bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-102 Serum Concentrations of FT4 and TSH in the First Six Months of L-Thyroxine Treatment in Infants with Congenital Hypothyroidism: Target Attainment Rates Should Be Improved
Authors: Leroux Stéphanie , Pascal Gächter , Gilbert Koch , Konrad Daniel , l’Allemand Dagmar , Welzel Tatjana , Pfister Marc , Szinnai Gabor 
Published: May 2020

Abstract
Levo-Thyroxine (L-T4) is the medication of choice for treating congenital hypothyroidism (CH). Adequate L-T4 treatment is essential for early neurodevelopment in affected patients. Both under- and overtreatment with L-T4 were associated with long-term adverse neurological outcomes. Based on clinical experience, initial L-T4 dosing does not always result in optimal TSH and FT4 concentrations in all CH patients. The purposes of this study were 1) to quantify FT4 and TSH target attainment rates (TAR) in the first six months of L-T4 treatment in infants with CH, 2) to compare characteristics of patients with FT4 concentrations “OUT of” versus “IN” the target range at first time of monitoring.
A multicenter retrospective analysis was conducted in infants born between 1995 and 2018. TSH and FT4 TARs were defined according to the most recent guidelines of the European Society for Paediatric Endocrinology (ESPE), as the percentage of concentrations “in” and “in the upper half” of the corresponding laboratory age-specific reference range for TSH and FT4, respectively.
We analyzed a total of 208 TSH and 186 FT4 serum concentrations from 60 patients during the first 6 months of L-T4 treatment. The pretreatment FT4 and TSH serum concentrations (mean±SD) were 8.3±5.7 pmol/L and 338±248 mU/L, respectively. CH severity according to ESPE guidelines was severe, moderate and mild for 32%, 27% and 32% of the patients. Postnatal age (PNA) (mean±SD) at start of treatment was 10±12 days. Starting dose of L-T4 (mean±SD) for severe, moderate and mild CH were 10±4, 10±3, and 7±4 µg/kg/day, respectively. Over the study period, TSH TARs of 63% did not further improve between the first monitoring (mean at 17 days of treatment) and fourth monitoring (mean at 4 months of treatment), while FT4 TARs increased from 22% to 45% paralleled with a decrease of too high FT4 values from 55% to 21%.
Comparing patients with FT4 concentrations “OUT of” versus “IN” the target range at first time monitoring (16 versus 18 days after starting treatment; p=0.45), they did not differ in pretreatment FT4 concentrations (p=0.2). In contrast, patients who had FT4 concentrations “OUT of” versus “IN” the target range received first dose of L-T4 at an earlier median PNA (7 versus 16 days; p=0.008), had higher pretreatment mean TSH concentrations (364 versus 181 mU/L; p=0.02) and received a higher mean initial L-T4 dose (10.3 versus 7.1 µg/kg/day; p=0.01).
First, our results show that FT4 and TSH target ranges were not reached in all patients in the first six months of treatment. Second, our data suggest that TARs could be improved by individualizing initial L-T4 dosing not only according to pretreatment FT4 but also to pretreatment TSH concentrations. L-T4 dosing optimization is needed in this population.
OR03-04 The Study of Cell Senescence in Cortisol-Producing Adrenocortical Adenomas
Authors: Gao Xin , Yamazaki Yuto , Pieroni Jacopo , Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Morimoto Ryo , Nakamura Yasuhiro , Satoh Fumitoshi , Sasano Hironobu 
Published: May 2020

Abstract
Introduction Aging is associated with the pathogenesis of many endocrine disorders such as cardiovascular diseases and diabetes. Cell senescence has been reported as one of their mechanisms. In addition, stress responsiveness has been reported to be associated with cell senescence. In addition, some genetic abnormalities such as mitochondrial DNA (mtDNA) damages or telomere shortening, have been detected in some endocrine disorders. Cortisol is a well-known stress-induced hormone and closely associated with aging. We previously reported that cortisol-producing adenoma (CPA) more abundantly expressed cell senescent markers such as p16 and p21 than other hormone-producing adrenocortical adenomas. However, the detailed pathophysiology of cell senescence and its association with histological features in CPAs have remained virtually unknown. Therefore, we analyzed cell senescent markers (telomere length, mtDNA copy number, mtDNA deletion and p16 and p21 immunoreactivity) and analyzed their correlation with clinicopathological factors in CPA patients.
