bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-LB302 Evaluating the Impact of a New Intake Process for British Columbia Children’s Hospital Gender Clinic
Authors: Fox Danya A , Tan Mabel , Lalani Robyn , Atkinson Louanna , Hursh Brenden , Metzger Daniel L
Published: May 2020

Our pediatric Gender Clinic is receiving a growing number of referrals, yet continues to operate with limited resources. To try to address this issue, a new clinical pathway was developed in 2017, which included an inter-professional assessment clinic run by nurses and social workers as the entry point for new referrals (known as ‘intake appointments’). These visits help to identify those youth who require urgent access to care (i.e. for imminent puberty), wayfinding to community supports and providers who can complete GnRH analog and hormone-readiness assessments, and information about potential medical interventions. The goals of this study were to (1) map out current processes, (2) evaluate wait times for patients referred in 2015-2016 (pre-intake) and 2018-2019 (post-intake), and (3) describe referral patterns and outcomes. Patients referred in 2017 were excluded, as this was a transitional year. In 2015-2016, 222 referrals were received, compared to 407 referrals in 2018-2019. Of the post-intake cohort, to date, 202/407 referrals have led to an intake appointment, of which 45 were via telehealth (a service not previously offered to families). Average wait time to physician visit was 171 days (range 10-1271; IQR 69-208) for patients in the pre-intake cohort, while the average wait time to intake appointment was 200 days (range 9-569, IQR 114-242) in the post-intake cohort. Wait time to physician visits cannot be assessed yet, due to the number of pending referrals. Fifty-four referrals were cancelled in the pre-intake, and 73 in the post-intake cohort. In both groups, the primary reason for cancellation was redirection by our team to other services (32% in both groups), and the second most common reason was cancellation by the family/no show to appointment (26% and 22% in the pre- and post-intake cohorts, respectively). Staffing resources and number of clinics per week have changed over the years, limiting our ability to attribute changes directly to the new clinical pathway. Moreover, most hormone-readiness assessments are completed by community providers. Therefore, wait times to physician visits partly reflect difficulty in accessing these community resources. However, using our new model of care, we have engaged with hundreds of patients and families within a similar time frame to the 2015-2016 cohort, despite an almost doubling of the number of referrals received by our clinic. Although these initial visits do not allow for initiation of medical therapy, they are a means to support patients and families through their gender journey. Moreover, the intake appointments have promoted inter-professional collaborative care, which is particularly beneficial in the face of limited resources. Thus, we believe this new model of care has led to improved quality of care for patients accessing our Gender Clinic.
MON-LB109 Transcutaneous Magnetic Stimulation: A Novel Treatment of Diabetic Peripheral Neuropathy
Authors: Satyarengga Medha , Munir Kashif M
Published: May 2020

Objective: Transcutaneous Magnetic Stimulation (TCMS) is reported to be an effective treatment in multiple neurologic conditions such as migraine headaches, lower back pain, and post-traumatic peripheral neuropathic pain1-3. The efficacy and safety of TCMS for diabetic peripheral neuropathy is not known. We evaluated whether TCMS is effective and safe in patients with diabetic peripheral neuropathy. Method: Eight patients with a previous diagnosis of diabetic peripheral neuropathy and baseline numerical pain-rating scale (NPRS) of 5 or greater in both feet were enrolled. NPRS scale was set from 0 to 10, 0 represents no pain and 10 representing the most severe pain. Each patient was treated with a single session of TCMS applied first on the plantar then the dorsal surface of both feet. Magnetic pulses (1.2 Tesla) were delivered every 6 seconds for 5 minutes in each foot on the plantar and dorsal surfaces, respectively. NPRS was repeated post-treatment over the course of 28-days follow-up period. Results: The mean baseline NPRS was 5.8 (± 1.0). Immediately post-treatment, mean NPRS improved to 1.3 (± 1.9), a 77.7 (± 36.5) % decrease. Mean NPRS at 7 and 28 days of follow-up was 2.9 (± 2.8) and 4.1 (± 3.3), respectively. These represent a 53.2(± 42.4) % improvement at 7 days and 30.5(±52.4) % improvement at 28 days of follow-up compared to baseline NPRS. None of the patients reported significant discomfort during the treatment, and no major side effects were observed during the study period. Conclusion: In this pilot study of patients with diabetic peripheral neuropathy, TCMS appears to be a safe and effective alternative in providing temporary pain relief. Longer and more frequent treatment sessions need to be explored to see if these can increase the effective duration.

References: 1. Barker AT, Shields K. Transcranial Magnetic Stimulation: Basic Principles and Clinical Applications in Migraine. Headache. 2017 Mar;57(3):517-524. 2. Leung A, Fallah A, Shukla S. Transcutaneous Magnetic Stimulation (tMS) in Alleviating Post-Traumatic Peripheral Neuropathic Pain States: A Case Series. Pain Medicine. 2014 Jul; 15(7): 1196-1199. 3. Lim YH, Song JM, Choi EH, Lee JW. Effects of Repetitive Peripheral Magnetic Stimulation on Patients with Acute Low Back Pain: A Pilot Study. Ann Rehabil Med. 2018 Apr; 42(2): 229-238.
SUN-LB73 Is It Possible to Optimize Resources in Bone-Alkaline Phosphatase Medical Request?
Authors: Sequera Ana M , Ruibal Gabriela Fernanda , Chavarria Eleonora Nuñez , Fideleff Gabriel , Iparraguirre María Jose , Farelo Hilda Ines
Published: May 2020

