bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-263 In Vitro Modeling of Brain-Bone Communication: Factors Secreted from Immortalized Female Kisspeptin Neurons Modulate Gene Expression in Osteoblasts
Authors: James Teagan , Weinman Marcus , Chappell Patrick Everett 
Published: May 2020

Abstract
While the sex steroid hormone estrogen (E2) is essential for maximum reproductive fitness, circulating E2 is also involved in maintaining skeletal homeostasis in females. E2 in male and female animals has been shown to stimulate cancellous bone formation via activation of estrogen receptor alpha (ERα), and it was widely thought that this effect was mediated directly at the level of bone. A recent study, however, demonstrated a large increase in bone density in female mice in which ERα was deleted from specific neuroendocrine neurons in the arcuate nucleus of the hypothalamus, specifically those expressing kiss1, a population required for fertility and pubertal progression. Bone from transgenic Kiss1-cre X ERα floxed females showed higher osteoblast functioning, accompanied by increases in the expression of sp7 and runx2, positing the existence of a direct neural-bone regulatory axis that is altered by circulating E2 at the level of the brain (Herber et al., Nat Commun 2019).
Our laboratory recently published a study demonstrating that GnRH and Kisspeptin, typically thought to act primarily within the neuroendocrine reproductive axis, are synthesized and secreted in an autocrine fashion by canine osteosarcoma cells in vitro, and that these neuropeptides can stimulate tumor cell proliferation (BMC Cancer 2019). Separately, our lab has also recently generated two immortalized Kiss1-expressing and –secreting cell lines, KTaR-1 (representative of female arcuate Kiss-1 neurons) and KTaV-3 cells (representative of female AVPV Kiss-1 neurons) (Endocrinology 2017). In the current study, we have combined these two in vitro models to explore if factors secreted by female ARC-derived KTaR-1 cells may affect multiple parameters of osteoblast function, including sp7 and runx2 expression (evaluated by qPCR), and ability to form bone matrix (evaluated by Alizarin Red assay). Preliminary results suggest that exposure canine osteosarcoma (COS) cells to conditioned media from KTaR-1 cells leads to increases in sp7 expression in an E2-dependent manner, such that 24h E2-deprivation of these neurons stimulates secretion of osteogenic factors. Additionally, media from both KTaR-1 and KTaV-3 cells stimulated Ca2+ production from cultured osteoblasts, as evaluated by Alizarin Red. We are continuing to explore these in vitro interactions using COS cells, as well as normal osteoblasts (cNOB) and immortalized cNOBs, and are evaluating media and exosomal proteomics to further characterize putative factors. While further study is required, these initial results suggest that our immortalized neuronal KP cell models may provide useful molecular tools to explore the regulation of this newly-proposed neural-bone axis.
MON-002 The Effect of GNRHR Autoantibody on Reproduction Function and Insulin Signaling Intermediates in a New Animal Model of Polycystic Ovary Syndrome
Authors: Li Hongliang , Guo Yankai , Zhang Gege , Deng Jielin , Fischer Hayley , Craig LaTasha B , Yu Xichun , Kem David C 
Published: May 2020

Abstract
Background: Polycystic ovary syndrome (PCOS), a metabolic and reproductive associated disease, defined as hyperandrogenism with reproductive dysfunction including menstrual disorder, anovulation, infertility, polycystic ovary and so on. We previously showed reported a high percentage of activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR) in PCOS patients, and further demonstrated elevated GnRHR-autoantibody (GnRHR-AAb) could induced insulin resistance in energy storage and peripheral tissue in immunized animals. In the present study, we have now induced specific GnRHR-ECL2 AAb in rats and explored the underlying mechanisms of their resultant reproductive dysfunction. Methods: Sixteen SD rats were randomly divided into 2 groups: a GnRHR group (n=8) and a control group (n=8). Rats in the GnRHR group were immunized with GnRHR ECL2 peptide while the controls were not. Epitope mapping of GnRHR-ECL2-directed AAb was performed using octapeptide multipin solid-phase peptides. Rat estrus cycle was measured through pudendum appearance and vaginal smears. Ovarian and pituitary tissues were collected to observe ovarian morphological