bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-235 Young Male with Persistent Central Diabetes Insipidus After a Car Accident
Authors: Yesaulava Liudmila , Houston Caroline , Sultana Sanjeda 
Published: May 2020

Abstract
BACKGROUND: Central diabetes insipidus (CDI) occurs in 20% of cases of traumatic brain injury (TBI). Most cases of post-TBI CDI resolve within 2–5 days. Only 6% of long-term survivors of TBI have evidence of persistent CDI.1 We report a patient with persistent CDI after TBI. Clinical Case: A 27 year old male was referred for polyuria. Three months prior he was in a rollover motor vehicle accident. At that time, CT head revealed frontal and occipital contusions with scattered subarachnoid, subdural, and intraventricular blood. There was no evidence of skull fracture, mass-effect, or midline shift. On hospital day 4, his urine output increased to &gt; 3L/day, with serum sodium of 146 mEq/L (n 135–145) and urine specific gravity of 1.015 (n 1.005–1.030). Repeat head CT revealed bilateral subdural hematomas causing mild mass effect. During the rest of his 2-month hospitalization, he continued to have polyuria with specific gravity as low as 1.005, and occasional hypernatremia, with a peak serum sodium of 149 mEq/L. Serum sodium on discharge was 144 mEq/L. On presentation to our clinic, his family and caretakers reported polydipsia, polyuria and nocturia. He had no history of diabetes mellitus or lithium use. On exam he was tachycardic but normotensive with no signs of dehydration. Neurologic exam was normal except for distractibility and impaired long- and short-term memory. After 3 hours of water deprivation, laboratory testing revealed serum sodium 150 mEq/L, serum osmolality 307 mOsmol/kg (n 270–295), urine osmolality 119 mOsmol/kg (n 300–900), and ADH 3 pmol/L (n &lt;/= 14); consistent with CDI. Oral desmopressin led to resolution of polydipsia and polyuria. Evaluation of anterior pituitary function was normal. Six months post TBI, CT head revealed increased left frontal subdural hematoma with effacement of the right lateral ventricle and 1cm left-to-right midline shift. A burr hole procedure was performed but CDI persisted. Conclusion: Animal studies have shown that neurohypophyseal apoptosis occurs by inducing intracranial hypertension lasting 12 hours or more.2 Persistent DI may herald rising intracranial pressure (ICP), as reflected by our patient’s case.1 Clinicians should be aware of the reciprocal association between increased ICP and persistent CDI following TBI.
References: (1) Tudor R. M., Thompson C. J. Posterior pituitary dysfunction following traumatic brain injury: review. Pituitary. 2019 Jun; 22(3):296–304. (2) Tan H., et al. Assessment of the role of intracranial hypertension and stress on hippocampal cell apoptosis and hypothalamic-pituitary dysfunction after TBI. Sci Rep. 2017 Jun; 7(1):3805.
SUN-093 Prospective Clinical Assessment Study in Children with Achondroplasia: The PROPEL Trial
Authors: Savarirayan Ravi , Kannu Peter , Dambkowski Carl L , Rogoff Daniela , Irving Melita 
Published: May 2020

Abstract
BACKGROUND: Achondroplasia (ACH) is the most common non-lethal form of skeletal dysplasia, affecting between 1 in 15,000 to 1 in 30,000 live births [Horton et al. 2007; Waller et al. 2008]. Children and adults with ACH have disproportionate short stature, with a final height of approximately 131 cm for males and 124 cm for females. They are prone to significant co-morbidities, including obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis and a propensity towards obesity. In some infants, narrowing of the foramen magnum may result in compression of the spinal cord with neurologic sequelae, requiring timely neurosurgical intervention. There are currently no approved therapies for the treatment of ACH in either the United States or the European Union, and management is generally supportive in nature. The PROPEL trial is a prospective, non-interventional study examining baseline growth parameters and health status in children with ACH being assessed for potential enrollment into interventional studies with infigratinib, an oral FGFR1-3 inhibitor in development for achondroplasia. Methods: Children with ACH between the ages of 2.5 and 10 years are eligible for enrollment in this prospective, non-interventional trial to evaluate growth parameters and determine clinical status. Participants will be assessed at baseline, month 3, month 6, and every 6 months thereafter. The primary endpoint is annualized height growth velocity. Secondary endpoints include change from baseline in other growth parameters (including body proportionality); analysis of bone biomarkers (e.g., bone alkaline phosphatase, collagen X fragment); and the occurrence of medical events and surgical procedures. Participants will be enrolled in the study for a minimum of 6 months up to a maximum of 2 years before being considered for enrollment in a QED-sponsored phase 2/3 interventional trial. Current status: The PROPEL study is underway with the first patient enrolled in August 2019. Planned total enrollment is 200 children with ACH.