INTRODUCTION: Bone metabolism assessment includes total alkaline phosphatase (ALP) and more specifically the bone-alkaline phosphatase (BAP) as markers of bone formation. Its measurement is important for diagnosis and in bone pathology treatment following-up. In our setting, a ten-fold price for BAP has raised the necesity to review in how many cases its request has been justified. AIM: Establish through an appropiate statistical analysis, cut-off values of ALP that could guarantee to perform BAP measurements. Its analysis would allow us to make a demand adequacy. MATERIALS AND METHODS: A retrospective study was carried out on laboratory analysis orders of 405 adult women. We separate them into the following groups: (G1): 48 premenopausal womens (pre) and 357 post menopausal women (pos): (G2)133 <60 years-old, (G3)135: 60-69 years-old and (G4)89: >70 years-old. All patients had measurements of both analytes; ALP (colorimetric method, Roche Cobas, Reference value (RefV)=40-130 UI/L) and BAP (QLIA, Liaison Diasorin, RefV pre=3-19 ug/mL, pos=6-26 ug/mL). Statistic analysis: ROC-Plot to define cut-off value (we define as true positive BAP values over RefV). Kruskal Wallis, Dunn test to compare all the groups. RESULTS: (median and range): ALP(UI/L) G1: 81(38-265) G2: 88(47-211)*, G3: 85(39-213) y G4: 80(40-138) (*p<0.05 G2vsG4). BAP (ug/L) G1: 13.6(5.1-106), G2: 14.3(3.5-61.5)*, G3: 13.9(2.9-52.5) and G4: 11.6(2.0-29.6), (*p<0.05 G2vsG4). We observe that 73% of G1, 93.5% of G2, 92.6% of G3, 97.7% of G4 has showed normal values. The ROC plot analysis showed the best cut-off for ALP in G1=87 (S=92%,Sp=85%,AUC=0.955). If, using this cut off we had processed 18 BAP which 6 patients would have been normal (33.4%). In G2=127 (S=100%, Sp=97.6%, AUC=0.996) using this cut off we had processed 13 BAP, which 4 patients would have been normal (30.8%). Meanwhile in G3=102(S=100%, Sp=85.6%, AUC=0.97) we had processed 30 BAP and G4=120 (S=100%, Sp=96.5%, AUC=0.966) we had processed only 6 BAP. CONCLUSIONS: Application of the calculated cut-off allowed us to investigate 97% of the pathological BAPs. The measurement of ALP first, would guarantee to process only 17% of the requested BAPs. This suggestion would result in a significant saving of our resources, maintaining the quality of care. It is necessary to apply cut-off according to age to justify the BAP assesment. Physicians must define the appropriate exceptions.
MON-LB111 Evaluation of Mixed Meal Test on the Diagnosis of Hyperinsulinemic Hypoglycemia After Bariatric Surgery
Authors: Asato Marilia Tomiyoshi , Azuaga Carolina Croce , Scalissi Nilza , Medeiros Monica De Aguiar , Salles Joao Eduardo , Parente Erika Bezerra , Napoli Thiago Fraga , Cury Adriano Namo , Scalco Renata Da Cunha , Franco Pedro Campos , Umeda Luciana Mela , Fukunaga Erika , Fernandez Monica , Lima Jose Viana
Published: May 2020

Background and aims: The physiopathology of hyperinsulinemic hypoglycemia (HH) after gastric bypass (GB) is not well understood, although it is a common adverse event after this procedure. The fast absorption of glucose after a meal, the high glucose variability, the increase in glucagon peptide 1 secretion or the hyperplasia of beta cell have been postulated as possible hypothesis. Mixed Meal Tolerance test (MMT) is used in clinical practice during HH investigation, but there is no consensus for HH diagnosis after bariatric surgery. In this scenario, we evaluated the MMT for the diagnosis of HH after GB. Material and Methods: This is an observational cross sectional descriptive study of adult (> 18 years) patients submitted to a MMT after GB from July 2016 to October 2019. 51 patients were divided in two groups: Group 1, with a history of predominantly neuroglycopenic symptoms (n = 24) and Group 2 (control) without symptoms of postprandial hypoglycemia (n= 27). The patients had no diagnosis of diabetes and weren’t using any hypoglycemic drugs. All subjects performed the MMT composed by a typical Brazilian breakfast with the following composition: 494 Kcal with 63.4% carb, 27.5% fat and 9.1% protein, in the morning after 8h fasting and blood samples (glucose, insulin, C peptide) were collected before the meal and every 30 minutes for 5 h after it. A positive test was considered if patient presents Whipple’s Triad: HH (plasma glucose was ≤ 55mg/dL with insulinemia ≥ 3 µU/mL, C peptide ≥ 0.6 ng/mL) and hypoglycemic symptoms. Statistical analysis were done using SPSS 13.0 version. Results:​ From 51 patients, 46 were female, mean age was 46.8 ± 9.2 years. 15 of the 24 patients with predominantly neuroglycopenic symptoms (Group 1) developed laboratory HH, but only 9 (37.5%) presented the Whipple’s Triad. Only one subject of the control group presented HH. All patients with neuroglycopenic symptoms during the test presented HH. From those with HH, 43% presented hypoglycemia at 90’, 50% at 120’ and 6.2% at 150’ during MMT. There were no difference between the two groups when compared the amount of weight loss neither the period of follow up after GB. Conclusion: Since all patients with neuroglycopenic symptoms during the test presented HH it might be a useful tool to exclude HH in patients with hypoglycemic symptoms after GB. This study suggests that the BMT doesn’t need to be 5h, since all of hypoglycemic episodes occur until 150’.
SUN-LB3 Relationship Between BMI and PCOS Symptoms Among Flo App Users in the United States
Authors: Negris Olivia , Brown Dannielle , Galic Isabel , Zhaunova Liudmila , Klepchukova Anna , Jain Tarun
Published: May 2020

