bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-402 Investigating Analogues of Parathyroid Hormone (PTH) and PTH-Related Peptide (PTHrP) to Improve Anabolic: Catabolic Response Ratios Using UMR106-01 Osteocytic Cells
Authors: Oladapo Oladipo Posi , Sugamori Kim S , Mitchell Jane 
Published: May 2020

Abstract
Osteoporosis, the most common bone disease in humans, is characterised by decreased bone mass and increased fracture risk1. Osteoporosis development is associated with an imbalance of bone resorption and deposition mediated by all three bone cell types; osteoblasts, osteocytes and osteoclasts2. Current treatments for osteoporosis either prevent further bone resorption (Bisphosphonates and anti-RANKL) or increase bone deposition through anabolism (Teriparatide and Abaloparatide)3. The two anabolic treatments are truncated analogues of endogenous peptides; parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP), respectively. Both are administered intermittently, act on PTH1R receptors on osteoblasts and osteocytes leading to an increase in bone mineral density and bone strength. However, both treatments also have side-effects of hypercalcemia and cortical bone porosity caused by osteoclast stimulation. We therefore compared an array of PTH and PTHrP analogues for potential stimulation of catabolic side effects and desired anabolic effects. Screening assays used are UMR106-01 osteocytic cells that have high levels of PTH1R to measure mRNAs involved in anabolic responses (suppression of WNT inhibitors SOST and Dkk1) and catabolic responses (stimulation of RANKL/OPG, IL6). Peptides were also analysed by real-time cellular impedance assays (xCELLigence) to measure unbiased receptor stimulation. xCELLigence assays showed PTH1-34, PTHrP1-34 and Abaloparatide had the highest potencies (3.7 nM,1.4 nM,1.7nM respectively) while Tyr1PTH1-34 and PTH2-34 had significantly decreased potencies (64nM and 130nM), the β-arrestin biased agonist, D-Trp12Tyr34PTH7–34, had no effect. PTH1-34 potently inhibited SOST (IC50 0.29nM), and catabolic genes (RANK/OPG EC50 0.5nM, IL6 EC50 2.5nM). PTHrP1-34 provided higher potencies for anabolic (inhibited SOST IC50 0.08nM) and catabolic (RANKL/OPG EC50 0.3nM, IL6 EC50 1nM) genes. Altering the first amino acid to Tyrosine; Tyr1PTH1-34 caused potent anabolic responses (SOST IC50 0.97nM) yet showed decreased potency for catabolic responses (RANKL/OPG EC50 20nM, IL6 EC50 &gt; 100nM). Removing the first amino acid of PTH to PTH2-34 drastically decreases the effectiveness of the peptide (OPG, SOST and RANKL IC50 – no effect, IL6 EC50 &gt; 100nM). These results indicate the importance of the N-terminal amino acid for PTH affinity and efficacy and suggest that Tyr1PTH1-34 may offer the best combination of bone stimulation without causing hypercalcemia.