Methods & Materials Forty CPA cases was immunohistochemically evaluated. Twenty CPA, ten adjacent ZF and six non-functional adenoma (NFA) were examined for mtDNA abnormalities. mtDNA deletion was evaluated by nested-PCR and mtDNA copy number and telomere length were measured using real-time PCR.
Results p21 immunoreactivity was significantly higher in CPA than that of adjacent ZF (P=0.0001) and significantly inversely correlated with tumor size (P=0.0004). Telomere length was much longer in CPA than that in adjacent ZF(P=0.0038), and NFA (P=0.0018). mtDNA copy number of NFA was significantly higher than that of CPA and adjacent ZF (P=0.0038). mtDNA copy number of compact cells was significantly higher than that of clear cells (P=0.0432). mtDNA copy number of compact cells was positively correlated with urinary free cortisol (UFC) (P=0.0428) and plasma cortisol (F) (P=0.0609). mtDNA copy number of clear cells were inversely correlated with F (0.0497). 4977 bp mtDNA deletion was more frequently detected in CPA (54%) and in adjacent ZF (50%) than in NFA (17%).
Discussion Results of our present study did reveal that CPA harbored more senescent phenotype as demonstrated by abundant p16 and p21, marked telomere shortening, frequent mtDNA 4977bp deletion and relatively low mtDNA copy number, possibly caused by long-term exposure of excessive cortisol in situ compared to NFA. In addition, clear tumor cells could represent more senescent histological phenotype because of their lower mtDNA copy numbers. This is the first study to demonstrate that compact tumor cells were biologically more active than clear tumor cells and could reflect clinical cortisol biosynthesis, resulting in marked functional intratumoral heterogeneity in CPAs.
MON-262 A Case of the Suprasellar Atypical Teratoid Rhabdoid Tumor (ATRT) Presenting in an Adult Treated with Intrathecal Chemotherapy
Authors: Oraibi Omar , Mau Christine , Daggubati Lekhaj , Khormi Yahya , Manni Andrea , Zacharia Brad 
Published: May 2020

Abstract
Background: Atypical teratoid rhabdoid tumors (ATRTs) are highly malignant tumors that usually present as a posterior fossa mass in children less than 3 years old. Only 38 cases have been reported in adults. They are also typically located in the supratentorial region. In none of the reported cases of suprasellar ATRT in the adult, intrathecal chemotherapy (via ommaya) has been used. Clinical case: A 70-year-old woman presented with a severe headache and magnetic resonance imaging (MRI) revealed a suprasellar mass measuring 2.9 x 2.1 x 3.0 cm. Shortly after her presentation, she developed an acute 3rd nerve palsy, and repeat MRI found dramatic interval growth. A transsphenoidal approach for biopsy/resection was attempted, but the lesion was not accessible via this corridor. She then underwent a right frontotemporal craniotomy and subsequently developed panhypopituitarism, including diabetes insipidus. Pathology revealed poorly differentiated malignant cells. Immunohistochemistry was positive for synaptophysin, Epithelial Membrane Antigen (EMA), Tumor protein p53, and negative for integrase interactor 1 (INI-1 antibody) with loss of expression in tumor nuclei with positive internal control in endothelial cells. These findings confirmed the diagnosis of ATRT. The Ki-67 index was 60% consistent with a highly proliferative tumor. One month later, she developed acute mental status change. Repeat computed tomography, and MRI showed recurrence of the tumor at the same location with new leptomeningeal enhancement involving the left facial nerve. Multimodal treatment was instituted, consisting of intraventricular/intrathecal chemotherapy with etoposide and topotecan plus fractionated external beam cranial irradiation (30 Gy in 10 fractions). She continued to deteriorate, and following consultation with her family, she was transferred to hospice care and died six months following her initial surgery. Conclusion: This is the first case of adult suprasellar ATRT that has been treated with intrathecal chemotherapy. There is no consensus on the best combination of chemotherapy, and often the St. Jude’s protocol used in the treatment of pediatric ATRT is used. In line with the biological behavior reported for this tumor in children and adults in different locations, the tumor was very aggressive, resulting in the patient’s death only after 6 months from the diagnosis despite aggressive surgical and medical treatment. Reference: 1. Athale, U. H., J. Duckworth, I. Odame, and R. Barr. 2009. Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J. Pediatr. Hematol. Oncol. 31:651-663. 2. Shonka N, Armstrong T (2011) Atypical teratoid/rhabdoid tumors in adults: A case report and treatment-focused review. J Clin Med Res 3: 85-92.
