bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-073 Hyperinsulinemic Hypoglycemia Responsive to Diazoxide Due to a Previously Unknown ABCC8 Dominant Mutation
Authors: Figueredo Veronica M , Diaz Alejandro , Banchs Pedro Pagan 
Published: May 2020

Abstract
Background: Hyperinsulinism is the most common cause of persistent hypoglycemia. It results from different genetic defects, the most common being recessive and dominant mutations in the ABCC8/KCNJ11 genes. The majority of recessive mutations have a poor response to Diazoxide, while dominant mutations are highly variable in both clinical presentation and response to treatment. Prompt recognition and management is critical to avoid irreversible brain damage. Clinical case: A 38-week gestation male, born via emergent c-section due to decreased fetal movement, presented with neonatal hypoglycemia. Pregnancy was uncomplicated and mother had a normal OGTT. Patient had a history of suspected sepsis, seizures, pulmonary hypertension and respiratory distress requiring intubation. Blood glucose was undetectable at birth and required multiple dextrose 10% boluses. A critical sample with a glucose of 47 mg/dL showed an elevated insulin at 30.3 m IU/mL with undetectable ketone levels. Lactic acid, ammonia, cortisol, GH, plasma amino acids, acylcarnitine profile and uric organic acids where all normal for a hypoglycemic state. He required intravenous glucose infusion with GIR up to 17 mg/kg/min to maintain normoglycemia. A brain MRI at 11 days of life showed findings of white matter injury. Subsequent genetic testing identified a heterozygous c.4051G&gt;A (p.Val1351Met) variant in ABCC8, classified as “of uncertain significance”. However, an entry in the ClinVar database (RCV000714711.1) exists from a research lab and was classified as likely pathogenic. Analysis of parental samples showed that the mother was heterozygous for the same genetic variant. She did not have a history of hypoglycemia. Patient was started on diazoxide (8 mg/kg/day) and chlorothiazide with resolution of hypoglycemia. At a follow up visit at 5 months of age, there was no history of hypoglycemia, and no need for adjustments of the diazoxide dose by weight (dose at that time of 7.4 mg/kg/day). Conclusion: The ABCC8 reported here is a dominant mutation causing hyperinsulinemic hypoglycemia responsive to diazoxide with a milder phenotype later in infancy. Longitudinal follow up of the case is warranted to understand the long term progress in patients with this particular mutation. Reference: Adam MP, Ardinger HH, Pagon RA, Wallace SE, et al. None. 1993. Familial hyperinsulinism.
SAT-222 Aggressive Phenotype Pheochromocytoma Associated with NF-1 and BRCA Mutation
Authors: Chaidarun Tanyawan , MacLeod Sara Rose , Chaidarun Sushela 
Published: May 2020

Abstract
Introduction
Pheochromocytomas are catecholamine-secreting tumors of the adrenal medulla that occur sporadically or with familial association. Familial predilection occurs in those with multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis Type 1 (NF-1). To date, more than 21 gene mutations have been identified that are involved in the development of pheochromocytomas. However, co-existence of two different mutations such as NF-1 and BRCA gene mutations with pheochromocytoma has not been well described.
Clinical Case
A 40 year-old woman with NF-1 and recently diagnosed left breast invasive ductal carcinoma, estrogen positive, progesterone positive, HER-2 negative BRCA2 positive breast cancer and right breast lobular carcinoma in situ underwent staging CT scan. A 2.7 cm left adrenal incidentaloma with heterogeneous texture and 69–100 HU was discovered. Symptom review revealed chronic headaches and increasing frequency of anxiousness and irritability. She had no personal or family history of hypertension. Laboratory analysis showed elevated catecholamine levels included plasma normetanephrine of 2.8 nmol/L (normal &lt;0.9), metanephrine of 0.9 nmol/L (normal &lt;0.5), 24 hour urine metanephrine 498 mcg/24 hr (normal &lt;180) and 24 hour urine normetanephrine of 1,152 mcg/24 hr (normal &lt;451). Findings were consistent with adrenal pheochromocytoma.
She was immediately started on phenoxybenzamine and encouraged to increase fluid intake to expand intravascular volume before surgery. She underwent laparoscopic left partial adrenalectomy fourteen days later. Surgical pathology revealed a 3.0 cm pheochromocytoma in a background of nodular hyperplasia of the medulla, described as an aggressive tumor phenotype based on morphological features.
