bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 <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

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

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>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<0.05). HbA1c was similar between the two groups (5.2 ± 0.4% TUM vs 5.0 ± 0.3% CON; p>0.05). Total cholesterol (5.2 ±1.1 vs 4.5 ± 0.8 mmol/l; p>0.05), LDL (3.1 ± 0.9 vs 2.7 ± 0.8 mmol/l; p>0.05) and triglycerides (2.1 ± 1.1 vs 1.1 ± 0,7 mmol/l; p<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<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

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<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<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

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 >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<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

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.
SAT-LB79 Biotin Depleting Procedure Does Not Impact the Reliability of TSH, LH and FSH Immunoassays
Authors: Gruson Damien , Pouplaert Marie
Published: May 2020

Background: Biotin interference has become a major problem with some laboratory immunoassays, leading to erroneous tests results and potentially harmful clinical consequences. There is therefore a clinical need to easily identify the interference and to overcome its effect to avoid harmful consequences for patients. The aim of this study was to demonstrate the VeraPrep BiotinTM procedure, a biotin depleting device, does not impact the immunoreactivity of TSH, LH and FSH immunoassays.Materials and methods: Nine samples (4 from women and 5 from men) were tested with two-sites electrochemiluminescent immunoassays (Cobas e602, Roche diagnostics) for the measurement of three pituitary hormones, TSH, LH and FSH. The samples were first measured without any treatment (baseline) and then retested after treatment with VeraPrep Biotin™ procedure. Percent (%) difference was calculated between post-treatment and baseline to determine if the biotin depleting device impact the immunoassays immunoreactivity.Results: The median baseline concentrations for TSH, LH and FSH were 2.3 mIU/L (standard deviation (SD): 1.5), 4.9 IU/L (19.0) and 5.3 IU/L (17.5), respectively. The median concentrations after treatment with the VeraPrep Biotin™ procedure for TSH, LH and FSH were 2.3 mIU/L (1.5), 4.9 IU/L (18.9) and 4.9 IU/L (16.5), respectively, and were not statistically different from baseline (P = 0.976). The mean recoveries after treatment were 99.5%, 98.6% and 95.4% for TSH, LH and FSH, respectively.Conclusions: The concentrations of the TSH, LH and FSH assays were not impacted by the pretreatment with the VeraPrep Biotin™ procedure, confirming its ability to help clinical laboratories to overcome biotin interference.
MON-LB004 Understanding the Influence of Endometrial Cancer Risk Factors Using Human Primary Endometrial Organoids
Authors: Murphy Alina R , Campo Hannes , Kim Julie
Published: May 2020

It is unclear how endometrial cancer risk factors such as obesity, high serum testosterone, and high serum levels of the endocrine-disrupting compound bisphenol-A (BPA) influence hormone action to promote carcinogenesis. We hypothesized that obesity, high testosterone, and BPA exposure alters the protective progesterone response in the benign endometrium. Primary human benign endometrial organoids, consisting of both epithelial and stromal cells, were exposed to each of these risk factors in vitro in the presence of cyclic levels of estradiol, progesterone, and testosterone for 14 days. Progesterone response genes HSD17B2, IGFBP1, PAEP, and PRL were measured by real-time qPCR and IHC. First, to simulate obesity, endometrial organoids were cocultured with increasing numbers of human adipocyte spheroids during the hormone treatment. Real-time qPCR analysis revealed dysregulation of expression of HSD17B2 and IGFBP1 by approximately 20% when cocultured with 30 adipocyte spheroids. In addition, PRL protein levels were significantly lower in the stroma of the endometrial organoids. Second, increasing concentrations of BPA and 3nM testosterone individually or in combination were added to endometrial organoids together with the 14-day menstrual cycle hormones. Treatment with 0.6 ng/mL of BPA decreased expression of HSD17B2, IGFBP1, and PAEP by 50% to 80%. However, this effect was not seen in the context of high testosterone, indicating that there may be crosstalk between these two risk factors. In summary, this study demonstrated that adipocytes, BPA exposure, and high testosterone directly alter progesterone action in benign endometrial organoids, suggesting a diminution of the protective effects of progesterone and an increased risk of endometrial cancer.
SAT-387 Testing for Parathyroid Hormone: Performances of a Novel Fully Chemiluminescent Automated Assay
Authors: Gruson Damien , Adamantidou Christina
Published: May 2020

