bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-070 European Registries for Rare Endocrine Conditions (EuRRECa): Results from the Platform for E-reporting of Rare Endocrine Conditions (e-REC)
Authors: Ali Salma R , Bryce Jillian , Cools Martine , Danne Thomas , Dattani Mehul T , Dekkers Olaf M , Hiort Olaf , Linglart Agnes , Netchine Irene , Nordenstrom Anna , Patocs Attila , Pereira Alberto M , Persani Luca , Reisch Nicole , Smyth Arlene , Sumnik Zdenek , Taruscio Domenica , Visser W Edward , Ahmed S Faisal
Published: May 2020

Background EuRRECa (European Registries for Rare Endocrine Conditions) is a group of web-based projects that work closely with the European Reference Network (ERN) for Rare Endocrine Conditions (endo-ern.eu) and helps the ERN with inventorying its clinical activity. To understand the number of new encounters of rare conditions within this network, it has launched an e-reporting programme for rare endocrine conditions (e-REC) that are covered within this network. Methods 46 endocrine centres within 18 countries volunteered to participate in e-REC from July 2018 to June 2019. An electronic reporting ‘card’ developed through REDcap was issued monthly to enquire whether clinicians had encountered a new case of any condition within the 8 Endo-ERN main thematic groups (MTGs). Results On a monthly basis over 1 year, a median of 14 (range 11, 21) paediatric centres and 13 (11, 25) adult centres actively reported cases. A median of 53 (22, 80) paediatric cases and 96 (42, 250) adult cases were reported monthly. Amongst paediatric cases, conditions within the Sex Development and Maturation (SDM) theme were most commonly reported comprising 38% of all reported conditions, with XY, DSD being the most commonly reported condition (24% of cases). Amongst adults, Pituitary and Thyroid conditions were most commonly reported, 34% and 26% of all conditions, respectively. Amongst conditions within the Pituitary group, pituitary adenoma was the most commonly reported condition (74% of cases) and non-metastatic thyroid carcinoma was the most commonly reported condition (95% of cases) amongst the Thyroid group. In children, the median number of cases reported per centre was 21 (9, 32) for conditions affecting SDM. In adults, a median of 37 (6, 75) Pituitary and 22 (5, 80) Thyroid cases were reported per centre. Conclusion e-REC is a simple, yet effective, platform that can be used to capture information on new encounters with patients with several rare conditions and can be adapted to serve the needs of other discrete networks that are interested in understanding the occurrence of rare conditions.
MON-367 Unusual Presentation of Hypercalcemia Preceding the Diagnosis of Methotrexate-Induced Pneumocystis Jirovecii Pneumonia from Treatment of Necrotizing Myopathy
Authors: Nguyen Minhthao , Mohiuddin Afshan
Published: May 2020

Background: Pneumocystis Jirovecii infection is a common opportunistic infection often seen severely immunocompromised individuals, such as those with HIV/AIDs. This is an unusual case where the patient displayed persistent hypercalcemia, with an eventual diagnosis of PCP likely due to immunosuppression from methotrexate (MTX) therapy.

Case: A 79 year old male was brought to the hospital for acute change in mental status and hypercalcemia (13.4mg/dl). The patient was acutely encephalopathic, oriented to self only; his baseline was a high level executive at a company. An extensive neurologic workup including CT, MRI, EEG, spinal fluid examination was negative with a persistent hypercalcemia. Additional workup showed no increase in bone turnover, suppressed PTH, non-elevated pPTHrP. He was found to have diffuse mild PET avidity of bilateral lungs on PET scan, with bronchoscopy for evaluation of potential granulomatous disease. PCR of the BAL fluid obtained during bronchoscopy was positive, and the patient was ultimately treated with an extended course of Atovaquone for Pneumocystis Jirovecii pneumonia (PCP). The patient was felt to have an immunosuppressed state secondary to being treated for a necrotizing myopathy with methotrexate. The patient’s mentation slowly but substantially improved with a combination of a prednisone taper and Atovaquone, with discontinuation of the MTX. The patient’s hypercalcemia improved with treatment of PCP.

Conclusion: Although a cause of hypercalcemia secondary to primary hyperparathyroidism causing necrotizing myopathy is known in the literature, it is unusual to see the opposite, where few case reports have documented hypercalcemia due to immunosuppression from low-dose methotrexate treatment for necrotizing myopathy resulting in pulmonary pneumocystis and hypercalcemia. Additionally, MTX induced immunodeficiency is often associated with severe immunosuppression or lymphoproliferative disorders - however the patient had an extensive work up with negative results for malignancy
MON-630 Elevating the Patient Voice in Type 1 Diabetes Clinical Trials: A Comparison of In-Depth Exit Interviews and Diabetes-Specific Questionnaires
Authors: Ervin Claire , Joish Vijay N , Castro Colleen , DiBenedetti Dana , Evans Emily , Carroll Amy , Lapuerta Pablo
Published: May 2020