SAT-075 Pulmonary Hypertension in a Patient with Neonatal Graves Disease
Authors: Wee Erica , Ramachandra Ramya , Paez Ana Maria , Brownlee John , Senguttuvan Rajan 
Published: May 2020

Abstract
INTRODUCTION
Neonatal hyperthyroidism is a transient disorder seen in neonates born to mothers with current or past history of Graves’ disease. We present a rare case of a Neonatal Graves’ disease with pulmonary hypertension (PH) which completely resolved with treatment of hyperthyroidism.
CLINICAL CASE
Baby B was a 3200 g term male born to a 40-year-old hypothyroid mother. He was prenatally diagnosed with Trisomy 21 and coarctation of the aorta (CoA). He developed respiratory distress soon after birth and was admitted to the NICU. His echocardiogram (echo) showed a large patent ductus arteriosus (PDA) and increased tortuosity of juxtaductal aorta with no significant gradient. Near-systemic pulmonary artery pressure was noted in the absence of any evidence of left heart failure. Cardiology determined his CoA to be hemodynamically insignificant and not the cause of his PH. Successive trials of 100% FiO2, Nitric Oxide (NO), and Sildenafil resulted in only minimal improvement of his PH.
Thyroid function tests (TFT) obtained on day of life (DOL) 8 showed serum TSH of 0.01 uIU/ml [0.87 - 6.43] and FT4 of 3.5 ng/dl [0.9 - 1.5]. Further interaction with the mother revealed that she had a history of Graves’ disease treated with radioactive iodine (RAI) and resultant hypothyroidism. Baby B’s TSH receptor antibody (TRAb) and thyroid stimulating immunoglobulin levels were elevated at 7.38 IU/l [0-1.75] and 3.38 IU/l [0-0.55], respectively.
He was thus diagnosed with Neonatal Graves’ disease and was started on Methimazole (MTZ) 1 mg/kg/day on DOL 8. Subsequently, potassium iodide was added. FT4 showed gradual normalization by DOL 15. Beta blockers were not added due to absence of hypertension or significant tachycardia. Serial echo showed improvement of PH, consistent with the decline in FT4 levels. Sildenafil and FiO2 were slowly weaned and discontinued by DOL 30. MTZ was then tapered and discontinued. A final echo showed complete resolution of PH, unobstructed aortic arch and persistent PDA.
DISCUSSION
Neonatal hyperthyroidism occurs due to transplacental transfer of TRAb from mother to fetus, stimulating the fetal thyroid to make excessive thyroid hormones. Risk correlates with TRAb titers in the mother. Our patient had pulmonary hypertension which did not resolve with FiO2, NO and Sildenafil. However, it showed complete resolution with normalization of FT4 levels by antithyroid drugs. Hyperthyroidism commonly presents with systemic HTN, but we found 3 neonatal cases in the literature presenting with PH that resolved with treatment of hyperthyroidism. The mechanism is unclear, but hypotheses include increased clearance of pulmonary vasodilators and decreased clearance of pulmonary vasoconstrictor and decreased surfactant production/function(1).
REFERENCES
1) Oden J, Cheifetz IM. Neonatal thyrotoxicosis and persistent PH necessitating extracorporeal life support. Pediatrics 2005-115: e105-8.
MON-008 Estrogen-Responsive and -Unresponsive Gene Expressions Promoted by Enhancers Specifically Hypomethylated in Endometriotic Cells May Become a Molecular Marker in Endometriosis Lesions
Authors: Izawa Masao , Azuma Yukihiro , Hori Naohiro , Taniguchi Fuminori , Harada Tasuku 
Published: May 2020

Abstract
BACKGROUND: Endometriosis is an estrogen-dependent, inflammatory disease, and the role of estrogen is obvious because the symptoms associated with endometriosis often disappear after menopause, and GnRH agonists or progestin relieve the pelvic lesions and endometriosis-associated pain. However, there are limitations to these treatments that target the estrogen reduction in endometriotic lesions. We sought to define an aberrant gene expression derived from an epigenetic background in endometriosis.Objective: In the hope of overcoming the limitations of endocrine treatments in endometriosis, we examined estrogen receptor (ER)-dependent and -independent gene expressions promoted by active enhancers specifically hypomethylated in endometriotic cells.