Polycystic ovary syndrome (PCOS) is known to affect 6%-12% of women of reproductive age in the United States. PCOS is a heterogeneous condition associated with menstrual cycle irregularity and androgen excess. Though many women with PCOS have a BMI classified as overweight or obese, information is limited on how specific symptoms and BMI mediate PCOS diagnoses in the general population. A questionnaire on PCOS-related symptoms and previous PCOS diagnosis was available to Flo users during one month (2019). Women aged 18-44 years seeking to track their cycle or to conceive, who were not pregnant, on active contraception or in stabilization mode after pregnancy, and had Flo app running in English met the study inclusion criteria. Participant characteristics including age and BMI were also collected from Flo app users during the sign-up process. All users in the study had agreed to the use of their de-identified and aggregated data for research purposes. The differences in clinical manifestation of PCOS symptoms between BMI groups were analyzed. Of US users with BMI data in the whole cohort, 8,808 women reported having physician-diagnosed PCOS, 5,551 women reported not having a PCOS diagnosis, and 58,478 reported that they had not been checked for PCOS. Of women with PCOS, 19.5% were normal weight (BMI 18.5-24.9), 19.7% were overweight (BMI 25.0-29.9), 20.4% were obese (30.0-34.9), 17.8% were severly obese (BMI 35.0-39.9), and 21.0% were morbidly obese (BMI 40+). The most common symptoms among PCOS positive women were bloating (38.7%), hirsutism (38.2%), and irregular cycle (26.0%). A direct relationship exists between BMI and having PCOS, as the percentage of PCOS in obese, severely obese, and morbidly obese BMI groups was higher (1.37, 1.87, and 2.12 times, respectively) than in the whole cohort. Similarly, among women who report acne, skin hyperpigmentation, bloating, hirsutism, heavy menses, baldness, family history of PCOS, high cholesterol, irregular cycle, and inability to conceive for > 1 year, there is a direct relationship between BMI and the percentage of women with PCOS. Moreover, when identifying symptoms and findings serving as strong predictors of a positive PCOS diagnosis, hirsutism, high glucose, and high levels of both cholesterol and glucose were the top symptoms and findings for women with BMI 18.5-34.9. Hirsutism, high glucose, and inability to conceive for > 1 year were the strongest predictors of PCOS for women with BMI 35+. Among all users with hirsutism, the percentage of women with PCOS increased 3.65 times compared to the whole cohort, making it the strongest predictor of PCOS. Understanding BMI patterns as they relate to PCOS symptoms allows for better understanding the pathophysiology of PCOS. Among women with PCOS in the United States, changes in BMI are associated with variations in the many symptoms of PCOS.
SUN-LB23 Translational Feasibility of Steroidogenic Factor-1 Antagonists as a Novel Targeted Therapy for Adrenocortical Cancer
Authors: Crowe Paul D , Tao Haiyan , Fox Ray , Raheja Neil , Thacher Scott McNear
Published: May 2020

Adrenocortical carcinoma (ACC) is an aggressive cancer with devastating outcomes. ACC is usually locally advanced or metastatic at diagnosis and, despite tumor resection plus chemotherapy, has a high rate of recurrence. The 5-year survival rate among metastatic ACC patients is less than 15%. ACC responds poorly to the single FDA-approved drug, mitotane, which is non-specifically adrenolytic and highly toxic. Other chemotherapy regimens tested have been unsuccessful in improving overall survival. Steroidogenic factor-1 (SF-1 or NR5A1) is an orphan nuclear receptor essential for growth and development of the adrenal gland and is the major, active transcription factor in ACC (1,2). To address the need for a targeted therapy in ACC, we have identified potent small molecule SF-1 antagonists that block SF-1 transcriptional activity through the ligand-binding domain (IC50 = 15-20 nM in a CHO cell reporter assay). In short-term dissociated cell cultures established from SJ-ACC3 (3), a pediatric ACC patient-derived tumor xenograft (PDX), the SF-1 antagonists OR-907S and OR-070 blocked DNA synthesis as measured by inhibition of EdU incorporation in SF-1+ cells (IC50 = 500-600 nM, >80% efficacy at 10 μM) whereas OR-907R, the 100-fold less potent enantiomer of OR-907S, is nearly inactive. Because the SF-1 antagonist sensitivity of the dissociated SJ-ACC3 cells declines markedly with repeated passage of the PDX in immunocompromised (C.B-17 SCID) mice, we have utilized an alternative model system for evaluating tumor target engagement and growth inhibition: the rat Leydig tumor cell line (R2C), which is growth-inhibited by the SF-1 antagonists OR-907S and OR-070 in vitro (IC50 = 60-100 nM) and as a xenograft in immunocompromised mice (CD-1 nude). The SF-1-responsive gene signature identified by RNAseq in R2C cell cultures by comparison of OR-907S and OR-907R was replicated by OR-070 and other orally-bioavailable lead antagonists in R2C xenografts following 3 days of dosing, indicating engagement of SF-1 by these compounds. Significantly, R2C tumors were growth-inhibited following daily oral dosing for 4 weeks with OR-070 (10-30 mg/kg). These findings suggest that SF-1 antagonists could be a targeted therapy for ACC. OR-070 has >30% oral bioavailability in rat and dog, indicating that this structural class of SF-1 antagonists has potential for clinical development.References: (1) Mohan, et al., Curr. Opin. Endocrinol. Metab. Res., 2019; 8:72; (2) Corces, et al., Science, 2018; 362:eaav1898; (3) Pinto, et al., Clin. Cancer. Res., 2013; 19:1740.
SAT-LB71 Is Late Diagnosis of Postsurgical Hypoparathyroidism the Rule, Not the Exception?
Authors: Fahrleitner-Pammer Astrid , Kern Martin , Scherkl Mario , Mader Julia K , Tmava-Berisha Adelina , Amrein Karin
Published: May 2020