Background: Parathyroid hormone (PTH) is one of the key regulators of the bone and mineral metabolism. Testing for PTH is essential for the management of hyper- or hypo calcemia. Measurement of PTH is also an important tool for the monitoring of patient with chronic kidney diseases. Our study objective was to determine the performances of a novel fully automated chemiluminescent assay for testing of intact PTH. Methods: We evaluated the Maglumi® (Snibe) PTH assay a fully automated two-sites immunoluminometric method based on a solid-phase, paramagnetic microbeads, coated with a monoclonal antibody targeting PTH epitopes. Assay imprecision was assessed with two levels of control materials. Reference values were determined with samples of 24 healthy volunteers. Method comparison was performed with an electrochemiluminescent immunoassay (ECLIA) (Roche diagnostics) with 24 patients’ samples. Results: The between-run coefficients of variation of the Maglumi® PTH assay were 5.1 and 3.7 % for concentrations of 33 and 992 pg/mL, respectively. The median PTH levels were 121 pg/mL (range: 18 - 369) with the Maglumi assay and 117 pg/mL with the ECLIA method (range: 10 - 482). The upper limit of the reference interval in the healthy volunteers was 63 pg/mL. The correlation between the both methods was good (r=0.87, p<0,001). Passing-Bablok regression analysis showed a slope of 0.96 (95% confidence interval (CI): 0.83 to 1.35) and an intercept of -2.14 (95% CI: -20.49 to -10.47). Bland-Altman plot evidenced a bias between the methods with a mean bias of 4.6 pg/mL. Conclusions: Our preliminary data showed excellent concordance and analytical performances for the PTH fully automated immunoassay associated to perspectives of automation and reduction of turn-around time of analysis.
MON-LB035 Adrenal Venous Sampling in the Lateralization of Acth-Independent Cushing Syndrome With Bilateral Adrenal Masses: A Case With a 5-Year Follow-Up
Authors: Kang Yu Mi , Majumdar Sachin
Published: May 2020

