bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU058 Impact Of A Smartphone App On Follow-up Of Adult Growth Hormone Deficiency (AGHD) Patients: Results From The Management Of AGHD (MAGHD) Study
Authors: De Vincentis Sara , Bellelli Alessio , Golinelli Caterina , Beltrami Elisa , Monzani Maria Laura , Magnani Elisa , Pederzoli Simone , Pacchioni Marco , Orsini Mirko , Diazzi Chiara , Rochira Vincenzo 
Published: October 2023

Abstract
Disclosure: S. De Vincentis: None. A. Bellelli: None. C. Golinelli: None. E. Beltrami: None. M. Monzani: None. E. Magnani: None. S. Pederzoli: None. M. Pacchioni: None. M. Orsini: None. C. Diazzi: None. V. Rochira: Grant Recipient; Self; Pfizer, Inc.
BACKGROUND: AGHD significantly impacts on metabolism, body composition and quality of life (QoL), including sexuality. AIM: To investigate the impact of a smartphone App on AGHD monitoring, especially QoL and comorbidities as well as on both body composition and biochemical parameters. METHODOLOGY: 83 AGHD patients were enrolled in this prospective, open-label, monocentric study (MAGHD Study) of 24-month duration. Patients were evaluated (clinical, biochemical and multidimensional investigations) every 6 months, for a total of 5 visits (from V0, V1, V2, V3 e V4). Multidimensional evaluation included the following questionnaires: QoL-AGHDA, QLS-H, WEMWBS, IPAQ, PSQI e IIEF-15 e FSFI for QoL and sexual function. Body composition was evaluated at V0, V2 and V4 by DEXA. After the first year (Phase 1), patients were grouped according to the acceptance to use (Group 1) or not (Group 2) the smartphone App (MAGHD App) for answering questionnaires. Thus, during the second year (Phase 2), 58 patients provided questionnaires answers through MAGHD App (Group 1) and the remaining 25 patients continued with standard compilation of questionnaires only at visits every 6 months without using MAGHD App (Group 2). RESULTS: The use of the MAGHD App resulted in a higher number of completely filled questionnaires in Group 1 (15.68±8.10) compared to Group 2 (10.33±2.09) (p&lt;0.001). QoL-AGHDA (p=0.001), QLS-H (p=0.030), IPAQ (p&lt;0.001), IIEF-15 (p=0.005) and FSFI (p=0.002) scores were significantly better in Group 1 than Group 2. Compliance to r-hGH therapy increased in Group 1 comparing Phase 1 to Phase 2, but without statistical significance (p&gt;0.05). Comorbidities resulted increased in number in Group 2 compared to Group 1 (p&lt;0,05). No differences were found between Group 1 and 2 in biochemical and hormonal outcomes. CONCLUSIONS: The use of an ad hoc designed smartphone App is well-accepted by patients and associated with a good adherence in its use, suggesting positive effects on QoL in AGHD patients. The integration of a smartphone App in the clinical practice is feasible and may help empowering patients with chronic diseases such as AGHD on daily self-monitoring of their disease trend, beyond helping physicians in tailoring the clinical management. This study belongs to the Pfizer Inc. ‘Independent Grant for Learning and Change, Dissemination & Implementation’ (Grant ID 34515061).
Presentation: Thursday, June 15, 2023
THU059 Increased Intracellular And Extracellular Myocardial Masses On Cardiac Magnetic Resonance Imaging In Patents With Acromegaly
Authors: Wolf Peter , Bouazizi Khaoula , Kachenoura Nadjia , Piedvache Celine , Gallo Antonio , Salenave Sylvie , Maione Luigi , Young Jacques , Prigent Mikaël , Lecoq Anne-Lise , Kuhn Emmanuelle , Agostini Helene , Trabado Severin , Redheuil Alban , Chanson Philippe , Kamenicky Peter 
Published: October 2023