Background The most prevalent etiology for hypoparathyroidism is postsurgical. In the literature, years or even decades of delay for the diagnosis have been reported, with sometimes extremely low calcium levels and dramatic clinical manifestations including heart failure and seizures requiring treatment in the emergency room or intensive care unit. Often,,typical“ hypocalcemic symptoms are absent in these patients.

Methods In this retrospective Austrian single-center cohort at the Medical University of Graz, we identified patients with low parathyroid hormone concentration (<25 pg/ml) and hypocalcemia using the hospital information system during 2004 and 2014. The time between neck surgery and the first reported diagnosis of postsurgical hypoparathyroidism and/or available low calcium levels was collected.

Results We identified a total of 119 patients treated between 2004 and 2014 at our institution. Most patients were women (78%), the average age was 61 ± 17 years. 12% had nonsurgical etiologies (ie. AIRE or 22q11 mutations), and 88% had postsurgical hypoparathyroidism (n=105). The median time between surgery and diagnosis of hypoparathyroidism was 5.5 years (range 0 -67 years). Only a third of all patients was diagnosed within the first year after surgery. Paresthesia and tetany were present in most patients at diagnosis, but in extreme hypocalcemia, other,,non-classic“ symptoms including severe heart failure, dyspnea and seizures appeared to be more prevalent.

Conclusion Our data suggest that diagnosis of permanent postoperative hypoparathyroidism is often delayed, as in our Austrian retrospective cohort the time lag between surgery and diagnosis or onset of hypoparathyroidism was often years or even decades. Whether this is truly a delayed occurrence of the disease or a delayed diagnosis of a condition already present for years or a combination of both can not be answered with our data, but certainly merits more intense research in the future.
MON-LB71 Adult Hypophosphatasia and Postmenopausal Osteoporosis: A Challenging Case
Authors: Abramof-Ness Rosane , Eizenberg Yoav , Sapir Mzia , Brill Gherta , Herzberg Dana
Published: May 2020

Introduction: Hypophosphatasia (HPP) is a rare disease that cause osteomalacia and premature tooth loss due to abnormal bone mineralization. The clinical presentation ranges from severe neonatal and infantile HPP with a high morbidity and mortalilty to mild Adult HPP. The ranging spectrum is possibly due to autosomal recessive versus autosomal dominant missense mutations at the gene that encodes TNSALP. The hallmark of the disease is a low serum total alkaline phosphatase level (ALP). It is important to diagnose adult HPP particularly to refrain from treating with bone antiresorptive medications. Low levels of alkaline phosphatase generally are undectected in the adult population even in patients with osteoporosis and fractures. We describe a case of a woman with postmenopausal osteoporosis without fractures diagnosed with adult HPP. The clinical course and management is described below. Case Description: A 62 y.o. women was referred for evaluation and treatment of osteoporosis. She had no fractures, including during childhood, no history of premature deciduous teeth loss, dental problems or nephrolithiasis. No family history of osteoporosis or fractures. Menopause at age 48 without hormone replacement therapy. Evaluation for secondary causes of osteoporosis was normal including serum TSH, calcium, phosphate, PTH, 24 hours urinary calcium and vitamin D-25. ALP ranged from 33-40 U/L (nl 37-126) before therapy. She was treated with raloxifene for 2 years. Therapy was switched to alendronate due to a decrease in bone density. She subsequently treated with alendronate for 5 years until 5/2012. Due to a decrease in bone density alendronate therapy was reinstituted between Jan 2013-Jan 2016 but in spite of therapy and a CTX level of 333 pg/ml bone density in the spine decreased significantly. In view of the low ALP and decreasing bone density while on bisphosphonate and a high B6 level (B6= 37 nl: -27) a genetic test for HPP and a compound heterozygote mutation in ALPL gene was detected. Her daughter was also found to have low ALP and carries the same mutation. Bone density has been stable since bisphosphonate therapy was stopped (spine T -3.2, LT femoral neck T -2.9) CTX 360 pg/ml. Recently therapy with raloxifene was initiated in view of the low bone density and high risk of fractures. Conclusion: The proper diagnosis and management of patients with adult HPP is challenging because the diagnosis may be missed in patients with borderline low ALP and on the other hand the proper managent of osteoporosis in these patients is not known.
SUN-LB97 Targeted Metabolomics as a Screening Tool in the Diagnosis of Endocrine Hypertension
Authors: Erlic Zoran , Amar Laurence , Larsen Casper K , Tetti Martina , Pamporaki Christina , Prehn Cornelia , Adamski Jerzy , Prejbisz Aleksander , Boscaro Marco , Eisenhofer Graeme , Mulatero Paolo , Assié Guillaume , Blanchard Anne , Zennaro Maria-Christina , Beuschlein Felix
Published: May 2020