Background Nearly 25% of adrenal Cushing syndrome (CS) patients with bilateral adrenal masses have unilateral hypercortisolism, making localization crucial for surgical planning. Since there is no standardized protocol for adrenal venous sampling (AVS) in lateralizing adrenal hypercortisolism, we share our experience with a case of CS with bilateral adrenal masses in which lateralization via AVS permitted unilateral adrenalectomy. Clinical Case A 59-year-old woman with hypertension, hyperlipidemia, and prediabetes was hospitalized for worsening back pain and hypertension. Her BMI was 26.5 kg/m2, BP 173/93 mmHg, HR 73/min, she was anxious, diaphoretic, and hirsute. Glucose was 118 mg/dL and HbA1c 6.6%. Abdominal computed tomography revealed a type B aortic dissection with both right (6.1 x 3.1cm and 3.6 x 2.4cm), and left (largest 1.7 cm) sided adrenal masses. Plasma and 24 hour-urine metanephrine, normetanephrine and catecholamines, as well as plasma renin and aldosterone levels, were normal. AM cortisol on three different occasions was 21.30, 20.70, and 21.30 mcg/dL. Midnight cortisol was 17.8 mcg/dL, and 24-hour urine free cortisol on two occasions was 163 mcg (urine volume 3.4L with creatinine 1.14) and 99.2 mcg (urine volume 1.15L). After 1mg dexamethasone her AM ACTH and cortisol were <5 and 18.70 mcg/dL, respectively. Preoperative AVS was performed and 8mg of dexamethasone was administered the night prior to ensure ACTH suppression during the procedure, and epinephrine was measured to ascertain adequate adrenal vein cannulation. Cortisol levels (in mcg/dL) from the common iliac, right and left adrenal veins were 14.7, 61.5, and 23.5 at 0 minute and 15.2, 61.0, and 22.7 at 2 minutes, respectively. Epinephrine levels (in pg/dL) from the common iliac, right and left adrenal veins were 42, 577, and 3225 at 0 minutes, and 46, 718, and 2989 at 2 minutes. Despite higher epinephrine levels from the left adrenal, the cortisol ratio of the right adrenal vein to peripheral vein was 4.18 with the right-to-left ratio of 2.59 and 2.68 at 0 and 2 minutes, suggesting hypersecretion of cortisol from the right adrenal gland. Unilateral right adrenalectomy revealed a 5.6 cm adrenal adenoma arising in a background of adrenal cortical hyperplasia. Morning postoperative cortisol was 2.2 mcg/dL. She was placed on hydrocortisone and tapered over a 10-month period with remission maintained for more than 3.5 years post-operatively. Conclusion This case demonstrates the safety, usefulness, and necessity, of AVS in localizing cortisol production when bilateral adrenal masses are present. In addition, this case suggests that the use of high dose dexamethasone and measurement of catecholamines may be helpful for more accurate interpretation. More data on AVS in CS patients with bilateral adrenal masses is needed so a well-validated and standardized CS-specific ACS protocol can be developed.
SUN-LB79 Efficacy of the Percutaneus Administration, Guided by Ultrasound, of Polidocanol Ablation for Cystic Thyroid Nodules
Authors: Castillo Marlen Alejandra Alvarez , Palomo Antonio Segovia
Published: May 2020

Introduction: The cystic thyroid nodule is a variant of nodular disease presentation, it can condition compressive symptoms, drainage is an alternative for its management, but it presents an elevated rate of recurrence, injection of ethanol is an alternative for refractory cases but it requires multiple sessions and is not exempt for recurrence, on the other hand, polidocanol may represent a best alternative for treatment. Objective: Determine the efficacy of polidocanol administration for cystic thyroid nodule disease. Study Design: An experimental, prospective, comparative of before and after and analytical study was made. Period and Population: Patients older than 18 years were selected, with diagnosis of cystic thyroid nodule disease in whom drainage was made with subsequent ablation with polidocanol 1%, considering therapeutic efficacy a reduction of at least 50% in regard of initial volume. Results: 39 patients were studied, 33 (84-6%) were women, with an age of 49.0 (15.0) years old. All with palpable nodules, time of identification of 14.1 (11.69) months and a palpable size of 3.53 (2.02) cms. The predominant location was the right lobule (51.3%), 24 (61.5%) referred growth before the procedure conditioning compressive symptoms. The main cystic composition was pure and unique in 20 (51.3%). 10 (25.6%) referred important cosmetic problem/ dysphagia. TSH was 1.73 (1.22) mU/ ml. An initial volume was of 13.99 (11.72) ml and a final volume of 6.6 (12.1) ml, p 0.000 (IC 95% 4.4, 10.2). 3 (7.7%) presented hematoma and 2 (6.1%) pain. Time of follow- up was of 24 weeks. Reduction percentage 78.7 (32). 33 (84.6%) achieved a reduction ≥50% and 21 (53.8%) ≥85% of the initial volume. Conclusion: Polidocanol is effective and safe for cystic thyroid nodule disease treatment, its use should be proposed in patients with this pathology.
SUN-LB43 DLK1 Expressing Cells Contribute to the Zonation of the Adrenal Gland
Authors: Mariniello Katia , Rognoni Emanuel , Guasti Leonardo
Published: May 2020