changes, to examine the expressions of proteins and genes of insulin signaling pathway by Quantitative real-time PCR respectively. The concentration of inflammatory cytokines in the ovary was detected by Bio-plex Pro™ magnetic bead-based assays on the Bio-plex®. Results: The GnRHR-AAb titers and activity in the GnRHR group were significantly higher than the control group, and the GnRHR-AAb from the immunized rats reacted predominantly with the peptide sequence FSQCVTHC of the GnRHR-ECL2. Numbers of LH pulses and concentration of testosterone in GnRHR group were significantly higher than control group. The GnRHR group exhibited lower frequency of in the appearance of proestrus and estrous phases while the control group represented had a higher frequency in the appearance of metestrus and diestrus stages on estrus cyclicity. The GnRHR-immunized group showed demonstrated increased atretic follicles, decreased corpora lutea, loosely packed granulosa cells, and thecal cell hyperplasia in ovarian tissue compared with controls group. There was GnRHR group represented increased expressions of IRS-1, PI3K and GLUT-1 in ovarian and pituitary tissues compared with control group. However, no obvious changes of inflammatory cytokines are observed in ovarian tissues between two groups. Conclusion: Chronic elevated GnRHR-AAb exerts induced reproductive dysfunction through increased ovarian LH secretion and androgen production, thus likely leading to compensatory hyperinsulinemia which ultimately enhanced insulin signaling in reproductive tissues to exert more and androgen production to, which may provide a novel etiological mechanism for PCOS.
SAT-207 Adrenocortical Carcinoma in Untreated Congenital Adrenal Hyperplasia
Authors: David Julia , Yagudayev Lev , Galagan Robert 
Published: May 2020

Abstract
Background:
Congenital adrenal hyperplasia (CAH) is a group of rare inherited autosomal recessive disorders characterized by a deficiency of various enzymes participating in steroid hormone synthesis. It occurs in 1 in 5000 to 1 in 15000 births. The most common (90-95%) cause of CAH is the absence of the enzyme 21-hydroxylase. We are presenting a case of a 34 year old male with untreated congenital adrenal hyperplasia due 21-hydroxylase deficiency and metastatic adrenocortical carcinoma.
Case:
A 34 year old male with a history of classic congenital adrenal hyperplasia (CAH) untreated since childhood presented with symptoms of right abdominal pain, anorexia and weight loss. His family history was significant for one brother diagnosed with CAH, father with liver and pancreatic cancer and another brother with colon cancer. After 2 weeks of treatment with NSAIDs for the pain, his abdominal pain worsened and patient also reported dyspnea with minimal exertion and dry cough. The patient was admitted to TUMC and his evaluation revealed a large right adrenal mass (17x11cm) with multiple liver and lung lesions suggestive of metastatic cancer. The adrenal mass was needle biopsied and pathology results were diagnostic of adrenal cortical carcinoma.
His baseline morning cortisol level was 22.45 mcg/dL, ACTH 13.2 (n=7.2-63.3), androstenedione 291 ng/dL (n=27-152), 17-hydroxy progesterone 10,850 ng/dL (n=27-199), testosterone 140 mg/dL, renin 1.295 ng/ml/h (n=0.167-5.38), aldosterone unable to assay due to interference and LDH 2011 U/L (n=87-241). He failed an overnight 1mg dexamethasone suppression test with cortisol of 20.17 in the morning. During hospitalization, his clinical condition gradually deteriorated with hypotension, altered mental status, acute respiratory failure and acute liver failure with an AST 2787 units/L (n &lt;39), ALT 399 (n=30-65) and ALP 1013 units/L (n=40-120). Oncology decided that the patient was a poor candidate for antineoplastic treatment therefore he was offered hospice care and eventually expired.
Discussion:
There have been reports of benign and malignant adrenal tumors in patients with CAH. It has been surmised that ACTH is the driver of adrenal tumor transformation in these patients. Our patient with adrenocortical carcinoma presented at a late stage with widespread metastases resulting in death. His elevated cortisol level occurred in association with low normal ACTH and the failed 1mg overnight dexamethasone suppression test are consistent with tumor production of cortisone. Considering that he had untreated CAH since childhood, we assume elevated ACTH levels were present until tumor transformation occurred.