Patients: Institutional Review Boards approved this project. We obtained the informed consent from all patients. The chocolate cyst lining in ovaries of patients with endometriosis was the source of endometriotic tissue. As the control, the eutopic endometrial tissues were obtained from uteri of premenopausal women who had uterine leiomyoma.Methods: Stromal cells were prepared from endometriotic and endometrial tissues. Gene expression was examined using RT-PCR. The potential function of hypomethylated gene sequence as an active enhancer was evaluated by ChIP analysis using anti-H3K4me1 and anti-H3K27ac antibodies and eRNA expression analysis. Using ChIP-seq and ChIA-PET analysis in silico, ER-specific loci within gene bodies and the up- and downstream regions were extracted. ER-dependent gene expression was examined using estradiol or SERM.Results: ER expression in endometriotic cells.1) Relative expression of ERα mRNA was estimated to be one tenth of that in endometrial cells. 2) Relative expression of ERβ1 mRNA was 40-fold higher than that in endometrial cells, which is at a comparable level of the ERα. 3) ERβ2 mRNA expression was at a comparable level of the ERβ1. From our DNA methylation and gene expression analysis, 6 genes were selected and classified into 3 categories: estrogen-responsive genes with specific methylation (ESR1 and ESR2) or without any methylation (TGFα and GREB1), and estrogen-unresponsive but upregulated genes depending on specific hypomethylation (GATA6 and CYP19). 4) ChIP-seq and ChIA-PET analysis in silico suggested the presence of ER-specific loci within gene bodies and the up- and downstream in estrogen-responsive genes. 5) ChIP and eRNA expression analysis predicted active enhancer regions both in estrogen-responsive and -unresponsive genes. 6) In response to estrogen, TGFα and GREB1 expressions were upregulated, but ESR1 and ESR2 showed marginal responses.Conclusion: We focused on estrogen-responsive and -unresponsive genes linked to the epigenetic environment of endometriotic lesions, and revealed a facet of gene expression in endometriotic cells.
OR34-01 11C Metomidate PET-CT Identifies More Unilateral Primary Aldosteronism Than Adrenal Vein Sampling
Authors: Puar Troy , Tan Colin , Tong Aaron , Zhang Meifen , Khoo ChinMeng , Tan Wai Kit Alvin , Kek Peng Chin , Loh Lih-Ming , Yee Szemen , Lee Daphne Hui Min , Chuah Matthew , Reilhac Anthonin , Totman John , Robins Edward , Foo Roger 
Published: May 2020

Abstract
Introduction. Adrenal vein sampling (AVS) is the current reference test to identify unilateral, surgically-curable primary aldosteronism (PA). However, AVS is invasive and technically difficult. Even in AVS-proven unilateral PA, up to 6% of patients with fail to have biochemical cure after surgery using the PASO criteria. 11C-Metomidate PET-CT offers a non-invasive alternative. We compared the accuracy of both PET-CT and AVS using post-surgery cure (PASO criteria) as the reference.
Methods. This multi-centre prospective trial recruited 25 patients with confirmed PA, and all underwent CT, AVS, and PET-CT tests. Sequential AVS under ACTH-stimulation was done by an experienced interventionalist, and cortisol gradient of &gt;5 was taken to be successful cannulation. Lateralization ratio &gt;4 was consistent with unilateral PA. All results were reviewed at a multidisciplinary meeting to decide on the diagnosis (unilateral or bilateral PA) and management (secondary outcome). Primary outcome was biochemical cure using PASO criteria at 6 months post-surgery (ClinicalTrials.gov: NCTxxxxxxxx).