Conclusions
It has been estimated that 1.5–14% of adrenal incidentalomas are pheochromocytomas. While only 3% of NF-1 patients have pheochromocytomas, 20–50% of NF-1 patients with concurrent hypertension have underlying chromaffin tumors. This association is significant when compared to the pheochromocytoma incidence of 0.1% in all hypertensive individuals. Interestingly, germline mutations of BRCA-1 associated protein-1 gene have been reported in patients with paragangliomas, therefore it may be plausible to consider interactions between NF-1 and breast cancer BRCA-2 gene mutations, resulting in an unusual and more aggressive pheochromocytoma phenotype, even when detected at an early stage, as in this case. It is also important to recognize and adequately treat pheochromocytoma prior to having surgery to avoid possible intraoperative hypertensive crisis, a concept that was underscored in this particular case when the patient was relatively asymptomatic and entirely normotensive preoperatively.
SAT-LB126 Metformin Attenuates Sodium Retention and Blood Pressure in Hypertensive Diabetic Mice by Reducing the Phosphorylation of Renal NCC and Its Association With the Actin Cytoskeleton
Authors: Gholam Mohammed F , Waleed Alina , Tuna Kubra M , Carson-Marino Morgan , Chacko Kevin M , Malik Zeeshan S , Schramm Whitney C , Lopez Juliana V Pena , Alli Abdel A 
Published: May 2020

Abstract
Metformin is the first-line drug in the treatment of type 2 diabetes mellitus. The aim of this work was to evaluate the efficacy of metformin treatment in reducing blood pressure and investigate the molecular mechanism using a preclinical animal model. Adult male and female diabetic db/db mice with a blood glucose of greater than 300 mg/dl were salt-loaded (8% NaCl) for 10 days to induce hypertension. The mice were subject to metabolic cage studies for 24 hour urine collections in order to measure urinary electrolytes, albumin, and creatinine. Blood pressure was measured weekly by the tail-cuff method to assess the effect of metformin or vehicle given by oral gavage (dose of 60 mg/kg of body weight per day). At the end of the study the mice was euthanized and the left kidney was formalin-fixed and paraffin-embedded for immunohistochemistry while the right kidney was homogenized for Western blotting. Western blotting showed attenuation of total NCC and phospho-NCC in diabetic db/db mice given an oral gavage of metformin (Pearson correlation coefficient: 0.9470 +/- 2.52e-3) compared to vehicle (Pearson correlation coefficient: 0.9800 +/- 2.86e-3). Immunohistochemical analysis showed less co-localization of the actin cytoskeleton protein filamin and phosphorylated NCC in the metformin treated group compared to the control group. Taken together, we show metformin decreases sodium retention and blood pressure by reducing the density of renal NCC at the luminal membrane and the association between NCC and the actin cytoskeleton.
MON-LB87 Recombinant Human TSH vs Thyroid Hormone Withdrawal Preparation for Radioiodine Ablation in Pediatric Differentiated Thyroid Cancer
Authors: Schumm Max A , Pyo Howard Q , Yeh Michael W , Kim Jiyoon , Tseng Chi-Hong , Leung Angela M , Chiu Harvey K 
Published: May 2020

Abstract
Introduction: Recombinant human TSH (rhTSH) is commonly used to prepare patients with differentiated thyroid cancer (DTC) for radioiodine (I-131) ablation after total thyroidectomy (TT). In adults, rhTSH is associated with equivalent oncologic efficacy and improved health-related quality of life in comparison to thyroid hormone withdrawal (THW). In this study, we aimed to measure disease-free survival after rhTSH stimulation vs. THW in pediatric patients with DTC. Methods: A prospective database was analyzed for pediatric patients under the age of 21 with DTC who underwent TT and I-131 ablation with rhTSH preparation at a single tertiary institution from 2012 through 2018. These patients were compared against historical controls prepared with THW. Tumor stage, I-131 treatment details, disease-free survival, structural recurrence, biochemical recurrence (defined as serum Tg &gt; 2 at one year), and postoperative serum TSH, thyroglobulin (Tg) and Tg antibody levels were recorded. The log-rank test was used to compare groups, and time to recurrence was estimated by Kaplan-Meier analysis. Results: Seventeen patients who received rhTSH (mean age, 16.6±3.2 [SD] years) were compared to 28 historical controls prepared with THW. No differences were observed in RAI dose (mean 2.3±0.7 mCi/kg), tumor stage, or follow-up time (median [IQR] 2.6 [1.1-3.1] years) between groups. The THW group exhibited a nonsignificantly greater recurrence rate (14 [50%], 7 with biochemical recurrence and 7 with structural recurrence) than the rhTSH group (three [18%], 2 with biochemical recurrence and 1 with structural recurrence, p=0.2). A trend toward improved disease-free survival was identified in those treated with rhTSH compared to THW. Conclusion: In this cohort of pediatric patients with DTC, we observed a trend toward improved disease-free survival among those prepared with rhTSH compared to historical controls prepared with THW. Long-term follow up is needed to better characterize outcomes associated with rhTSH stimulation prior to I-131 ablation in the pediatric population.