Arterial hypertension [HT] is a global epidemic that requires adequate treatment to reduce cardiovascular morbidity and mortality. Secondary causes of HT and specifically endocrine hypertension [EHT] (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL] and Cushing syndrome [CS]) can potentially be cured by surgery or treated by targeted medication. However, diagnosis of EHT requires expertise in test selection and interpretation of test results. The availability of experts outnumbers its demand. Thus, preselecting tools are necessary to identify patients who require further referral to an expert. Since targeted metabolomics [TM] is a new method showing promising results in profiling cardiovascular diseases and endocrine conditions associated with HT, we tested the ability of TM in discriminating primary hypertension [PHT] from EHT cases. The study included 282 adult patients (52% female; mean age 49 years) from the European multicentre consortium ENSAT-HT (www.ensat-ht.eu). Of these, 59 were diagnosed with PHT and 223 with EHT (40 CS, 107 PA and 76 PPGL). TM was performed on stored blood samples with a mass spectrometry based approach using the AbsoluteIDQTM p180 Kit (BIOCRATES Life Sciences, Austria). In total, 188 metabolites were determined, of which 155 were eligible for statistical analyses according to established selection criteria. To identify relevant discriminating metabolites, a series of univariate and multivariate analyses were applied. Since the distribution of the patients between the clinical entities was different according to sex (p<0.001) and age (p=0.001), analyses were also performed separately for each sex and age group (cut-off 50 years). Thereby, we identified 4 common metabolites (C18:1, C18:2, spermidine, ornithine) from the comparison of PHT with each endocrine hypertension subgroup (CS, PA, PPGL) separately. The ROC curve for discrimination between PHT and EHT built upon these 4 metabolites had an area under the curve (AUC) of 0.79 (95%CI 0.73-0.85). In the comparison of PHT and EHT as a common group 38 metabolites were identified. Using the top 15 metabolites from the latter comparison (C3-DC, C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC20:4, PCaaC38:6, PCaaC40:6, PCaaC42:1) the AUC was 0.86 (95%CI 0.81-0.91). We conclude that TM is associated with distinct metabolic pattern in PHT and EHT and is a promising pre-screening tool for identifying EHT patients.
SAT-LB127 Regulation of ENaC by Exosomal Lipids in the Diabetic Kidney
Authors: Tuna Kubra M , Ramsay Hunter G , Nouri Mohammad-Zaman , Denslow Nancy D , Alli Abdel A
Published: May 2020

Effective treatment of hypertension (HTN) in patients with diabetes may help to significantly reduce the risk of those patients developing additional complications including vascular disease and diabetic nephropathy. Blockers of the renin-angiotensin system including angiotensin converting enzyme inhibitors and angiotensin receptor blockers are not always effective in treating HTN in diabetic patients. Therefore, the aim of this study was to use an animal model of type 2 diabetes to investigate a novel mechanism of diabetes associated HTN involving exosomal lipids in the upregulation of epithelial sodium channel (ENaC) activity in the kidney. We performed metabolic cages studies using male and female hypertensive (salt-loaded induced) diabetic db/db mice and healthy age-matched wild-type control mice in order to isolate and characterize urinary exosomes from each group by nanoparticle tracking analysis, Western blotting, and transmission electron microscopy. Our mass spectrometry based lipidomic studies identified key lipids that were differentially expressed in the kidney derived exosomes from the hypertensive diabetic mice compared to control mice. Sphingomyelin quantification assays showed total sphingomyelin content was elevated in the exosomes from the hypertensive diabetic mice compared to the control group. Single channel patch clamp studies showed urinary exosomes enriched in sphingomyelins from hypertensive diabetic mice compared to controls increase ENaC activity (at the level of channel density and open probability) in cultured distal tubule renal epithelial cells. Moreover, exogenous application of sphinomyelin-6 to cultured mouse cortical collecting duct (mpkCCD) cells resulted in an increase in amiloride-sensitive transepithelial current. Taken together, our data show various lipids are enriched in exosomes from hypertensive diabetic mice compared to controls and these exosomes positively regulate ENaC activity in distal tubule and collecting duct cells.
MON-LB44 Cushing’s Syndrome and Illegal Receptors
Authors: Poku Caroline , Eldin Randa Sharag , Mohamed Abubakr Hassab Elrasoul Babiker , Sobia Sadiq
Published: May 2020

Case presentation: A 48-year-old female with HTN presented to the endocrinology clinic for the evaluation of incidental bilateral adrenal masses noted on chest CT for dyspnea workup. At the time of the presentation, she reported generalized fatigue, significant weight gain in the past year and shortness of breath. Her physical exam was remarkable for central obesity. Lab work showed elevated cortisol after 1 mg dexamethasone suppression test x 2 and elevated 24- hour urine cortisol. Plasma free metanephrine levels and aldosterone/ renin ratio were normal. MRI abdomen was done and showed bilateral adrenal masses (left: 5.6 cm, right: 3.2 cm). Patient was diagnosed with Cushing’s syndrome secondary to primary bilateral adrenal hyperplasia and was referred to endocrine surgery who recommended unilateral adrenalectomy. The decision was made to remove the larger left side adrenal mass. On post-operative day one her am cortisol decreased to 2.1 and she was started on hydrocortisone 20 mg in the morning and 10 mg in the evening.