The adrenal cortex is a dynamic organ that undergoes self-renewal and remodeling in response to the demand for steroids. In the mouse it is divided into two concentric layers, the outer zona glomerulosa and the inner zona fasciculata (ZF), that secrete aldosterone and corticosterone, respectively. Cell fate mapping studies have shown that the maintenance of the cortex relies on a pool of stem/progenitor cells located in the capsular and subcapsular compartments. Two interconnected cell populations have been identified, subcapsular undifferentiated cells secreting the morphogen Sonic Hedgehog (Shh) and capsular Gli1+ cells, which can transduce the Shh signal (1); both populations are precursors of steroidogenic cells and newly formed cells migrate in a centripetal fashion to repopulate the gland until they reach the juxtamedullary region where they undergo senescence and apoptosis. Moreover, our lab has shown that the Notch atypical ligand Delta-Like homologue 1 (Dlk1) is expressed in partially undifferentiated cells of the subcapsular region in rat (2)and human (3)adrenals, whilst it is mostly expressed in capsular cells in mice (4,5). To investigate whether Dlk1 expressing cells contribute to the zonation of the adrenal cortex we conducted lineage tracing analyses using a tamoxifen inducible Dlk1CreERT2mouse model carrying the R26tdTom reporter. Pregnant dames were injected with tamoxifen at embryonic day (e) 12.5 and pups were culled at postnatal day (p) 10 and p38. Analysis of tdTomato expression showed that 35% (p10) and 24% (p38) of Steroidogenic Factor 1(Sf1)+cortical cells were tdTomato+, revealing that capsular Dlk1+cells are steroidogenic precursors. On the other hand, postnatal tamoxifen injections (p0) showed tdTomato+/Sf1+ cells only in 1-2% in cortical cells after 24-months chase, suggesting that the contribution of Dlk1+cells to adrenocortical self-renewal is limited postnatally.However, the Dlk1+population could be reactivated in the adult mouse treated with dexamethasone and was shown to contribute to the regeneration of the ZF once dexamethasone treatment was ceased. 1. King P, et al. Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. Proc Natl Acad Sci(2009) 106:21185-211902. Guasti L, et al. Dlk1 Up-Regulates Gli1 Expression in Male Rat Adrenal Capsule Cells Through the Activation of β1 Integrin and ERK1/2. Endocrinology(2013) 154:4675-46843. Hadjidemetriou I, et al. DLK1/PREF1 marks a novel cell population in the human adrenal cortex. J Steroid Biochem Mol Biol(2019) 193:1054224. Guasti L, Candy Sze WC, McKay T, Grose R, King PJ. FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development. Mol Cell Endocrinol(2013) 371:182-1885. Heikkilä M, et al. Wnt-4 Deficiency Alters Mouse Adrenal Cortex Function, Reducing Aldosterone Production. Endocrinology(2002) 143:4358-4365
MON-LB018 Paediatric Type 2 Diabetes in a Single Centre in East London in the Period 2009-2018
Authors: Gevers Evelien F , Giuffrida Anna
Published: May 2020

Background: The incidence of Paediatric type 2 diabetes is increasing, especially in areas of deprivation.

Aim: To describe the cohort of CYP with T2D in Royal London Hospital over the period 2009-2018.

Methods: Retrospective analysis of patient cohort.

Results: Number of new patients doubled from 2.6/year in 2009-2013 to 5.3/year in 2014-2018. Prevalence in our cohort is 7.5% (national average of 2.5%, NPDA 2017-2018). Fourty patients (25 female, 15 male) were diagnosed in 2009-2018, with a mean age at diagnosis of 13.9+/-1.7 yrs. Males had more frequently learning difficulties compared to females (40% vs 20%). Sixty % of patients were Asian compared to 28% in our T1D cohort.

BMI at presentation was 31.5 kg/m2 (23 females) and 33.85 kg/m2 (13 males). BMI remained stable for females for the first year after diagnosis but in males increased to 34.6 kg/m2 (n=10, non significant (ns)).

At diagnosis, Metformin was started in 38/40 patients although 7 patients reduced the dose and 6 stopped due to side effects. 12/36 patients started also on long-acting insulin (0.28+/-0.17U/kg), in 6 combined with prandial insulin (0.42+/-0.20U/kg). Seven patients started long-acting insulin at a later stage and 6 required prandial insulin too. 1 patient was treated with Sitagliptin.

