bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB78 Hyperfunctioning Papillary Thyroid Carcinoma With a BRAF Mutation
Authors: Shinkai Shinsuke , Ohba Kenji , Matsushita Akio , Kuroda Go , Sakai Yuki , Nishino Nobuhiko , Kakudo Kennichi , Oki Yutaka , Sasaki Shigekazu 
Published: May 2020

Abstract
Background: Hyperfunctioning papillary thyroid carcinoma (PTC) is a rare tumor and accounts for less than 0.1% of all thyroid tumors. Information about its driver mutations is limited. Our literature search yielded 16 cases wherein a mutational analysis was conducted. Thyrotropin receptor (TSHR) mutations were identified in 11 of these cases. One case revealed a combination of TSHR and KRAS mutations. No mutations were identified in the other four cases. BRAFV600E is a prominent oncogene in PTC; however, hyperfunctioning PTC with this mutation has not yet been reported.
Clinical Case: In a 48-year-old man, ultrasonography (US) during an annual medical checkup revealed a nodule at the right lobe of the thyroid gland. He visited the outpatient clinic for further evaluation. Thyroid function tests indicated that he was hyperthyroid with TSH level of 0.01 mIU/L (reference range: 0.05-5.00), free thyroxine level of 1.8 ng/dL (reference range: 0.9-1.7), and free triiodothyronine level of 4.3 pg/mL (reference range: 2.3-4.0). Serum thyroglobulin was 62.1 ng/mL (reference range: &lt;33.7) and TSHR autoantibodies (TRAb) was &lt;0.8 IU/L (reference range: &lt;2.0 IU/L). B-mode US revealed a hypoechoic, heterogeneous nodule with largest diameter of 25 mm, and it had a jagged border and microcalcification. Color Doppler US revealed increased intranodular vascularity. The 99mTc thyroid scintigram revealed a round, right-sided focus of tracer uptake by the nodule with suppression in the remainder of the gland. These findings were consistent with an autonomously-functioning thyroid nodule. The patient underwent total thyroidectomy because fine-needle aspiration cytology revealed a malignant cytological diagnosis. The histopathological diagnosis of the patient was PTC, tall cell variant, pT2, pEx0, pN1b, and M0. Subsequent mutational analysis of BRAF (exon 15), TSHR (exons 9 and 10), GNAS (exons 7-10), KRAS, NRAS, HRAS (codons 12, 13, and 61), and TERT promoter (C250T and C228T) only identified a heterozygous point mutation in BRAFV600E in tissue samples.
Conclusion: We report for the first time a case of hyperfunctioning papillary thyroid carcinoma with a BRAF mutation.
MON-LB57 Impact of Imputation Method and Response Cutoffs on Results From the Phase 3 OPTIMAL Study of Oral Octreotide Capsules in Adult Patients With Acromegaly
Authors: Samson Susan Leanne , Nachtigall Lisa B , Fleseriu Maria , Gordon Murray B , Jensterle Mojca , Elenkova Atanaska , Ludlam William Henry , Patou Gary , Haviv Asi , Biermasz Nienke , Trainer Peter James , Strasburger Christian Joseph , Kennedy Laurence , Melmed Shlomo 
Published: May 2020

Abstract
Objective: The phase 3 CHIASMA OPTIMAL study assessed efficacy and safety of oral octreotide capsules (OOC) in patients with acromegaly controlled on injectable somatostatin receptor ligands (SRLs). Sensitivity analyses were conducted for efficacy endpoints using two methods of imputation (i.e., the process of replacing clinical data with substitution values) to address missing data points due to some subjects reverting back to their prior injectable SRL treatment. Methods: Patients were ≥18 years of age and had evidence of active acromegaly with an average IGF-I ≤ 1.0 x ULN (utilizing the IDS iSYS assay calibrated to WHO recombinant reference standard 02/254). At baseline, patients were randomized to receive OOC or placebo for 36 weeks. The primary endpoint was proportion of patients maintaining biochemical response, defined as IGF-I ≤1.0 x ULN (2-value average at weeks 34 and 36) (Samson et al. ENDO 2020). Per study protocol, patient study discontinuations were considered non-responders regardless of clinical