MON-LB127 Pulmonary Embolism in the Setting of Diabetic Ketoacidosis. an Under-Recognized Complication
Authors: Ahmed Adeel Jabran , Ahmed Taha , Amir Maryam , Khabbaza Deena 
Published: May 2020

Abstract
The relation between Diabetic Ketoacidosis and Venous Thromboembolism is important to appreciate for early recognition and management. 90 year old female with Type 2 DM was brought to the ER after a syncopal episode. Family reported the patient to be lethargic with a decreased appetite for one week. On arrival, patient had a blood pressure of 84/44 mmHg. Oxygen saturation was 89% at room air and improved to 93% on supplemental O2. Patient was afebrile with a respiratory rate of 16 and heart rate 89/minute. On exam, she was dehydrated with decreased skin turgor, dry oral mucosa. Labs revealed blood glucose of 621 mg/dL, Bicarbonate 16 mmol/L, B-Hydroxybutyrate 5.00 mmol/L, Anion Gap 21, pH of 7.26 on ABG. Urinalysis was suggestive of a urinary tract infection. After initiation of IV antibiotics and insulin, she was transferred to the intensive care unit. In the ICU, her blood pressure failed to improve with fluid resuscitation, ultimately requiring vasopressors. Due to hypotension with hypoxia, CT Chest was performed which revealed extensive bilateral PE. She was started on IV heparin infusion. Pro-Brain Natriuretic Peptide was elevated at 4,716 pg/mL. Echocardiogram confirmed right heart strain with severely dilated right ventricle, positive McConnell’s sign, systolic and diastolic septal flattening and an estimated RSVP 67mmHg consistent with moderately severe pulmonary hypertension. Tissue plasminogen activator was recommended however given the patient’s age and functional status; family decided against systemic thrombolysis. Duplex ultrasound of her lower extremities also showed bilateral acute deep venous thrombosis. She was continued on intravenous anticoagulation and eventually was able to come off vasopressors. As the patient’s blood glucose levels improved and her anion gap closed, she was transitioned to basal/bolus insulin and transferred to the general medical floor. She was started on Apixaban and discharged home per family’s request after her code status was changed to DNR-Comfort Care Arrest.Pulmonary embolism is a serious venous thromboembolic event that is rarely reported in association with DKA. Proposed mechanisms include some of the same mechanisms implicated in arterial thrombosis, namely abnormalities in coagulation factors, increased platelet aggregation, impaired fibrinolysis and endothelial injury due to hypertonicity. Also, severe dehydration associated with DKA may contribute by virtue of increased red blood cell rigidity and increased blood viscosity establishing DKA as an underlying cause or contributing factor of pulmonary thromboembolism2.1 Langevin C et al Presumed paradoxical embolus in a patient with diabetic ketoacidosis Int J Gen Med 2015;8:297–301 2015 Sep 18
2 Scordi Bello I et al Fatal Pulmonary Thromboembolism in Patients with Diabetic Ketoacidosis A Seven-Case Series and Review of the Literature Acad Forensic Pathol 2016;6(2):198–205
SUN-LB84 Riedel’s Thyroiditis: A Diagnostic and Therapeutic Challenge
Authors: Sliwinska Aleksandra , Jalil Fatima , Millar Danielle , Malchoff Carl D 
Published: May 2020

Abstract
Background: Riedel’s thyroiditis is a rare thyroid pathology which presents a challenge for clinicians to diagnose and treat. Etiology remains largely unknown, although data suggests an association with Hashimoto thyroiditis, systemic fibrosis, and IgG-4 related systemic disease. Presentation of Riedel’s thyroiditis can mimic malignant thyroid neoplasm, lymphoma, or a fibrous variant of Hashimoto thyroiditis. Due to its rarity, there is no consensus on the treatment. Clinical case: A 36-year old woman presented with a two-month history of gradually progressing neck swelling. She developed associated neck pain, decreased range of motion, hoarseness, and dysphagia, without difficulty breathing. One year prior to