SAT-216 Retroperitoneal Paraganglioma: Case Report
Authors: Silva Eugénia Morado , Ferreira Rute , Cunha Clara , Boligo Sofia , Branco Cláudia , Araújo Ana Virgínia , Oliveira Manuela , Duarte Sequeira 
Published: May 2020

Abstract
Introduction: Paraganglioma (PGL) is a rare type of neuroendocrine neoplasm able to secrete neuropeptide and catecholamines. It can occur in any location between the neck and the pelvis. Most of the PGLs are diagnosed in the third to fifth decades and clinical presentation is variable and depends upon catecholamine secretion and tumor location. PGLs occur in the abdomen in 85% of cases. There are no unique imaging characteristics specific for PGLs, consequently, these tumors can be mistaken with other primary abdominal tumors.
Clinical-Case: We present the case of a 65-year-old woman with history of hypertension (diagnosis at 40 years) and dyslipidemia. She denied family history of hypertension. In the context of a recent diagnosis of type 2 Diabetes Mellitus, she underwent abdominal ultrasound which revealed a large, heterogeneous nodular formation with partial liquid content, measuring 12x15 cm, adjacent to the left hepatic border. Abdominal CT scan revealed an intra-abdominal mass, with 14cm (largest diameter), showing intimate contact, with no cleavage plan with the posterior wall of the gastric fundus, suggesting Gastrointestinal Stromal Tumor. A left adrenal nodule with 3.3 cm was also present, rounded, hypoechogenic, with regular margins and homogeneous. Echoendoscopy with biopsy of the retro-gastric mass showed a neuroendocrine neoplasia. At this point she was sent to an endocrinologist. When questioned she referred headache, diaphoresis and anxiety complaints for 3 years. At examination, a painless abdominal mass in the epigastrium and left hypochondrium was found. Laboratory evaluation revealed urinary metanephrines 11738 (64-302) ug/day, urinary normetanephrines 5832 (162-527) ug/day, renin 15.5 (1-8.2) pg/mL, aldosterone 28.6 (10-160)ng/dL, cortisol after 1 mg dexamethason 1,18 µg / dl (less than 1,8ug/dl) and chromogranin A 36.6 nmol / L (less than 3nmol/l). MIBG scintigraphy revealed fixation only in the large known retroperitoneal mass. The patient underwent excision of the retroperitoneal mass and of the left adrenal gland without complications. The histological diagnosis revealed, respectively, paraganglioma and adrenal cortical adenoma. Four weeks after surgery laboratory results were normal (urinary metanephrines 202 ug/24h and normetanephrines 382.0 ug /day; Chromogranin A 2.60 nmol/l). The results of the genetic tests including SDHB, SDHD, SDHC, VHL and MAX were negative.
Conclusion: This report emphasizes the necessity to include paraganglioma in the differential diagnosis and management of retroperitoneal tumors avoiding the risk of the biopsy in this kind of tumors.
SAT-124 Optimization of Experimental Conditions for Mimicking Hypoxia in Cultured Breast Cancer Cells by Using Cobalt(II) Chloride (CoCl2)
Authors: Chen Karin , Satlof Leo , Kothapalli Udithi , Ziluck Noah , Lema Maribel , Poretsky Leonid , Avtanski Dimiter 
Published: May 2020

Abstract
Hypoxia is a common phenomenon in solid tumor development caused by a decrease in either oxygen concentration or oxygen pressure as a result of rapid tumor cell growth. Hypoxia is characterized by stabilization of the alpha subunit of the hypoxia-inducible factor (HIF-1α) and its nuclear translocation and heterodimerization with HIF-1β. Activation of this signaling pathway involves multiple downstream effectors including carbonic anhydrase 9 (CA9, s. CAIX). A reliable method to mimic hypoxia utilizes cobalt(II) chloride (CoCl2), which directly induces the expression of HIF-1α. The aim of this study was to optimize the experimental conditions for CoCl2 treatment of breast cancer cells in vitro using three human breast cancer cell lines (MDA-MB-231, T-47D, and MCF-7 cells). We performed time- and concentration-response experiments, using various concentrations of CoCl2 (50, 100, 200, and 300 μM) for 24 and 48 hours, and measured the expression of HIF-1α and CA9 by qRT-PCR and Western blot analyses. Results demonstrated that CoCl2 downregulated HIF-1α mRNA levels but upregulated CA9 mRNA levels in a concentration- and time-dependent manner. Concomitantly, CoCl2 treatment resulted in a significant induction of HIF-1α protein levels. We further investigated the effect of the CoCl2 concentrations listed above on cell apoptosis using an in situ apoptosis detection kit. The results demonstrated that concentrations of CoCl2 up to 100 μM had no significant effect on cell apoptosis.