response at the time of discontinuation (non-response imputation). Additional exploratory analyses were performed utilizing the last observation carried forward (LOCF) analysis, as well as a completers analysis of response among the subgroup that completed the entire 36 weeks on study drug. The response rates reported for the primary end point are slightly adjusted for stratification differences as prespecified in the statistical analysis plan. Results: Twenty-eight patients received OOC and 12 failed to maintain biochemical response based on the primary endpoint. Seven of these 12 patients discontinued treatment early - 5 due to treatment failure and 2 due to AEs. The remaining 5 patients completed the 36-week protocol on study drug. Of these 5 patients, 4 had IGF-I values between &gt;1.0 and ≤1.3 x ULN and 1 completed the study with an IGF-I of 1.7 x ULN with no clinical symptoms. 58.2% of patients in the OOC group met the primary endpoint of maintenance of biochemical response at the end of study using the non-response imputation. Using LOCF imputation, 64.3% (18/28) of patients met this endpoint. Of those completing the study (N=21), 76.2% maintained response. Conclusion: CHIASMA OPTIMAL primary endpoint was assessed using the non-response imputation for patients who discontinued treatment early, with a 58.2% response rate. However, when assessing the response rate based on LOCF imputation, or in study completers, similar to other phase 3 studies for acromegaly, the rate was imputed at 64.3% and 76.2%, respectively.
MON-LB5 A Longitudinal Cohort Study of Serum Decorin Levels in Normal and Preeclamptic Pregnant Women
Authors: Cano – Bermúdez Maria Alejandra , Rodríguez – Navarro Haiver Antonio , Buell – Acosta Julieth Daniela , Acosta – Álvarez Jaidy , Parra- Pineda Mario Orlando , Parada - Baños Arturo José , Caminos Jorge Eduardo , Garces Maria Fernanda 
Published: May 2020

Abstract
Background: Decorin (DCN) is a leucine-rich proteoglycan that regulates diverse cellular processes such as organization and stability of extracellular matrix, extracellular signaling by the maintenance of surface receptors and growth factors and enzymes activities. Additionally, DCN is an important mediator of inflammation, angiogenesis, trophoblast migration, placentation, tumor growth and autophagy. Objective: We aimed to evaluate DCN serum levels throughout gestation in a longitudinal cohort study in normal and preeclamptic pregnant women. Methods: In this nested case-control study design within a prospective cohort of 450 pregnant women, 50 healthy and 20 preeclamptic pregnant women were followed during each pregnancy trimester and three months postpartum. Likewise, healthy non-pregnant women in the follicular and luteal phase of their menstrual cycle were included (n = 20). Serum DCN concentrations were measured by ELISA. Results: In healthy non-pregnant women, DCN levels did not differ significantly between the two stages of the menstrual cycle. On the other hand, serum DCN levels decreased significantly in both healthy and preeclamptic pregnant women in each trimester of pregnancy when compared to non - pregnant women (p &lt;0.001) and were re-established three months postpartum (p &lt;0.001). Moreover, serum DCN levels were significantly lower in the second trimester of gestation in normal pregnant women (p &lt;0.05). On the other hand, serum DCN was significantly higher in preeclamptic compared to healthy pregnant women in the third trimester of pregnancy (p &lt;0.01). Conclusion: The present study found that DCN serum levels decreased significantly throughout pregnancy in healthy and preeclamptic pregnant women. Thus, low levels of DCN may play crucial physiological and pathological roles during pregnancy. DCN has been shown to inhibit different growth factors such as vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF). Hence, low levels of DCN during pregnancy might play a critical role in the control of angiogenic process.