Abstract
Disclosure: P. Wolf: None. K. Bouazizi: None. N. Kachenoura: None. C. Piedvache: None. A. Gallo: None. S. Salenave: None. L. Maione: None. J. Young: None. M. Prigent: None. A. Lecoq: None. E. Kuhn: None. H. Agostini: None. S. Trabado: None. A. Redheuil: None. P. Chanson: Research Investigator; Self; Pfizer. P. Kamenicky: None.
Background: Acromegaly is associated with an increased left ventricular mass, as reported in echo-based and more recently in few cardiac MRI studies. One possible explanation of this increased ventricular mass could be water retention and consequently edema of the ventricular wall. Methods: In this prospective, cross-sectional study 26 patients with active acromegaly and 31 control subjects of comparable age and sex were investigated by cardiac MRI. Patients were explored before and after GH/IGF-I lowering treatment. Cardiac morphology, function and myocardial tissue characteristics were assessed. T2 times were used as a reflect of intramyocardial water content. Results: Ventricular mass (58.08 (54.71; 68.6) vs 46.02 (41.27; 49.82) g/m2; p&lt;0.001) and volume (97.25 (88; 101.21) vs 81.64 (78.08; 96.23) mL/m2; p= 0.0069) were higher in patients compared to controls, without affecting cardiac function. T2 times were not increased in active acromegaly. Both, intracellular (87.9 (71.2; 103.6) vs 67.2 (51.6; 76.9) g/m2; p&lt;0.001) and extracellular (31.9 (26.1; 36.6) vs 21.8 (19.2;24.7) g/m2; p&lt;0.001) myocardial mass were higher in patients compared to controls. GH, but not IGF-I strongly correlated with myocardial mass (r=0.756; p&lt;0.001). In multiple regression analysis, in addition to male sex and HDL cholesterol, the presence of acromegaly was an independent predictor of total myocardial mass and extracellular mass, whereas systolic arterial blood pressure predicted intracellular mass. GH/IGF-I lowering treatment reduced intracellular mass and ventricular volume, without affecting other myocardial tissue characteristics. Discussion: Acromegaly results in a disease specific form of myocardial hypertrophy, characterized by an increase in intra- and extracellular mass, which is reversed after GH/IGF-I lowering treatment. This increase in ventricular mass is thus different to previous observations in essential hypertension. No differences in T2 times suggest against myocardial water retention in active acromegaly as explication of increased extracellular mass.
Presentation: Thursday, June 15, 2023
THU060 Time To First Remission, Medical Therapy And Survival In Acromegaly: UK Acromegaly Register (UKAR) Study
Authors: Deshmukh Harshal , Ssemmondo Emmanuel , Adeleke Kazeem , Batten Lucy , Aye Mo , Sathyapalan Thozhukat 
Published: October 2023

Abstract
Disclosure: H. Deshmukh: None. E. Ssemmondo: None. K. Adeleke: None. L. Batten: None. M. Aye: None. T. Sathyapalan: None.
Introduction: There are limited data on the effect of time to remission of acromegaly and survival in people living with acromegaly Methods: The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly. We defined remission of acromegaly as Growth hormone (GH) controlled at ≤2 μg/l following the diagnosis of acromegaly. Time to first remission was defined as the difference between the date of diagnosis and the first GH date ≤2 μg/l in the longitudinal follow-up data (following surgery and/or medical therapy). We used a t-test to compare the mean survival and used the cox-proportional hazard model to assess the effect of time to remission on survival in acromegaly. Results: The study consisted of 3750 participants in the UK acromegaly register with complete data, of which 2472 (65%) participants achieved remission of acromegaly. The mean time to remission with somatostatin analogs (SA) and dopamine agonist (DA) therapy was 4.5 yrs and 7.3 years, respectively (P&lt;0.001). The mean survival was significantly higher in those who achieved remission of acromegaly as compared to those who did not (25.5 yrs vs 21.9yrs P&lt;0.001) achieve remission. In those who achieved remission, (median follow-up period of 23.9 years), there was 15% mortality in those who achieved remission within 1 year and 23% mortality in those who needed more than 1 year to achieve remission. In the cox-proportional hazard model adjusted for, baseline GH, age at diagnosis, and gender, a shorter time to regression of acromegaly was associated with improved survival (HR=0.92(0.91-0.93) P&lt;0.001). Conclusion: This large population-based study of acromegaly showed that a shorter time to remission is associated with improved survival.
Presentation: Thursday, June 15, 2023
THU089 Natural Course Of Non-Functioning Pituitary Adenoma According To Age And Sex: A Longitudinal Observational Study
Authors: Park Seung Shin , Kang Ho , Ahn Chang Ho , Kim Suhong , Kim Yong Hwy , Kim Jung Hee 
Published: October 2023