References
1 A.Gupta, L. March. (2016) Treating osteoporosis, Aust Prescr
2 Chen X, et al. (2018) Osteoblast–osteoclast interactions. Connect. Tissue Res
3 Tu KN, et al. (2018) Osteoporosis: A review of treatment options. P T
SAT-352 Severe Primary Hyperparathyroidism, Hypercalcemic Crisis, Acute Pancreatitis and Fatality: Complications of Atypical Parathyroid Adenoma, a Case Report
Authors: Hashem Sherin , Lin Grace , Vavinskaya Vera , Fadare Oluwole 
Published: May 2020

Abstract
BACKGROUND: Atypical parathyroid adenomas (APAs) are a controversial and rare entity. These tumors show some features of carcinomas including adherence to adjacent structures, banding fibrosis, mitotic activity, and tumor cells trapped within capsule; however, they lack definitive capsular, vascular, or perineural invasion. Patients are often asymptomatic, or have vague symptoms such as fatigue. Studies and literature have reported that the elevation in parathyroid hormone (PTH) and calcium levels in APAs are intermediate between those of adenomas and carcinomas, and that the clinical course is generally benign. Clinical Case: A 41-year old woman with diabetes mellitus, Hashimoto’s thyroiditis, and obesity was noted to have mild asymptomatic hypercalcemia during routine tests performed at an outside hospital several months prior to presentation. A few weeks prior to presentation, she started complaining of anorexia, nausea, vomiting and abdominal pain. At the time of presentation, she was critically-ill with a picture of severe acute pancreatitis. Laboratory tests showed hypercalcemia (13.9 mg/dL, normal 8.5-10.6 mg/dL) and elevated lipase (1134 U/L, normal 13-60 U/L); however, a magnetic resonance cholangiopancreatography showed no biliary obstruction. Further testing revealed markedly elevated PTH (&gt;5000 pg/ml, normal 15-65 pg/ml), and subsequent neck ultrasound showed a solitary mass on the left side of the neck. Despite maximum medical treatment, the patient continued to rapidly decompensate and passed away rapidly. Autopsy examination revealed a picture of severe acute pancreatitis including a markedly enlarged necrotic pancreas (360 grams, normal: 60-100 grams), extensive omental fat necrosis, ascites, and dusky discoloration of the abdominal organs. A well-circumscribed mass (6.6 x 3.5 x 1.5 cm) was found on the superior aspect of the left thyroid lobe. The tumor showed parathyroid cell proliferation admixed with banding fibrosis, no unequivocal invasion into the surrounding capsule, blood vessels or perineural spaces, and no evidence of lymph node involvement or distant metastasis, consistent with a diagnosis of APA. Her cause of death was the left neck APA and its associated sequelae of significant hypercalcemia and acute pancreatitis. Conclusion: This patient had asymptomatic hypercalcemia for months prior to presentation with PTH/hypercalcemic crisis, highlighting the importance of ruling out primary hyperparathyroidism in the assessment of patients with asymptomatic hypercalcemia. While it’s generally appreciated that parathyroid carcinomas usually cause more profound hypercalcemia and are more likely to cause fatality from metabolic complications, and that APAs follow a generally more benign course, this case shows that APAs can grow into significantly large lesions and could follow a severe and abrupt clinical course if not surgically removed.
SAT-604 The Role of the Focal Adhesion Kinase Family in Leptin Receptor Signaling
Authors: Hadley Colleen , Cakir Isin , Cone Roger D 
Published: May 2020

Abstract
Overweight and obesity are global concerns affecting nearly one third of the world population. These conditions are characterized by increased adiposity and are accompanied by a proportional increase in circulating leptin, an anorexigenic adipokine. Leptin is responsible for signaling peripheral energy status to the central nervous system to modulate food intake and energy expenditure. As such, neurons within the hypothalamus expressing the long isoform of leptin receptor (LepRb), a type I cytokine receptor, are primarily responsible for mediating the effects of leptin, which signal predominantly through the JAK2-STAT3 transduction mechanism. STAT3 is a latent transcription factor activated upon phosphorylation, which triggers its homodimerization and nuclear translocation. Evidence, however, for JAK2-independent, STAT3-dependent leptin receptor signaling mechanisms exist. FAK (focal adhesion kinase, Ptk2) and Pyk2 (protein tyrosine kinase 2b, Ptk2b) are a subset of nonreceptor protein tyrosine kinases and comprise the focal adhesion kinase family. FAK and Pyk2 are implicated in the regulation of cytokine receptor signaling. Furthermore, Pyk2 knockout mice have an obesity prone phenotype. Here, we studied the role of the focal adhesion kinases in leptin receptor signaling using genetic and pharmacological approaches. We found that overexpression of Pyk2 or FAK increased STAT3 phosphorylation (activation). Overexpression of a FAK or Pyk2 construct with impaired kinase activity, however, attenuated STAT3 phosphorylation, suggesting the increase in STAT3 phosphorylation is largely dependent upon kinase activity of FAK/Pyk2. Treatment of cells with a small molecule dual inhibitor of FAK and Pyk2 (PF431396) attenuated leptin-induced STAT3 phosphorylation in a mouse hypothalamic cell line. Importantly, this effect is independent of JAK2, as PF treatment of two independent JAK2-deficient cell lines exhibited similar attenuation of leptin-induced STAT3 phosphorylation. To assess the physiological relevance of FAK/Pyk2 in leptin receptor signaling in vivo, we administered PF compound to the lateral ventricle of 24-hour fasted lean wild-type mice followed by peripheral leptin administration. Intracerebroventricular (ICV) administration of PF suppressed the anorectic effect of leptin as evidenced by impaired inhibition of food intake upon refeeding. Accordingly, analysis of total hypothalamic lysates from these mice showed ICV PF impaired leptin-induced STAT3 phosphorylation. Taken together, these data suggest that Pyk2 and/or FAK play a role in leptin signal transduction.