MON-LB82 Plasma Expression Level of MiRNA -21 Is Related With the Presence of Papillary Thyroid Cancer
Authors: Zilaitiene Birute , Kondrotiene Aiste , Pamedytyte Daina , Simanaviciene Vaida , Dauksiene Dalia , Zvirbliene Aurelija , Kazokaite Mintaute , Klimaite Raimonda , Sarauskas Valdas , Dauksa Albertas , Verkauskiene Rasa 
Published: May 2020

Abstract
Introduction.: There is no effective and reliable biomarker to distinguish benign thyroid nodules (BTN) from papillary thyroid carcinomas (PTC). In this study we analyzed a set of four miRNA molecules in plasma of patients with papillary thyroid cancer, benign nodules and healthy controls to identify miRNA molecules that may be markers of PTC.Aim.: We aimed to investigate the dysregulation of plasma miRNAs in PTC and evaluate the diagnostic value for differentiation of PTC from BTN. Methods.: The expression levels of 4 miRNAs (miR-221, miR-222, miR-146b, miR-21) were measured in 48 PTC patients before thyroidectomy and again after thyroidectomy in a subgroup of 36 patients. Preoperative and postoperative plasma miRNA expression levels were compared with baseline levels established in plasma from the heathy controls group (N=57) and patients with BTN (N=22). MicroRNA-222 and miR-146b, miR-221, miR-21 were included in a panel because they all reportedly were overexpressed in PTC compared to benign nodules or normal thyroid tissue.Results.: Compared with baseline levels in the healthy controls group, miR-221, miR-222, miR-146b, miR-21 levels were significantly higher in the preoperative PTC group (P &lt;0.0001, P=0.002, P=0.028, P =0.021, respectively). A significant reduction in miR-21 expression was observed in postoperative PTC patients. MiR-21 decreased by 5.98-fold (P=0.046) in post- operative samples compared with preoperative samples in the PTC patients.In comparison MiRNRs expression levels in BTN group with healthy controls, miR-221, miR-21 expression levels were significantly higher in the BTN group (P=0.003, P=0.048, respectively). No significant difference was observed between the preoperative PTC group and the preoperative BTN group with regard to the expression of these four miRNA’s. Conclusions: The expression levels of miR-222, miR-146b in plasma were significantly higher in patients who had PTC than in healthy volunteers, whereas levels of miR-221, miR-21 in plasma were significantly higher in patients who had either PTC or BTN before thyroidectomy than in healthy volunteers. Furthermore, miR-21 showed a significant reduction of expression levels after thyroidectomy in PTC patients. However, value of these four miRNAs is still limited in differential diagnosis of PTC and benign nodules.
SAT-LB93 Rapid Reduction of Insulin Requirement in a Hyperglycemic Patient Treated for Hemophagocytic Lymphohistiocytosis
Authors: Schweisberger Cintya , Amos Lauren , Wood Nicole , Halpin Kelsee 
Published: May 2020

Abstract
Background: Hemophagocytic lymphohistiocytosis (HLH) is life-threatening disorder of immune dysregulation involving macrophage and T-cell activation resulting in massive cytokine release causing multi-organ dysfunction. Similar release of cytokine products from fat tissue is associated with obesity-related insulin resistance. Our case presentation is an example of HLH and insulin resistance, two conditions with overlapping pathophysiology, occurring simultaneously. Clinical Presentation: A 17-year-old male, with no history of hyperglycemia, underwent renal transplant due dysplastic kidneys. He received 500mg IV methylprednisolone during surgery followed by a prednisone taper starting at 70mg daily. Serum glucoses post-transplant ranged from 97 to 129 mg/dL. Three weeks post-transplant he was admitted for fever and dehydration. BMI on admission was the 85th percentile. Serum glucose was 371 mg/dL without ketosis. He started on insulin therapy, requiring 60 units per day (0.8 units/kg). It was suspected his new-onset diabetes was due to his immunosuppressant regimen (prednisone 