Abstract
Disclosure: S. Park: None. H. Kang: None. C. Ahn: None. S. Kim: None. Y. Kim: None. J. Kim: None.
Backgrounds: Non-functional pituitary tumors (NFPTs) are the most common tumor among pituitary adenomas. Surgical treatment is recommended when patients present a mass effect such as a headache, visual field defect, or hormonal dysfunction. However, there is a lack of data regarding the natural course of NFPTs according to sex and age. Herein, we aimed to characterize age and sex-dependent tumor growth in patients with NFPTs. Methods: We enrolled 435 patients (males, n= 162) who were diagnosed with NFPTs and followed up at least one time and more than 12 months from 1997 to 2021 at a tertiary center. Study subjects were divided into three groups according to their age (ages≤50, 51≤age&lt;65, age≥65 years). The characteristics and tumor growth of NFPTs were compared according to sex and age groups. Results: Male patients were older than female patients (median [range], 58.0 [47.0;65.0] vs. 50.0 [39.0;60.0], P&lt;0.001). Annual tumor volume and percent change were higher in male patients compared to female patients (P&lt;0.001, P=0.009, respectively). Despite the shorter follow-up duration in males (61 months in males vs. 71 months in females), male patients underwent surgery more often than female patients (25.9% vs. 11.4%, P&lt;0.001). In male patients, there was no significant difference in the rate of tumor growth between different age groups. However, in female patients, a more rapid increase in annual tumor volume percent change was observed in the older age group compared to the younger age group (2.2 [-3.5;15.2] in females ≤50 years, 6.7 [-2.1;23.7] in 51≤ female &lt;65 years, 10.1 [2.9;25.7] in female≥65 years, P=0.018). The relative risk of tumor growth of more than 20 percent, as compared with the reference group in females younger than 51 years, was 1.81 in the female group aged between 51 to 64 years (95% CI 1.06-3.08, P=0.029), and 2.45 in the female group older than 65 years (95% CI 1.16-5.18, P=0.019) compared to reference group of females younger than 51 years. Conclusion: The NFPT grows more rapidly in males than in females. The growth of NFPT was not significantly different according to age in males, however, in females, the growth of NFPT was more rapid in the older age group. Therefore, males and old females among patients with NFPTs should be more closely followed-up.
Presentation: Thursday, June 15, 2023
SAT669 Development And Biophysical Characterization Of A Humanized FSH-blocking Monoclonal Antibody Therapeutic Formulated At An Ultra-high Concentration
Authors: Rojekar Satish , Pallapati Anusha Rani , Gimenez–Roig Judit , Sant Damini , Gera Sakshi , Korkmaz Funda , Sultana Farhath , Barak Orly , Moldavski Ofer , Cheliadinova Uliana , Gumerova Anisa Azatovna , Miyashita Sari , Kannangara Hasni Suhasha , Frolinger Tal , Witztum Ronit , Macdonald Anne , Georgii Pevnev , Sims Steven Lee , Caminis John N , Meseck Marcia , Ryu Vitaly , Kim Se-Min , Lizneva Daria , Yuen Tony , Zaidi Mone 
Published: October 2023

Abstract
Disclosure: S. Rojekar: None. A.R. Pallapati: None. J. Gimenez–Roig: None. D. Sant: None. S. Gera: None. F. Korkmaz: None. F. Sultana: None. O. Barak: None. O. Moldavski: None. U. Cheliadinova: None. A. Gumerova: None. S. Miyashita: None. H.S. Kannangara: None. T. Frolinger: None. R. Witztum: None. A. Macdonald: None. P. Georgii: None. S.L. Sims: None. J.N. Caminis: None. M. Meseck: None. V. Ryu: None. S. Kim: None. D. Lizneva: None. T. Yuen: None. M. Zaidi: None.
Highly concentrated antibody formulations are oftentimes required for subcutaneous, self-administered biologics. Here, we report the creation of a unique formulation for our first-in-class FSH-blocking humanized antibody, MS-Hu6, which we propose to move to the clinic for osteoporosis, obesity, and Alzheimer’s disease. The studies were carried out using our Good Laboratory Practice (GLP) platform, compliant with the Code of Federal Regulations (Title 21, Part 58). We first used protein thermal shift, size exclusion chromatography, and dynamic light scattering to examine MS-Hu6 concentrations between 1 and 100 mg/mL. We found that thermal, monomeric, and colloidal stability of formulated MS-Hu6 was maintained at a concentration of 100 mg/mL. The addition of the antioxidant L-methionine and chelating agent disodium EDTA improved the formulation's long-term colloidal and thermal stability. Thermal stability was further confirmed by Nano differential scanning calorimetry (DSC). Physiochemical properties of formulated MS-Hu6, including viscosity, turbidity, and clarity, conformed with acceptable industry standards. That the structural integrity of MS-Hu6 in formulation was maintained was proven through Circular Dichroism (CD) and Fourier Transform Infrared (FTIR) spectroscopy. Three rapid freeze-thaw cycles at −80°C/25°C or −80°C/37°C further revealed excellent thermal and colloidal stability. Furthermore, formulated MS-Hu6, particularly its Fab domain, displayed thermal and monomeric storage stability for more than 90 days at 4°C and 25°C. Finally, the unfolding temperature (Tm) for formulated MS-Hu6 increased by &gt;4.80°C upon binding to recombinant FSH, indicating highly specific ligand binding. Overall, we document the feasibility of developing a stable, manufacturable and transportable MS-Hu6 formulation at a ultra-high concentration at industry standards. The study should become a resource for developing biologic formulations in academic medical centers.
Presentation: Saturday, June 17, 2023
THU090 18F-FET PET-MRI; A Novel And Improved Technique For Detection Of Small Functional Pituitaryadenomas
Authors: Pruis Ilanah , Verbrug Erik , Smits Marion , Vernooij Meike , Feelders Richard Abraham , Blavers Rutger , Velthuijzen Sophie , Neggers Sebastian J CM M 
Published: October 2023