Healthcare decisions are more effective when the patient voice is included in clinical research, and the Food and Drug Administration encourages the patient’s voice in drug development and regulatory decision-making. Clinical trials should not only demonstrate the effect of a drug on clinical outcomes but should also demonstrate that these outcomes are important or meaningful to patients. Several qualitative and quantitative methods are available to collect patient experience data (e.g., traditional patient-reported outcome [PRO] measures, interviews with clinical trial participants). We aimed to understand if in-depth exit interviews were more effective assessments of the patient experience in recent type 1 diabetes (T1D) clinical trials than existing diabetes-specific PROs. In-depth qualitative interviews were conducted with 41 adults with T1D who had completed or withdrew from a phase 3 study of sotagliflozin, a dual inhibitor of SGLT1 and SGLT2. A targeted literature review was conducted to identify diabetes-specific PROs used in randomized controlled clinical trials of novel T1D medications reported over the past 5 years. Included trials had to investigate a pharmaceutical intervention for adults with T1D and report a diabetes-specific PRO. The concepts assessed in the PRO measures were mapped against those elicited during the 41 exit interviews. A total of 336 publications were identified in the literature search of which 26 were eligible for analysis. Eight diabetes-specific PROs were identified and reviewed from which 54 concepts related to the patient experience were identified. The patient exit interviews included 42/54 (78%) of the patient experience-related concepts identified across all 8 PROs from the literature review. Of the 8 PRO instruments, the Diabetes Quality of Life Measure (DQOL) covered the most concepts (18/54, 33%), followed closely by the Audit of the Diabetes-Dependent Quality of Life (ADDQoL; 16/54, 30%). Some of the most prominent concepts from both approaches were related to impact on life and family; fear of complications; and impact on physical activity, lifestyle and social perceptions. There were several concepts identified in the exit interviews that were not covered in any of the 8 PRO instruments (related to keeping blood sugars within a desired range, ability to manage changes in insulin use). Overall, the exit interviews appeared to provide a more comprehensive picture of patient experience domains. Although existing diabetes PRO measures cover a range of concepts and may adequately assess changes in certain outcomes, data from patient exit interviews provide more comprehensive insights into the patient experience. Exit interview data may provide a more detailed understanding of the disease burden and impact of treatment on improvements in well-being, daily functioning, and treatment satisfaction.
SAT-163 Status at 10 Years: Long-Term Follow-Up for a Phase 2a Study of High-Specific-Activity (HSA) I 131 Iobenguane in Patients (Pts) with Relapsed/Refractory High-Risk Neuroblastoma
Authors: Villablanca Judith G , Maris John M , Stambler Nancy , Zhou Duo , DiPippo Vincent A , Matthay Katherine K
Published: May 2020

Background: Metaiodobenzylguanidine (MIBG; iobenguane), a guanethidine derivative, is a substrate for norepinephrine reuptake transporter which is highly expressed on the surface of neuroblastoma cells. AZEDRA® (HSA I-131 MIBG) has been approved by the FDA for the treatment of pheochromocytoma and paraganglioma, in pts 12 years and older with MIBG avid, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. The aim of this study was to establish the maximum tolerated dose in children with neuroblastoma, with secondary aims of assessing overall response and tumor and organ dosimetry. Here we report current long-term survival and toxicity data. Methods: Eligible pts were 1-30 years old with resistant neuroblastoma. A diagnostic dose of HSA I-131 MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. To prevent prolonged myelosuppression, autologous hematopoietic stem cells were infused 14 days after therapy. Response and toxicity were evaluated on day 60. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/µL within 28 days, or platelets to greater than 20,000/µL within 56 days, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions. Results: First pt was enrolled in June 2008. 15 pts total were evaluable at 12 (n=5), 15 (n=3), and 18 (n=7) mCi/kg. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight pts had 13 soft-tissue lesions with tumor-absorbed doses of 26-378 Gy. MYC-N amplification was present in two of 11 pts with available results. Of the 15 treated pts, 1 had a complete response, 3 had a partial response, 1 had a mixed response and 6 had stable disease. The remaining 4 had progressive disease. Twelve of the 15 evaluable pts received non-protocol therapy after HSA I-131 MIBG, the remaining 3 died due to tumor without further therapy. At 3.6 years of follow-up the overall survival was 26.7% (95% CI, 8.3%-49.6%). As of March 2018, one remaining pt is in long term follow up with an overall survival of 8.4 years. This pt was previously reported to have a secondary malignancy of myelodysplastic syndrome which has been in remission since receiving an allogenic bone marrow transplant in March 2014. Conclusions: HSA I-131 MIBG contributed to long term median survival of two years and was well tolerated. Treatment showed promising activity in the absence of significant nonhematologic toxicity.
SAT-679 Autoimmune Hypoglycemia: A Treatment Challenge
Authors: Santana Nadyeschka Angelique Rivera , Lopez Zahira Marie Lugo , Diez Andrea del Toro , Sanchez Ernesto Jose Sola , Garcia Michelle Marie Mangual , Ortiz Ivan Laboy
Published: May 2020