HbA1c at diagnosis (n=27) was 75.2+/- 20mmol/mol, similar for males and females.HbA1c dropped to 55.0+/-17.4mmol/mol after 3 months (P<0.0001), to increase again to 63.0+/-25.8 and 67+/-28 after one (n=25, ns) and 2 years (n=23, ns).

Nineteen of 38 patients achieved a HbA1c < 48 at least once, but only 9 of 35 achieved an HbA1c < 48 for a year. Of these, 3 continued to be on insulin and in 1 patient insulin was stopped. Two patients relapsed.

Complications were as follows: 11/21 hypertension, 6/28 sleep apnoea, 10/30 raised ALT and 9/24 fatty liver.

Conclusion: Learning difficulties in patients with T2D are frequent. Complications of obesity/T2D are common in this cohort. Current treatment does not achieve permanent reduction in BMI and HbA1c in most patients although temporary reduction of HbA1c is possible. New treatment approaches are needed to improve outcomes.
MON-LB108 Measurement Of Carotid Intima,hepatic Steatosis And Inflammatory Markers In Obese Children
Authors: Bazan Maria Cristina
Published: May 2020

Measurement of carotid intima,hepatic steatosis and inflammatory markers in obese children. Elevated levels of inflammatory factors and increased mean intimal carotid thickness (IMT) would increase the risk of atherothrombotic events and contribute to the progression of cardiovascular disease in obese children. Objectives: Evaluate inflammatory factors, metabolic syndrome and non-alcoholic liver steatosis and carotid IMT as an early cardiovascular risk marker. Patients and methods: Descriptive cross-sectional exploratory study. Consider 41 obese children both sexes between 6- 12 years old. Evaluated: anthropometry and determinations of lipid and liver profile, blood glucose, insulin, HOMA, ultrasensitive CRP, fibrinogen. Hepatic ultrasound and measurement of carotid IMT with ESAOTE Mylab 50 Exdicion equipment. . Results: From 41 studied patients, 57% were female. 51% presented MS and 68% elevated triglycerides. CRP> 1 was found in 71% of cases. Hepatic steatosis was observed in 60%, which only 10% had altered transaminases. 12% presented high fibrinogen. Patients with MS had a significant positive difference in the IMTCC (X = 0.41 ± 0.12; p 0.024), HDL (X 37.89 ± 1.72; p 0.004) triglycerides (X 149.42 ± 10.69; p 0.002) in relation to patients without MS. Conclusion: CRP is an inflammatory risk factor associated with elevated BMI and MS. There was a higher prevalence of MS in our study. The increase in the average intimal thickness is significantly related to the presence of MS and RCP>1. The determination of marker molecules of an inflammatory state and measurement of carotid IMT would contribute to the implementation of strategies to prevent cardiovascular, hepatic and metabolic risk since childhood.
SAT-LB88 Recurrent Dysphagia Due to an Esophageal Stricture in a Patient With Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)
Authors: Johnson Timothy , Gabriely Ilan
Published: May 2020

