bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR33-02 The Treatment of Partial Lipodystrophy in the Setting of Neutralizing Antibody Against Metreleptin with Leptin Receptor Agonist REGN4461
Authors: Akinci Baris , de Freitas Maria Cristina Foss , Baker Mark , Hench Rita , Neidert Adam , Boutros Sabine , Akinci Efe Yagiz , Oral Elif A 
Published: May 2020

Abstract
Background: An 18-year-old patient with atypical partial lipodystrophy had a transient initial metabolic response to metreleptin that deteriorated when neutralizing antibodies against metreleptin developed. A therapeutic trial with setmelanotide did not result in any metabolic benefit as desired. Because her status continued to deteriorate, we attempted to treat her with REGN4461, a fully human monoclonal antibody that is an agonist to the human leptin receptor (LEPR). Clinical Case: A compassionate use protocol (IND No. 144013) was initiated to treat the patient with REGN4461. The treatment consisted of 5 mg/kg intravenous infusion followed by 300 mg weekly subcutaneous injections of REGN4461. The primary endpoint was achievement of fasting triglycerides &lt; 500 mg/dL without the need for ongoing plasmapheresis. Treatment-emergent adverse events were also followed. Here, we report her first 21-week response to treatment with REGN4461. The treatment resulted in a reduction of triglycerides from 1288 mg/dL to 344 mg/dl and allowed her to discontinue plasmapheresis. She lost 3.4 kilograms so far, and her liver size reduced per liver span measured by physical examination. Also, the liver MRI at week 12 showed a significant reduction in liver size and fat content (from 29.9% to 16.6%). Although her glucose control is still challenging, a slight reduction in her HbA1c was observed at week 12 along with improvements in her average glucose levels and total daily insulin requirement so far. No untoward signals were detected in her safety measurements. Conclusion: To date, treatment with REGN4461 offered substantial clinical benefit by improving the metabolic abnormalities in this unique patient. This experience represents the longest human exposure with REGN4461. The improvements noted in metabolic parameters and hepatic steatosis are similar to previous observations in lipodystrophic humanized LEPR mice. Our results suggest that REGN4461 showed clinical benefit even in the presence of neutralizing antibodies to metreleptin.
SAT-251 New Diagnosis of Acromegaly with DKA as Initial Presentation
Authors: Gundluru Rajani , Verma Ritika , Regunath Hariharan , Gardner Michael J , Huynh Kiet 
Published: May 2020

Abstract
Background: While diabetes mellitus from growth hormone related insulin resistance is not uncommon in GH secreting tumors, initial presentation with diabetic ketoacidosis is rare.
Clinical Case: 31 YO male with no significant past medical history presented with c/o fatigue, 40 lb weight loss, polyuria, polydipsia. Clinical features of acromegaly with frontal bossing, protruding jaw, large hands and feet, thick spade like fingers, hammer toes, high arches and thickened fat pads on both feet were noted. Initial labs were consistent with DKA with anion of 31 mmol/L (0-20), blood glucose 241 mg/dl, bicarb 12 mmol/L (22-29), serum betahydroxy butyrate &gt; 8 mmol/L (0-0.29), urine positive for glucose, ketones, protein. Patient was initially treated with IV insulin per DKA protocol, transitioned to subcutaneous insulin.
MRI brain showed 2.1x1.3x2.1 cm pituitary macro adenoma. Labs showed elevated IGF1 LC/MS, S 1094 ng/ml (54-310), IGFBP3 14 mcg/ml (3.5-7), Z score IGF MS Mayo &gt; 3 (-2 to +2), normal FSH 7.1 m unit/ml (1.5-12.4), normal LH 3.4 m unit/ml (1.7-8.6), normal prolactin 6 ng/ml (4-15), normal ACTH 10 pg/ml, cortisol 13.4 mcg/dl, low total testosterone 48.2 ng/dl (193-836), normal free testosterone 7.92 ng/dl (4.85-19), normal TSH 1.55 mc unit/ml (0.27-4.2) and free T4 1.17 ng/dl (0.93-1.7). The patient was discharged home on 120+ units of total daily dose of insulin, after initial hospital admission.