Background: Upon evaluation of patients with recurrent hypoglycemia, both exogenous and endogenous causes should be excluded. Among endogenous hyperinsulinemic hypoglycemia (EHH) pathologies, Insulin Autoimmune Syndrome (IAS), even though extremely rare, must be considered. Most cases of IAS have been reported in the Oriental population, mostly Japanese. No gold standard of care for this condition has been established. Clinical Case: This is the case of an 82 year-old obese female patient with dyslipidemia, obstructive sleep apnea, and osteoarthritis that comes to the Endocrinology clinics for evaluation due to recurrent episodes of hypoglycemia. She refers that for the last three years she had been presenting with multiple episodes of symptomatic hypoglycemia, even levels as low as 30 mg/dL, requiring multiple hospitalizations. Consequently, she refers a 15-pound weight gain because of multiple daily snacks. Home medications were simvastatin and diclofenac. She denies using insulin, sulfonylureas, other hypoglycemic agents, alcohol, or illicit substances. Abdominal MRI and PET CT scan were remarkable only for an atrophic pancreas without focal masses. Patient was hospitalized for a supervised 72-hour fast, resulting in severe hypoglycemia within 14 hours with elevated insulin levels at 46.3 uIU/mL (1.7-31.0 uIU/mL), elevated C-peptide levels at 5.79 ng/mL (0.9-4.3 ng/mL) and elevated insulin antibodies 53µU/mL (<5µU/mL). Patient showed sufficient hepatic reserve after glucagon administration as well as intact cortisol and growth hormone axis upon severe hypoglycemia. With these results, a diagnosis of IAS was made; not associated with other autoimmune diseases, or with medications with sulfhydryl groups, such as the cases already reported on literature. This condition represents a therapeutic challenge because there is no gold standard of care. Literature recognizes diverse treatment options that range from diet modification to more aggressive therapies, including plasmapheresis and immunosupressants. Our patient was managed with diet modification including frequent snacks and Diazoxide with the goal of decreasing insulin levels and inducing hyperglycemia. Diazoxide therapy achieved a steady euglycemic state and decreased insulin antibodies. Patient developed intolerable bilateral lower extremity edema and treatment was modified to complex carbohydrates, frequent snacks in the daytime and Diazoxide only at bedtime, which is the longer fasting period. Patient has remained without episodes of hypoglycemia and diabetes has not been diagnosed since starting treatment two years ago. Conclusion: Early recognition of IAS is essential in order to avoid unnecessary studies and procedures which could delay management. Although no gold standard therapy has been identified for this condition, our case report identifies Diazoxide as a compelling medical treatment.
SAT-342 Humerus Fracture & Dislocation of Right Shoulder Following a Seizure in Non-Epileptic Patient Due to Hypoparathyroidism
Authors: Doub Najah Younes , Hashem Waleed Abdulgafour , alhamdan ali
Published: May 2020

Introduction: Hypoparathyroidism is a rare disease. The most common etiology of hypoparathyroidism is the surgical resection of the parathyroids.

Primary hypoparathyroidism can cause a wide spectrum of manifestations, mainly due to low serum calcium effect on internal organs, and directly correlates with the rate of development of hypocalcemia.Parathyroid Hormone (PTH) is one of the key regulators of the rate of bone remodeling. A reduction or absence of circulating PTH leads initially to a decrease in bone resorption then to a coupled reduction in bone formation.

Case Presentation A 36-year-old male nurse in primary health care, not known to have any medical illness, presented to the emergency department with generalized tonic-clonic seizures associated with right shoulder dislocation and communicated fracture of the humerus. However, the day before his presentation, he has had two episodes of convulsion, but he did not seek medical attention.He had developmental delay in walking and teeth eruption as well as frequent generalized tonic-clonic which were treated by traditional healer. This information could point out to the possibility of congenital origin.Upon arrival to the emergency department, he has teeth decay all over his oral cavity with right shoulder dislocation and right humerus fracture. Chvostek sign and trousseau sign were positive.The patient was treated initially with calcium gluconate intravenously followed by oral treatment of calcium carbonate 1.2 g three times daily and alfacalcidiol 1 mcg twice daily and upon discharge teriparatide 20 mcg subcutaneously daily was given.

Conclusion

Treatment of hypoparathyroidism with recombinant parathyroid hormone may reduce bone mineral density (BMD) but concomitantly strengthen bone.

This is a treatable disorder that may have catastrophic results if overlooked but also its symptoms may be completely reversed with prompt treatment.

It is of utmost importance routine vitamin D, phosphorous, and calcium monitoring, as well as renal calcium excretion evaluation to prevent complications of overtreatment with CA and active Vit D.

References

• Bilezikian JP, Khan A, Potts JT Jr, Brandi ML, Clarke BL, Shoback D, et al. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target- organ involvement, treatment, and challenges for future research. J Bone Miner Res. 2011;26(10):2317-37.
SAT-410 Long Term Evaluation of TSH Receptor Antibodies and Thyroid Stimulating Immunoglobulin After Radioiodine Therapy for Thyrotoxicosis
Authors: Marui Suemi , Irigoitia Bruna , Lenczuk Aline , Rocha Nelisa Helena , Brito Luciana Pinto , Watanabe Tomoco
Published: May 2020

