bluuebunny/crossref_metadata_2025 huggingface dataset:
Quasi-4-dimension ionospheric modeling and its application in PPP
Authors: Gu Shengfeng , Gan Chengkun , He Chengpeng , Lyu Haixia , Hernandez-Pajares Manuel , Lou Yidong , Geng Jianghui , Zhao Qile
Published: November 2022

Ionospheric delay modeling is not only important for Global Navigation Satellite System (GNSS) based space weather study and monitoring, but also an efficient tool to speed up the convergence time of Precise Point Positioning (PPP). In this study, a novel model, denoted as Quasi-4-Dimension Ionospheric Modeling (Q4DIM) is proposed for wide-area high precision ionospheric delay correction. In Q4DIM, the Line Of Sight (LOS) ionospheric delays from a GNSS station network are divided into different clusters according to not only the location of latitude and longitude, but also satellite elevation and azimuth. Both Global Ionosphere Map (GIM) and Slant Ionospheric Delay (SID) models that are traditionally used for wide-area and regional ionospheric delay modeling, respectively, can be regarded as the special cases of Q4DIM by defining proper grids in latitude, longitude, elevation, and azimuth. Thus, Q4DIM presents a resilient model that is capable for both wide-area coverage and high precision. Four different sets of clusters are defined to illustrate the properties of Q4DIM based on 200 EUREF Permanent Network (EPN) stations. The results indicate that Q4DIM is compatible with the GIM products. Moreover, it is proved that by inducting the elevation and azimuth angle dependent residuals, the precision of the 2-dimensional GIM-like model, i.e., Q4DIM 2-Dimensional (Q4DIM-2D), is improved from around 1.5 Total Electron Content Units (TECU) to better than 0.5 TECU. In addition, treating Q4DIM as a 4-dimensional matrix in latitude, longitude, elevation, and azimuth, whose sparsity is less than 5%, can result in its feasibility in a bandwidth-sensitive applications, e.g., satellite-based Precising Point Positioning Real-Time Kinematic (PPP-RTK) service. Finally, the advantages of Q4DIM in PPP over the 2-dimensional models are demonstrated with the one month's data from 30 EPN stations in both high solar activity year 2014 and low solar activity year 2020.
Perceived occupational prestige of physiotherapy in Nigeria among physiotherapy undergraduates: implication for public and healthcare professionals’ awareness of the role of physiotherapy
Authors: Odunaiya Nse A. , Oladele Abimbola Kafilat , Sanuade Comfort Titilope , Adesanya Temilade Boluwatife , Odole Adesola C.
Published: November 2022

Background

The occupational prestige of any occupation is of interest to its members and prospective members. A profession’s occupational prestige influences its desirability, marketability, professional autonomy and social esteem, and career selection among prospective university undergraduates. This study aimed to assess the perception of the occupational prestige of physiotherapy in Nigeria among physiotherapy undergraduates and to explore its determining factors.

Methods

This study employed a mixed method design. The quantitative component involved 280 students from four universities in Nigeria, while the qualitative part involved 35 students. The participants in the survey completed a questionnaire on occupational prestige, and the data obtained were analysed using descriptive and inferential statistics. In addition, the qualitative data was analyzed using content thematic analysis.

Results

The perception of occupational prestige obtained from the cross-sectional survey showed that 12.1% of the participants perceived it as low, 49.3% as intermediate, and 38.6% as high. Overall, 49.3% of the participants ranked physiotherapy fourth, following medicine, engineering and law. The qualitative component corroborated these findings and further explained that the perceived status resulted from public perception of the profession in relation to other jobs, especially within the health care team.

Conclusion

Physiotherapy is ranked intermediate occupational prestige by most physiotherapy undergraduates. The significant determinants of this ranking are poor knowledge and awareness of physiotherapy among other health care professionals and the general public. To enhance the occupational prestige of physiotherapy, there is a need for public awareness of physiotherapy and its role and inter-professional education among health care professionals.
Prevalence of knowledge on maternal physical activity among pregnant women: a protocol for a systematic review
Authors: Perera Madhawa , Dissanayake Kumara , Senarathna Lalith
Published: November 2022

Background

Maternal physical activity is beneficial to pregnant women, fetus and newborns. Evidence suggests that the level of physical activity in this group is not up to the expectation around the world. Lack of knowledge on the benefits of physical activity during pregnancy and not being aware of the recommendations are major reasons for this situation. Although individual studies have reported various levels of knowledge on maternal physical activity in different populations, no studies have systematically reviewed the literature to provide global evidence on the topic that is useful in initiating multinational approaches to improve maternal physical activity. The proposed study aims to systematically review prevalence of knowledge on maternal physical activity among pregnant women in different regions in the world.

Methods

The proposed systematic review is designed according to the guidelines for conducting systematic reviews of prevalence and will be reported following the recommendations in the PRISMA statement. Quantitative cross-sectional, descriptive and observational studies published from year 2000 to 2022 will be included in the review. PubMed, Scopus, CINAHL, Embase, SPORTDiscus and Web of Science Core Collections will be searched using keywords relevant to physical activity, pregnant women and knowledge. Grey literature on the topic will be located through searching grey information sources, hand searching of reference lists and communicating with experts in the field. Screening of search results, selection and quality assessment of studies and data extraction will be independently performed by two reviewers. Assistance of a third reviewer will be sought to resolve any disagreement during the selection and quality assessment steps. After appraising the quality and consistency of selected studies, a premade data collection form will be used for data extraction. Narrative synthesis approach will be used in this review to analyze the evidence in primary studies.