He underwent trans sphenoidal resection of pituitary macro adenoma one month after his initial presentation. Surgical pathology confirmed growth hormone producing adenoma. He was successfully weaned off from insulin in one month following surgery.
Conclusion: DKA is an unusual initial presentation of growth hormone producing tumors. As more cases are being reported it is important to be vigilant to look for DKA presentation in these patients and adjust/wean patients insulin once the growth hormone producing tumor is treated either with surgery or medications.
SAT-468 Anticoagulation Conundrum: A Case Of Embolic Stroke Due To Thyrotoxic Atrial Fibrillation
Authors: Munshi Laishiya , Gorantla Yamuna , Mascarell Susana 
Published: May 2020

Abstract
Background: Thyrotoxicosis is not incorporated into any of the atrial fibrillation (AF) CVA risk stratification methods, including CHADS2VASc, as neither the American College of Cardiology/American Heart Association nor the American College of Chest Physicians view it as an independent risk factor of CVA. However, the literature has reported numerous cases of patients with thyrotoxic AF and low CHADS2VASc scores who developed CVA. It is unclear which patients with thyrotoxic AF would benefit from prophylactic anticoagulation (AC).
Clinical Case: A 50-year-old male without past medical history presented for palpitations. He was found to be in AF with rapid ventricular rate. Labs revealed thyrotoxicosis (TSH &lt;0.010 [RR 0.34-5.6 μIU/mL], FT4 3.57 [RR 0.61-1.64 ng/dL], FT3 5.26 [RR 2.5-4.5 pg/mL], and TSI negative). He was started on methimazole but no AC, as his CHADS2VASc score was 0. A few hours after admission, he developed a right-sided facial droop and weakness & aphasia. CT head showed acute left MCA infarct. CTA head/neck revealed occlusive embolus in the distal left M1 segment. He underwent IR-guided embolectomy and received intra-arterial tPA. Echocardiogram did not show thrombi or atrial level shunt but showed right atrial dilation. After extensive work-up, etiology of CVA was determined most likely a cardioembolic source due to thyrotoxic AF. Patient was treated with PTU and steroids initially for two days due to recent contrast exposure (CTA and embolectomy) and poor neurologic status, in order to obtain the added benefit of decreased T4 to T3 peripheral conversion. Patient was started on AC two weeks after his CVA (given initial risk of hemorrhagic conversion due to large CVA burden), at which time his weakness and aphasia were slowly improving, but he remained with significant neurologic deficits.
Discussion : The current thought that thyrotoxicosis is not an independent risk factor of CVA in patients with AF has led to recommendations against prophylactic AC for this specific group. Although recent research has suggested that patients with thyrotoxic AF are at a lower risk of CVA than patients with non-thyrotoxic AF, there have still been many reported cases of CVA in patients who have thyrotoxic AF but no other risk factors for CVA. This discrepancy in association between thyrotoxic AF and CVA needs to be clarified.
Conclusion: This case of a middle-aged man with thyrotoxic AF who developed a debilitating CVA after being treated according to his CHADS2VASC score of 0 (he was not given prophylactic AC) mirrors multiple cases in the literature. It highlights the potential benefit of examining thyrotoxic patients with AF more closely in order to more effectively risk stratify them for CVA or further exploring the relationship between thyrotoxicosis and CVA. This may help to identify more patients who could benefit from AC and thus prevent devastating consequences of CVA.
MON-614 Degree of Diabetes Control Determines the Admission Severity of Diabetic Ketoacidosis
Authors: Grover Harshwant , Dhillon Puneet , Gopisetti Neethu , Rosenberg Daniel Evan , Patel Rajeshkumar 
Published: May 2020

Abstract
Objectives: To determine whether the degree of diabetes control correlates with the admission severity of diabetic ketoacidosis (DKA).