Background: Chronic Mucocutaneous Candidiasis is one of the hallmark features of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED). Untreated esophageal candidiasis may lead to complications such as esophageal stricture, rupture and or fistula formation1,2. Case Presentation:A 31-year-old man with a past medical history significant for APECED with involvement including hypoparathyroidism, hypothyroidism and adrenal insufficiency presented to the Emergency Department with dysphagia and globus sensation after eating. This was the fourth time in the last 2 years that the patient had presented with this chief complaint. The patient underwent emergent esophagogastroduodenoscopy (EGD) where a large meat bolus was identified at approximately 20 cm and removed. A discrete esophageal tear at 19-20 cm was identified and clipped. The esophagus was noted to be diffusely narrowed with mild corrugation, and biopsies showed evidence of esophageal candidiasis. A chest CT scan demonstrated diffuse pneumomediastinum and soft tissue emphysema throughout the esophagus, suspicious for a tear. Fluoroscopic Esophagogram showed mild narrowing of the upper third of the esophagus without evidence of gross extravasation. The patient was placed on NPO (nothing by mouth) diet, started total parenteral nutrition, and treated with IV Fluconazole, administered for 10 days and then transitioned to oral Fluconazole for a total of 21 days, with improvement. A subsequent repeat fluoroscopic esophagogram showed absence of extravasation at the previously identified level of the esophagus. The patient is currently scheduled for a repeat EGD in 3 months. Conclusion:This case demonstrates a significant complication of APECED involving esophageal candidiasis. Timely diagnosis and treatment of esophageal candidiasis in APECED may prevent life-threatening esophageal pathology.

References:1)Kim, Byung-Wook et al. Esophagomediastinal fistula and esophageal stricture as a complication of esophageal candidiasis: A case report. Gastrointestinal Endoscopy, Volume 52, Issue 6, 772 – 775.2)Hyun J, Chun H, Keum B et al. Candida esophagitis complicated by esophageal stricture. Endoscopy 2010; 42(S02): 180 - 181. doi:10.1055/s-0029-1244014.
OR25-03 The Effects of Crinecerfont (NBI-74788), a Novel CRF1 Receptor Antagonist, on Adrenal Androgens and Precursors in Patients with Classic Congenital Adrenal Hyperplasia: Results from A Multiple-Dose Phase 2 Study
Authors: Auchus Richard J , Sarafoglou Kyriakie , Fechner Patricia Y , Vogiatzi Maria , Giri Nagdeep , Roberts Eiry , Sturgeon Julia , Farber Robert
Published: May 2020

Introduction: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD CAH) is a rare autosomal recessive disease that results in impaired cortisol synthesis and excess androgen production. Compounds that inhibit adrenocorticotropic hormone (ACTH) release could reduce adrenal androgen production and thus the amounts of exogenous glucocorticoids needed to decrease these androgen levels. This study evaluated the effect of crinecerfont (NBI-74788), a novel, non-steroidal, and selective corticotropin-releasing factor-1 (CRF1) receptor antagonist on adrenal androgens and precursors in adults with 21OHD CAH.

Methods: This open-label, multiple-dose study enrolled men and women (18–50 years old) with 21OHD CAH. A sequential-cohort design evaluated 4 crinecerfont oral dosing regimens: 50 mg QHS (Cohort 1); 100 mg QHS (Cohort 2); 100 mg QD (Cohort 3); and 100 mg alternative dosing (Cohort 4). Each regimen was administered for 14 consecutive days. ACTH, 17-hydroxy-progesterone (17OHP), and androstenedione (A4) were measured serially over a 24-hour period, at baseline and after 14 days of dosing.

Results: Analyses included 23 participants: Cohort 1 (4 women, 4 men: mean age 31.1 years); Cohort 2 (5 women, 2 men: mean age 32.9 years); and Cohort 3 (3 women, 5 men: mean age 30.9 years). Cohort 4 is ongoing. At baseline, median plasma ACTH, serum 17OHP, and serum A4 levels were as follows: Cohort 1 (ACTH, 151 pg/mL; 17OHP, 5352 ng/dL; A4, 270 ng/dL); Cohort 2 (ACTH, 232 pg/mL; 17OHP, 12821 ng/dL; A4, 597 ng/dL); and Cohort 3 (ACTH, 470 pg/mL; 17OHP, 6451 ng/dL; A4, 299 ng/dL). After 14 days of once-daily crinecerfont 50 mg, Cohort 1 patients had median percent reductions from baseline in plasma ACTH (-54%), serum 17OHP (-60%), and serum A4 (-21%). Median percent reductions were generally larger with 100 mg in Cohort 2 (ACTH, -67%; 17OHP, -75%; A4, -47%) and Cohort 3 (ACTH, -69%; 17OHP, -55%; A4, -43%), consistent with a dose-related response. Adverse events were mostly mild; no clinically significant findings from routine laboratory tests, vital signs, or electrocardiograms were noted.