50mg daily, tacrolimus) and/or acute illness. With persistent fevers and negative infectious workup, there was concern for HLH. The diagnosed was confirmed with ferritin level of 65,962 ng/mL (27-265), hemoglobin 6.5 gm/dL, platelets 88,000, triglycerides 765 mg/dL, soluble IL-2 receptor 2,717 u/mL (45 - 1,105). For HLH treatment, he received methylprednisolone 800 mg daily x 3 doses. During this time his insulin requirements increased to 188 units per day (3.6 units/kg). He was transitioned to dexamethasone 20mg daily. His insulin requirements increased over the next 72 hours to 388 units per day (5.2 units/kg). He was found to be positive for Ehrlichiosis, a known precipitant of HLH. Doxycycline therapy was initiated for a 14 day course. One week into his doxycycline course his ferritin had decreased to 999 ng/mL. He remained on dexamethasone 20 mg daily but developed severe hypoglycemia to 29 mg/dL with altered mental status. All insulin therapy was held. Fasting glucoses over the next 4 days ranged from 94-154 mg/dL and post-prandial glucoses 116-288 mg/dL. He discharged home with only short acting insulin for glucoses above 250 mg/dL, which he did not require. Case Lessons: Cytokine release from macrophages is implicated in the pathology of both HLH and insulin resistance associated with obesity. Glucocorticoids used to treat HLH can also exacerbate insulin resistance. Providers should be aware of the risk of hyperglycemia and large insulin requirements in patients with HLH, and the potential for rapid reduction of insulin needs as HLH is successfully treated.
MON-LB56 Metabolic Profile in 107 Patients With Childhood Onset Growth Hormone Deficiency (CO-GHD) at the Time of Transition From Pediatric to Adulthood Endocrine Care
Authors: Doknic Mirjana , Stojanovic Marko , Milenkovic Tatjana , Zdravkovic Vera , Jesic Maja , Todorovic Sladjana , Mitrovic Katarina , Vukovic Rade , Miljic Dragana , Pekic Sandra , Soldatovic Ivan , Petakov Milan 
Published: May 2020

Abstract
Vulnerability of the transitional period from childhood to adulthood is particularly challenging in treatment of adolescents with CO-GHD. Altered metabolic profile is well described in GHD, but relevant large monocentric studies in transition patients and young adults with CO-GHD are lacking.Patients and Methods: In a monocentric, observational, retrospective cross-sectional study conducted from 2005-2019, 107 CO-GHD patients were analyzed (17-26 years old, 80 males) at the time of transfer from pediatric to adult endocrine care. Median age at transfer was 19.6 ± 2.2 years. Subjects with congenital and idiopathic GHD (CON) were compared with age-, sex- and BMI-matched patients with hypothalamic/pituitary tumor history (TUM). Glycaemia and insulin during OGTT (peak and AUC), HbA1c, serum total cholesterol, HDL, LDL and triglycerides were analyzed in all patients.Results: Congenital and idiopathic causes of CO-GHD were more frequent than hypothalamic/pituitary tumoral causes (74.8% vs. 25.2%). All patients received GH replacement during childhood for average duration of 5.4 ± 1.4yrs. GH replacement was discontinued prior to transfer for 2.7 ± 0.9yrs. Glycaemia peak, glycaemia AUC and insulin peak in OGTT were not significantly different in TUM vs. CON (p&gt;0.05). However, insulin AUC in OGTT was significantly higher in TUM compared to CON (134.38 ± 23.2 vs 114.62 ± 12.4; p&lt;0.05). HbA1c was similar between the two groups (5.2 ± 0.4% TUM vs 5.0 ± 0.3% CON; p&gt;0.05). Total cholesterol (5.2 ±1.1 vs 4.5 ± 0.8 mmol/l; p&gt;0.05), LDL (3.1 ± 0.9 vs 2.7 ± 0.8 mmol/l; p&gt;0.05) and triglycerides (2.1 ± 1.1 vs 1.1 ± 0,7 mmol/l; p&lt;0.05) were increased in TUM compared to CON, while HDL was decreased in TUM group (1.0±0.1 vs 1.4±0,3 mmol/l; p&lt;0.05).Conclusion: Patients with CO-GHD caused by hypothalamic/pituitary tumors are burdened with a worse metabolic profile at the time of childhood to adulthood transition compared to matched transition patients with congenital CO-GHD.