Methods: A Retrospective chart review was performed for patients admitted with DKA to the medical ICU at Abington Memorial Hospital between January 1, 2017 and January 1, 2018. Laboratory Data required to determine an acute physiology and chronic health evaluation (APACHE) score, hemoglobin A1C, length of hospital stay was recorded. The APACHE score was used to determine the severity of disease at admission. Patients were divided into two groups: low severity (APACHE &lt;15) and high severity (APACHE &gt;15).
Results: A total of 50 patients were included in the analysis. The mean age of the patients was 47 yrs (range 17-85 yrs). 52%(n=26) of the population were males. The overall mean APACHE II at admission was 15 (range 3-28). The low severity group (APACHE &lt;=15) and high severity group (APACHE &gt;15) were equally matched at 25 patients each. The mean APACHE scores were 9.9 and 18.7 for the low and high severity groups respectively. The mean hemoglobin A1C values for the low and high severity groups were 10.5 and 15 respectively. The average length of ICU/hospital stay was 1.6/3.65 and 1.54/3.61 days for the low and high severity groups respectively.
Conclusions: According to our study, a higher severity of DKA (higher APACHE) was associated with a higher hemoglobin A1C level. However, the study did not find any difference in the average length of ICU/hospital stay between the two groups.
SUN-241 Adult Exposure to Iodoacetic Acid Leads to Abnormal Expression of Key Genes Related to Hypothalamic and Pituitary Control of Reproductive Function
Authors: Gonzalez Rachel , Weis Karen E , Gonsioroski Andressa V , Flaws Jodi A , Raetzman Lori T 
Published: May 2020

Abstract
Water disinfection byproducts (DBPs) are formed when chemicals used to decontaminate water come into contact with natural or synthetic organic material. DBPs have been linked to a range of health concerns including reproductive disfunction. One such DBP, the monohalogenated iodoacetic acid (IAA), is formed when iodide reacts with a disinfectant, for example, chlorine. IAA is of particular health concern; not only is iodide widely present in the water supply, especially in coastal communities and those near fracking sites, but IAA has been found to be one of the most cyto- and genotoxic DBPs. Further, a previous study has indicated that in vitro IAA exposure significantly inhibits antral follicle growth and reduces estradiol levels in ovaries. However, little is known about how IAA affects the other major components of the reproductive axis: the hypothalamus and pituitary. The reproductive axis relies on homeostatic release of hormones to communicate from one organ to another and alterations at any level may impact reproduction. So, we set out to test the hypothesis that exposure to IAA would lead to disrupted expression of key hypothalamic and pituitary genes related to reproductive function. We continually exposed female adult CD1 mice to 0.5, 10, 100, or 500 mg/L IAA in their drinking water for approximately 35 days (postnatal day 40 (P40) to their first day in diestrus following P75.) Whole pituitaries and hypothalamic punches containing the arcuate nucleus (ARC), anteroventral periventricular zone (AVPV), and medial preoptic nucleus (mPOA) were collected and processed for qPCR analysis. We find that while kisspeptin (Kiss1) expression in the AVPV - the population responsible for generating the LH surge - is unchanged, 0.5 mg/L IAA exposure significantly increases Kiss1 in the ARC, which controls pulsatile GnRH release, and there is a trending increase (p=.056) at 10mg/L. We also measured ARC expression of Neurokinin B (NKB; Tac2), a neuropeptide secreted by kisspeptin co-expressing neurons to autosynaptically stimulate Kiss1 release. We found no change in mRNA levels of Tac2. We also saw no significant changes in GnRH (Gnrh1) mRNA expression. At the level of the pituitary, there is no change in Lhb mRNA levels. Exposure to 10 mg/L IAA leads to significantly reduced Fshb expression, however FSH serum levels are not significantly changed. These data, taken together with previous findings in the ovary, indicate that IAA has the potential to disrupt each major level of the reproductive axis: ovarian follicle development and steroid synthesis, hypothalamic arcuate Kiss1 synthesis, and Fshb synthesis from the pituitary. Further research is necessary to elucidate at which levels IAA acts directly and at which it acts through action on another component of the axis. Additionally, future studies can clarify the mechanism through which IAA has these effects.