MON-164 Determinants of Quality of Life in Primary and Secondary Adrenal Insufficiency from Two Large Tertiary Care Centers in the United States
Authors: Li Dingfeng , Genere Natalia , Xhikola Majlinda , Behnken Emma , Abbondanza Tiffany , Vaidya Anand , Bancos Irina 
Published: May 2020

Abstract
Background: Patients with primary adrenal insufficiency (PAI) and secondary adrenal insufficiency (SAI) report impaired quality of life. Predictors of adverse outcomes include duration of disease, supraphysiologic glucocorticoid (GC) use, and presence of other comorbidities. There is limited evidence to suggest that quality of life is disproportionately affected in one subtype of adrenal insufficiency.
Objective: To identify determinants of quality of life in patients with PAI vs SAI.
Method: Survey study of patients with the diagnosis of AI between 2015 and 2019 was evaluated at two large tertiary medical centers in the United States. Collected variables included data on circumstances of AI diagnosis, symptoms, management, burden of disease, and overall well-being. Patients with AI due to exogenous glucocorticoid use were excluded.
Results: Patients with PAI (n=310, 65% women) were diagnosed at a younger age (37 ± 19 vs 48 ± 16 years, p&lt;.01) than patients with SAI (n=255, 57% women). Patients with SAI were more likely not to understand their diagnosis (13% vs 4% in PAI, p&lt;.01), or to report a discordant diagnosis (16% vs 9% in PAI, p=.02). Patients with PAI were on a higher dose of daily GC (23.8 mg vs 18.5 mg hydrocortisone (HC) equivalent, p &lt;.01), with higher number of patients on HC&gt; 25 mg/day (33% vs 15%, p&lt;.01). Patients with PAI reported a higher compliance with wearing medical alert ID (79% vs 64%, p=.01) and higher availability of injectable GC (74% vs 58%, p&lt;.01). Patients with PAI reported a higher frequency of at least one adrenal crisis within the last 12 months that required self- injectable GC (32% vs 16%, p&lt;.01), or prompted ER visits (56% vs 29%, p&lt;.01) compared to those with SAI. Nevertheless, patients with PAI were more likely to report good general health (78% vs 65% in SAI, p&lt;.01). When adjusted for current age, sex, duration of disease, supraphysiologic GC use, number of current symptoms and recent adrenal crises, patients with SAI had HR of 2.6 (CI 95% 1.5-4.3) for poor health, 1.6 (CI 95% 0.95-2.8) for physical limitations, 1.7 (CI 95% 1.1-2.7) for fatigue, and 2.7 (CI 95% 1.5-4.9) for social limitations compared to those with PAI.