Discussion

The proposed review will summarize evidence on the level of knowledge on maternal physical activity among pregnant women in different populations and delineate interregional discrepancies. The study will locate high priority regions with poor knowledge and identify elements of knowledge that needs attention.
LBSUN132 Adipocyte-specific Ablation Of Fgf23 Attenuates Diet-induced Obesity In Female Mice
Authors: Park Min Young , Tu Chia-Ling , Chang Wenhan , Sitara Despina
Published: November 2022

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis and vitamin D metabolism. In addition to its central role in mineral balance, recent findings suggested that FGF23 is associated with chronic metabolic conditions including cardiovascular disease, diabetes mellitus, and obesity. Circulating FGF23 levels are elevated in obese individuals, and they are correlated with body fat mass and abdominal obesity. Moreover, consumption of high fat diet (HFD) increases serum FGF23 levels. However, the actions of FGF23 in adipocytes and its role in lipid metabolism have not been demonstrated. To understand the role of FGF23 in adipocytes, particularly in obesity, we generated adipocyte-specific Fgf23 null mice using Cre recombinase under the control of the mouse adiponectin (Adipoq) promoter. Both male and female control (Fgf23flox/flox) and knockout (KO, AdipoqCreFgf23flox/flox) mice were fed either HFD (60%kcal fat) or normal fat diet (NFD) at 8 weeks of age for 24 weeks. Body weight measurements were taken every week and percentage of body fat was determined after longitudinally during 24 weeks of diet interventation using in vivo by an EchoMRI scannermicroCT. Serum, adipose tissue, and liver were collected upon sacrifice. After 24 weeks of HFD, male control and KO mice had comparable gain in body weight (BW) and body fat percentage. However, female KO mice had significantly lower body weight and percentage of body fat. Moreover, serum total cholesterol levels were reduced in female KO mice. Triglyceride (TG) content in the liver was significantly reduced in female KO mice, and it corresponded with downregulation of lipid droplet protein Perilipin and fatty acid transporter CD36 mRNA expression in the liver. Transcript levels of hepatic PPARγ, which is positively correlated with fat accumulation in obesity, were also suppressed in female KO mice compared to controls. Obesity is associated with low-grade chronic inflammation, and we found that hepatic mRNA expression of the inflammatory cytokine TNFα was diminished in female KO mice, suggesting that adipocytic Fgf23 modulates lipid accumulation and inflammation. In summary, our results demonstrate for the first time that adipocyte-specific ablation of Fgf23 alleviates attenuates diet-induced obesity and regulates lipid metabolism in a sex-specific manner.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP001 AKR1C2 Activity in Abdominal Adipose Tissue of Women with or without Excess Visceral Adiposity
Authors: Ostinelli Giada , Gauthier Marie-Frédérique , Bouvet-Bouchard Léonie , Julien François , Tchernof André
Published: November 2022

Background

Adipose tissue is known to play an active role in androgen turnover, as illustrated by the presence of enzymes of the aldo-keto reductase 1C family such as AKR1C2 and AKR1C3, respectively coding for 3α-hydroxysteroid dehydrogenase type 3 and 17β-hydroxysteroid dehydrogenase type 5. Our group demonstrated that these enzymes are mainly expressed in mature adipocytes and that in women, trunk fat percentage is positively associated with adipose tissue mRNA abundance of both AKR1C2 and AKR1C3. In this context, our aim was to assess whether abdominal adipose tissue activity of AKR1C2 relates to excess visceral adiposity index (VAI) in women.

Methods

AKR1C2 activity was measured in visceral (VAT) and subcutaneous adipose tissue (SAT) of 31 women (age: 39 ± 7; BMI: 51 ± 6) undergoing bariatric surgery. Adipose tissue homogenate activity was measured by fluorimetry in a 12-hour kinetic experiment using the chemical compound cumberone, a competitive substrate in the inactivation of 5a-dihydrotestosterone to 3α-androstanediol by AKR1C2. Visceral adipose tissue excess was quantified using the previously published VAI equation and using the age-specific cut-offs for women, who were categorized into either high VAI or low VAI. Other markers of adipose tissue dysfunction included diacylglycerol acyltransferase 2 (DGAT2) and glutathione peroxidase 3 (GPX3) mRNA abundance, adipocyte size and pericellular fibrosis.

Results

Our technique allowed us to detect significant AKR1C2 activity in SAT (13.5±5.7 fluorescence units (FU)/min) and VAT (8.3±4.8 FU/min). Using the VAI equation, we identified 18 women with high VAI and 13 with low VAI. Women with high VAI were characterized by significantly higher VAT AKR1C2 activity when compared to women with low VAI (9.5 ± 4.4 vs. 6.4± 3.6 FU/min, p<0. 05). AKR1C2 mRNA abundance in either VAT or SAT was not significantly different as a function of VAI. Women with high VAI also had larger VAT adipocyte diameter and lower mRNA abundance of GPX3 in both adipose tissue depots compared to women with low VAI (p<0. 05 for all). No differences were seen in DGAT2 mRNA abundance, pericellular fibrosis or SAT adipocyte diameter as a function of VAI.

Conclusion

In women with severe obesity, excess visceral adiposity as indicated by a high VAI, is associated with higher AKR1C2 activity in VAT only. Similarly, adipose tissues of women with high VAI displayed features of adipose tissue dysfunction such as increased VAT adipocyte diameter and decreased GPX3expression in comparison to women with low VAI. Taken together our results confirm the link between adipose AKR1C2 and excess visceral adiposity.