Results. Recruitment for the study has been complete with 25 patients, 49.2 ± 9.5 yr, 14 females (56.0%). All 25 patients had successful AVS. 22 of 25 patients (88.0%) had unilateral PA, and 3 patients (12.0%) had bilateral PA. PET-CT identified unilateral PA in 18 of 22 patients (sensitivity 81.8%), while AVS identified unilateral PA in 15 of 22 patients (sensitivity 68.2%). In one patient, repeat AVS done simultaneously without ACTH-stimulation aided to identify unilateral PA, when initial AVS failed to do so. Other cases where AVS failed to identify unilateral PA were due to venous anomalies, and limitation of the lateralization cut-off of 4. 18 of 22 patients have undergone surgery, with 3 patients awaiting surgery, and 1 opting for medical treatment. Post-surgery, all patients had complete normalization of aldosterone-renin ratio, and hypokalemia (if present). 2 patients had bilateral PA on both PET-CT and AVS. 1 patient had discordant AVS and PET-CT results, with AVS lateralizing to right, and PET-CT to left. This patient was classified as bilateral PA and treated medically.
Conclusion. This is the first study to demonstrate that 11C-Metomidate PET-CT may identify cases of unilateral PA not detected with AVS, using the stringent PASO criteria for post-operative biochemical cure.
SUN-480 An Unusual Clear Cell Carcinoma in the Thyroid. Where Is the Primary?
Authors: Lin Kuan-yu , Shih Shyang-Rong , Lee Jih-Hsiang 
Published: May 2020

Abstract
Background: Clear cell carcinoma in the thyroid gland is rare. It is important to distinguish primary thyroid clear cell carcinoma from metastases, since its clinical behaviors and treatment options were different.
Clinical Case: A 47-year-old woman without past medical history presented to our outpatient surgery department with right neck mass for 8 months. Thyroid ultrasonography revealed a 3.9 cm nodule in the right thyroid. Thyroid function test was within the normal range. Fine needle aspiration cytology of the nodule showed suspicious for neoplasm. She underwent radical total thyroidectomy and lymph node dissection. Pathology revealed an unusual carcinoma comprising cuboidal cells with irregular nuclear contours, some eosinophilic or clear cytoplasm, arranged in infiltrating nests or cords with marked stromal hyalinization, highly suggestive of a clear cell carcinoma. Ectopic thymic tissue was present adjacent to the tumor. By immunohistochemical (IHC) staining, tumor cells were p63 (+), TTF-1 (-), thyroglobulin (-), PAX8 (-), synaptophysin (-), CD5 (-), and CD117 (-). Tumor genetic sequencing detected EWSR1-CREM fusion genes. For disease extent evaluation, two out of seven lymph nodes obtained during operation were positive of tumor metastases. Whole body computed tomography (CT) 3 months after operation revealed no residual thyroid tissue, neck lymphadenopathies or intra-abdominal metastases. A pulmonary ground-glass opacities of 7mm in diameter was found, which was stationary at a repeated CT scan 6 months later.
Clinical Lesson: Clear cell carcinoma in the thyroid gland could be primary, arising from clear cell change of follicular or papillary thyroid carcinoma. The negative IHC stain of thyroglobulin, TTF, PAX8, as well as lack of papillary or follicular architecture made primary thyroid clear cell carcinoma unlikely. Most of the metastatic clear cell carcinoma to the thyroid gland arose from renal primary. However, there was no clinical or radiographic evidence of renal tumor in our case. Although ectopic thymic tissue was identified on pathology, negative IHC staining of PAX8, CD5 and CD117 made thymic origin less likely. Positive IHC staining of p63 and a novel EWSR1-CREM fusion gene confirmed the diagnosis of salivary clear cell carcinoma. According to our literature review, there were only 3 cases of clear-cell carcinoma with EWSR1-CREM fusion gene (1), and our case is the first case who presented with clear cell carcinoma in the thyroid. In conclusion, the importance of IHC stain and molecular testing in determining the primary origin of clear cell carcinoma were addressed in our case.
Reference: (1) Chapman E, et al. Am J Surg Pathol. 2018;42(9):1182-1189
MON-185 ACTH-Derived Peptide Antagonists as an Alternative Treatment Strategy for Congenital Adrenal Hyperplasia
Authors: Schubert Tina , Nicke Lennart , Schanze André , Reisch Nicole , Geyer Armin , Koehler Katrin , Huebner Angela 
Published: May 2020

Abstract
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by different enzyme deficiencies in the steroid hormone synthesis leading to a disturbed cortisol biosynthesis. The medical treatment of CAH includes suboptimal ACTH-suppressing high glucocorticoid doses to reduce adrenal hyperplasia and overproduction of androgens. These inappropriate corticoid substitutions are often associated with undesirable side effects such as arterial hypertension, growth failure and obesity. Since the current therapy of patients with CAH is often unsatisfactory, innovative treatment options are required.
