development and function. Reference: (1) Sapolsky et al., Brain Res Rev. 1986 11(1):65–76. (2) Taves et al., Endocrinology. 2015 156(2):511–522.
SAT-422 Evaluation of the Siemens Thyroid Stimulating Immunoglobulin (TSI) Assay for Diagnosis and Prognosis of Graves’ Disease
Authors: Paul Heather , Moledina Nadia , Robinson Jason , Chin Alex , Kline Gregory A , Sadrzadeh Hossein 
Published: May 2020

Abstract
Background: Hyperthyroidism due to Graves’ disease (GD) is an autoimmune condition caused by thyroid stimulating hormone receptor (TSHR) autoantibodies. Autoantibodies to the TSHR can stimulate or block thyroid hormone production, therefore testing specifically for stimulating antibodies would be beneficial for diagnosis of GD.
Objectives: The primary objective of the first phase of this trial is to assess the diagnostic capability of the Siemens Thyroid Stimulating Immunoglobulin (TSI) immunoassay in diagnosing GD and to compare it with the Roche TSH Receptor Antibody (TRAb) assay.
Design and Methods: Two hundred patients with suspected GD are being enrolled in this single-center multiphase prospective cohort study. Consenting patients undergo biochemical testing including thyroid stimulating hormone (TSH), free T3 (FT3) and T4 (FT4), TRAb and TSI measurements. GD diagnosis was confirmed by endocrinologists that were blinded to TSI results.
Results: To date, 85 patients were included in the analysis, of which 66 were diagnosed with GD. For the primary analysis, all patients taking anti-thyroid drugs (ATD) at time of sample collection (n=14) were removed. The respective sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for TSI was 98, 84, 94 and 94%, which were comparable to those generated by TRAb (98, 95, 95, and 98%). In patients with clinical findings of GD (ie. orbitopathy or goiter, n=33), both the TSI and TRAb assays had identical sensitivity and specificity at 96% and 80% respectively. In patients without orbitopathy or goiter (n=38), the TSI assay had perfect sensitivity and excellent specificity of 100% and 86% respectively (TRAb had 100% sensitivity and specificity). Sensitivity, specificity, NPV, and PPV were slightly lower for both TSI and TRAb in patients treated with ATDs compared to patients without treatment (TSI: 85, 84, 62, 95%; TRAb: 91, 95, 75, 98%). Of ten patients with GD and false negative TSI results, nine were on ATDs. Of this subset, four patients had discordant results between TSI (negative) and TRAb (positive). Notably, one of these patients had normalization of their FT3 and FT4 on the day of sample collection.
Discussion and Conclusion: Based on our preliminary results, TSI is an excellent marker for diagnosing GD, particularly in untreated GD patients. The performance of the TSI assay has been comparable to the TRAb assay and correlates well with clinical findings. Discordant false negative results were only seen in patients on ATD. One potential explanation is that the TSI assay is detecting a decrease in stimulating autoantibodies when there is normalization of FT3 and FT4. Importantly, all discordant samples will be tested by a TSI bioassay to confirm diagnosis. Further patient enrollment is occurring, and prognostic assessment of these assays will soon be possible.
SAT-484 Presyncope as Initial Presentation of Massive Pericardial Effusion with Tamponade in a Patient with Primary Hypothyroidism
Authors: Garcia Susan , Tin Su Lei 
Published: May 2020