Presentation: No date and time listed
ODP006 Multidisciplinary Weight Management Improves Body Weight And Body Mass Composition In Breast Cancer Women Undergoing Adjuvant Chemotherapy
Authors: Nguyen Vivien , Chen Juliana , Preda Veronica
Published: November 2022

Weight gain during chemotherapy for breast cancer is a well-documented adverse side effect. The prevalence of metabolic syndrome (MetS), including glucose intolerance, hypertension and dyslipidaemia in breast cancer patients are further exacerbated by menopause. This impact on mortality is relevant as many women with early-stage breast cancer may be treated however experience a greater risk of developing chronic disease, higher rates of cancer recurrence, and post-diagnosis death. Intentional weight loss of 5-10% body weight and muscle mass preservation has found to improve metabolic markers. We evaluated how multidisciplinary weight management involving endocrinology, dietitian and exercise physiology care, in a real-life Healthy Weight Clinic (HWC) could affect body weight and mass composition outcomes in breast cancer women receiving adjuvant chemotherapy compared to a cohort of non-cancer women who have been matched by age, ethnicity, smoking and menopausal status. Body weight (kg), BMI (kg/m 2), skeletal muscle mass (SMM %), fat mass (FM %) and waist circumference (cm) were collected at three time points: baseline 0-months at the first HWC appointment, 3-months after baseline, and 6-months after baseline. A total of 32 women were included in the study, 11 in the breast cancer cohort and 21 in the control cohort. There were significant changes in weight, BMI, SMM, FM and waist circumference for the breast cancer cohort at all time intervals. By 6-months, the breast cancer women had a mean weight change of -6.99kg (SD=3.87, p=. 003, n=11) and change in BMI by -2.72kg/m 2 (SD=1.62, p=. 004, n=11). There was a change in SMM of 1.21% (SD=0.73, p=. 005, n=11), a change in FM of -2.76% (SD=1.33, p=. 002, n=11) and a change in waist circumference of -8.13cm (SD=4.21, p=. 031, n=3). The control cohort had similar trend changes in weight, BMI and waist circumference, however there was no statistically significant change in SMM or FM over time. By 6-months in the breast cancer cohort, there was a larger reduction in body weight in women who did not have MetS (-8.72kg, SD=2.41, n=6) in comparison to women with MetS (-2.65kg, SD=3.75kg, n=3) (p=. 045). For the control cohort, anthropometric outcomes were not impacted by MetS status (p>. 05). Although these findings are in a small sample size, it appears that multidisciplinary weight management has a positive role in early-stage breast cancer survival through improving body weight and mass composition outcomes. Targeting pre-existing MetS status through lifestyle changes is also an important consideration, beyond a specific weight focus.

Presentation: No date and time listed
LBODP009 Resection Of An Adrenocorticotropic Hormone Secreting Pheochromocytoma In A Jehovah'S Witness Patient
Authors: Andalahao Edzele Marie Fernandez
Published: November 2022

Background: Pheochromocytomas are rare neuroendocrine tumors arising from chromaffincells in the adrenal medulla, and the excessive catecholamine secreted causes serious cardiovascular effects to the patient. Adrenalectomy is the definitive treatment with a morbidity rate of 40% and a mortality rate of 2%. Intraoperative bleeding is a major concern with any surgical procedure, thus preparation of blood products for possible transfusion during the perioperative period is prudent. A religious group known as the Jehovah's witnesses recommend blood transfusion refusal to its members. We encountered a case of a Jehovah's witness with pheochromocytoma requiring adrenalectomy. CASE: A case of 54 year old, Filipino male, a Jehovah's witnesses, hypertensive for 14 years, complained of 1 week vague right upper quadrant abdominal pain and bouts of headache. A CT scan of the abdomen with contrast revealed an 11.7x 12.2×10.3cm mass on the right adrenal. Biochemical tests were consistent with pheochromocytoma that is co-secreting with ACTH, but with no physical features of hypercortisolism. An elevated levels of 24 hours urine Metanephrine (8.95 mg/ 24hrs),24 hours urine cortisol (173.98 mcg /24 hours), serum ACTH (57 pg/ml), 8am serumcortisol (22.44 mcg/dl), and 1 mg Dexamethasone suppression 8am cortisol (18.85mcg/dl). Patient consented to surgery but signed a waiver of refusal to any blood transfusion. Erythropoietin 5000 IU SC three times per week was then initiated 1month prior to the surgery. Terazosin 25 mg three times a day followed by Metoprolol25 mg twice daily, for adequate alpha and beta blockade, and hydration prior to surgery was done. The Estimated blood loss during surgery was 600 ml, patient's hemoglobin level dropped to 98 g/L on the 7th post-operative day from pre-operative level of 125 g/L, hence, the Erythropoietin was continued until was discharged. The Histopathology report showed round cell neoplasm, with positive immunohistochemical stain for synaptophysin and chromogranin, and a weak positive of NSE (Neuro-specific enolase) consistent with pheochromocytoma. References: 1. Narita et al, Surgery without Blood Transfusion for Giant Paraganglioma in a Jehovah's Witness Patient, Case Rep Oncol 2014;7: 233–238, DOI: 10.1159/0003608132. Bachman et al, Pheochromocytoma, Fulminant Heart Failure, and a Phenylephrine Challenge. The Perioperative Management of Adrenalectomy in a Jehovah's Witness Patient: A Case Report, The Journal of Critical Care Medicine 2022; 8(1): 55-60, DOI: https://doi.org/10.2478/jccm-2021-0038

Presentation: No date and time listed
LBODP012 A Case of Addison's Disease Presented With Rhabdomyolysis And Psychosis
Authors: Kasimoglu Ismail Hakki , Dai-Ju Jenny Qian
Published: November 2022

Background

Addison's disease is a disorder of deficiencies in glucocorticoids and mineralocorticoids, mostly resulting from destruction of the adrenal cortex. Rhabdomyolysis and psychosis can be symptoms presented in cases of adrenal crisis.