Conclusions: Patients with PAI receive higher daily GC and experience a higher number of adrenal crises when compared to patients with SAI. However, patients with PAI report a better general perception of health, possibly due to a more robust knowledge of their disease and higher comfort level managing AI. More effort is needed to ensure patients with AI are appropriately educated regarding their medical condition and therapy.
SUN-276 Pembrolizumab-Induced Secondary Adrenal Insufficiency Presenting as Severe Hyponatremia in an 80-Year-Old Male
Authors: Kawaji Leslie Daphne R , Villanueva Mary Grace M , Villa Michael L 
Published: May 2020

Abstract
Background
Pembrolizumab is an anti-programmed death 1 (PD-1) antibody designed to incite an immune response against malignant cells. By virtue of this mechanism of action, its use has given rise to immune-related adverse events including those affecting the endocrine system. Adrenal insufficiency can occur rarely with anti-PD-1 therapy, and symptoms are usually non-specific.
Clinical Case
An 80-year-old male, known case of non-small cell lung cancer stage IV presented with a 2-week history of progressive body weakness with anorexia, shortness of breath and low-grade fever. He had just received the 4th cycle of pembrolizumab prior to the onset of symptoms. Past medical history was significant for hypertension and type 2 diabetes mellitus which were both controlled, and pulmonary tuberculosis with completed treatment.
On physical examination, he was drowsy but oriented. He was normotensive (110/70 mmHg) and tachypneic (28 cpm) with rales on both lung fields. Baseline capillary glucose level was 107 mg/dL. Chest radiograph showed hazy opacities in the right upper to middle region. Blood chemistry revealed severe hyponatremia (114 mmol/L, NV 135-145 mmol/L) and low serum osmolality (247 mOsm/kg, NV 280-300 mOsm/kg). Random (taken 1230H) ACTH and cortisol were &lt;5.00 pg/mL (NV &lt;46 pg/mL) and 2.00 μg/dL (NV 4.30-22.40 μg/dL), respectively. Such levels were judged to be low in the background of an acute illness. Thyroid function tests were normal – TSH 0.993 μIU/mL (NV 0.55-4.78 uIU/mL), FT3 3.890 pg/mL (2.30-4.20 pg/mL), FT4 1.450 ng/dL (0.89-1.76 ng/dL). Magnetic resonance imaging of the pituitary gland did not show abnormal parenchymal enhancement or enlargement.
Pembrolizumab-induced secondary adrenal insufficiency was the most probable cause of the hyponatremia. He was started on IV hydrocortisone, as well as piperacillin-tazobactam for pneumonia. Oxygen support via nasal cannula was given. Feeding via nasogastric tube was decided to ensure nutrition and prevent aspiration. He was transferred to the intensive care unit for careful monitoring. Serum sodium level was corrected gradually, with marked clinical improvement thereafter. Within 48 hours, he was transferred to regular room and oral feeding commenced. Hydrocortisone was shifted to prednisone on discharge, with steroid tapering schedule and close follow-up with endocrinologist advised.
Conclusion
We presented a case of secondary adrenal insufficiency which likely resulted from hypophysitis induced by pembrolizumab. Hypophysitis following anti-PD1 treatment occurs in &lt;1% of patients on immunotherapy. In such cases, ACTH deficiency is usually isolated and pituitary imaging is frequently normal. Since more patients are being placed on immune-checkpoint inhibition, clinicians should be vigilant for these adverse events, particularly the endocrinopathies which may have non-specific symptoms and may be irreversible.
MON-619 Predictors of Complications with Fasting the Holy Month of Ramadan in Patients with Diabetes
Authors: Al Qarni Ali Ahmed , Alamoudi Reem Mohammad , Al-Aidarous Salwa , Alshahrani Awad Saad , Abuhelalah Munir , Ahmed Gasmelseed 
Published: May 2020

Abstract
Background: For a whole month, every year Muslims fast daily from dawn to sunset. Those with health conditions that put them at risk are exempted from fasting, yet most of patients with diabetes choose to fast. Clinical and metabolic complications of diabetes during this month are issues of concern for patients and their managing physicians. This study is designed to evaluate the impact of fasting Ramadan on safety of patients.
