bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-370 Novel CASR Gene Mutation as a Cause of Familial Isolated Primary Hyperparathyroidism
Authors: Juneau Andrea K , Opoku-Boateng Adwoa , Uwaifo Gabriel Ikponmosa 
Published: May 2020

Abstract
BACKGROUND: Primary hyperparathyroidism (pHT) is one of the most common causes of hypercalcemia. About 10% of these patients have a familial cause of which MEN and the hyperparathyroid-jaw tumor syndrome (HJTs) are most common. Familial hypocalciuric hypercalcemia (FHH) due to loss of function mutations of the calcium sensing receptor (CASR) gene is an important familial mimic of this that needs to be distinguished. Beyond this are still a group of patients with familial isolated primary hyperparathyroidism (FIpHT). Recognition of this entity is important because of the different prognostic and surgical treatment strategy for their management compared to regular sporadic pHT. Clinical Case: A 58 yr old postmenopausal lady on topical HRT was referred for thyroid nodular disease. Her initial lab tests showed primary hyperparathyroidism with mild hypercalcemia. Her initial neck sonogram showed multiple benign appearing nodules that did not warrant biopsy. There was a history of hypothyroidism in her mother and thyroid cancer in a maternal cousin. In addition, her father and two sons have history of hypercalcemia that required repeated hospital admissions for treatment. Her two daughters to date have had no hypercalcemia, nephrolithiasis nor thyroid problems. There was no family history of jaw, renal nor brain or pituitary tumors and no history of severe dyspeptic disease nor familial cancers. She had hypercalciuria, normal bone density and non-obstructive nephrolithiasis. MEN-1 gene testing was normal. Parathyroid scan suggested a possible right sided parathyroid lesion and she had elective parathyroidectomy of an ectopic right parathyroid that was hypercellular on histology. The intra-operative PTH dropped following the lesion extraction by ~ 51%. Post operatively the patient’s mild pHT and hypercalcemia persists but imaging studies have been unrevealing. Further genetic testing for other possible etiologies of familial pHT were -ve for HJTs but revealed a novel somatic mutation of the CASR gene; c.1868G&gt;A (p.Gly623Asp) whose present significance is unclear. This variant has been described in one family with FHH but In silico predictive analyses of the mutation suggests a possible deleterious effect. Given her known family history of symptomatic hypercalcemia this novel mutation appears to be a hitherto unrecognized cause for FIpHT. The patient is presently being conservatively managed and monitored. Conclusion: While familial pHT is relatively uncommon its recognition is important as it can inform planned surgical intervention and expected prognosis for anticipated cure. While MEN and HJTs are the most common etiologies for familial pHT other possibilities need to considered when the history suggests possible FIpHT and our case highlights a novel CASR mutation as diagnostic consideration.
MON-274 Analysis of Perioperative Prophylactic Steroid for Pituitary Surgery Using a National Inpatient Database in Japan
Authors: Hattori Yujiro , Tahara Shigeyuki , Aso Shotaro , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo , Morita Akio 
Published: May 2020

Abstract
BACKGROUND: There is not enough evidence regarding the need for perioperative prophylactic steroid at the time of transsphenoidal pituitary surgery [1], and it is currently administered empirically. In patients with normal preoperative adrenal function, the meta-analysis of nonrandomized studies [2] and only two randomized controlled studies [3,4] suggested no necessity to routine steroid administration, but the number of the studies subjects was small. Analysis using big data has not been performed. Therefore, this study examined the relationship between perioperative steroid administration and complications using a nationwide Diagnosis Procedure Combination database in Japan.
Method: We performed a retrospective study on patients who had undergone pituitary surgery (excluding meningiomas, Cushing’s disease, and preoperative steroid administration) between July 2010 and March 2016. To this end, a nationwide inpatient database in Japan was used, and the patients were divided into a prophylactic steroid-administered group and a nonadministered group. Patients’ complications, including hypopituitarism, diabetes insipidus, meningitis, hyponatremia, and hypokalemia, and discharge status were examined by inverse probability of treatment weighting using propensity score.
Result: A total of 7,725 inpatients received prophylactic steroids, whereas 864 did not. The inverse probability of treatment weighting using propensity score revealed that the incidence of hypopituitarism and diabetes insipidus was significantly higher in the prophylactic steroid group than in the nonsteroid group (3.5% vs. 0.5%, P 0.001 and 9.6% vs. 6.0%, P = 0.001, respectively). There were no significant differences in the incidences of meningitis, electrolyte abnormalities, and length of hospital stay.