Clinical Case

A 42-year-old male was hospitalized for rhabdomyolysis (CK 5200 U/L), hyponatremia (Na 117 mmol/L), hyperkalemia (K 6.4 mmol/dL) and acute renal failure (Creatinine 4.4 mg/dL). Past medical history was significant for a similar episode of rhabdomyolysis: negative EMG, muscle biopsy nonconclusive, diagnosed with autoimmune hypothyroidism and started on levothyroxine 50 mcg daily five years ago. Renal function improved and electrolyte abnormality was resolved with IV hydration. ACTH was elevated (580 pg/mL), cortisol and aldosterone were undetectable; patient was discharged on hydrocortisone 10 mg bid from outside hospital. His mood and personality changed significantly after he started hydrocortisone. One week later he was admitted to a psychiatry unit due to mania and psychosis, and was started on risperidone and divalproex sodium. Cosyntropin stimulation test confirmed primary adrenal insufficiency, likely autoimmune adrenalitis with positive 21-hydroxylase antibody. Hydrocortisone was replaced with prednisone 5mg daily and fludrocortisone 0.2 mg daily. Psychiatric symptoms completely resolved in two months; patient was taken off psychiatric medications. Clinical condition was stable in follow-up visits. Electrolytes and blood pressure continued to stay in normal range. This case of Addison's disease initially presented with rhabdomyolysis as a first symptom, manifested by acute psychosis in the course of treatment with hydrocortisone. The association between adrenal insufficiency and rhabdomyolysis has been reported, but the underlying mechanism is not clear. Several theories have been proposed to explain neuropsychiatric manifestations secondary to adrenal insufficiency (1); there is no definite answer yet.

Conclusion

Adrenal insufficiency should be evaluated in patients with rhabdomyolysis. Mental disturbances triggered by adrenal crisis and treatment should be considered by both endocrinologist and psychiatrist. Reference: (1) Farah, J., et al. Severe Psychotic Disorder as the Main Manifestation of Adrenal Insufficiency. Case Rep Psychiatry. 2015; 2015: 512430.

Presentation: No date and time listed
LBODP013 Hypophysitis And Adrenalitis Associated With The Use Of Immunotherapy "clinical Case Report"
Authors: Ramos Andres Felipe Garcia , Gonzalez Juanita , Vargas Laura Valentina Estupiñan , Vargas Hernando , Buenaventura Daisy , Monsalve Claudia , Torres Jose Luis , Pompey Nestor Alfonso Lopez , Ramirez Alex , Garcia Franco Vallejo , Aguilar Carolina , Aristizabal Natalia
Published: November 2022

Background

we present a case of hypophysitis with gonadotropic and somatotropic axis compromise and adrenalitis secondary to the use of nivolumab and ipilimumab.

Clinical Case

A 74-year-old woman with a history of metastatic renal cell carcinoma treated with ipilimumab and nivolumab for 10 months, suspended treatment due to pneumonitis. Three months later, she consulted the emergency department due to limitations in daily activities, asthenia, and drowsiness. physical examination was unremarkable except for hypotension. Laboratory studies showed profound hyponatremia (106 mEq/l, n: 135 a 145 mEq/l), low serum osmolality (236 mmol/kg n: 275 - 295 mmol/kg) and a basal cortisol (5 μg/dL n: 3.7 - 19.4 μg/dL). Hypophysitis was suspected and a pituitary profile revealed low somatomedin C (25 ng/ml n: 54 204 ng/ml), FSH (20.6 UI/L n: 26.7 -133.4 UI/L), and strikingly elevated ACTH (91.9 pg/mL n: 4.7 - 48.5 pg/mL). Pituitary MRI had no structural anomaly. A diagnosis of hypophysitis and primary adrenal insufficiency secondary to adrenalitis due to the use of immunotherapy was made. The compromise of the gonadotropic and somatotropic axis with a normal image can occur in up to 23% of patients with this clinical entity. The patient had significant clinical improvement with glucocorticoid and mineralocorticoid replacement.

Conclusions

To our knowledge this is the first reported case of hypophysitis and adrenalitis secondary to immunotherapy. Hypophysitis has a prevalence up to 8% with the combination of ipilimumab plus nivolumab. It should be considered despite a normal pituitary MRI. However, adrenalitis associated with the use of these drugs has only been reported in 2.6% and the coexistence of both entities is even rarer

Presentation: No date and time listed
LBODP015 A Pheochromocytoma Presenting With Hypertensive Emergency With A Rare Complication Of Unilateral Adrenal Hemorrhage
Authors: Arif Aneela , Siu Alfonso , Ahmed Nazaakat , Martini Alma , Shripad Namratha
Published: November 2022

Introduction

Adrenal hemorrhage is an uncommon finding in patients and is estimated to be present in 0.14-1.8% of postmortem examinations. Clinical diagnosis is challenging due to its non-specific presentation and most cases are diagnosed incidentally on imaging. Here we discuss the clinical presentation, diagnostic procedures, and outcome of this rare case.

Clinical Case

A 74-year-old Asian female presented to the ED with a sudden onset of severe epigastric pain with 9/10 intensity, radiating to her upper back while walking on the street. She was found in severe distress with a blood pressure of 214/80 mmHg, heart rate of 72 bpm, respiratory rate of 20 breaths/min, and oxygen saturation of 98% on room air. The physical exam was unremarkable. Laboratory findings were significant for elevated troponin of 1. 040 ng/ml (0. 00-0. 03 ng/ml), lactate 2.36mmol/L (0.70-2. 00 mmol/L), and lipase 481U/L (23-300 U/L). Chest X-ray was within normal limits. A CT angiogram of the chest and abdomen were negative for aortic dissection, however, a retroperitoneal hemorrhage measuring 6×8.5×6.5 cm was seen but an underlying adrenal gland mass could not be excluded. The patient was started on nitroglycerine drip for blood pressure control. Hemoglobin trend showed an acute drop, requiring 2 units of red blood cell transfusion. This raised concerns of worsening hemorrhage. Repeat imaging showed no significant change in the left adrenal hematoma, but arterial phase imaging still suggested active bleeding. Interventional radiology was consulted, and embolization of the left superior and inferior renal artery was done with stabilization of the patients hemodynamics. Laboratory work for secondary causes of hypertension was done. It showed elevated normetanephrines 1281 mcg/24hr (122 - 676 mcg/24hr) and total 24-hour urine metanephrines, 114 mcg/24hr (224-832 mcg/24 hr). The patients blood pressure was controlled and therefore asked for follow-up as an outpatient.