SAT-119 Targeting Glutamate Metabolism and Signaling in ER+, Endocrine Therapy-Resistant Breast Cancer
Authors: Olukoya Ayodeji O , Stires Hillary , Guerra Yanira , Persaud Sonali , Ma Shihong , Raj Ganesh V , Riggins Rebecca B 
Published: May 2020

Abstract
Estrogen receptor-positive (ER+) breast cancer is the most commonly diagnosed form of this malignancy. Aromatase inhibitors and selective estrogen receptor modulators or degraders (SERMS, SERDs) can be highly effective in treating ER+ breast cancer, but de novo and acquired resistance to these interventions is a persistent clinical problem. Endocrine therapy resistant breast cancer cells rewire their metabolism to support cellular demands associated with rapid proliferation and/or increased invasion and metastasis. An important feature of this metabolic flexibility is conversion of glutamine to glutamate, an amino acid integral to protection of cells from oxidative stress. Consistent with this, we show multiple cellular models of ER+, endocrine resistant breast cancer cells markedly increase glutamate release and upregulate expression of essential glutamine/glutamate metabolic enzymes and transporters, including the glutamate/cystine antiporter xCT, glutamate dehydrogenase (GLUD1/2), and/or the glutamine importer SLC1A5. Riluzole (RIL) is FDA-approved for the treatment of amyotrophic lateral sclerosis (ALS), and has several proposed mechanisms of action, including suppression of glutamate release and increased glutamate uptake. We show ER+, endocrine responsive and resistant breast cancer cells are growth-inhibited by RIL. This is due to an increase in cell death, particularly in endocrine resistant breast cancer cells, and cell cycle arrest. Interestingly, histologic subtype confers a different cell cycle arrest profile, with invasive ductal cancer (IDC) models arresting in G1 but invasive lobular cancer (ILC) models arresting in G2/M. Isobologram analysis of RIL plus SERMs or SERDs shows additive-to-synergistic activity in a subset of ER+ cell line models, and preliminary studies show combination activity in patient-derived explants (PDEs). Mechanistically, we tested whether signaling through metabotropic glutamate receptors (mGluRs, GRMs) and/or cystine import contribute to RIL’s growth-inhibitory phenotype. Antagonists of mGluRs/GRMs don’t phenocopy the effects of RIL, suggesting extracellular glutamate signaling through these receptors is not a key mechanism. Rescue experiments with β-mercaptoethanol to promote cystine uptake through transporters other than xCT show partial reversal of RIL-mediated cell cycle arrest in some cells, suggesting xCT may contribute to RIL-induced growth inhibition. In summary, we show RIL may be a viable addition to endocrine therapy in ER+ breast cancer. Ongoing studies will test additional mechanism(s) by which RIL may attenuate the growth of ER+ breast cancer models in vitro, including inhibition of protein kinase C and casein kinase 1 delta. We are further testing RIL efficacy alone and in combination with a SERD in primary tumors and lung metastases in a ER+ patient-derived xenograft (PDX) model.
SAT-479 Atypical Presentation of Recurrent Cardiac Tamponade Following Pericardial Window in the Setting of Uncontrolled Hypothyroidism
Authors: Khan Sara Atiq , Sarwar Chaudhry M S , Avichal Dipa 
Published: May 2020

Abstract
INTRODUCTION:
Classically, cardiac tamponade presents with hypotension, distant heart sounds and tachycardia (Beck’s triad). Pericardial window is considered effective treatment. Pericardial effusions are relatively common in hypothyroidism (3-6%) (1). Cardiac tamponade, however, is rarely seen in patients with hypothyroidism secondary to pericardial distensibility and the slow accumulation of fluid, allowing significant fluid accumulation without hemodynamic compromise (2).