SUN-076 Somatic and Neurodevelopmental Outcome and Muscle Tone in 5 to 9 Year Old Children Born After Intracytoplasmic Sperm Injection
Authors: Snajderova Marta , Kraus Josef , Zemkova Daniela , Mardesic Tonko 
Published: May 2020

Abstract
Introduction: Assessing the development and health status of children born after assisted reproductive techniques is very important. This also applies to somatic and neurological development. Little is known on the development of muscle tone in children. Aim of our study was to evaluate the somatic and neurological development in children born after intracytoplasmic sperm injection (ICSI) with special focus on proximal muscle tone.
Material and methods: A group of 82 singletons (ICSI) aged 5–9 years (42 M, 40 F) and a control group of 82 singletons spontaneously conceived (SC), all with low morbidity, were compared by age and sex. Comprehensive assessment by endocrinologist, clinical anthropologist and pediatric neurologist was performed.
Results: Both ICSI and SC children had normal somatic development. In the standard neurological testing, motor development did not differ significantly in ICSI children compared with the general population. Nevertheless, some coordination abnormalities tested by diadochokinesis and by the finger-nose test, were found in all but 7 ICSI children (ICSI in 91 % versus SC in 9 %; p&lt;0.001). A prominent hypotonia of upper girdle muscles tested by the scarf sign was found in all but 4 ICSI children (ICSI in 95 % versus SC in 61 %; p&lt;0.001). In the contrary, no difference was found for lower girdle muscle tone in ICSI versus SC children. Any of the factors tested for possible relationship to upper girdle muscle hypotonia was not found to be significant.
Conclusions: As far as we know, this study is the first evaluation of proximal muscle tone in ICSI children aged 5 - 9 years. Subtle changes in the neurological status were revealed comparing ICSI and SC children, i. e. the prominent upper girdle muscle hypotonia and the coordination changes. The hypotonia can be explained by a slight change in the muscle tone maturation and movement coordination. The ICSI method very likely does not have any negative effect on the neurodevelopmental outcome of children. Nevertheless, the development of muscle tone and coordination in ICSI children should be monitored. Early diagnosis of these abnormalities helps to early initiation of appropriate therapy and thus avoids possible complications.
MON-LB306 Association Between Cancer Related Beliefs and Diabetes Medication Adherence Among Breast Cancer Survivors With Comorbid Type 2 Diabetes
Authors: McLeggon Jody-Ann , Itty Jennifer , James Janey , Chen Wenjing , Goel Mita , Harris Yael T , Lin Jenny J 
Published: May 2020

Abstract
Introduction: Cancer and diabetes mellitus (DM) are leading causes of death in the United States. Each year, over 245,000 women are diagnosed with breast cancer, and approximately 18% of patients diagnosed have preexisting DM. The presence of a comorbidity, such as DM increases women’s mortality risk by 40%. While studies have shown decreased adherence to hypoglycemic medications after cancer diagnosis, the effect of cancer related beliefs on DM medication adherence has not been fully explored. In this study, we evaluated the association between cancer related beliefs and DM medication adherence in survivors of breast cancer.
Hypothesis: Patients with greater positive beliefs about cancer (including personal control, treatment control and understanding) would exhibit greater adherence to DM medication.
Methodology: We enrolled women &gt;55 years with Stage 0-IIIA breast cancer diagnosed in the past 10 years, who had completed chemotherapy and/or were prescribed hormonal therapy and had pre-existing type 2 DM treated with at least 1 oral DM medication. Cancer related beliefs were assessed using the Illness Perception Questionnaire (IPQ). Medication adherence was evaluated using the Medication Adherence Rating Scale (MARS). Adherence was dichotomized at a mean MARS score of ≥4.5. Wilcoxon rank-sum tests were used to examine the relationship between patients’ cancer related beliefs and DM medication adherence.