Conclusion

The majority of adrenal hemorrhages diagnosed are found incidentally, but initial symptoms of abdominal or loin pain are very important. Early acute findings may include tachycardia, hypotension, and severe abdominal pain. Subacute symptoms include flank tenderness, diarrhea, malaise, nausea, and vomiting. Unilateral adrenal hemorrhage may be the initial presentation of an underlying adrenal mass, cyst, coagulopathy or metastasis. Elevated cortisol and catecholamines released by an expanding hematoma are often seen along with elevated blood pressure, suggesting pheochromocytoma. The Hormonal analysis includes urine metanephrine and vanillylmandelic acid to rule out active pheochromocytoma. In our case, the patient had elevated urine metanephrines and normetanephrines suggestive of pheochromocytoma.

Presentation: No date and time listed
LBSAT65 Search For A Duplicitous Pheochromocytoma
Authors: Gupta Gunjan , Riaz Aiman , Jabiev Azad , Jamal Issra
Published: November 2022

Introduction

Pheochromocytomas are discovered during work up of adrenal incidentalomas and can be biochemically and clinically silent. We present a case of a patient who presented with typical "adrenergic spells" suggestive of pheochromocytoma but negative biochemical testing and non-confirmatory imaging findings.

Case Report

39-year-old male presented with 4 weeks history of episodes of throbbing headaches, palpitations, sweating. He was found to be hypertensive, blood pressure of 220/110 mm Hg. Losartan was initiated, but symptoms persisted. Work-up for endocrine causes of hypertension revealed normal plasma renin activity 1.123 ng/ml/hr (0.167 to 5.380) and undetectable aldosterone level <1 ng/dl (0. 0-3. 0), mildly elevated random plasma normetanephrine 270 pg/ml (0-210), normal plasma metanephrines 49 pg/ml (0-88). Low-dose dexamethasone suppression test showed unsuppressed morning cortisol of 2.1ug/dl, undetectable ACTH <5 pg/ml, dexamethasone level 486 ng/dl. 24 urinary cortisol and 2 midnight salivary cortisol samples failed to confirm the diagnosis. 24-hr urine studies showed mildly elevated 24-hr normetanephrine 735 ug/24 hr (156-729), normal 24-hr metanephrines 197 ug/L (58-276), normal 24 hr epinephrine and dopamine levels. Repeat testing revealed normal plasma metanephrines levels and mildly elevated plasma normetanephrine levels 287 pg/ml (less than twice above the upper limit of normal). Dopamine and Chromogranin A levels were undetectable. Abdominal CT showed 2 cm round soft tissue density 42HU in right adrenal gland. Left adrenal gland contained 3 nodules measuring 11, 15 and 16 mm–all with density <10HU. MRI findings for the 2.2 cm right adrenal nodule was without significant drop in signal intensity on the in and out of phase sequences appearing moderately T2 hyperintense and T1 hypointense. Differential included atypical/fat poor adenoma, pheochromocytoma, or metastasis. On GA 68 Dotatate PET-CT this 2.2cm adrenal nodule had minimal to low radiotracer uptake. Since a pheochromocytoma could not be ruled out, patient was started on alpha blockade. Preoperative genetic testing was negative for common mutations associated with pheochromocytoma/paraganglioma syndromes. Patient underwent laparoscopic right adrenalectomy. Histopathology report confirmed 2.8 cm pheochromocytoma with a low PASS (2/20) and low GAPP score.

Conclusion and Discussion

Patients with borderline nor metanephrine elevations represent a diagnostic and therapeutic dilemma. The patient presented with adrenergic paroxysms strongly suggestive of underlying pheochromocytoma. Labs and imaging were not typical for pheochromocytoma and were indeterminate. Given strong clinical suspicion for a pheochromocytoma, we decided to proceed with adrenalectomy after pre-treatment with alpha blockers. Final histopathologic report confirmed the diagnosis of pheochromocytoma.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP303 Cushing's Syndrome Due to Ectopic Adrenocorticotropic Hormone-Secreting Metastatic Neuroendocrine Tumor
Authors: Cipriani Allison , Fernandes Jyotika , Sora Nicoleta , Tofil Kathrin
Published: November 2022

Introduction

Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS), is an infrequent form of ACTH-dependent CS. EAS results from unregulated ACTH secretion by neuroendocrine tumors (NETs) of various locations resulting in severe hypercortisolism. The progression of CS is usually precipitous. To improve outcomes, it is imperative to recognize early so that treatments of cortisol-induced comorbidities and targeted treatments can be initiated.