CLINICAL CASE:
A 84 year-old female with history of post-surgical hypothyroidism (on levothyroxine 150 mcg) following total thyroidectomy for thyroid cancer, cardiac tamponade requiring pericardial window formation two years prior, presented for dyspnea on exertion and pedal edema for several days. She was tachypneic to 22/min with heart rate 47/min and blood pressure 92/62. Distant heart sounds were noted on exam.
EKG demonstrated sinus bradycardia, low voltage QRS and T wave flattening. Further workup revealed TSH elevated to 44 uIU/mL (N:0.27–4.2 uIU/mL), free T4 0.17 ng/dl (N:0.93-1.7 ng/dl) and undetectable T3 (N: 80-100 ng/dl). Echocardiogram unexpectedly demonstrated a large circumferential pericardial effusion with diastolic collapse of the right atrial, right ventricular free wall, significant respiratory variations and interventricular dependence. These findings were consistent with cardiac tamponade physiology. She underwent a video assisted left thoracotomy pericardial window formation along with drainage of 400cc of yellow pericardial fluid. Fluid cytology and tissue histopathology were negative for malignancy. Her uncontrolled hypothyroidism was considered the cause for recurrence of cardiac tamponade and her levothyroxine dose was increased to 175 mcg. At two week follow up, she reported symptomatic improvement on the higher levothyroxine dose. Echocardiogram did not show reaccumulation of fluid.
CONCLUSIONS:
Sinus tachycardia is found in most patients with cardiac tamponade, except in hypothyroid patients (2). A high degree of suspicion is needed to diagnose cardiac tamponade in hypothyroidism, even in patients who have undergone presumed definitive therapy with a pericardial window in the past. The recent onset of pedal edema and low blood pressure were important indicators of impending cardiac compromise in our patient.
Hypothyroid patients may be at higher risk of pericardial window failure compared to patients with cardiac tamponade of other etiologies, especially if thyroid replacement therapy is inadequate. The scientific literature is lacking in this regard and warrants further investigation.
References:
1 Bajaj R, et al. Cardiac tamponade in hypothyroidism. BMJ Case Rep. 2014;:bcr2014204076
2 Wang JL, et al. Hypothyroid cardiac tamponade: clinical features, electrocardiography, pericardial fluid and management. Am J Med Sci 2010;340:276–81.
OR17-02 Changes in Hepatokines and Apolipoproteins Are Associated with Metabolic Response to Metreleptin in Partial Lipodystrophy
Authors: Akinci Baris , Ajluni Nevin , Eldin Abdelwahab Jalal , Swaidan Mario , Hench Rita , Neidert Adam , Luo Yingying , de Freitas Maria Cristina Foss , Oral Elif A 
Published: May 2020

Abstract
Introduction Metreleptin treatment may improve the metabolic aspects of partial lipodystrophy; however, the treatment response is heterogeneous. This study aimed to explore changes in circulating apolipoprotein concentrations, as well as ANGPLT3, ANGPLT4, and IGF-1 levels in patients treated with Metreleptin as part of a clinical study investigating the efficacy of Metreleptin in nonalcoholic steatohepatitis (NASH) associated with partial lipodystrophy (ClinicalTrials.gov identifier: NCT01679197). Methods Serum samples of 18 patients with partial lipodystrophy who underwent a full metabolic evaluation and paired liver biopsies before and after Metreleptin were studied. Patients were tested at baseline, month (M) 3, M6, and M12. Glycemic response was defined as “more than 1% HbA1c reduction from baseline”. Lipid response was defined as “more than 30% decrease