Conclusions: Results of this Phase 2 study of crinecerfont, a novel, orally administered, selective CRF1-receptor antagonist, indicated clinically meaningful reductions of elevated ACTH, 17OHP, and A4 in adults with 21OHD CAH after 14 days of treatment. Further studies are warranted to evaluate the effects of chronic crinecerfont therapy on maintenance of adrenal steroid production, clinical endpoints of disordered steroidogenesis, and reductions in GC exposure in both adult and pediatric patients with 21OHD CAH.
SAT-LB40 Adrenalectomy - A Rural Teaching Hospital Experience
Authors: Shen Alice S
Published: May 2020

Background: Studies characterize the surgical managements of adrenal tumors are not common in rural hospitals. Methods: A retrospective study conducted at a single rural teaching hospital with subjects including 37 patients who had laparoscopic or open adrenalectomy between 2011 and 2017. Baseline characteristics and postoperative outcomes of patients were examined using univariate and multivariate methods. Logistic regression models were used to analyze perioperative complications. Truncated negative binomial regression models was used to analyze hospital length of stay. Pathologic distribution, correlation of pre-op and pathologic diagnoses were also analyzed.Results: On average, five adrenalectomies per year were done for primary adrenal pathology. Adrenocortical adenoma and pheochromocytoma were the two most common pathologic diagnoses. Length of stay increased in patients with open surgery, RR 3.78 (1.60-8.91), and malignancy, RR 3.18 (1.43-7.06), based on multivariate analysis. Factors associated with post-operative complications in univariable analysis are tumor size odds ratio (OR) 1.02 (95% confidence interval 1.00 to 1.05), and open surgery, OR 4.29 (0.96-21.52). This significance was not present at the multivariable analysis. Conclusions: Evaluation and surgical management of adrenal tumors in a rural hospital for seven years were characterized. The results of this study will contribute to future epidemiological research on adrenal incidentalomas and surgical managements of adrenal tumors in rural hospitals.
SUN-LB127 In Experimental Peripheral Arterial Disease MIR29a Modulation Improves Perfusion Recovery and Muscle Function to a Greater Extent Than ADAM12 Augmentation in Mice With Type 2 Diabetes
Authors: Lamin Victor
Published: May 2020

Diabetes Mellitus (DM) is a major risk factor for developing peripheral arterial disease (PAD) and individuals with DM have worse PAD outcomes but the molecular mechanisms involved are poorly understood. We previously identified a disintegrin and metalloproteinase gene 12 (ADAM12) as a key genetic modifier of post-ischemic perfusion recovery in experimental PAD that it is regulated by miR29a through direct interaction. In ischemic hind limbs non-diabetic mice, miR29a expression is downregulated and allows ADAM12 upregulation. However, in ischemic hind limbs of type 2 DM (DM2) mice miR29a expression remains elevated and prevents ADAM12 upregulation. Hence, we hypothesized that inhibition of miR29a or augmenting ADAM12 would improve the impaired perfusion recovery typical of mice with DM2 in experimental PAD. Here, in mice with DM2 we compare the therapeutic effectiveness of miR29a inhibition (miR29aINH) to ADAM12 gene overexpression on perfusion recovery in experimental PAD.

26 - 28 weeks old C57BL/6 mice on high fat diet were randomized into 3 treatment groups: sham (saline), miR29aINH, or ADAM12 plasmid. Agents were delivered by micro-bubbles at 5 days and 1 day pre-surgery. Experimental PAD was achieved by unilateral ligation and excision of the femoral artery of the left hind limb. The right hind limb serves as non ischemic control. Peripheral blood flow is measured by Laser Speckle Contrast Imaging. Tibialis anterior contractile function was assessed using an Aurora 300B-LR. ADAM12 and miR29a expression levels were quantified using qPCR on day 3 post surgery since perfusion at this point is similar between the experimental groups. Data are expressed as means ± SEM. Statistical significance of P < 0.05 as significant is performed with the independent Student’s t-test.