Case Presentation

A 74-year-old female presented to an outside hospital with fatigue, bilateral lower extremity edema and intractable hypokalemia. She was later transferred to our facility, where workup of CS was initiated. She underwent a 1mgdexamethasone suppression test (DST)which resulted in an unsuppressed 8amcortisol of 34.7 ug/dL (<2 ug/dL). This was followed by a 4mgDST, again resulting in an unsuppressed 8amcortisol of25.4 ug/dL. A 24-hour urine cortisol level was collected and resulted at 2,108.9 ug/d (<45 ug/d). ACTH level was elevated at 136 pg/ml (7.2-63.3 pg/ml). CT abdomen/pelvis identified liver lesions concerning for metastatic disease. PET DOTATATE revealed multiple liver lesions and a few pulmonary nodules. Biopsy of liver lesions demonstrated strongly positive staining of synaptophysin and chromogranin confirming NET, with a weak TTF-1 positivity suggestive of pulmonary origin. Lanreotide injections were initiated for tumor control and ketoconazole for treatment of persistent hypercortisolism. Despite titration of ketoconazole, symptoms and labs showed minimal improvement. Osilodrostat was then added as a third line and examethasone was initiated in a block and replace approach. The regimen of lanreotide, osilodrostat and ketoconazole improved her24-hoururine cortisol to 15 from 2,109 ug/24hr. Subsequently patient underwent trans-arterial chemoembolization (TACE) of the liver lesions with resolution of hypercortisolism. She is currently only on Lanreotide for tumor control.

Discussion

NET with ectopic ACTH production is rare. While primary tumor location was not definitively identified, multiple lung lesions and histopathology suggested primary lung tumor with hepatic metastases. 20-40% of all NETS originate in the chest. Patient management necessitates a multidisciplinary approach not only for the diagnosis and treatment of CS but also for the specific management of neuroendocrine tumors (NET). This case highlights a rare presentation of EAS, and aggressive treatment modalities needed to treat symptoms of excess cortisol production and tumor progression.

Presentation: No date and time listed
ODP305 Differentiation Potential of Marginal Layer-Derived Adult Pituitary Stem/Progenitor Cells into Vascular Endothelial Cells and Pericytes in Mice
Authors: Higuchi Masashi , Shintani Aran
Published: November 2022

The anterior lobe (AL) of the pituitary gland consists five types of hormone-producing cells and fenestrated sinusoids (i. e., vascular endothelial cells and pericytes) that cooperate to maintain the physiological function of the gland. In addition, the population of cells located in pituitary stem/ progenitor cell niche, the marginal layer, which faces the residual lumen of the Rathke's pouch, serve to renew pituitary cells throughout life. We recently established a protocol for isolating marginal layer-derived adult pituitary stem/progenitor cells (MPSCs) by using differences in cell adhesion (1), and then showed differentiation potential into hormone-producing cells by subjecting MPSCs to three-dimensional culture. However, it is unclear whether MPSCs are capable of differentiating into all types of cells that constitute the pituitary gland. In this study, we performed DNA microarray analysis in MPSCs, which were proliferated by two-dimensional (2D) culture, for studying comprehensively gene expression profiles. Next, we investigated what kind of cells MPSCs would differentiate into. Comparing gene expression profiles of the AL and MPSCs, in MPSCs, 1776 genes were increased more than 4-fold and 1715 genes were decreased 4-fold compared to the AL (p<0. 05, respectively). The upregulated genes included pituitary stem/progenitor cell markers (ex. Sox2, Sox9, Klf4, Prrx1), niche markers (ex. Cdh1, Krt8), and cell surface antigens (ex. Cd9, Cd34, Cd44). On the other hand, most of the downregulated genes were differentiation markers (ex. Pou1f1, Gata2, Tbx19, Kdr). Next, immunofluorescent analysis revealed that most of the MPSCs were positive for CD34, the hematopoietic stem cell marker. After further 2D culture of MPSCs for 5-7days, vascular endothelial marker PECAM1-positive cells were detected by immunofluorescent analysis, but pericyte marker CSPG4-positive cell not. When TGFβ was applied to 2D culture of MPSCs, CSPG4-positive cells were detected instead of PECAM1-positive cells. Expression levels of Pecam1and Cspg4 were also examined by qPCR analysis, which corresponded to the results of immunofluorescent analysis. On the other hand, expression levels of anterior hormone genes were almost unchanged. These results have demonstrated that MPSCs could differentiate into vascular endothelial cells and pericytes. The present study suggests that pituitary stem/progenitor cells, which derived from the marginal layer, are a source of not only hormone-producing cells but also cells that constitute blood vessels. Reference: (1) Shintani and Higuchi, Stem Cell Res. 2021 Feb 2;52: 102223.

Presentation: No date and time listed
ODP315 Hypoglycemia: Neuroendocrine Tumor of the Pancreas with Liver Metastasis and Transformation to Insulinoma
Authors: Ali Basim , Chatterjee Ritodhi , Chen Rui , La Betty , Nguyen Son , Tetlay Maryam , Vasudevan Madhuri , Villareal Dennis
Published: November 2022

Background

Neuroendocrine tumors (NETs) are rare, can be found in any part of the body including the gastrointestinal tract, lung, and pancreas and have potential for metastasis.