MON-238 A Diagnostic “Headache” in a Pregnant Woman with Diabetes Insipidus: Blame the Placenta or the Pituitary?
Authors: Aziz Khalid , Pokhrel Ashna , Ramirez Beatriz E , Sultana Sanjeda , Houston Caroline 
Published: May 2020

Abstract
Background
Diabetes insipidus (DI) occurs in 1/30,000 pregnancies and can be difficult to recognize due to normal peripartum physiology. The most common etiology is excess production of placental vasopressinase, which degrades maternal anti-diuretic hormone. Although rare, hypothalamic and pituitary disorders must also be considered in pregnant patients presenting with DI. We present the case of a pregnant woman presenting with diabetes insipidus and pituitary apoplexy.
Clinical case
We were called to see a 33 year old female with polyuria and polydipsia on post-partum day #2. She had presented to the ED at 29.4 weeks of her 5th pregnancy (G5P4) with an unrelenting headache, nausea, and vomiting for 12 hours. She was tachycardic, hypertensive, and had no focal neurologic deficits. Fetal evaluation was reassuring. Admission labs included serum sodium of 147 mEq/L (n 136-145), serum potassium 2.8 mEq/L (n 3.4-4.4), and urine specific gravity of 1.003 (n 1.005-1.030). Glycemic parameters, renal function, and hepatic function were normal. She remained tachycardic despite vigorous IV fluid administration. Overnight into hospital day #3 she began to have uterine contractions with fetal decelerations, and betamethasone was given. It was noted that she had produced 8L of urine over the preceding 24 hours. Serum sodium was 159 mEq/L with urine osmolality of 78 mOsmol/kg (n 300-900). A presumptive diagnosis of gestational DI was made and 2 mcg of subcutaneous DDAVP was given. Shortly thereafter she delivered a healthy infant. Maternal blood loss was minimal. Over the next 12 hours her urine became concentrated and her serum sodium decreased, but by the next morning she re-developed dilute polyuria.
At the time of our evaluation, her headache had resolved and she had no focal neurologic deficits. She had no apparent signs of glucocorticoid or thyroxine deficiency but had not begun to lactate. Biochemical evaluation included early morning cortisol of 4.6 ug/dL (n 3.5-18.3), TSH 0.46 uIU/mL (n 0.35-4.94), free T4 0.76 ng/dL (n 0.70-1.48), and prolactin 26.6 ng/mL (n 5.2-26.5). Pituitary MRI showed a mildly enlarged gland with central T1 hyperintensity, consistent with apoplexy. A regimen of hydrocortisone and DDAVP was initiated.
Conclusion
Pituitary apoplexy is uncommon during pregnancy but is potentially life-threatening for the mother and fetus if it goes unrecognized. The significant physiologic growth of the pituitary during pregnancy may increase the risk of apoplexy. A severe headache is the most common symptom and may be accompanied by signs of pituitary dysfunction. Although diabetes insipidus is more often caused by placental physiology, pituitary apoplexy must also be considered in a pregnant woman who has concurrent neurologic symptoms.