presentation, she had been diagnosed with hypothyroidism. She did not have a family or personal history of thyroid malignancy, however, she lived near Chernobyl during her childhood. On exam, the anterior and lateral neck was hard and enlarged, but nontender. The neck range of motion was diminished. The initial ultrasound of the thyroid demonstrated asymmetrically enlarged heterogenous diffusely nodular right thyroid and isthmus measuring 1.9cm. A CT of the chest with contrast showed diffusely enlarged thyroid extending superiorly beyond the image with mild tracheal displacement. Initial laboratory results included TSH of 17.40 uU/ml (ref: 0.35-4.94 uU/ml), free T4 of 1.06 ng/dl (ref: 0.61-1.82 ng/dl). She had a significantly increased thyroid autoantibodies (Anti-TPO &gt;700 IU/ml with ref: 0.0-9.0 IU/ml, Anti-TG &gt;2000 IU/ml with ref: 0.0-4.0 IU/ml). PTH and calcium were normal, and calcitonin was low. In the interim, the patient was evaluated by ENT without evidence of airway compromise. She underwent a core biopsy of the right thyroid lobe which demonstrated dense fibrous connective tissue mixed with mature lymphocytes. Pathology and immunostaining results were suggestive of Riedel’s thyroiditis. The patient was started on prednisone 60mg daily, which she tolerated for 6 weeks. Due to side effects, prednisone dose was titrated down and tamoxifen was added. Over the following 6 months, compressive symptoms resolved, and the ultrasound showed a significant decrease in the thyroid size. TSH normalized with thyroid hormone replacement. To date, she is asymptomatic and continues on tamoxifen and low dose prednisone without evidence of progression. Conclusion: Riedel’s thyroiditis is a rare condition that can progress into a medical emergency and should be suspected in patients presenting with a thyroid mass. Clinical awareness of Riedel’s symptomatology and laboratory findings should enhance our ability to distinguish and make the diagnosis. Instituting effective treatment that results in the improvement of symptoms and reduction in thyroid size can be challenging due to possible poor response or development of side effects.
SUN-LB54 Nutritionally-Induced Alteration in KNDy Neuronal Expression in the Arcuate Nucleus of Ewes
Authors: Prezotto Ligia D , Lents Clay A , Redmer Dale A , Grazul-Bilska Anna T , Thorson Jennifer F 
Published: May 2020

Abstract
Kisspeptin, neurokinin B, and dynorphin are imperative for GnRH/LH pulsatility and reproductive cyclicity. Neurons co-expressing these neuropeptides, KNDy neurons, within the arcuate nucleus of the hypothalamus (ARC) are positioned to integrate energy balance signals from neuronal and glial cells. Energy balance mediates neurokinin B expression in the ARC and LH pulse amplitude. Dynorphin mediates progesterone negative feedback on GnRH neurons. The hypothesis that the number of KNDy-expressing neurons in the ARC of ewes during the luteal phase of the estrous cycle is influenced by energy balance was tested using ovary-intact, mature ewes fed to lose, maintain, or gain body weight. Fluorescent multiplex immunohistochemistry was employed to identify and quantify neurons expressing a single neuropeptide and co-expressing kisspeptin, neurokinin B, and dynorphin in the ARC. Kaminski et al. (1) reported previously that concentrations of insulin and leptin differed between ewes fed to achieve different body weights and that ewes fed to gain body weight had increased concentrations of progesterone in the luteal phase of the estrous cycle. Moreover, tanycyte density and cellular penetration into the ARC are increased in ewes fed to gain body weight (2). Number of neurons in the ARC expressing kisspeptin (14.9 ± 2.7 neurons, 20.9 ± 3.6 neurons, and 51.5 ± 3.3 neurons in ewes fed to lose, maintain, and gain body weight, respectively), neurokinin B (21.5 ± 3.2 neurons, 31.3 ± 4.3 neurons, and 56.0 ± 3.9 neurons in ewes fed to lose, maintain, and gain body weight, respectively), and dynorphin (10.1 ± 2.4 neurons, 14.9 ± 3.2 neurons, and 