Methods: A multicentercross-sectional survey was conducted in four hospitals under the Ministry of National Guard Health Affairs; King Abdulaziz Hospital,Al-Ahsa, Imam Abdulrahman bin Faisal Hospital, Dammam, King Abdulaziz Medicalcities, Riyadh and Jeddah. All patients with diabetes followed in the diabetes clinics of all four centers who fulfilled the study inclusion and exclusion criteria were approached within three months post Ramadan and consented for participation in the survey, then filled a self-administered validated questionnaire that consisted of 15 items.
Results: Socio-demographic,clinical, and laboratory characteristics of 1438 patients with diabetes were analyzed. The majority 1207 (83.9%) had type II diabetes, and 828 (57.6%) were females.The mean age was 57.9 ± 14.9 years, and mean BMI 25.25 ± 5.39.The majority 1060 (73.7%) had concomitant diseases. 36 (2.5%)were on diet therapy alone, 147 (10.2%) on metformin monotherapy, and 261 (18.2%) on insulin therapy alone. The remaining 994 (69.1%) were on combination of insulin and oral agents. Health education was received on average by 688 (57.8%) of patients. Out of the 1191 (82.8%) who fasted the full month, 497 (41.7%) experienced acute glycemic complications. Multivariate analyses revealed that significant predictors for unsafe fasting were: type I diabetes [OR 1.8 (95%CI 1.2 - 2.8), p-value 0.007], insulin therapy [OR 1.8 (95% CI 1.4 - 2.3), p-value0.0001], previous history of breaking fast for glycemic reasons [OR 2.1 (95% CI1.5 - 2.9), p-value 0.0001], and not receiving health education [OR 1.6 (95% CI1.2 - 2.0), p-value 0.0006]. Blood sugar control, presence of concomitant diseases, and history of diabetes related hospitalization were not statistically significant predictors [(OR 1.25, 95% CI, 0.9 - 1.7, p-value 0.15),(1.3, 95% CI, 0.9 - 1.8, p-value 0.14), (1.1, 95% CI, 0.8 - 1.6, p-value 0.45)] respectively.
Conclusion: A significant proportion of patients with diabetes do not receive specific education pertinent to fasting Ramadan. Lack of health education, in addition to; type I diabetes, insulin therapy, and previous experience of complications are predictors for unsafe fasting. This highlights the need for better structured educational programs and further research in the field.
SAT-146 A Rare Combination of Severe Ectopic Cushing’s Syndrome and Graves Hyperthyroidism: A Case Report
Authors: Violago Janelle , Hasan Farhad 
Published: May 2020

Abstract
BACKGROUND: Ectopic ACTH secretion (EAS) is a rare cause of Cushing’s syndrome. Olfactory neuroblastoma (ONB) is a malignant tumor derived from the olfactory epithelium and can rarely be a source of ectopic hormone production. There are only 19 reported cases of EAS from ONB. We report a case of severe ectopic Cushing’s due to ONB. Interestingly, the patient also presented with Graves disease, which is an unusual pathophysiologic combination since supraphysiologic levels of glucocorticoids suppress the immune system, thereby ameliorating autoimmune processes. Remarkably, Graves disease improved following the removal of the source of ectopic ACTH. CASE PRESENTATION: A 41year old male presented with epistaxis, anosmia, and headaches. He also reported recent weight gain, muscle weakness, and new onset hypertension. Cross-sectional imaging revealed a right nasal cavity mass with intracranial extension. Endonasal biopsy was consistent with a diagnosis of ONB. Biochemical evaluation demonstrated hypokalemic alkalosis, hyperglycemia, and severe hypercortisolism [ACTH 734 (9-46 pg/ml), am cortisol 110 (2-15 ug/ml), late night salivary cortisol 9.8 and 22.53 (&lt;0.09 ug/dl), 24 hour UFC 41,337.3 (4-50 mcg) and non-suppressed cortisol 110 (1.8 