in triglycerides from baseline”. The hepatic response was defined as “a decrease of 2 points or more from baseline in NASH score, without an increase in fibrosis”. Patients with “any 2 of 3 above” at M12 were defined as metabolic responders. Results Metreleptin treatment resulted in significant reductions in triglycerides (346 mg/dL vs. 253 mg/dL; F: 8.474; p &lt; 0.001), apo B (145.24 mg/dL vs. 111.09 mg/dL; F: 9.266: p &lt; 0.001), apo CII (18.65 mg/dL vs. 15.95 mg/dL; F: 6.663: p = 0.001), apo CIII (62.95 mg/dL vs. 49.33 mg/dL; F: 5.640, p = 0.002), apo E (8.16 mg/dL vs. 6.52 mg/dL; F: 11.056, p &lt; 0.001), and ANGPLT3 (14.36 ng/mL vs. 12.00 mg/dL; F: 4.348; p = 0.008) over time. IGF-1 levels significantly increased at M3 (134 ng/mL vs. 139 ng/mL; p = 0.001), however the difference was not significant over time. Metabolic responders had lower baseline leptin (12.4 ng/mL vs. 27.8 ng/mL; p = 0.024) and IGF-1 (95 ng/ml vs. 151 ng/mL; p = 0.008), and higher apo CII (39.06 mg/dL vs. 17.90 mg/dL; p = 0.011), apo CIII (173.57 mg/dL vs. 51.51 mg/dL; p = 0.015), apo E (18.41 mg/dL vs. 5.89 mg/dL; p = 0.002), and ANGPLT3 (17.33 ng/mL vs. 10.06 ng/mL; p = 0.04). Metabolic responders had a significant increase in IGF-1 (95 ng/mL vs. 134 ng/mL; p = 0.019), which was statistically distinguished from non-responders (p = 0.004). Responders also had a greater reduction in apo CII (20.51 mg/dL vs. -1.84 mg/dL; p = 0.001), apo CIII (32.59 mg/dL vs. -7.83 mg/dL; p = 0.007), apo E (8.17 mg/dL vs. 0.22 mg/dL; p = 0.001), and ANGPLT3 (6.08 ng/mL vs. -0.16 ng/mL; p = 0.005) early after treatment at M3. Conclusions Metreleptin treatment lowers levels of apolipoproteins associated with triglyceride metabolism as well as ANGPLT3 in patients with partial lipodystrophy. Metabolic response to Metreleptin appears to be correlated with early changes in these factors and an increase in IGF-1 levels.
SUN-188 Intra-Articular Triamcinolone Injections - a “Slipped” Cause of Cushing’s Syndrome
Authors: Shi Melody , Balikcioglu Pinar Gumus , Benjamin Robert , Freemark Michael 
Published: May 2020

Abstract
Background:
Triamcinolone injections are used to treat various orthopedic and rheumatologic conditions; their effects on the hypothalamic pituitary adrenal axis have not been well characterized.
Clinical Case:
A 14 yo female was referred to our clinic for evaluation of low TSH (0.16 µIU/mL) and possible hyperthyroidism. There was no goiter and she appeared euthyroid and had normal free T4 (1.01 ng/dl) but she had typical features of Cushing syndrome (CS), including round facies, thinning of hair, fatigue, truncal adiposity, violaceous striae, facial hirsutism and oligomenorrhea. She was previously healthy and participated in many sports. She did not report any history of exogenous glucocorticoid use but the fasting ACTH (4 pg/ml) and cortisol (0.1 µg/dl) levels were suppressed. Subsequent chart review revealed that she received intra-articular Triamcinolone (TA) to treat “slipping rib” syndrome. This included 3 injections of Kenalog 40 mg/mL, the last in July 2019. Her cumulative TA dose was 440 mg, the equivalent of prednisone 550 mg. Triamcinolone acetonide 1.4 mcg/dL (normal 0-0.1, analyzed by LC-MS/MS) was detected in the urine over 3 months after her last injection.
Conclusion:
- Levels of ACTH and cortisol can be suppressed for several months after intra-articular corticosteroid injections, placing the patient at subsequent risk for adrenal crisis
- In some cases, high doses of Triamcinolone administered by intra-articular injection can cause clinical Cushing syndrome