This study using big data suggests that prophylactic steroid administration may not be necessary in patients with an intact adrenocortical function undergoing transsphenoidal pituitary surgery.
1. Fleseriu M, et al. J Clin Endocrinol Metab. 101:3888–3921 (2016)
2. Tohti M, et al. PLoS One 10: e0119621 (2015)
3. Sterl K, et al. Neurosurgery 85: E226-e232 (2019)4. Lee HC, et al. Neurosurg (2020, in press)
SAT-385 A Normal FGF23 Does Not Preclude Tumor Induced Osteomalacia (TIO)
Authors: Nandam Neeharika , Ejaz Sadia , Styner Maya 
Published: May 2020

Abstract
BACKGROUND: The phosphaturic, bone-derived hormone FGF23, mediates bone loss in TIO. Tumor resection typically results in skeletal healing and reversal of biochemical defects.
Case: A 45-year-old Caucasian man with no past medical history presented with non-traumatic fractures of bilateral metatarsals. Over the subsequent 2 years, he sustained fragility stress fractures in bilateral femurs, eventually rendering him non-ambulatory; though he continued to work as a property manager in an office setting. History included 30 pack-years of smoking as well as osteochondrosarcoma in his mother. Labs showed a low phosphorus at 2.1 mg/dL [2.7–4.5], along with calcium 8.8 mg/dL [8.4–10.4], iPTH 48 pg/mL [12–88], and ALP of 155 [IU]/L [34–104]. 25-OH vitamin D and 1,25-(OH)2 vitamin D were 27 ng/mL [30–80] and 12 pg/mL [20–80], respectively. Free testosterone was 4.4 ng/mL [5–21] and LH 2.2 mIU/mL [3.0–10.0]. Other pituitary hormones and brain MRI were unremarkable.
Vitamin D3, calcitriol, phosphate and testosterone were prescribed. Testosterone was discontinued 6 months later, after diagnosis with DVT/PE. Incidental rib fractures on CXR prompted a 3-phase 99Tc-MDP bone scan, revealing multiple sites of uptake: ribs, scapulae, sternum, thoracolumbar spine, sacrum, bilateral ankles and feet. DXA revealed T-scores of -2.8 in the spine and -1.9 in the femoral neck.
Labs pointed to ongoing phosphate wasting, despite compliance with calcitriol 0.25 mcg, cholecalciferol 5000 IU and phosphorus 2250 mg in divided doses. Calculated TRP was 64% [&gt;80%] and TmP/GFR 1.74 mg/dL [2.5–4.5], consistent with low phosphate reabsorption. Urine 24-hour calcium was 244.8 mg. Testing for causal mutations of hypophosphatemic rickets and osteogenesis imperfecta was negative. FGF23 was within the reference range at 138 RU/mL [LabCorp ELISA 44–215], interpreted as inappropriately normal given ongoing phosphate loss. This prompted a search for a suspected TIO locus.
Two years after presentation, 18F-FDG-PET exhibited a hypermetabolic focus at the left suprapatellar recess. Biopsy was consistent with a mesenchymal tumor and chromogenic in situ hybridization (Mayo Clinic) was positive for FGF23 mRNA. After surgical resection of the 1.7 cm tumor, serum FGF23 declined to &lt;50 RU/mL and was 90 RU/mL 3 weeks later [Mayo &lt;180 RU/mL]. Calcitriol and phosphorus supplementation were discontinued. One year post-operatively phosphorus was 3.6 mg/dL [2.5–5.0], with a normal calcium, iPTH and 25-OH vitamin D. Lumbar spine T score improved to -1.0 (+46.43%).
Conclusion: A high clinical index of suspicion is required for TIO in the setting of phosphaturic osteomalacia, particularly with a normal serum FGF23. Recently, similar microRNA profiles were noted in osteosarcomas and TIO1. This, along with our patient’s family history raises the question of a possible predisposition to skeletal neoplasms.
1. Green et al. Bone Reports, 2017.
MON-463 Thyroid Abscess Due to Intravenous Drug Use: A Rare Cause of Thyroid Storm
Authors: Mathai Christine , Coppola Anthony , Vaz Cherie 
Published: May 2020

Abstract
Objective: Our objective is to discuss the clinical presentation, diagnosis and management of thyroid storm due to thyroid abscess.
Methods: We report a case of thyroid abscess due to intravenous drug use (IVDU) resulting in thyroid storm.