Gene expression analysis 3 days post ischemia showed miR29a inhibitor reduced miR29a levels (miR29aINH: 0.70±0.06, n=5, ADAM12: 0.62±0.06, n=4, p=0.3938 and Sham: 1.02±0.06, n=5, p= 0.004 for miR29aINH vs Sham) and increased ADAM12 expression to a greater extent than ADAM12 gene transfer (miR29aINH: 208.62±24.52, n=3, ADAM12: 20.71±2.98, n=4, p= 0.0003 and Sham: 11.75±4.94, n=4). 3 weeks post-surgery, there was significantly higher perfusion recovery in mice treated with miR29aINH compared to ADAM12 gene transfer (miR29aINH: 97.59±6.14, n= 10, ADAM12: 58.45±4.87, n=8, p=0.002 and Sham: 42.52±5.35, n=5). Muscle contraction in the ischemic limb was >2-fold stronger in the miR29aINH treated mice compared to ADAM12 gene transfer (miR29aINH: 0.54±0.08, n=7, ADAM12: 0.26±0.06, n=7, p= 0.0170 and Sham: 0.17±0.06, n=6).

Our result reveals for the first time that inhibiting elevated microRNAs may be a more effective therapeutic approach than gene transfer to improve blood flow and muscle function in type 2 DM and PAD.
SAT-LB136 A Proteomic Approach to Identify Circulating Glucocorticoid Responsive Proteins in Humans
Authors: Inder Warrick John , Keshvari Sahar , Barclay Johanna L , Ruelcke Jayde E , Stoll Thomas , Mohamed Ahmed , Nolan Brendan J , Cesana-Nigro Nicole , Hill Michelle M
Published: May 2020

Glucocorticoids used in pharmacological doses for the treatment of a variety of medical conditions, and endogenous glucocorticoid excess - Cushing’s syndrome, may result in several adverse effects, but currently there is no clinically useful biomarker of glucocorticoid activity. We have applied a proteomic approach to the discovery of glucocorticoid-responsive proteins potentially measurable in human serum samples. To minimise the masking by abundant serum proteins, we conducted discovery proteomics on the secretome of ex vivo-stimulated peripheral blood mononuclear cells (PBMC) isolated from 12 volunteers. The PBMC were divided into 4 treatment groups; +/- dexamethasone 100 ng/mL (dex) for 4h, or +/- dex for 24h. In all treatment groups, media was changed to serum free for 3h before collection. Media samples were processed for proteomics, with 561 and 273 proteins analysed by label-free quantification (LFQ) for the 4h and 24h secretome, respectively. Paired statistical analysis at the 2 time points generated a shortlist of 43 candidate biomarker proteins, which was verified using a multiple reaction monitoring (MRM) assay, confirming the differential secretion of 12 proteins at both 4h and 24 h. Five proteins were selected for validation using enzyme linked immunosorbent assay (ELISA) in an independent cohort: β2 microglobulin (B2M), lysozyme C (LYZ), high-mobility group protein 2 (HMG2), nucleophosmin (NPM1) and nucleolin (NCL). Twenty new volunteers (10M and 10F) had venous blood drawn at baseline and 12h after 4 mg oral dex. Four proteins were detectable by ELISA, three of which showed statistically significant change in concentration. Serum LYZ and NPM1 significantly decreased following dex: LYZ - 101 ± 5.5 vs 67 ± 4.4 ng/mL, (P<0.0001); NPM1 - 17.4 ± 1.0 vs 14.3 ± 0.9 ng/mL, (P<0.01), while HMG2 significantly increased - 819 ± 34 vs 984 ± 60 pg/mL (P<0.01). These results demonstrate that an ex vivo proteomic approach using PBMC in conditioned media can identify glucocorticoid-responsive proteins measurable in human serum.