SAT-366 Hypercalcemia Due to Castleman’s Disease
Authors: Khan Sarah Adil , Shah Neel L 
Published: May 2020

Abstract
Castleman’s disease is a group of poorly understood lymphoproliferative disorders in which pro-inflammatory cytokines are hyper-produced, causing a constellation of symptoms. This patient was diagnosed with a rare subtype of idiopathic multicentric Castleman’s called TAFRO, which is a subclass characterized by thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). This is a case of hypercalcemia likely secondary to Castleman’s disease. To our knowledge, only two such cases have been reported, and none with this rare subtype of the disease. The mechanism of hypercalcemia in Castleman’s disease is thought due to lymph node macrophages expressing vitamin D activating enzyme 25-hydroxyvitaminD 1-alpha-hydroxylase, and possibly due to increased bone-turnover from osteoclasts production by IL-6. The treatment is managing the primary cause of the disorder: high doses of systemic steroids, immunosuppressants and IL6-inhibitors. We present a case of a 53 year old Hispanic female with a PMH of type 2 diabetes mellitus. She had hypercalcemia with a corrected calcium 12 mg/dl and a normal PTH 16.2pg/ml, with low levels of 1,25-OH vitamin D 8.3pg/ml, and 25-OH vitamin D 16.6ng/ml. PTHrP was undetectable. Phosphorous was normal at 3.3 mg/dl. Given that the iPTH was low normal, and with low 25-OH and 1,25-OH vitamin D levels, primary hyperparathyroidism was thought unlikely. SPEP showed a chronic disease pattern. TSH was also noted to be normal. Quantiferon tuberculin test, HHV6, HHV8 and HIV were negative. IgG, IgA, IgM levels were normal. She also had elevated alkaline phosphatase at 108 U/L. No other bone markers were checked. After steroid therapy, her corrected calcium came down to 10.1. Her Castleman’s disease was diagnosed via histopathology of lymph node biopsy showing follicular hyperplasia with atretic germinal centers, penetrating blood vessels, expanded mantle zones, hypervascular interfollicular regions and intense interfollicular plasmacytosis consistent with Castleman’s disease. Initial CT Chest with contrast showed diffuse lymphadenopathy in the retropectoal, axillary, prevascular, pretracheal, paratracheal, and retroperitoneal regions. She had anasarca with ascites, requiring paracentesis with ascites fluid that was negative for malignancy. She was also diagnosed with acute thrombotic microangiopathy via kidney biopsy for workup of thrombocytopenia and acute renal injury. She was initially treated with PLEX and dexamethasone 40mg, then switched to methylprednisolone, was also tried on riuxamab and cylclosporine. She failed therapy with an IL-6 inhibitor, Siltuximab, due to pulmonary edema requiring hospitalization. Currently, she is on a drug holiday and will resume lower doses of cyclosporine. Clinicians should consider an underlying lymphoproliferative disorder in the differential for a patient with hypercalcemia.
SUN-684 The Dance of Diabetes
Authors: Thakkar Aditi , Jalil Fatima , Taxel Pamela 
Published: May 2020

Abstract
Nonketotic hyperglycemic chorea-ballism (NKHCB) is a rare movement disorder typically associated with uncontrolled type 2 diabetes. It is often the result of a focal lesion of the contralateral basal ganglia. Here we present a case of a patient who presented with hyperglycemic chorea as the initial manifestation of their diabetes. A 73 year old caucasian female with no known past medical history was brought to the emergency room with involuntary movements of the left face, arm and leg. These movements were sudden in onset and not suppressible. Her vitals were stable on arrival and exam was benign apart from choreiform movements of the left arm, left leg and left perioral muscles. Her labs were significant for a random blood glucose level of 418 mg/dl and HbA1c of 12%. As part of her workup she underwent a CT head which showed an asymmetric hyperdensity involving the right putamen. She underwent additional workup of chorea to exclude infection, vitamin deficiencies, heavy metal poisoning, electrolyte imbalances, liver dysfunction, all of which returned negative. She eventually underwent an MRI of the brain which showed symmetric, mildly bright T1 signal within both putamen suggestive of mild bilateral calcium deposition bilaterally. The patient was further evaluated by neurology who felt that her overall clinical presentation and imaging findings were consistent with a diagnosis of NKHCB. She was placed on an insulin regimen with significant improvement in blood glucose levels. Her symptoms resolved within two weeks as noted on outpatient follow up. NKHCB is a rare condition that manifests in the setting of uncontrolled nonketotic diabetes mellitus. The exact underlying pathophysiology of changes seen on imaging of patients with NKHCB is not fully understood. The diagnosis is based on typical clinical and radiological features including the presence of ballistic or choreiform movements in the setting of marked hyperglycemia and the absence of ketoacidosis. This case is unusual as her chorea was the presenting symptom of her diabetes which was previously undiagnosed. The characteristic radiological feature is a high signal intensity basal ganglia lesion on the T1-weighted brain MRI. The mainstay of treatment includes normalization of the blood glucose, although in some cases antipsychotic use has been described. In most cases, complete resolution of symptoms has been reported within 10 months. Given the excellent prognosis with management of blood glucose, non ketotic hyperglycemia is an important differential to consider in a patient presenting with chorea-hemiballismus.