Results: A 28 year old female with history of IVDU and no known thyroid disease presented with neck pain and fever after injecting heroin into her neck 10 days prior. CT Neck showed an early bilateral thyroid abscess 3.0 cm on the left and 2.0 cm on the right, with heterogeneous enhancement in the rest of the thyroid concerning for thyroiditis. TSH 0.4 m[iU]/L (0.34–5.60 m[iU]/L). She was started on antibiotics but left AMA. She returned 9 days later with worsening neck swelling and pain. CT neck showed a multiloculated, bilateral thyroid abscess 8.6 cm on the left and 5.3 cm on the right. She suffered a cardiac arrest, was intubated, and resuscitated with defibrillation and epinephrine. WBC 25.9 K/mm3, ANC 9.8 K/mm3, TSH &lt;0.01 m[iU]/L (0.34–5.60 m[iU]/L), fT4 4.25 ng/dL (0.89–1.76 ng/dL), T3 96.0 ng/dL (70–204 ng/dL), TSI &lt;89 (&lt;140%). Burch-Wartofsky score was 60. She was treated with propylthiouracil (PTU) and hydrocortisone. She developed transaminitis post-arrest due to shock liver, AST 2881 U/L (15–37 U/L), ALT 981 U/L (16–61 U/L) and PTU was discontinued. Two days later TSH &lt;0.005 m[iU]/L (0.4–4.5 m[iU]/L), fT4 3.06 ng/dL (0.89–1.76 ng/dL), T3 62.0 ng/dL(60.0–181.0 ng/dL). Neck ultrasound showed enlarged, heterogeneous thyroid with numerous loculated fluid collections. Incision and drainage (I&D) drained 100 cc of pus and drains were left in situ. Cultures grew MRSA. Patient was treated with vancomycin, clindamycin, and metronidazole. Following I&D, thyroid function improved to normal and eventual hypothyroidism by postoperative day 8, fT4 0.59 ng/dL, T3 32.1 ng/dL, TSH 1.2 m[iU]/L. She was initiated on levothyroxine 50 mcg daily with follow up testing for possible resolution of thyroiditis-induced hypothyroidism.
Discussion: Thyroid abscess causing acute suppurative thyroiditis presenting as thyroid storm is rarely seen1. There are no reported cases of thyroid storm occurring as a complication of IVDU. Acute suppurative thyroiditis has been reported following MSSA bacteremia from a forearm abscess due to IVDU, TSH 0.02U/mL, fT4 3.89ng/dL, fT3 of 5.1pg/mL2. Presentation was consistent with thyrotoxicosis but not thyroid storm2. It is important to consider thyroid abscess as a rare cause of thyroid storm, in patients with risk factors such as IVDU. Management with antithyroid drugs (ATD), steroids, antibiotics, and I&D produced successful outcomes in this patient after cardiac arrest.
Conclusion: Thyroid abscess resulting in thyroiditis can be a rare cause of thyroid storm that resolves following I&D. Successful management includes use of antibiotics, steroids, and ATD for thyroid infection, thyroid inflammation and thyroid hormone levels.
SAT-408 Bioactivity of Long Acting PTH Fusion Molecules Tested in a Novel Non-Surgical Animal Model of Hypoparathyroidism
Authors: Wilkinson Ian R , Ramezani-Pour Narjes , Esfahani Sayyed Hamid Zarkesh , Eastell Richard , Ross Richard John M 
Published: May 2020

Abstract
Introduction: There is an unmet need for the development of long-acting PTH molecules to treat patients with hypoparathyroidism. We have established a novel non-surgical rodent model of hypoparathyroidism using oral Cinacalcet-HCl to test long acting analogues of PTH. Here we have tested the pharmacodynamics properties of two long acting PTH fusion molecules.
Methods: PTH fusion molecules tested: Fusion-1 is PTH (1–34) linked to GHBP (residues 1–238), and Fusion-2 is a Hybrid PTH-PTHrP (1) linked to GHBP (residues 1–238). For in vivo studies, normal male wistar rats were gavaged with 30 mg/kg Cinacalcet-HCl, immediately followed by a subcutaneous dose of PTH Fusion at 20 nmol/kg. Control animals received PTH (1–34) and vehicle only. Serum samples were taken and analysed for ionised calcium (iCa).