Clinical Case

A 39-year-old male with stage IV high grade neuroendocrine tumor of the pancreas with metastasis to the liver and lymph nodes whose disease progressed despite treatment with systemic therapy who presented with severe hypoglycemia. Diagnosis and management of his hypoglycemia was difficult. For the diagnosis, patient's serum blood glucose did not always correlate with his capillary blood glucose via finger sticks, which lead to a delay in his diagnosis. Also, his diagnosis was not straight forward as he did not respond adequately to the glucagon following a serum glucose of less than 55 mg/dL (normal 70-110 mg/dL) during a diagnostic fast. Once critical labs were obtained, it took days for the results. In the interim, his hypoglycemia was managed with dextrose infusions at 10%, 20% and as high as 50%, frequent meals, and high dose steroids, yet he still had daily symptomatic hypoglycemia. A diagnosis of insulinoma was made with the following critical lab results: insulin 70.4 uIU/mL (2.6-24.9), C-peptide 12.6 ng/mL (1.1-4.4), proinsulin 407.6 pmol/L (0. 0-10. 0), beta-hydroxybutyrate <0. 050 mmol/L (0. 02-0.27), insulin antibodies <5. 0 uU/mL, negative sulfonylurea screen, insulin-growth factor-1 (IGF-1) 77 ng/mL (90-278), and insulin-growth factor binding protein three (IGF-BP3) 2133 ug/L (2571-5982). Patient was treated with both diazoxide and hepatic artery embolization to reduce tumor burden. His dose of diazoxide was titrated to maintain normoglycemia. He had mild tumor lysis syndrome that did not require dialysis. His hypoglycemia resolved within a few days of treatment and was discharged from the hospital with a continuous glucose monitor (CGM), diazoxide and hydrocortisone. It is our belief that transformation of the liver lesions to insulinoma was the cause of his hypoglycemia.

Conclusion

We recommend that patients with metastases from their neuroendocrine tumor who develop hypoglycemia be evaluated for insulinoma and if found should be treated with diazoxide and if not surgical candidates to consider hepatic artery embolization.

Presentation: No date and time listed
ODP325 Inverse Relationship Between IL-6 and Sodium Levels in Patients With COVID-19 and Other Respiratory Tract Infections
Authors: Monnerat Sophie , Atila Cihan , Bingisser Roland , Siegemund Martin , Lampart Maurin , Rüegg Marco , Zellweger Nuria , Osswald Stefan , Rentsch Katharina , Christ-Crain Mirjam , Twerenbold Raphael
Published: November 2022

Background

Hyponatremia is highly prevalent in patients with COVID-19. One of the most common causes of hyponatremia in these patients is the syndrome of inadequate antidiuresis (SIAD). Interleukin 6 (IL-6) is a key mediator of inflammation in COVID-19. We hypothesized that hyponatremia in COVID-19 is due to IL-6 mediated non-osmotic arginine vasopressin (AVP) secretion, and that the inverse association between IL-6 and plasma sodium concentration is stronger in COVID-19 compared to other respiratory infections. METHODS This is a secondary analysis of a prospective, observational, cohort study including patients with COVID-19 suspicion admitted to the Emergency Department, University Hospital of Basel, Switzerland, between March and July 2020. We included patients with PCR-confirmed COVID-19 and patients without COVID-19 but similar symptoms, further subclassified in bacterial and other viral respiratory infections. The primary objective was to investigate the association between plasma sodium levels and IL-6 levels.

Results

500 patients were included, of whom 184 (37%) with COVID-19, 92 (18%) with bacterial respiratory infections, 224 (45%) with other viral respiratory infections. Hyponatremia prevalence was higher in patients with COVID-19 compared to patients with other viral respiratory infections (28% vs 12%, p<0. 01), and similar to patients with bacterial respiratory infections (28% vs 30%, p<0.41). In all three groups, median [IQR] IL-6 levels were significantly higher in hyponatremic compared to normonatremic patients (COVID-19: 43.4 [28.4, 59.8] vs 9.2 [2.8, 32.7] pg/ml, p<0. 0001; bacterial: 122.1 [63. 0, 282. 0] vs 67.1 [24.9, 252. 0] pg/ml, p<0. 05; viral: 14.1 [6.9, 84.7] vs 4.3 [2.1, 14.4] pg/ml, p<0. 05). IL-6 levels were negatively correlated with plasma sodium levels in COVID-19, whereas the correlation in bacterial and other viral infections was weaker (COVID-19: ρ = − 0.52, p < 0. 001; bacterial: ρ = − 0.24, p = 0. 056, viral: ρ = − 0.24, p < 0. 001).

Conclusion

IL-6 levels were inversely correlated with plasma sodium levels, with a stronger correlation in patients with COVID-19 compared to patients with bacterial and other viral infections. IL-6 might stimulate AVP secretion and lead to higher rates of hyponatremia due to the syndrome of inadequate antidiuresis in these patients.

Presentation: No date and time listed
ODP335 Mutual Effects of Orexin and BMPs on Gonadotropin Expression by Mouse Gonadotrope LβT2 Cells
Authors: Hirata Shinichi , Nakayama Nanako , Soejima Yoshiaki , Iwata Nahoko , Nakano Yasuhiro , Yamamoto Koichiro , Suyama Atsuhito , Nada Takahiro , Fujisawa Satoshi , Otsuka Fumio
Published: November 2022

Orexins are neuropeptides that express primarily in the hypothalamus and are produced in two isoforms, orexin A and orexin B. There are two kinds of G protein coupled receptors, orexin type 1 (OX1R) and type 2 (OX2R) receptors. Orexin has been reported to have key roles on sleep-wake regulation and feeding behavior in the central nervous system, whereas its receptors are also expressed in peripheral tissues including the endocrine organs, and orexin affects the regulation of the endocrine system. In our previous experiments, we have revealed the impact of orexins on anterior pituitary functions. For instance, we reported that orexin A plays an inhibitory role in prolactin production through the suppression of endogenous bone morphogenetic protein (BMP) activity in rat pituitary lactotrope GH3 cells. It was also reported that orexin A enhances pro-opiomelanocortin (POMC) transcription by upregulating corticotropin-releasing hormone (CRH) receptor signaling and by downregulating BMP-Smad signaling in mouse corticotope AtT20 cells. However, the effects of orexin on the endocrine function regarding gonadotrope cells remain unclear. We have recently uncovered that core clock genes and BMPs have mutual effects on luteinizing hormone (LH) expression in a phase-dependent manner by mouse gonadotrope LβT2 cells. In the present study, we investigated the effect of orexin on pituitary gonadotropin expression using LβT2 cells, which express OX1R and OX2R, by focusing on the functional involvement of BMP system and clock genes. It was revealed that orexin A stimulation increased LHβ and FSHβ mRNA expression in a concentration-responsive manner in the absence of GnRH, and interestingly, GnRH co-treatment further upregulated LHβ mRNA expression in LβT2 cells. Regarding the interrelationships between the signalings of orexin and BMPs, it was also revealed that orexin A pretreatment enhanced the BMP receptor signaling detected as the Smad1/5/9 phosphorylation, indicating that orexin enables to upregulate the BMP actions in LβT2 cells. In our previous studies, we reported that several BMP ligands such as BMP-6, -7 and 15 expressed in LβT2 cells can promote gonadotropin transcription, in which BMP-6 regulates GnRH-stimulated LH expression by modulating the sensitivity to somatostatin analogs. Based on the present results, it was implied that endogenous orexin can be functionally involved in the underlying mechanisms of gonadotropin expression. Collectively, orexin enhances gonadotropin expression by regulating BMP signaling in gonadotrope cells. Here, we will also discuss functional involvement of clock genes in the regulatory system of gonadotropin secretion induced by orexin and BMPs.