Background Radioioactive iodine therapy (RAI) is an excellent choice to treat thyrotoxicosis, particularly Graves′ disease (GD) patients. After RAI therapy, it is well known that TSH receptor antibodies (TRAb) rise in GD patients and autoimmunity can eventually surge in patients with toxic multinodular or uninodular goiter (TNG). Recently, biological assay distinguishes stimulating TRAb, called thyroid stimulating immunoglobulin (TSI) bringing a new perspective on follow-up, as TSI is involved in Graves′ pathogenesis of persistent thyrotoxicosis and ophthalmopathy after RAI therapy. Objective Analyze TRAb and TSI levels after 6 and 12 months of RAI therapy for thyrotoxicosis. Patients and Methods Patients were evaluated prospectively immediately before and 6 to 12 months after RAI therapy for thyrotoxicosis. Thyroid hormones were all measured using immunoassays (Roche Diagnostics Ltd). TRAb was analyzed by Elecsys Anti-TSHR assay (Roche Diagnostics, Germany) and was considered negative if < 1.75 IU/L (analytical range: 0.3 to 40 IU/L). TSI was measured by Immulite TSI assay (Siemens Healthcare, UK) and was considered negative if < 0.55 IU/L (analytical range: 0.1 to 40 IU/L). Clinical data and comparison of assays were analyzed by SPSS and MedCalc softwares. Results From 2017 to 2019, 54 patients (44 females) were prospectively evaluated after 6 months of RAI therapy, mostly because of GD (40 patients). A high degree correlation was observed between TRAb and TSI (Spearman correlation coefficient =0.875; p < 0.0001, 95% CI 0.784 to 0.929). After 6 months, among patients with GD, 5/40 patients had negative TRAb levels and 2/40 had negative TSI levels, whereas all TNG patients had both negative TRAb and TSI levels. In GD group, 4 patients showed subclinical hyperthyroidism and relapse occurred in 1 case. All patients with TNG showed euthyroidism status with or without thyroid medications. One year after RAI therapy, we evaluated 32 patients (23 GD) and 4/23 of GD had negative TRAb levels and only 1/23 had negative TSI level. All patients with TNG had negative TRAb and TSI levels after one year fo treatment. Subclinical hyperthyroidism was diagnosed in 5 patients with GD but none with TNG. Along follow-up, 4 patients with clinical diagnosis of GD with TRAb negative before RAI therapy became positive after RAI therapy and 3 patients became TSI positive. Conclusions Long term after RAI therapy for thyrotoxicosis treatment, TRAb and TSI are still positive in most GD patients and few cases can even turned to positive levels. Nevertheless, in TNG patients, RAI therapy is safe as TRAb and TSI maintained at negative concentrations and thyrotoxicosis is properly resolved.
MON-388 Total and Free 1,25dihydroxyvitamin D Levels in Postmenopausal Patients with Primary Hyperparathyroidism
Authors: Meng Lingqiong , Shapses Sue A , Wang Xiangbing
Published: May 2020

Background: Vitamin D3 is metabolized to 25-hydroxyvitamin D [25(OH)D] in liver, and only after it goes to kidney is it converted to its biologically active form, 1,25-dihydroxyvitamin D [1,25(OH)2D]. Also, the majority of both total 25(OH)D and 1,25(OH)2D are tightly bound to vitamin D bind protein (DBP) and only a small portion remains in free form. In certain patient populations, like primary hyperparathyroidism (PHPT), concentrations of free vitamin D metabolites may be affected by altered levels of binding protein.

Objective: To evaluate total and free 1,25(OH)2D levels in PHPT patients and healthy controls.

Methods: Thirty female patients with PHPT and 30 healthy age and body mass index (BMI) matched controls were enrolled (57.1 ± 9.8 years and BMI of 32.2 ± 7.2 kg/m2). Serum levels of calcium, intact parathyroid hormone (iPTH), DBP, total 25(OH)D and 1,25(OH)2D levels were examined. Serum free 25(OH)D and 1,25(OH)2D levels were calculated using equations adapted from Bikle et al.

Results: There were no significant differences in age and BMI between groups. Compared to controls, patients with PHPT had lower total 25(OH)D (25.2 ± 7.5 vs. 19.3 ± 6.4 ng/mL; p <0.001) and DBP levels (40.7± 3.1 vs. 36.5 ± 5.7 mg/dL; p <0.001). There were no significant differences in total 1,25(OH)2D levels or calculated free 25(OH)D levels between PHPT patients and controls; but the calculated free 1,25(OH)2D levels were 27% higher in the PHPT patients compared to controls (p<0.001). The calculated free (but not total) 1,25(OH)2D level was inversely correlated with DBP (r=-0.35, p<0.01) and positively correlated with iPTH levels (r=0.33, p<0.01).

Conclusion: Postmenopausal patients with PHPT had lower serum total 25(OH)D, but similar free 25(OH)D levels. In contrast, total 1,25(OH)2D levels did not differ between patients and controls; however, patients had higher free 1,25(OH)2D. Because total 25(OH)D and 1,25(OH)2D levels do not reflect free levels, standard clinical measures of circulating vitamin D may not be an accurate estimate of true vitamin D status in patients with PHPT.

References: Bikle et al. Serum Protein Binding of 1,25-Dihydroxyvitamin D: A Reevaluation by Direct Measurement of Free Metabolite Levels. JCEM 1985;61:969-75.
OR05-04 Steroid Receptor Co-Activators Complexes Cooperate with Progesterone Receptors (PR) to Reprogram Metabolic Pathways that Drive Therapy Resistant Populations in ER+ Breast Cancer
Authors: Truong Thu H , Benner Elizabeth , Ostrander Julie Hanson , Lange Carol A
Published: May 2020