Results: Oral administration of Cinacalcet-HCl caused a reduction in iCa that was significantly different from vehicle controls at 2 to 24hrs post dose (ANOVA P &lt; 0.0001). PTH 1–34 maintained iCa levels for 2 hours after administration above that of Cinacalcet-HCl (AUC±SD (mmol/L).hr from baseline, 0.076 ±0.047 and 0.168±0.0874, t-test P=0.0289) but then levels fell and recovered as for Cinacalcet-HCl alone. Subcutaneous doses of both fusions were able to abrogate the effects of Cinacalcet-HCl from 4hrs post dose onwards giving a prolonged response, with iCa levels quicker to return to baseline levels at 48hrs compared to Cinacalcet-HCl. The AUC±SD (mmol/L).hr from baseline for iCa over 72 hours was 3.93±1.4 for Fusion-1, 5.0±2.7 for Fusion-2 & 10±2.8 for Cinacaclet-HCl and were significantly reduced for both fusions compared to Cinacalcet-HCl alone (t-test P = 0.0028 & P = 0.019, respectively) and not significantly different from vehicle only.
Conclusions: Cinacalcet-HCl behaved as expected in terms of iCa lowering (2). PTH maintained iCa but only for 2 hours. Both PTH fusion molecules showed a delayed and prolonged response and reduced the impact of Cinacalcet-HCl induced low iCa levels from 4hrs to 24hrs. These data provide proof of concept for long acting biological activity of these novel PTH fusion proteins.
References:
1. Shimizu M, Joyashiki E, Noda H, Watanabe T, Okazaki M, Nagayasu M, et al. Pharmacodynamic Actions of a Long-Acting PTH Analog (LA-PTH) in Thyroparathyroidectomized (TPTX) Rats and Normal Monkeys. J Bone Miner Res. 2016;31(7):1405–12.
2. Nemeth EF, Heaton WH, Miller M, Fox J, Balandrin MF, Van Wagenen BC, et al. Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. The Journal of pharmacology and experimental therapeutics. 2004;308(2):627–35.
SAT-312 Beta-Arrestin 2 Is Required for Dopamine Receptor Type 2 Inhibitory Effects on Akt Phosphorylation and Cell Proliferation in Pituitary Tumors
Authors: Mangili Federica , Giardino Elena , Treppiedi Donatella , Barbieri Anna Maria , Catalano Rosa , Locatelli Marco , Lania Andrea G , Spada Anna , Arosio Maura , Mantovani Giovanna , Peverelli Erika 
Published: May 2020

Abstract
Dopamine receptor type 2 (DRD2) agonists are the first-choice treatment for PRL-secreting pituitary tumors but are poorly effective in non-functioning pituitary neuroendocrine tumors (NF-PitNETs). DRD2 reduces AKT phosphorylation in lactotrophs, but no data are available in NF-PitNETs. DRD2 effects on AKT are mediated by a β-arrestin 2-dependent mechanism in mouse striatum.
The aim of this study was to investigate DRD2 effects on AKT phosphorylation and cell proliferation in human primary cultured NF-PitNET cells and in rat tumoral lactotroph cells MMQ, and to test β-arrestin 2 involvement.
We found that DRD2 agonist BIM53097 induced a reduction of p- AKT /total-AKT ratio in MMQ (-32.8±17.6%, p&lt;0.001 vs basal) and in a subset (n=15/41,36.6%) of NF-PitNETs (subgroup 1). In the remaining NF-PitNETs (subgroup 2), BIM53097 induced an increase of p- AKT. The ability of BIM53097 to reduce p-AKT correlated to its antimitotic effect, since the majority of subgroup 1 NF-PitNETs was responsive to BIM53097 and nearly all subgroup 2 NF-PitNETs were resistant. β-arrestin2 was expressed in MMQ and in 80% of subgroup 1 NF-PitNETs, whereas it was undetectable in 77% of subgroup 2 NF-PitNETs.
In MMQ, β-arrestin 2 silencing prevented DRD2 inhibitory effects on p-AKT and cell proliferation. Accordingly, β-arrestin 2 transfection in subgroup 2 NF-PitNETs conferred to BIM53097 the ability to inhibit both p-AKT and cell growth.
In conclusion, we demonstrated that β-arrestin 2 is required for DRD2 inhibitory effects on AKT phosphorylation and cell proliferation in MMQ and NF-PitNETs, paving the way for a potential role of β-arrestin 2 as a biomarker predicting NF-PitNETs responsiveness to treatment with dopamine agonists.