mcg/dl) by 1 mg dexamethasone]. Pituitary MRI showed no sellar pathology. Following a period of cortisol suppression with Ketoconazole then with Etomidate infusion, the patient underwent resection of the ONB, followed by chemo- and radiotherapy, which resulted in improvement of severe hypercortisolism. Histopathology showed positive ACTH immunostaining. Pre-operative evaluation also demonstrated hyperthyroidism: TSH &lt;0.010 (0.3-5uIu/ml), FT4 3.11 (0.89-1.76 ng/dl), normal TT3 0.81 (0.6-1.81 ng/ml). Thyroid auto-antibodies were negative; however, radioiodine scan and uptake demonstrated diffusely increased uptake in the enlarged thyroid gland. Pre-operative euthyroidism was achieved with a combination of methimazole, SSKI and cholestyramine. After 6 months of methimazole therapy the patient presented with hypothyroidism (TSH 72.37, FT4 0.1). Methimazole was discontinued and he achieved euthyroidism on subsequent evaluations. CONCLUSION: EAS due to ONB is a very rare cause of Cushing’s syndrome. To our knowledge, this is the first reported case of a male presenting with EAS and concurrent Graves hyperthyroidism. An extensive review of the literature and seeking expert opinion did not provide a convincing pathophysiologic explanation to this unusual concurrence. We therefore hypothesize that, while the two endocrine conditions were simultaneous, they were likely unrelated.
SAT-405 Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHP): A Useful Tool?
Authors: Santos Lívia Marcela , Ohe Monique Nakayama , Pallone Sthefanie Giovanna , Kunii Ilda Sizue , Silva Renata Elen Costa , Sakane Eliane Naomi , Vieira Jose Gilberto , Lazaretti-Castro Marise 
Published: May 2020

Abstract
Background: PHP is a common disorder, and regardless of being an asymptomatic entity, often leads to bone loss and osteoporosis. TBS is a software-based assessment method of trabecular bone structure of the spine based on the analysis of pixels in dual energy x-ray absorptiometry (DXA) images. The aim of this study was to evaluate TBS measurements in combination with DXA values by searching for more accurate bone fragility risk assessment among PHP patients.
Methods: From June/2017 to January/2019, all patients who met the criteria for PHP diagnosis prior to surgery were selected to take part in this study. Control group was composed by non-family related healthy volunteers. Bone mineral density (BMD) by DXA (DXA; Hologic QDR 4500) at the lumbar spine, total hip, femoral neck, distal third of the non-dominant radius and TBS values by InSight were determined in 64 PHP patients and 63 controls. Total and ionized calcium, PTH, 25-hydroxyvitamin D (25(OH)D), creatinine, alkaline phosphatase, P1NP and CTX were measured in all patients and control group.
Results: Primary hyperparathyroidism patients presented significant lower BMD values in all evaluated sites compared to controls. TBS measurements were also statistically different among PHP patients and controls (mean TBS PHP=1233 vs TBS controls= 1280, p=0.044). Patients and controls didn’t differ in age, sex, menopausal state or BMI (body mass index). Osteoporosis diagnosis by DXA analysis was observed in 50% of PHP patients and in 26.6% of controls. Self-reported or image-diagnosed fracture occurred in 15 PHP (23.4%) patients and in 11 (17.5%) controls. Among these fractures, vertebral fracture account for 9 (14%) in PHP group and 4 (6.3%) in controls. ROC curve analysis showed that the TBS value &lt; 1187 is associated to significant high risk of vertebral fracture (sensibility 87.5%, specificity 67.3%) among PHP patients.
Conclusion: TBS, used as a complement to DXA measurements, is a useful tool to better assess fragility risk among PHP patients.