Results: Thus far, 108 women have completed baseline surveys. Of these participants, 37% were black, 31% white, 14% Hispanic, 6.5% Asian, and 8.3% other. The mean age was 65 years. Cancer survivors who were adherent to DM medication had a greater sense of personal control over their cancer (median score 22.0 vs. 19.0, p&lt;0.001) and endorsed a better understanding of their cancer (median score 20.0 vs. 14.0, p=0.03). No associations were seen between beliefs about the duration and consequences of cancer and DM medication adherence.
Conclusion: Among breast cancer survivors with comorbid DM, having a greater sense of control over and understanding of cancer was associated with DM medication adherence. Working with breast cancer survivors to increase their perceived control over and understanding of their cancer may help improve adherence to DM medication.
SUN-LB41 The Role of Androgen Receptors in Female Mouse X-Zone Loss During Aging and Pregnancy
Authors: Frucci Emily C , Taylor Matthew J , Xing Yewei , Hammer Gary D , Rainey William E 
Published: May 2020

Abstract
Introduction: Sex differences are prevalent in the risk and manifestation of numerous human diseases as well as in the response to most therapeutic interventions. While marked sexual dimorphism is observed in the development, homeostasis and most diseases of the adrenal cortex, the impact of these differences on adrenal function remains poorly understood. Sex differences include the timing of adrenal fetal zone (X-zone) regression, which occurs during male mouse puberty but only after pregnancy or advanced age in females. The mechanisms driving regression, particularly in females, are unknown. A potential regulator of adrenal sexual dimorphism and X-zone regression is androgen exposure. Through adrenocortical-specific deletion of the androgen receptor (AR), we tested the hypothesis that androgen signaling is responsible for X-zone post-pubertal regression in male mice and post-pregnancy/aging related regression in female mice.
Methods: Adrenocortical-targeted Ar deletion was accomplished by crossing heterozygous aldosterone synthase-Cre mice to mice with a floxed exon 2 of Ar (ARΔAdr). Mice were sacrificed at 25 or 50 weeks of age and compared to ARf/f littermates (controls). Adrenals were processed for histology (H&E), immunofluorescence (IF) and whole adrenal mRNA RT-PCR to detect AR and X-zone specific markers Akr1c18 (20αHSD) and Pik3c2g.
Results: In all mice, Ar mRNA expression was significantly decreased in ARΔAdr mice compared to control littermates. As expected, 25 week control females had higher expression of Akr1c18 (6740-fold) and Pik3c2g (198-fold) compared to 25 week control males. 25 week ARΔAdr males retained expression of Akr1c18 (20864-fold) and Pik3c2g (2802-fold) compared to controls, and also exhibited positive 20αHSD staining, confirming X-zone retention. 50 week control females exhibited histologic loss of the X-zone with negligible expression of Akr1c18 and Pik3c2g compared with 25 week control females. However, 50 week female ARΔAdr mice exhibited a histologic X-zone retention and concomitant high expression of X-zone genes (Akr1c18 67-fold, Pik3c2g 75-fold) compared to female control littermates. Furthermore, 20αHSD IF demonstrated undetectable levels in controls and positive staining in ARΔAdr, indicating that age-associated X-zone loss may be AR-mediated. Post-pregnant 25 week control mice had ~99% lower expression of both X-zone markers compared to virgin female controls. Post-pregnant ARΔAdr mice displayed higher expression of Akr1c18 (19-fold) and Pik3c2g (5-fold) compared to post-pregnant controls, though neither group had detectable 20αHSD by IF.
Conclusion: Our findings indicate that AR signaling not only causes post-pubertal X-zone loss in males, but also plays a major role in the loss of the X-zone observed in aged female mice. Conversely, AR signaling may only play a minor role in X-zone regression following pregnancy.