33.1 ± 2.9 neurons in ewes fed to lose, maintain, and gain body weight, respectively) protein was increased (P &lt; 0.0001) in ewes fed to gain body weight. Number of KNDy neurons in the ARC expressing kisspeptin, neurokinin B, and dynorphin protein was decreased in ewes fed to lose body weight (1.0 ± 0.5 neurons; P = 0.01) and increased in ewes fed to gain body weight (6.7 ± 0.6 neurons; P = 0.0005) when compared to ewes fed to maintain body weight (3.3 ± 0.7 neurons). These findings suggest that expression of kisspeptin, neurokinin B, and dynorphin protein in the ARC during the luteal phase of the estrous cycle may be influenced by nutritionally-induced alterations in circulating concentrations of progesterone that drive changes in morphology and density of tanycytes. Moreover, these results demonstrate that changes in KNDy neurons within the ARC occur as an adaptation to energy balance, potentially regulated divergently by metabolic milieu.
References: (1) Kaminski et al., Theriogenology. 2015 83:808-16. (2) Prezotto et al., Domestic Animal Endocrinology. 2020 Accepted.
SUN-LB9 Pharmacokinetics of Sublingual Versus Oral Estradiol in Transgender Women
Authors: Doll Elizabeth E , Gunsolus Ian , Lamberton Nathan , Tangpricha Vin , Sarvaideo Jenna Lynne 
Published: May 2020

Abstract
Sublingual administration of estradiol (E2) may be a safer and more effective hormone replacement therapy (HRT) route than oral estradiol, the most commonly used formulation, but it has yet to be investigated in transgender women. Unlike oral E2, sublingual E2 is thought to bypass the first pass effect by the liver, making it less likely to impact hepatic clotting factor synthesis, and thus decreasing the risk of thromboembolic events posed by oral administration, such as VTE and ischemic stroke (1). Additionally, studies in cisgender women have demonstrated a 13-fold higher peak serum concentration and a decreased estrone (E1) to estradiol ratio with sublingual administration, suggesting that sublingual E2 is more a physiologically potent route (2). To advance the understanding of sublingual E2 as an alternative method of administration in transgender HRT, we investigated the pharmacokinetics of estradiol when administered orally versus sublingually in transgender women. Ten transgender women naïve to estrogen were provided 1.0 mg of oral estradiol. Blood samples were collected via percutaneous intravenous catheter at baseline and at T=1,2,3,4,6, and 8 hours post-dosing. After a 7-day washout period, 1.0 mg of sublingual estradiol was dosed with identical sampling over time. Analysis of serum samples was performed using LC-MS/MS and estradiol immunoassay. Initial results demonstrate a higher peak serum concentration within 8 hours with sublingual dosing in both LC-MS/MS and immunoassay quantification (178±47 and 150±31 pg/mL, respectively) compared to oral administration (36±5 and 35±4 pg/mL, respectively; N=5). Peak concentration was reached at T=1 hour for sublingual E2 in both LC-MS/MS and immunoassay analysis, whereas oral E2 reached peak serum concentration at T=8 hours in LC-MS/MS analysis and T=6 hours in immunoassay analysis. Sublingual E2 still maintained higher overall mean concentrations of estradiol across the 8 hours compared to oral E2. Importantly, subjects reported high satisfaction with sublingual administration due to rapid dissolution (&lt;2 minutes) and minimal taste; as a result, subjects predicted high ease of adherence in future HRT, which indicates the feasibility of sublingual E2 as an alternative to oral E2. Additional analysis of half-life and oral clearance will be performed at the completion of the study, in order to further establish pharmacokinetic differences and potency between the two routes. This pharmacokinetic data will allow future studies on optimal dosing, safety, and efficacy compared to oral estradiol in hormone replacement therapy. (1) Hembree et al. J Clin Endocrinol Metab. 2017;102(11):3869-3903. (2) Price et al., Obstet Gynecol. 1997.