Discussion: Primary bilateral adrenal hyperplasia is a rare cause (< 2 %) of endogenous Cushing’s syndrome, usually occurs in a bimodal age distribution, in childhood and in the fifth- sixth decades. Presentation is variable with most patients having no symptoms or subclinical Cushing’s. The theory is the larger nodule size corelates with the higher cortisol production. Studies have shown between 60-70% of cases has aberrant ectopic hormone receptors which leads to increased cortisol production not only from ACTH but also from other ligands such as serotonin and vasopressin. Aberrant receptor testing examines whether cortisol or other steroid production increases in response to either physiologic or pharmacologic stimulus. Multiple genetic mutations have been associated, the most frequent is mutations in the Armadillo repeat- containing 5 gene identified in 2013. Treatment can either be medical or surgical. Medical therapy can be initiated if testing for an aberrant receptor is positive. In recent years there has been a trend towards doing unilateral adrenalectomy instead of bilateral, with initial remission of symptoms reported in about 84% of cases after unilateral adrenalectomy although there is a small risk of recurrence. Post operatively after unilateral adrenalectomy patients should be monitored for adrenal insufficiency. Our patient declined aberrant receptor testing and opted for surgery and is doing well post operatively.

Conclusion: Primary bilateral adrenal hyperplasia is a rare cause of endogenous Cushing’s syndrome which can be treated either medically or surgically.
SAT-LB72 Design of the PaTH Forward Phase 2 Trial of TransCon PTH, a Long-Acting PTH, in Patients With Hypoparathyroidism
Authors: Khan Aliya Aziz , Rejnmark Lars , Schwarz Peter E , Vokes Tamara J , Clarke Bart Lyman , Rubin Mishaela Ruth , Hofbauer Lorenz C , Erikson Erik , Palermo Andrea , Pagotto Uberto , Marcocci Claudio , Ahmed Intekhab , Mourya Sanchita , Markova Denka , Karpf David B
Published: May 2020

Background:

Hypoparathyroidism (HP) is caused by a deficiency in parathyroid hormone (PTH), which leads to hypocalcemia and hyperphosphatemia. Standard of care (SoC), i.e. large doses of calcium (Ca) and active vitamin D, worsens hypercalciuria and increases the serum Ca (sCa) x serum phosphate (sP) product. Studies have shown that continuous subcutaneous infusion of PTH(1-34) normalizes sCa, sP, serum magnesium, urine Ca (uCa) and bone turnover better than SoC or once- or twice-daily injections of PTH in HP patients. TransCon PTH, an investigational long-acting prodrug of PTH (1-34) transiently bound to an inert carrier via a linker, is under development as a potential once-daily replacement therapy for HP. Under physiological conditions, linker auto-cleavage occurs, releasing active PTH at a controlled rate with ~60 hour half-life. Phase 1 trial results demonstrated that once-daily TransCon PTH provided a flat, infusion like profile within the normal range of PTH 24 hours per day, increasing sCa while controlling uCa and decreasing sP, with no evidence of bone anabolic activity.

Phase 2 Design:

PaTH Forward is a global phase 2 trial evaluating the safety, tolerability, and efficacy of TransCon PTH in adult subjects with HP. Patients with HP treated with SoC were randomized at sites worldwide to daily TransCon PTH 15, 18 or 21 µg PTH(1-34) or daily blinded placebo via pen-injector for 4 weeks. The primary composite endpoint requires 1) normal albumin-adjusted sCa, and 2) normal Fractional Excretion of Ca (or ≥50% decrease from baseline), and 3) not taking active D, and 4) taking ≤1000 mg/d of Ca. After four weeks, all subjects enter an open-label extension period with the opportunity to receive TransCon PTH individually optimized to doses of 6 to 30 µg daily to evaluate long-term safety and efficacy. Other endpoints include the impact of treatment on patient experience, CaxP product, bone turnover markers, and bone mass by DXA and TBS to confirm the lack of anabolic effect.

Preliminary Results:

Approximately 55 subjects are expected to be randomized and dosed. Preliminary diary data on the initial 8 subjects completing 4 weeks of follow-up in the extension trial shows that all have discontinued SoC. Additional information will be presented at ENDO 2020. The Phase 2 trial is designed to inform the starting dose for a global pivotal phase 3 trial and evaluate TransCon PTH as a “true” PTH replacement therapy.
MON-LB106 The Effect of the Ketogenic Diet on Aldosterone Over 6 Weeks
Authors: Belany Paul A , Zhao Songzhu , Kluwe Bjoern , Kackley Madison , Buga Alex , Kline David , Brock Guy , Volek Jeff , Joseph Joshua
Published: May 2020

Introduction: A ketogenic diet improves type 2 diabetes, metabolic syndrome, and cardiovascular disease. Weight loss studies using caloric reduction have demonstrated a decrease in aldosterone, but there is limited data on the effect of a ketogenic diet on aldosterone. Thus, we evaluated the impact of a ketogenic diet on aldosterone in overweight or obese individuals over 6 weeks. Methods: This 3-arm prospective controlled feeding study evaluated aldosterone and renin concentrations over 6 weeks on a hypocaloric (25% energy restricted) ketogenic diet + placebo (KD+PL), ketogenic diet + ketone salt supplement (KD+KS), and a low-fat diet (LFD). Sodium intake consisted of 6100 mg, 2300 mg, and 2000 mg for the KD+KS, KD+PL, and LFD groups, respectively. Both ketogenic diets provided 40 grams(g) day of carbohydrates, 1.5 g/kg reference weight of protein and remaining calories provided as fat. The LFD provided 25% total fat, 1.5 g/kg reference weight of protein, and 100g of carbohydrates. Serum aldosterone was drawn fasting in upright position at 0, 2, 4, and 6 weeks. Scatter plots were used to explore the residual and predicted associations between aldosterone with other measures after accounting for time and group effect.Results: Twenty-four participants in the ketogenic diet groups were matched for age and body mass index, then randomized to either the KD+PL or KD+KS group. A separate group of 12 matched participants were specifically recruited for the LFD group. The median age was 33 years. Weight decreased 6, 8, and 7 kg on average in the KD+KS, KD+PL, and LFD groups, respectively, over 6 weeks (p<0.05 for all). Systolic blood pressure (SBP) improved from 117 and 115 mmHg in the KD+KS and KD+PL groups to 110 mmHg over 6 weeks while the baseline mean SBP 118 in the LF group did not change. Baseline mean aldosterone of 13.6 and 13.6 ng/dL in the KD+KS and KD+PL groups increased to 33.3 and 27.3 ng/dL over 6 weeks (p<0.001). Baseline mean aldosterone of 8 ng/dL in the LF group non-significantly changed to 11.5 ng/dL over 6 weeks (p>0.05). Using predicted value associations, increases in ketones were positively associated with higher aldosterone (R2=0.86; p<0.001). Conclusion: Participants on a ketogenic diet had significantly elevated aldosterone levels throughout the study while participants on low fat diet had little change. Unexpectedly, aldosterone was significantly higher in the high sodium vs. low sodium ketogenic diet. There was a significant association between ketones and aldosterone suggesting that ketones may play a stimulatory role on aldosterone synthesis or secretion.
MON-LB70 The Association of Paget’s Disease With Inclusion Body Myositis and Fronto Temporal Dementia (IBMFTD)
Authors: Miller Clare , Mcquaid Siobhan E
Published: May 2020