Late recurrence of metastatic disease stemming from acquired therapy resistance remains a significant health burden for women with ER+ breast cancer. Disseminated ER+ tumor cell populations can remain quiescent for years to decades, and contributing factors include breast cancer stem cells (CSCs), which are non-proliferative and frequently exist as a minority population in recurrent therapy-resistant tumors. Progesterone receptors (PR) are known drivers of normal stem and breast CSCs. Our objective was to define novel signaling pathways governing cell fate transitions involved in driving therapy resistance in ER+ breast cancer. We reported that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, drive breast CSC outgrowth. SRC-3 knockdown abrogated PELP1-induced CSC expansion and target genes required for cell survival, suggesting an essential role for PELP1/SRC-3 complexes. PELP1 also forms a signaling and transcriptional complex with ER and PR-B. Phospho-PR species are key mediators of stemness in ER+ breast cancer models. Accordingly, PR knockdown and antiprogestins disrupted PELP1/SRC-3 complexes and blocked PELP1-induced breast CSC outgrowth. Mammary stem cell (MaSC) populations were increased in vivo in MMTV-tTA;TRE-cyto-PELP1 transgenic mice as well as in MMTV-tTA;TRE-hPR-B mice. To better understand PELP1-mediated pathways, we performed RNA-seq on MCF-7 PELP1+ models grown in tumorsphere conditions to enrich for CSC populations (ALDH+, CD44+/CD24-). Cytoplasmic PELP1-expressing cells had a different global gene profile relative to WT PELP1 (i.e. nuclear). Gene sets associated with stem cell biology, hypoxic stress, and cancer metabolism were differentially regulated, including members of the glycolytic bi-functional kinase/phosphatase PFKFB family. Seahorse metabolic phenotyping demonstrated cytoplasmic PELP1 influences metabolism by increasing both glycolysis and mitochondrial respiration. Cytoplasmic PELP1 interacted strongly with PFKFB3 and PFKFB4, and inhibition of PFKFB3 or PFKFB4 kinase activity blocked PELP1-induced tumorspheres and protein-protein interactions with SRC-3. Additionally, antiprogestin and PFKFB inhibitors were synergistic when combined with ER+ targeted therapies. These aspects of PELP1/SRC-3 biology were phenocopied in therapy resistant models (tamoxifen resistant [TamR], paclitaxel resistant [TaxR]). Together, our data suggest that PELP1, SRC-3, PR, and PFKFBs form complexes that reprogram cellular metabolism to drive breast CSC expansion. Identifying the mechanisms that regulate recurrent ER+ tumor cell populations will enable specific targeting within heterogeneous breast tumors and may lead to the development of non-ER targets that can be used in combination with endocrine treatments to overcome therapy resistance.
SAT-559 Patients with Hyperaldosteronism Have Higher Prevalence of Obstructive Sleep Apnea. From the National Inpatient Sample
Authors: Ahmed Fatima , Abugroun Ashraf , Patel Pragnesh , Elhassan Manar , Msallaty Zaher , Seyoum Berhane
Published: May 2020

Introduction: Previous studies suggested that aldosterone excess may worsen obstructive sleep apnea (OSA) through causing peri-pharyngeal edema. Objective: In this study we sought to examine if hyperaldosteronism is associated with OSA. Methods: The National Inpatient Sample (NIS) data was queried for adults with diagnosis of primary and secondary hyperaldosteronism during the years 2012 - 2015. Patients with hyperaldosteronism were identified using the international classification of disease (ICD-9). Each patient who was diagnosed with hyperaldosteronism was matched to randomly selected controls at a 1:4 ratio by age, gender and year of hospitalization. A multivariable logistic regression model was used to estimate the adjusted odds ratio (aOR) of OSA among patients with hyperaldosternoism. We adjusted for patient demographics, socioeconomic factors, hospital factors and clinical comorbidities. Subgroup analysis was performed based on gender, race and age groups; young adults (aged 18–35 years), middle aged (> 35-<55 years) and older adults (aged > 55 years). Results: There were 23,465 patients diagnosed with hyperaldosteronism identified. The mean age was 59 (standard error of the mean (SEM): 0.1. Females represented 48.5%. Compared to control, patients with hyperaldosteronism had higher prevalence of hypertension, CHF, stroke, obesity, diabetes, renal failure and lower prevalence of tobacco use and COPD. The proportions of African Americans were higher among patients with hyperaldosteronism compared to the control 30.1 vs 15.5, p<0.001. Patients with hyperaldosteronism had higher prevalence of OSA 16.4 vs 8.3, p<0.001. On multivariate analysis, hyperaldosteronism was independently associated with higher odds for OSA with aOR 2.01 (95%CI: 1.81–2.23) p<0.001. On subgroup analysis, similar findings were observed irrespective of gender, age group or race. Conclusion: Prevalence of OSA is higher among patients with hyperaldosteronism. Physicians may need to consider a case detection of hyperaldosteronism in patients with OSA and hypertension. Similarly we suggest to evaluate patients with hyperaldosteronism for OSA.
SUN-245 Sensory Neuron Metabolism Mediates Changes in Ovarian Function via LKB1
Authors: Lenert Melissa E , Burton Michael D
Published: May 2020