Presentation: No date and time listed
ODP345 Pituitary Metastasis from Clear Cell Renal Cell Carcinoma
Authors: Cristiano Elizabeth , Pagadala Prathyusha , Crow Hanna
Published: November 2022

A 63-year-old female presented with a two month history of intermittent diplopia and headaches. Her past medical history was relevant for renal carcinoma status post right nephrectomy four years prior, she did not receive any adjuvant therapy. She underwent MRI brain which showed a 2.1×2. 0×1.6 cm sellar/suprasellar enhancing mass with mass effect on the optic chiasm and extending into the right cavernous sinus, consistent with pituitary macroadenoma. Visual field testing was also done showing mild bitemporal quadrantanopia. Lab evaluation did not show evidence of pituitary hormone excess or deficiency. Serum sodium was normal, IGF-1 117 ng/ml (reference range 35-201 ng/ml), GH 0.19 ng/ml (0. 01 -3.61 ng/ml), alpha subunit 0.4 ng/ml (<1.8 in postmenopausal females), ACTH 15 pg/ml (7-63 pg/ml), prolactin 20.8 ng/ml (3.3 -26.7 ng/ml), TSH 2.36 MCU/ml (0.35-5 MCU/ml) and FT4 0.9 ng/dl (0.6 -1.6 ng/dl). Neurosurgery evaluated the patient and she underwent transsphenoidal surgery. Her postoperative period was unremarkable without evidence of diabetes insipidus or secondary adrenal insufficiency. Final pathology revealed clear cell lesion/carcinoma consistent with metastatic renal cell carcinoma. Transcription marker testing was positive for SF1, consistent with a gonadotroph pituitary adenoma.

Presentation: No date and time listed
ODP361 A Case of Panhypopituitarism in the Setting of Metastatic Large Cell Neuroendocrine Carcinoma
Authors: Engle Kelly , Hupfeld Chistopher
Published: November 2022

Introduction

Metastasis to the pituitary gland is an uncommon cause of panhypopituitarism. The pituitary gland is an infrequent site overall for metastasis, with breast and lung cancer as most often found primary sites. Large cell neuroendocrine carcinoma is a rare form of lung cancer, and while metastasis to brain is not uncommon is this form of cancer, metastasis to the pituitary gland has rarely been reported.

Clinical Case

Patient was a 64 year old male with history of homelessness and substance use who had repeated hospitalizations for right sided pneumonia. Eventually bronchoscopy was performed, and tissue obtained via biopsy revealed a high-grade large cell neuroendocrine carcinoma. Initial brain imaging noted extensive brain metastases with numerous enhancing lesions in the cortex, as well as a 13×9×8 mm suprasellar mass abutting the optic chiasm. Thickening of the infundibulum was also noted. Lab testing demonstrated hypopituitarism with free thyroxine 0.52 (reference 0.93-1.7) ng/dL, thyroid-stimulating hormone 0.11 (2.7-4.2) ulU/mL, sodium 139 (135-147) mEq/L, total testosterone <0.1 (2.8-8) ng/ml, follicular-stimulating hormone 0.4 mlU/ml, lutenizing hormone <0.10 mlU/ml, prolactin 25.7 (4-15.2) ng/ml, cortisol <2 (3-12) ug/dL, and adrenocorticotropic hormone <5 (6-50) pg/mL. Diabetes insipidus was not present. Metastatic cancer was treated with dexamethasone and atezolizumab plus carboplatin and etoposide. Panhypopituitarism was treated with levothyroxine, testosterone replacement, and glucocorticoid replacement. One month later, patient represented with shortness of breath and headache. Repeat brain imaging showed an enhancing sellar mass measuring 21×15×11 mm extending superiorly to involve the pituitary stalk and hypothalamus. The extending suprasellar mass was noted to have enhancement and characteristics akin to remainder of brain metastases. The patient passed away from complications of metastatic carcinoma about three months after initial biopsy proven diagnosis.

Conclusion

This patient developed extensive brain metastases from pulmonary large cell neuroendocrine carcinoma, which included a metastasis in the sella resulting in panhypopituitarism. While pituitary metastases from primary cancer are very rare events (with lung and breast carcinoma the most frequent sources), only a single case report exists describing a pituitary metastasis from a large cell neuroendocrine carcinoma. This case is also an important reminder to consider the pretreatment anatomy of the sella in patients subsequently exposed to immunomodulating chemotherapy, as a mass lesion seen during treatment may represent a preexisting metastasis rather than treatment-induced hypophysitis.

Presentation: No date and time listed