Background: Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is a rare, autosomal dominant condition, characterized by adult-onset muscle weakness, early-onset PDB, and premature frontotemporal dementia. Paget’s disease is a chronic disorder of bone resulting in increased bone resorption, followed by a disorganized and excessive formation of bone.

Clinical Case: A 43 year old gentleman was referred to neurology services with foot drop, limb weakness and cognitive impairment. Following a prolonged period of diagnostic evaluation a mutation in valosin-containing protein (VCP) gene was uncovered IBMPFD has a variable phenotype which may include PDB. This gentleman denied bony pain and had an alkaline phosphatase within reference range. Plain film radiographs at multiple sights demonstrated no signs of PDB. An MRI whole body was performed which reported coarse trabecular markings in L2 vertebral body and multilevel degenerative changes with bridging osteophytes in the lumbar spine consistent with PDB.

At initial review in endocrine clinic, he denied fractures or bone pain. He had no signs of increased cardiac output or cranial nerve deficits. A radionuclide bone scan identified intense radiopharmaceutical accumulation in L2 vertebral body consistent with MRI findings and also curvilinear increased activity in the left occipital bone and low-grade activity in the left hip, thus confirming polyostotic Paget’s disease.

He received a 5mg IV infusion of zolendronate, side effects of which included myalgia, pyrexia and lethargy.

Six months following the zoledronate infusion a repeat bone scan demonstrated that the extent of uptake at affected sites had decreased significantly.

He subsequently fractured his left femur following a mechanical fall. PDB can affect up to 50% of patients with IBMFTD. PDB can lead to complications such as bone pain, localized pain and deformity of the long bones, pathologic fractures and deafness. This case highlights the association of Paget’s disease with IBMFTD and as it can be asymptomatic, as in our case, radiological imaging is required for diagnosis. It also reminds us that Paget’s disease can be due to genetic causes. Understanding the role of VCP in the cell cycle may help in further understanding bone physiology.
MON-LB45 Posterior Hypothalamic Involvement on Pre-Operative Magnetic Resonance Imaging as a Predictor for Hypothalamic Obesity in Craniopharyngiomas
Authors: Rachmasari Kharisa N , Strauss Sara B , Phillips C Douglas , Lantos Joshua , An Anjile , Schwartz Theodore H , Dobri Georgiana A
Published: May 2020

Craniopharyngioma (CP) is a rare embryonic tumor of the sellar and parasellar region with benign histology (World Health Organization grade I) thought to arise from embryonic remnants of Rathke’s pouch. Despite its high survival rates, this tumor can lead to severe morbidity secondary to destruction of adjacent structures. Hypothalamus (HT) is a brain region that has a central role in regulating body weight through a complex mechanism involving central and peripheral signaling pathways. Destruction of its distinctive nuclei induces hyperphagia, hyperinsulinemia and weight gain. Seventy-five patients with CP who underwent first surgical resection in a single center by the same neurosurgeon between February 2005 and March 2019 were screened; those who have had prior radiation, were aged below 18 years, or did not have follow up body mass index (BMI) after surgery were excluded. Ultimately, this study included 45 patients with a mean age 50.5 years, 73.3% women. Pre and post-operative MRI were independently reviewed by three neuroradiologists to determine involvement of the hypothalamic regions: anterior, anterior and posterior, or no hypothalamic involvement. Body mass index were recorded pre operatively and subsequently after TSS up to 24 months post operation. Association between hypothalamic region involvement and BMI as well as endocrine function were examined. Posterior hypothalamic involvement seen in pre operative MRI (N=28) was significantly associated with higher BMI at 3-6 month, 7-12 month, and 13-24 month follow up (p < 0.05) in comparison to involvement of anterior hypothalamic alone or no hypothalamic involvement. Similarly, posterior hypothalamic involvement in the pre and post-operative MRI was significantly associated with development of diabetes insipidus (DI) (p < 0.05) compared to anterior or no hypothalamic involvement. There was no association between pre-operative BMI and hypothalamic involvement. Although the weight gain was accelerated after surgery, there was no association between post operative MRI and ensuing BMI, suggesting that the damage of the hypothalamic nuclei was done by the CP rather than surgical procedure. Conclusion: Assessment of hypothalamic involvement by anterior and posterior regions on pre operative MRI can be helpful in predicting development of obesity in patients with CP.
MON-LB128 Phosphoinositide 3-Kinase (PI3K) Inhibitor Induced Hyperglycemia With Alpelisib
Authors: Barsukova Yuliya , Jouneghani Nasrin Saleh , Islam Julie Rizwana , White Wendy
Published: May 2020