Bi-directional communication between sensory neurons to peripheral tissue to mediate physiology has become an area of interest. Previous research on peripheral neuron control of ovarian function shows that lesioning the superior ovarian nerve resulted in decreased estradiol release from the ovary; but there has been little research on how sensory neurons affect ovarian physiology. Interestingly, the metabolic activity of sensory neurons that control ovarian and follicular function may have profound effects on tissues they innervate. LKB1 (Liver Kinase B1) is a metabolic kinase that regulates cell growth and polarity. When downregulated in cortical neurons in vitro, leads to shorter axons with less branching. Female mice with LKB1 removed from their peripheral sensory neurons have litters more often and increased litter sizes compared to wild-type mice, which led to the investigation into the mechanisms into the role of LKB1 in sensory neurons in ovarian function. Nav1.8cre-LKB1fl/fl mice were used to assess the removal of LKB1 from Nav1.8-expressing neurons on the mechanisms behind reproductive viability. The estrus cycle was tracked by using vaginal lavage to collect cells from the vagina twice per day for ten days, and cytology was assessed to determine phase. Ovaries were collected from mice in all phases of the estrus cycle, sectioned at 8 micron thickness, stained with H&E. Follicle sizes and numbers were measured on 8 sections per ovary. Sensory innervation was measured by clearing whole ovary using ScaleS1 and using confocal microscopy to image through the whole tissue for sensory neurons tagged with tdTomato and DAPI. Our data indicate that Nav1.8-expressing neurons innervate the ovary from celiac ganglia, upper lumbar, and lower thoracic dorsal root ganglia. Nav1.8cre-LKB1fl/fl mice have larger litters and breed more frequently compared to cre-negative litter mates (WT). Nav1.8cre-LKB1fl/fl mice have larger ovaries, spend less time in proestrus, and have greater follicular turnover compared to WT mice. Phase-matched ovaries from Nav1.8cre-LKB1fl/fl mice in proestrus show greater numbers of antral and degenerating follicles than WT mice, but similar numbers of immature follicles; however, the size of all follicles from Nav1.8cre-LKB1fl/fl mice are smaller than follicles from WT mice. Nav1.8cre-LKB1fl/fl mice have improved reproductive viability by increased follicular turnover rate, more mature follicles, and shortened estrus cycle length.
MON-039 Prenatal Anti-Mullerian Hormone (pAMH) Exposure in Mice Induces Changes in Pubertal Onset, Fertility, and Stress Response in Both Male and Female Offspring
Authors: Ho Emily V , Shi Chengxian , Mellon Pamela L
Published: May 2020

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, classically presenting with disrupted ovulation, polycystic ovaries, and androgen excess, as well as many non-reproductive comorbidities. For instance, PCOS patients exhibit increased stress reactivity and higher rates of depression and anxiety compared to the general population. The prenatal anti-Mullerian hormone (pAMH)-induced model of PCOS was recently shown to recapitulate reproductive phenotypes in female mice, however little remains known about the consequences of pAMH exposure. We first aimed to expand upon this model by investigating pAMH-induced effects on offspring of both sexes. Pregnant dams on a C57Bl/6 background received daily i.p. injections of either AMH (0.12 mg/kg/d) or VEH late in gestation. Offspring were born into 4 groups (pAMH vs. VEH females, pAMH vs. VEH males) and assessed starting at weaning for changes in body weight, anogenital distance, pubertal onset, estrous cyclicity, fertility, and reproductive senescence. Statistical differences were determined by t-test or 2-way ANOVA when applicable, and significance set at p<0.05. As expected, pAMH increased anogenital distance in females but not males. Pubertal onset was delayed not only in females as previously reported, but also in males. Additionally, pAMH adult females showed significant disruptions in estrous cycling at P60 (increased time spent in diestrus, decreased number of cycles, increased cycle length), only mild disruptions by P90, then robust disruptions at 8 mo, 10 mo, and 12 mo of age that were distinct from reproductive senescence. When paired with wildtype untreated mates for a fertility assay starting at 3 mo of age, pAMH females had smaller and fewer number of litters, while pAMH males showed only delayed plugging behavior. Although pAMH males showed no difference in testis weight, pAMH females also had significantly reduced ovarian and uterine weights in diestrus. Interestingly, during the fertility assay, we found increased fetal death from both the pAMH females and males, even though pAMH males were paired with wildtype untreated females. We hypothesized that the increased fetal death could be the result of an pAMH-induced stress phenotype in both sexes. Using a simple stress response test measuring defecation and urination during exposure to a novel environment, we found that pAMH robustly increased stress response in both sexes at multiple timepoints. We also assessed glucocorticoid response to a restraint stress paradigm in adult females. While we observed no differences in baseline serum corticosterone levels, the pAMH group showed increased peak levels followed by a prolonged elevation levels after 2 hr. Together, these results enhance existing knowledge of the effects of pAMH exposure by demonstrating alterations in both male and female mice on both reproductive and non-reproductive measures.
OR21-05 Primary Thyroid Lymphoma Developing from a Background of Lymphocytic Thyroiditis: First Report in Mice
Authors: Yasuda Yoshinori , Pani Fabiana , Caturegli Patrizio
Published: May 2020

Primary thyroid lymphoma is rare, accounting for less than 5% of all thyroid malignancies. It typically develops in patients with Hashimoto thyroiditis who have approximately a 70 fold higher risk than other patients. The mechanisms underlying the development of thyroid lymphoma remain unclear, and no mouse model has been described. For our studies of papillary thyroid cancer and lymphocytic thyroiditis, we crossed TPO-Cre-ER transgenic mice and hBRAFV600E knock-in mice onto the NOD.H2h4 background to establish TPO-Cre-ER_ hBRAFV600E NOD.H2h4 strain where papillary thyroid cancer is induced by the injection of tamoxifen and thyroiditis by the administration of iodine in the drinking water. Mice injected with corn oil or drinking regular water served as control. In 3 of 121 mice, TPO-Cre-ER_ hBRAFV600E NOD.H2h4 mice injected with corn oil and drinking iodinated water we observed the development of thyroid lymphoma. At about 6 months after the injection of corn oil, these mice developed a marked increase in the size of the thyroid gland, which appeared hypoechoic on thyroid ultrasound. Fine needle aspiration on the thyroid gland under ultrasound was performed, along with measurement of TPO antibodies, H&E thyroid histology, immunohistochemistry, and flow cytometry at the time of sacrifice. Histology established a diagnosis of Hodgkin lymphoma with the typical Reed Sternberg cells. Flow cytometry identified an increased frequency of CD8+ effector memory T cells in the thyroid lymphoma. TPO antibodies were significantly higher in mice with thyroid lymphoma than in those without, perhaps suggesting their utility as predictive biomarkers. In summary, we report a mouse model of thyroid lymphoma that evolves from a background of lymphocytic thyroiditis with a predictable natural course that can be monitored by thyroid ultrasound and TPO antibodies. This model can be used to study the mechanisms and development of thyroid lymphoma in patients.
MON-137 Evaluation of the Timeliness of Serial Denosumab Administrations at the University of Colorado Hospital
Authors: Zaman Adnin , Billups Sarah J , Rothman Micol S
Published: May 2020