Abstract
Presyncope as initial presentation of massive pericardial effusion with tamponade in a patient with primary hypothyroidism
Background: Hypothyroidism is an endocrinologic disorder that affects multiple systems ranging from cardiovascular, central nervous system, musculoskeletal, etc. One of the possible cardiovascular complications of hypothyroidism is pericardial effusion which is only rarely associated with tamponade. In this case report we have a 49 years old woman who presented with impending pericardial tamponade secondary to chronic primary hypothyroidism. Clinical case: A 49 years old woman with history of hypothyroidism presented to the hospital on account of headache, dizziness with presyncope episode, generalized weakness and shortness of breath for 7 days, physical exam showed normal vital signs, distant heart sounds, laboratory tests showed TSH:29.5 uIU/mL (normal range 0.270- 0.4200 uIU/mL), fT4: &lt;0.1ng/dL (normal range 0.9–1.8 ng/dL), fT3: 1.68 pg/mL (normal range 1.80–4.60 pg/mL. Electrocardiogram showed low voltage QRS, chest CT showed large pericardial effusion with findings suggestive of right heart failure, Echocardiogram showed left ventricular dysfunction and large pericardial effusion. The patient was taken to the operating room for emergent pericardial window creation with pericardiectomy and was admitted to the Cardiac Care Unit for management of tamponade status post pericardial window. Levothyroxine 150 mcg, Liothyronine 25 mcg and Hydrocortisone 50 mg were started, the steroid was discontinued after adrenal insufficiency was ruled out. The pericardial drain was removed after 8 days and repeated tests showed TSH: 13.1 uIU/mL, fT3: 3.37 pg/mL, fT4: 0.5 ng/dL, studies of pericardial fluid only showed polymorphonuclear cells. The patient’s symptoms resolved and she was discharged on Levothyroxine 150 mcg and Liothyronine 25 mcg. During follow up visits the thyroid function tests were normal, Liothyronine was discontinued and a repeated Echocardiogram showed normal systolic function. Conclusions: Pericardial effusion can be found in 3–30% of patients with hypothyroidism but only in very rare cases (less than 3%) is associated with cardiac tamponade and occurs when there is a severe underlying condition like myxedema coma or prolonged untreated hypothyroidism (1). It is important not to miss that dizziness and presyncope in a patient with hypothyroidism may be a manifestation of cardiac tamponade. Once the diagnosis of hypothyroidism is made it is imperative to start treatment early as untreated hypothyroidism can cause severe cardiovascular complications but even when such are present, they can be reversible with thyroid replacement therapy. Reference: (1) Kahaly, G. and Dillmann, W. (2005). Thyroid Hormone Action in the Heart. Available at: https://academic.oup.com/edrv/article/26/5/704/2355198 [Accessed July 12 2019].
MON-025 Activin a Increases Human Trophoblast Invasion by Up-Regulating Integrinb1 Through ALK4
Authors: Zhu Shiqin , Leung Peter C , Ma Jinlong , Li Yan 
Published: May 2020

Abstract
Activin A Increases Human Trophoblast Invasion by Up-regulating Integrin β1 Through ALK4
Following implantation, extravillous trophoblast cells (EVTs) derived from trophectoderm invade into the maternal decidua to a certain extent, which is tightly regulated by a variety of factors. Activin A, a member of the TGF-β superfamily, has been shown to stimulate the invasion of human trophoblasts (1). Integrin β1 has been implicated in cancer cell invasion and is consistently expressed in human preimplantation embryos (2). However, whether integrin β1 is integrated in activin A signaling and mediates activin A increased-human trophoblast invasion remain unknown. The objective of our study was to investigate the possible mediation role of integrin β1 in the pro-invasive effect of activin A on trophoblasts and illustrate the underlying molecular mechanisms. Primary and immortalized (HTR8/SVneo) cultures of human trophoblast cells were employed as study models. Real-time qPCR, Western blot, and small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin A-mediated functions. The integrin β1 protein levels in poorly invasive BeWo,JAR and JEG-3 human choriocarcinoma cells were lower than that in highly invasive HTR8/SVneo cells and primary human EVTs, suggesting the possible essential role of integrin β1 in mediating human trophoblast invasion. The expression levels of integrin β1 were up-regulated in a time-dependent manner after activin A treatment in HTR8/SVneo cells. Importantly, siRNA-mediated down-regulation of integrin β1 significantly attenuated both basal and activin A-induced cell invasion in HTR8/SVneo cells as measured by transwell invasion assay. Interestingly, the TGF-β type I receptors (ALK4/5/7) inhibitor SB431542 abolished activin A-induced activation of SMAD2/SMAD3 as well as activin
A-up-regulated integrin 1 expression. Moreover, siRNA-mediated down-regulation of ALK4 or SMAD4 attenuated activin A-up-regulated integrin β1 in both HTR8/SVneo cells and human primary EVT cells. These results reveal that activin A promotes human trophoblast cell invasion by up-regulating integrin β1 expression through ALK4-activated SMAD2/3-SMAD4 signaling pathway.
Reference: (1) Bearfield et al., Eur J Endocrinol 2005;152:909–16. (2) Campbell et al., Hum Reprod 1995;10:1571–8.