SUN-678 Telediabetes Improves A1C and Patient Satisfaction: A Pilot Study in a VA Institution
Authors: Behari Gauri , Vinales Karyne Lima , Correa Ricardo Rafael , Reaven Peter , Harman Sherman Mitchell 
Published: May 2020

Abstract
Introduction: Rural Americans experience significant health disparities and have poorer health outcomes compared to their urban counterparts. Access to health care services in rural areas remains an ongoing challenge. Telehealth services can efficiently and effectively improve access to healthcare for people living in rural and remote areas. However, it is unclear if telemedicine services would be effective in the veteran population. Therefore, we have initiated a pilot studyto verify the effectiveness and satisfaction of diabetes care delivered through telehealth (Telediabetes) in a Phoenix VA community-based outpatient clinic (CBOC).
Methods: The Southeast CBOC is a remote VA clinic in Phoenix with the largest volume of patients with diabetes. Inclusion criteria were patients with type 2 diabetes that have been seen at least one time in the endocrinology clinic at the Phoenix VA and were willing toparticipate in telemedicine. Of the 36 patients that qualified for the study, 20 (55%) were scheduled, 11 (31%) were unreached, and only 5 (14 %) declined. Interventions included optimizing use of newer diabetes medications such as GLP-1 agonists and SGLT2 inhibitors andefforts to improve adherence to treatment regimens. Methods to improve adherence included offering home self-monitoring of blood glucose, increased frequency of visits, including home video conferencing and recommending referrals to nutrition and clinical pharmacists for amultidisciplinary approach. Patient satisfaction was assessed through a validated 5-question survey using a Likert scale 1-5 immediately after each visit. The primary outcomes were change in A1c and patient satisfaction.
Results: 95% (17/18) of the participants were males, the mean age was 62.5±.14.0 years-old, and the mean BMI was 34.4±6.8 kg/m2. Median follow-up time was 189 days (range: 89-417). During follow-up, A1c decreased by 0.8% (baseline: 9.5±2.2 vs. post-visit: 8.7±2.0%, p=0.017).Overall, all patients were fully satisfied (Likert score of 5) with the telediabetes visits and 94% of the patients would choose telehealth over face-to-face appointments. Up to now 37% of patients have had at least a second visit with telediabetes.
Conclusion: Telediabetes is an effective alternative to face-to-face visits for rural veterans, as demonstrated in other communities. The high patient satisfaction and decrease in A1c in this study showed that the program can be expanded to increase access to diabetes care in remoteareas.
SAT-714 Cadmium, an Endocrine Disruptor of the Reproductive Axis in Mice
Authors: Fiordelisio Tatiana , Santiago Yorgui , Romero Itayetzi 
Published: May 2020

Abstract
Endocrine disruptors, are chemicals that can alter organism endocrine system. Within these, the heavy metal cadmium is one of the most toxic industrial and environmental metals. Neuroendocrine system act in precise amounts and moments in time, disturbances caused by endocrine disruptors are suspected to be implicated in the recent declining fertility. The effect of cadmium, intraperitoneally injected, on the intracellular calcium activity of gonadotropes was evaluated in an ex vivo preparation of the entire pituitary gland of male BalbC mice by calcium imagenology techniques. In preliminary results, an increase in baseline intracellular calcium activity was observed, as well as an increase in the number of gonadotropes that respond to a GnRH and express gonadotropins. In addition, a change in the pattern of response to GnRH was observed, the biphasic type response being predominant, and an oscillatory depolarization of greater intensity and duration in response to KCl, which is not affected by nifedipine. The results allow us to infer that cadmium affects the function of pituitary gonadotropes and thus probably fertility.