OR07-06 The Roles of GNAQ and GNA11 in Calcium-Sensing Receptor (CaSR) Signalling
Authors: Gluck Anna K , Stevenson Mark , Falcone Sara , Inoue Asuka , Breitwieser Gerda E , Gorvin Caroline M , Lines Kate E , Thakker Rajesh V 
Published: May 2020

Abstract
The G-protein subunits Gα 11 and Gα q, which share &gt;90% peptide sequence identity and are encoded by the GNA11 and GNAQ genes, respectively, mediate signalling by the calcium-sensing receptor (CaSR), a class C G-protein coupled receptor (GPCR) that regulates extracellular calcium (Ca2+e) homeostasis. Germline Gα 11 inactivating and activating mutations cause familial hypocalciuric hypercalcaemia type-2 (FHH2) and autosomal dominant hypocalcaemia type-2 (ADH2), respectively, but such Gα q mutations have not been reported. We therefore investigated the DiscovEHR cohort database, which has exomes from 51,289 patients with matched phenotyping data, for such GNAQ mutations. The DiscovEHR cohort was examined for rare GNAQ variants, which were transiently expressed in CaSR-expressing HEK293A Gα q/11 knockout cells, and their effects on CaSR-mediated intracellular calcium (Ca2+i) release and MAPK activity, in response to increasing concentrations of extracellular calcium were assessed using a nuclear factor of activated T-cells response element (NFAT-RE) luciferase reporter construct and a serum response element (SRE) luciferase reporter construct, respectively. Responses were compared to those of wild-type (WT), inactivating FHH2-associated GNA11 mutations (Leu135Gln and Phe220Ser), and engineered GNAQ mutations that were equivalent to the FHH2-causing GNA11 mutations. Gα q/11 protein expression was confirmed by Western blot analysis. Six rare missense GNAQ variants (Arg19Trp, Ala110Val, Gln299His, Ala302Ser, Ala331Thr, Val344Ile) were identified in DiscovEHR individuals, all of whom had mean plasma calcium values in the normal range (8.30–10.00 mg/dL). Functional characterisation of all six Gα q variants showed no significant difference to WT Gα q responses, thereby indicating that these variants are unlikely to be disease-causing mutations. In addition, the FHH2-causing GNA11 mutations (Leu135Gln and Phe220Ser) had significantly reduced responses, compared to WT Gα 11; however, this could be compensated by WT Gα q. GNAQ Leu135Gln and Phe220Ser, in contrast to their Gα 11 counterparts, showed no differences in protein expression or signalling responses when compared to WT Gα q. Our study, which provides mechanistic insights into the differences between Gα q and Gα 11, indicates that Gα q, unlike Gα 11, does not play a major role in the pathogenesis of FHH2 or ADH2.
SUN-629 Text for Success in Gestational Diabetes: Development and User Experience Testing of a Text Messaging Program
Authors: Blair Rachel A , Dias Jennifer M , McDonnell Marie E , Seely Ellen W 
Published: May 2020

Abstract
Background: Gestational diabetes mellitus (GDM) affects 5–10% of pregnancies in the United States. Poorly controlled GDM can lead to serious fetal and maternal complications. Women diagnosed with GDM are asked to form many new self-management habits. Studies have shown that text messaging is an effective, easily accessible way to improve management of diabetes outside of pregnancy, but this method has not been studied in GDM.
Objective: Obtain user feedback and iteratively incorporate it into a personalized text messaging program for women with GDM.