BACKGROUND:

Denosumab is an antiresorptive medication commonly used in the treatment of osteoporosis that works by slowing bone loss. This medication should not be delayed or interrupted without initiation of an alternative treatment (i.e. bisphosphonates) as studies have shown that this can lead to rapid bone loss, very high markers of bone turnover, and increased vertebral fracture (VF) risk. It is unknown how frequently dosing is delayed in practice settings and how best practices can ensure timely dosing. Our study aimed to (1) evaluate the frequency and causes of delayed denosumab doses at our institution and (2) compare the incidence of delayed doses before and after implementation of a new electronic ordering process.

METHODS:

We performed a retrospective chart audit for all patients receiving two or more denosumab doses at our institution between 1/1/16-8/11/18 and categorized those whose doses were >/=214 days (7 months) as delayed. We reviewed notes, imaging, and labs in a subset of this population to assess reasons for the delay. On 8/11/18, a new outpatient infusion center (OIC) therapy plan went into place. This plan bundled a one-year denosumab order (2 doses) with an automatic referral to the OIC along with physician reminders for renewal. We compared rates of delayed denosumab dosing before and after implementation of this new order process.

RESULTS:

Between 1/1/16-8/11/18, 385 patients received 1295 doses of denosumab, with 160 (41.6%) receiving 193 instances of delayed doses. We reviewed the charts of 98 individuals who received 111 instances of late doses between 7/6/16-8/11/18. The most prevalent reasons for delays were: delays in follow-up by the patient (27.9%), delays in the provider placing an order for the drug and OIC referral simultaneously (27.9%), and delays in OIC scheduling (18%). During the 14 months after implementation of the new ordering process, 347 patients received 614 instances of denosumab, of which 123 (35.4%) received 128 instances of delayed dosing. This is a relative decrease of 17.5% (p=0.09) for the proportion of patients with a late dose.

CONCLUSIONS AND FUTURE DIRECTIONS:

Nearly half of the patients on denosumab in our hospital received delayed denosumab dosing. Delays were often due to a lack of coordination between subsequent dose order placement and referral to the OIC. Our institution successfully implemented a bundled therapy plan to improve timely dosing. By March 2020, we expect to reassess the post-intervention group to further describe reasons for dosing delays. We also will compare rates of VFs associated with delayed denosumab dosing pre- and post-intervention periods.
MON-490 Calcitonin-Based Thyroidectomy Is a Safe Approach in Patients with Germline RET Mutation and Permits to Delay Surgery in Children
Authors: Prete Alessandro , Romei Cristina , Tacito Alessia , Ramone Teresa , Bottici Valeria , cappagli virginia , Viola David , Matrone Antonio , Agate Laura , Lorusso Loredana , Valerio Laura , Giani Carlotta , Puleo Luciana , Molinaro Eleonora , Elisei Rossella
Published: May 2020

Introduction: Medullary thyroid cancer (MTC) arises from C cells secreting calcitonin. In familial MTC cases, a germline RET mutation is discovered in 98% of cases. Nowadays, an early diagnosis and radical surgery are the only curative approach. However, thyroidectomy in children is associated with a higher rate of surgical adverse events, compared to surgery in adults. The best clinical approach in patient harboring germline RET mutation (gene carriers, GC) is still undefined. Methods and materials: since 1994 to 2018 we identified 174 GC by RET screening. 56 GC underwent total thyroidectomy and lymph node dissection for the evidence of high calcitonin levels at the first clinical evaluation, whereas 27 GC underwent surgery for high stimulated calcitonin levels during the active surveillance (median 16 months, range 13-118). 90 GC are still in follow up. Results: In the group of 27 GC patients who underwent surgery during the active surveillance, 15 GC had only C cells hyperplasia (CCH) foci and 12 were affected by MTC. These carcinomas were all confined to the thyroid, without any lymph node and distant metastasis. All these patients are still in clinical remission, after a median follow-up of 4 years (range 1-11). At time of the surgery, the patients affected by MTC were significantly older than patients harboring only CCH (median 49 vs 30 years old, respectively). Among these 27 GC, 7 were diagnosed as GC when they were younger than 18 years (median 7 years old, range 2-18) and they underwent surgery after a median period of 3 years (range 1-10 years), when they were all older than 7 years. In this group, 6 of 7 were affected by CCH and only one case by a microMTC. There were not any persistent surgical adverse events and all of them are still in clinical remission. 41 of 90 GC, who are still in active surveillance, were younger than 18 years at time of RET screening: nowadays, 10/41 are older than 18 years and 15/41 are older than 14 years, all with calcitonin still in the normal range. Conclusions: we demonstrated that the calcitonin-based thyroidectomy is a safe approach in GC. Intriguingly, this approach seems to be interesting especially in children in order to perform still an early and safe surgery but when they are older, possibly adults.
MON-642 Genetic Knockout of Intestinal Hexokinase Domain-Containing Protein 1 Affects Whole-Body Glycemic Control and Triglyceride Metabolism
Authors: Zapater Joseph Louis , Khan Wasim , Layden Brian T
Published: May 2020