The aim of our study was to specifically block the melanocortin 2 receptor (MC2R) signaling pathway as an alternative treatment strategy for CAH. We tested ACTH-derived selective peptides with incorporation of various synthetic non-natural amino acids in the activation motif of ACTH. To study the antagonistic activity of the peptides, cAMP production of MC2R/MRAP stably transfected human embryonic kidney (HEK) 293 cells were measured. All new synthesized peptide antagonists reduced ACTH-stimulated MC2R activity as competitive inhibitors indicated by a reduced in vitro cAMP response. Cells pre-incubated with peptide LNP009 showed the most efficient blockade of the MC2R and the highest shift of EC50 of ACTH (33.8 nM ± 0.08 vs. 7.3 nM ± 0.09). LNP009 was additionally tested for specificity concerning the other known melanocortin receptors and showed no antagonistic effect up to 1 μM on MC3, MC4 or MC5 receptor transiently transfected HEK 293 cells. To further investigate the inhibitory effect of our most potent antagonist peptide LNP009 on the steroid hormone response, we assessed steroidogenic enzyme expression of the human adrenocortical tumor cell line NCI-H295RA and performed mass spectrometry analyzes of steroids in the cell culture supernatant. Pre-incubation with LNP009 reduced the expression of the genes CYP21A2, CYP11B1 and HSD3B2 in NCI-H295RA cells and significantly reduced the synthesis of aldosterone (P=0.046; n=3), cortisol (P=0.020; n=3) and corticosterone (P=0.035; n=3).
With the successful blocking of the ACTH binding and signal transduction by our antagonistic peptides, we anticipate an alternative approach for optimizing the treatment of CAH patients lacking the side effects of the currently used ACTH-suppressing corticoid therapy.
MON-159 High Mortality Rate in Oral Glucocorticoid Users: A Case-Control Study
Authors: Einarsdottir Margret , Ekman Per , Trimpou Penelope , Olsson Daniel S , Johannsson Gudmundur , Ragnarsson Oskar 
Published: May 2020

Abstract
Objective. Long-term oral glucocorticoid (GC) use is associated with increased mortality in patients with rheumatoid arthritis and inflammatory bowel disease. The aim of the study was to investigate whether there is excess mortality among oral GC users, regardless of the underlying disease.
Methods. This was a retrospective case-control study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients receiving ≥5 mg prednisolone (or equivalent dose of other GC) daily for ≥21 days between 2007-2014 were included. For each patient, a control person, matched for age and sex, was included. The cause of death was obtained from the Swedish Cause-of-Death Registry. Hazard ratio (HR) for mortality was calculated by using Cox proportional hazard model and by the log-rank test. The GC users were divided into four groups according to the length of GC treatment: 1) single-occasion users 2) occasional users (&lt;300 tablets/year); 3) medium-term users (&gt; 300 tablets/year for ≤ 2 consecutive years); and 4) long-term users (&gt;300 tablets/year for &gt; 2 consecutive years).
Results. Of 1,585,335 inhabitants in Western Sweden, 223,211 GC users (women 55.6%) were identified for the analysis. The mean age was 48 ± 24 years. Median follow-up time was 3.6 years for GC users and 3.9 years for matched controls. The overall HR for death in oral GC users was 2.26 (95% CI 2.21-2.31). After exclusion of patients with malignant neoplasm, the HR for death was 1.41 (95% CI 1.38-1.45); 1.33 (95% CI 1.27-1.38) in single-occasion GC users (n=112,196), 1.36 (95% CI 1.30-1.42) in occasional users (n=63,862), 1.89 (95% CI 1.79-1.99) in medium-term users (n=19,129) and 1.67 (95% CI 1.51-1.84) in long-term users (n=7,191). The highest HRs were observed for deaths from heart failure (HR 1.71, 95% CI 1.63-1.80), sepsis (HR 1.71, 95% CI 1.51-1.94), and pulmonary embolism (HR 1.87, 95% CI 1.58-2.21).
Conclusion. GC users have excess mortality compared to the background population. This illustrates the importance of surveillance for patients on oral GC treatment where adverse effects should be monitored and, when indicated, appropriately treated.