Methods: We performed user experience testing of a text messaging program (Txt4GDM), which was created by a multidisciplinary team based on the Health Belief Model. The program includes: 1) reminders to check blood glucoses sent 4 times per day based on self-reported mealtimes, 2) positive feedback for each blood glucose reported by a user (with an algorithm instructing users to contact their care team if too high/low), 3) one educational message and 4) one motivational message per week.
Women with GDM received simulated messages on a study smartphone. Subjects participated in semi-structured interviews about the content and phrasing of text messages. Interview replies were categorized into themes and used to iteratively optimize the program.
Results: 10 women completed user experience testing. All participants thought the program would be useful for women with newly diagnosed GDM and would use it during their first pregnancy with GDM. There were several features of the program that participants particularly liked, which were categorized into two themes: 1) customization of timing of messages and 2) messages including information not adequately covered in routine care (such as healthy snack ideas and exercise).
Several themes emerged from the semi-structured interviews that were used to optimize the program. 1) Further customization of message timing: We added the ability to enter different mealtimes for weekends and weekdays, which was well-received in subsequent iterations. 2) Minimization of jargon: Multiple women did not know what the “M” in GDM stood for, so we removed “GDM” from the messages. 3) Women wanted the messages to be more specifically related to GDM. For example, an educational message said: “Drinking water, instead of soda or juice, is healthy for you.” The phrase “and can help regulate your blood sugar” was added based on participant feedback.
Conclusions: Overall, women with GDM would use the Txt4GDM text messaging program and think it would be helpful for GDM self-management. Based on user feedback, enhanced customization of timing of text message delivery, minimization of jargon, and language specific to GDM in educational messages were added. We are testing the optimized text messaging program in an ongoing usability study.
MON-621 Prescription Analysis Shows High Metformin Use and Acceptance in a Diabetes Specialty Centre in Eastern India
Authors: Mishra Sanat Kumar , Mishra Susant , Sahoo Abhay Kumar , Padhi Rajesh Kumar , Jena Biswaranjan , Jena Apurba Ranjan , Khatua Ranjit Kumar , Pradhan Santosh Kumar , Jena Sanghamitra , Khuntia Monalisa , Mahapatra Hariballav 
Published: May 2020

Abstract
Background and aims: Achieving glycemic goals is crucial in the overall management of diabetes. Selecting the right medication for the individual patient is of paramount importance in the present day’s patient centric glucose control. Metformin is the first line and gold standard antihyperglycemic agent that can be offered to type 2 diabetics. Addition of a second or third agent or insulin should be considered in those whose HbA1c remains high despite the up-regulated metformin dose or those who do not tolerate metformin. We aimed to find the pattern of metformin use in type 2 diabetic subjects in a diabetes specialty centre in coastal Odisha.
Materials and methods: This observational study was conducted in a diabetes setup in coastal Odisha in June 2018. After obtaining consent from patients, authors looked into the prescriptions of all type 2 diabetic adults. Subjects who were prescribed metformin (in any dose) were enrolled in the study. Those with established nephropathy, coronary artery disease, stroke or cancers were excluded.
Results:There were 802 footfalls noted during the study period, of which 723 metformin taking participants (298 females, 41.2%) were considered for analysis (79 persons were excluded: not meeting inclusion criteria/ not willing to participate/ history of nephropathy/ CAD/ stroke). Mean age, diabetes duration, FPG, HbA1c, serum creatinine, eGFR of the study population were 51.6±10.6 years, 11.9±11.2 years, 138.7±51.7 mg/dl, 7.8±2.1%, 0.93±0.29 mg/dl and 96.5±11.1ml/min respectively. Patients were prescribed metformin in various doses, i.e., 500mg (42 patients, 5.8%), 850mg (47 patients, 6.5%), 1000mg (396 patients, 54.8%), 1500mg (13 patients, 1.8%), 1700mg (86 patients, 11.9%) and 2000mg (130 patients, 18.0%), and 2500mg (9 patients, 1.2%). Metformin was prescribed as monotherapy (n=34, 4.7%) or along with other OADs (n=589, 81.5%) or in combination with insulin (n=178, 24.6%). Retrospective analysis of the medical records and further questioning revealed that gastric intolerance was the commonest reason for withdrawal of metformin in otherwise eligible subjects.
Conclusion: Metformin was the most commonly prescribed antidiabetic drug and the daily dose of more than 85% of the metformin administered individuals was 1000mg or above.