Intorduction: Breast cancer is estimated to be the third leading cause of cancer-related death in women. A commonly mutated pathway in breast cancer is the phosphoinositide-3-kinase (PI3K) pathway. Newer agents inhibiting PI3K are now available for the treatment of advanced cancers. Metabolic complications of new onset diabetes/hyperglycemia and hyperlipidemia are commonly seen. The precise mechanism through which PI3K inhibitors cause hyperglycemia is unknown. We present a patient who developed hyperglycemia within 2 weeks of starting alpelisib. Clinical Case: A 68 y.o female with history of metastatic invasive lobular carcinoma of the right breast HR-positive, HER-2 negative who presents for evaluation of hyperglycemia. She was diagnosed with metastatic breast carcinoma and failed multiple treatment options. She was started on alpelisib 2 weeks prior and had no history of glucose intolerance. Her pretreatment HbA1c was 5.5% (n <5.7%). After initiation of alpelisib, fasting blood glucose ranged between 100-140 mg/dL (n 100-125 mg/dL), while post-prandial blood glucose ranged between 150-300 mg/dL (n <140 mg/dl). Her HbA1c rose to 7% (n <5.7%). She did not manifest any macrovascular or microvascular complications, but did have a family history of type 2 diabetes mellitus. After initially being started on metformin, the dose increased to 1500 mg daily with the addition of glimepiride 1 mg. She eventually achieved stable euglycemia on metformin alone.

Conclusion: Hyperglycemia has been reported to commonly occur with PI3K inhibitor therapy, the mechanism of which is poorly understood. One purposed mechanism is the effect on AMP kinase pathway which may also affect the efficacy of metformin. Here, we present a case of new onset T2DM in the setting of HR-positive, HER-2 negative breast cancer effectively treated with metformin. Future studies are needed to establish the prevalence and incidence of drug-induced hyperglycemia in patients administered PI3K inhibitors, as well as the best management approach to ensuing hyperglycemia. Reference: André F, Ciruelos EM, Rubovszky G, et.al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940.

Guena, E, Roda, D, Rafii, S. Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on phase I clinical trials. Br J Cancer. 2015;113:1541-1547

Busaidy, NL, Farooki, A, Dowlati, A. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol. 2012;30:2919-2928.
SAT-LB303 Severe Refractory Volume Overload With Diazoxide in the Treatment of Insulinoma
Authors: Pasha Pouneh , Meneilly Graydon S , Kapeluto Jordanna Esther
Published: May 2020

Background: Insulinoma is the most common neuroendocrine tumor (NET), occurring in 1-4 people per million. Surgical resection remains standard of care for symptomatic control and long-term remission. Where surgery is not feasible medical therapy with diazoxide and somatostatin analogues is used as supportive management. Case: A 88-year-old male with background hypertension, remote myocardial infarct and chronic kidney disease (CKD) (Cr 130-150 umol/L; N 60-115) was diagnosed with insulinoma following a presentation for confusion and CBG of 0.9 mmol/L. Diagnosis was confirmed by 72 hour fast with inappropriate insulin (85 pmol/L; N<95) and elevated c-peptide (1875 pmol/L; N 325-1090) with documented hypoglycemia (2.8 mmol/L). CT abdomen localized a 1.2 cm exophytic lesion in the pancreatic tail suggestive of insulinoma. Normal morning cortisol (547 nmol/L) excluded adrenal insufficiency. Initial management included resuscitation with dextrose infusions. Due to advanced age and high cardiac risk profile, the patient was not a candidate for surgical resection of the NET. Endoscopic ultrasound (EUS) ablation was deferred at time of initial hospitalization due to stabilization of hypoglycemia with high glycemic diet. An episode of nocturnal hypoglycemia prompted initiation of diazoxide 100 mg as an outpatient. Subsequent dyspnea (NYHA IV) developed and acute on chronic kidney injury (peak Cr 416 umol/L) with evidence of anasarca secondary to diazoxide use prompted readmission to hospital. With conversion to octreotide, discontinuation of diazoxide and treatment with multiple diuretics, volume overload did not improve. The patient was deemed not a candidate for intermittent hemodialysis and the decision was made to change goals of care. The patient died of complications of volume overload from cardiorenal syndrome 21 days after the initiation of diazoxide. Conclusion: Volume overload has been documented as a complication of diazoxide use in both hypoglycemia and hypertension, occurring in up to 50% of cases, however mortality is not common with supportive management.1, 2 Risk factors for refractory volume overload appear to include reduced ejection fraction, extremes of age and history of CKD3. Possible mechanisms for acute decompensation in CKD include increased unbound diazoxide levels, prerenal effect from hypotension and sodium retention4,5. This case highlights the need for close monitoring with diazoxide use in high risk patients. Clinicians should consider echocardiogram, close monitoring of clinical volume status and renal parameters. References: 1) Goode PN. (1986). World J Surg 10: 586. 2) Komatsu Y. (2016) Endocr J. 63(3): 311. 3) Tarçin O. (2018). Endocrine Abstracts56 EP4. 4) Pearson RM. (1977) Clinical Pharmacokinetics vol 2: 198. 5) Allen WR. (1983). Pharmacology 27: 336.