Hexokinase domain-containing protein 1 (HKDC1) is a recently discovered putative fifth hexokinase that is widely expressed in a variety of human and mouse tissues. Previous work indicate that HKDC1 is important for whole-body glucose homeostasis and utilization in pregnancy and aging, and suggest roles for HKDC1 in nonalcoholic fatty liver disease development and progression of hepatocellular carcinoma. Prior work in the lab further showed that global heterozygous-deleted HKDC1 mice exhibit blunted uptake of triglycerides following an olive oil bolus compared to wild-type mice, suggesting a role for intestinal HKDC1 expression in intestinal lipid metabolism (unpublished results). To specifically study the significance of intestinal HKDC1 on whole-body glucose and lipid homeostasis, we utilized Cre-mediated recombination of HKDC1 in which Cre was expressed under the control of the villin gene promoter, creating a mouse model in which HKDC1 expression is specifically deleted in the intestinal epithelium. Quantitative RT-PCR data confirmed the knockout of HKDC1 within the mouse intestine in young and aged mice, while HKDC1 expression in other tissues was comparable to wild-type mice. Next, intestinal HKDC1 knockout mice and their wild-type littermate controls were either maintained on a normal diet or were switched to a high fat diet at 6 weeks of age to simulate the state of impaired glucose tolerance, and the effects of intestinal HKDC1 on glucose and lipid homeostasis were analyzed between 28-34 weeks of age. Mice fed a normal diet did not exhibit any differences in serum glucose or triglyceride during oral/intraperitoneal glucose tolerance tests or oral olive oil bolus, respectively, regardless of intestinal HKDC1 status. Interestingly, mice lacking intestinal HKDC1 that were on a high fat diet demonstrated improved overall glycemic control compared to wild-type mice after the administration of an oral glucose load, all while there were no changes in insulin levels, gluconeogenesis or insulin tolerance related to HKDC1 status. Additionally, introduction of an intraperitoneal glucose load to mice fed a high fat diet did not alter glucose control in the presence or absence of intestinal HKDC1. However, high fat diet-fed mice lacking intestinal HKDC1 did not have a significant increase in serum triglyceride following an oral olive oil bolus, while their stool fat and triglyceride content were comparable to wild-type. Collectively, these data indicate that intestinal HKDC1 has important roles in glucose and triglyceride metabolism within the intestinal epithelium, and further suggest a role in whole-body glucose homeostasis and in the development of insulin resistance and diabetes.
MON-595 Severe Copper Deficiency Post-Bariatric Surgery with Serious Preventable Complications
Authors: Aljaberi Asma Khaled , Boharoon Hessa
Published: May 2020

Copper is an essential cofactor in many enzymatic reactions vital to the normal function of the hematologic, vascular, skeletal, antioxidant, and neurologic systems. Parenteral nutrition and chronic tube feeding are used in various mal-absorptive syndromes, including following gastrectomy and gastric bypass surgery. Features of copper deficiency include hematologic abnormalities (anemia, neutropenia, and leukopenia) and myeloneuropathy; the latter is a rarer and often unrecognized complication of copper deficiency.

We describe a 36 -year-old Emirati woman who was referred to endocrinology service because of generalized body weakness and fatigue post bariatric surgery. The patient initially noted a lower extremity swelling in feet bilaterally that worsened in severity over time and progressed up to knees. Over a 3 month period, her ability to ambulate gradually deteriorated. She also noticed maculopapular skin rash over both shins. Patient had Sleeve Gastrectomy in 2011. Followed by conversion of sleeve to RYGB surgery in 2018 due weight loss failure. Patient is known to have well controlled hypothyroidism on thyroxine. She was prescribed vitamin D, neurobion, iron and multivitamins tablets post surgery but never been compliant. The patient was admitted with severe malnutrition due to poor oral intake over the last 5 months prior to admission. Her total weight loss was 34.5 kg (32% weight change, BMI 28 .52kg/m2) in less than 9 months post surgery. Initial labs revealed severe hypoalbuminemia, normochromic anemia and neutropenia. Iron, folate, thiamine, and vitamin B12 levels were normal. Vitamin B6 level was normal at 11 mcg/L (normal = 5-50 mcg/L). The serum copper level was low at 310 µg/l (normal = 794-2023µg/l). Zinc level was low at 447 µg/l (normal = 551-925µg/l). Nutritional needs were estimated using the following formulas; 22-25 kcal/kg ideal body weight (IBW)/d and 1.5-2.0 g protein/kg IBW/d, 30-35 ml IVF/kg /d. The patient’s input/output, body weight, and clinical status were monitored. Parenteral nutrition additive copper 0.3 mg/day and oral copper 8 mg daily, resulted in the rapid correction of hematologic indices over one week. Combined multivitamins supplementation and oral copper supplements alone normalized serum copper levels over 4 weeks and resulted in resolution of weakness and body edema.

This report serves to alert physicians of the association between bariatric surgeries and subsequent severe copper deficiency in order to avoid diagnostic delays and to improve treatment outcomes.