SUN-075 A Guide to Professional Development: Funding Your Research Through NICHD
Authors: Eisenberg Esther , Halvorson Lisa , Ravindranath Ravi , Winer Karen 
Published: May 2020

Abstract
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) leads research and training efforts to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all. Under the “New Strategic Plan 2020”, NICHD will focus on priorities to: 1. Understand the Molecular, Cellular, and Structural Basis of Development; 2. Promote Gynecologic, Andrologic, and Reproductive Health; 3. Set the Foundation for Healthy Pregnancies and Lifelong Wellness; 4. Improve Child and Adolescent Health and the Transition to Adulthood; and 5. Advance Safe and Effective Therapeutics and Devices for Pregnant and Lactating Women, Children, and People with Disabilities. Cross-cutting topics include health disparities, prevention, infectious disease, nutrition and global health. NICHD is committed to funding the largest number of meritorious projects, while allowing flexibility to support high program priorities and respond to emerging scientific opportunities. Mechanisms to support individual research and training include research project grants (RPGs), training and career development awards (K awards) and fellowships (Pre and Postdoctoral). There are specific eligibility requirements for each of these mechanisms. Applicants are advised to contact a program officer (PO) and discuss the idea, its relevance to program priorities of NICHD, and potential funding opportunities available. While preparing your application, receive guidance on the grantsmanship from the PO, in addition to peers working at your institution. The PO can help you to understand the peer review process at NIH and suggest study sections with a good fit to review your application. The peer review process is independent of the program administration at NIH. Applicants can avoid some common errors in writing applications by reviewing the NIH website and understanding the NIH grants process. The NIH has recently revised its approach to the review and monitoring of vertebrate animal and human subject research. Applicants may receive guidance both at their institution (from which the application is submitted) and NIH. NICHD has developed new guidelines and processes to enhance and improve clinical trials. Currently, applications may be submitted to separate funding opportunity announcements for “clinical trials required” and “clinical trials optional”. The goal is to ensure adequate clinical trial-specific information in the grant applications for thorough review. Additional new review criteria consider training in good clinical practice and expanded registration and results reporting in ClinicalTrials.gov.
MON-673 Use of Metabolic Syndrome Severity to Assess Treatment with Vitamin-E and Pioglitazone for Non-Alcoholic Steatohepatitis
Authors: DeBoer Mark Daniel , Mack Jasmine A , Gurka Matthew J 
Published: May 2020

Abstract
BACKGROUND: Non-alcoholic steatohepatitis (NASH) represents inflammatory and fibrotic changes in the setting of non-alcoholic fatty liver disease (NAFLD) and can progress to cirrhosis. While clinical management of NASH has proven difficult, the Pioglitazone, Vitamin E or Placebo NASH study (PIVENS) demonstrated that treatment with either pioglitazone or vitamin-E increased odds of NASH-resolution. NASH is strongly associated with insulin resistance and the metabolic syndrome (MetS) as both a predictor and an outcome, though this has only been studied using dichotomous MetS criteria (e.g. ATP-III). We previously formulated a sex- and race/ethnicity-specific MetS severity Z-score (MetS-Z) that serves as a continuous measure of metabolic dysregulation. We hypothesized: 1) there would be a decrease in severity of MetS over the course of intervention in PIVENS and 2) the degree of decrease in MetS-Z early in the course of treatment would be a predictor of future NASH resolution. METHODS: Participants in PIVENS (n=201) had biopsy-confirmed NASH at baseline and were randomized to receive pioglitazone, vitamin E or placebo for 96 weeks, when they received repeat biopsy to assess for NASH resolution. We compared levels of MetS-Z and its standardized effect size (the absolute observed difference in MetS-Z for an individual divided by the overall baseline standard deviation of MetS-Z) at baseline, 48 weeks and 96 weeks and used logistic regression to determine associations between baseline MetS and the change in MetS from 0–48 weeks on ultimate NASH resolution—both overall and by intervention group. RESULTS: During the 96 weeks of intervention, 73 participants (363%) exhibited NASH resolution. Baseline MetS-Z was inversely associated with odds of NASH resolution, such that those with higher MetS severity at baseline were less likely to experience NASH resolution (odds ratio [OR] per 1-SD of MetS-Z-score: 0.54, 95% confidence interval [CI] 0.33,0.88). Of the three intervention groups, the decrease in MetS-Z during initial 48 weeks of intervention was greatest for pioglitazone treatment (effect-size: -0.31, CI -0.15,-0.48). During treatment with vitamin E, those with significant 48-week changes in MetS-Z tended to be those with vs. without ultimate NASH resolution (-0.18 vs. -0.05). In the group overall, 48-week change in MetS-Z was inversely associated with NASH resolution (OR of per 1-SD change: 0.56, CI 0.35,0.88). CONCLUSION: Individuals with more severe metabolic derangement at baseline were less likely to exhibit NASH resolution, suggesting that individuals may have a threshold of MetS-severity beyond which successful treatment is unlikely. As hypothesized, a decrease in MetS-Z over time was associated with improved odds of NASH resolution. As an integrated marker of metabolic abnormalities, MetS-Z may be a new way non-invasively follow for successful treatment of NASH.