Abstract
Disclosure: I. Pruis: None. E. verbrug: None. M. smits: None. M. vernooij: None. R.A. Feelders: None. R. Blavers: None. S. velthuijzen: None. S.J. Neggers: None.
Background Small functional pituitary adenomas can cause severely disabling symptoms and early death, however, surgical planning is often complicated due to inconclusive diagnostic MRI in up to 40% of patients and therefore hamper cure rates. We here introduce a novel method for the detection of small functional pituitary adenoma by O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET-MRI. Methods Patients with Cushing’s disease (CD) or acromegaly with a suspected primary or recurrent small functional pituitary adenoma underwent [18F]FET PET-MRI. Focal uptake of [18F]FET was evaluated by a single nuclear radiologist and MRI was separately evaluated by a single neuroradiologist. Outcomes were compared with clinical follow-up and sensitivity and positive predictive values (PPV) were calculated. Findings Consecutive 28 patients, 68% female, mean age 50 years (range: 24–71), with CD (n=22; 79% or acromegaly (n=6; 21%) were scanned. 17 CD patients with a primary diagnosis had also undergone IPSS and 3 (50%) had a primary acromegaly diagnosis. 14/22 CD patients (64%) and 1/6 acromegaly underwent transsphenoidal surgery after [18F]FET PET, others are waiting or refused. Twenty-two CD patients (100%) had a positive [18F]FET PET, allowing to identify pituitary adenomas as small as 3 mm in size on accompanying MRI. 11/14 CD patients who underwent subsequent transsphenoidal surgery are biochemically in remission; rendering an estimated sensitivity of 100% and a PPV between 78–100% to detect CD. Four acromegaly patients (67%) had a positive [18F]FET PET. One acromegaly patient was biochemically in remission after transsphenoidal surgery. Conclusion [18F]FET PET-MRI shows high accuracy for localizing small functional pituitary adenoma in patients with CD and acromegaly. The diagnostic yield of this hybrid imaging technique exceeds that of MRI alone and IPSS and provides a welcome improvement for diagnosis, planning of surgery and follow-up.
Presentation: Thursday, June 15, 2023
THU120 Validation Of A Novel Automated System, Fluispotter®, For Serial Sampling Of Dried Blood Spots
Authors: Krogh Jesper , Plomgaard Peter Stendahl , Frikke-Schmidt Ruth , Velschow Sten , Johannesen Jesper , Hilsted Linda , Schrøder Malene , Feldt-Rasmussen Ulla 
Published: October 2023

Abstract
Disclosure: J. Krogh: None. P. Plomgaard: None. R. Frikke-Schmidt: None. S. Velschow: None. J. Johannesen: None. L. Hilsted: None. M. Schrøder: None. U. Feldt-Rasmussen: None.
Repeated blood sampling is required in certain clinical and research settings, which is currently performed by drawing blood from venous catheters requiring manual handling of each sample at time of collection. Collecting samples in a stressful environment, e.g. during the night or admission as inpatient to hospital potentially influences the hormone concentrations to be studied. The hypothesis of this study was that a novel body-worn device for repeated serial samples, Fluispotter®, with automated extraction, collection and storage of up to 20 venous dried blood spot samples over the course of 20 hours may overcome problems with current methods for serial sampling. The purpose of the study was to assess the performance and safety of Fluispotter for the first time in healthy subjects and perform cortisol measurements from the blood spots by mass spectrometry. Fluispotter consists of a cartridge with tubing, reservoir for flushing solution, pumps and filter-paper and a multi-lumen catheter placed in the brachial vein. We recruited healthy subjects for testing in an in-hospital setting. Fluispotter was attached to 22 healthy subjects of which 9/22 (40.9 %) participants had all 20 samples taken, which was lower than the expected 80% (p = 0.02). The main reason for sample failure was clogging of blood flow which was observed in 11/22 (50 %) of the participants. No serious adverse events occurred, and the participants rated the pain from insertion and removal of catheter as very low. A cortisol profile showed nadir values at midnight and highest values at 5 a.m. Although full sampling was not successful in all participants, the Fluispotter technology proved safe and highly acceptable to the participants producing the expected cortisol profile in an undisturbed environment without the requirement of staff during sample collection. The minor technical problems of blood clotting can be solved by increasing the flow of the rinsing fluid between samples. The Fluispotter may thus facilitate future circadian hormone assessments e.g. in patients on pituitary cortisol replacement with a perspective of improving management of patients with pituitary insufficiency.
Presentation: Thursday, June 15, 2023
FRI273 Generation And In Vitro Characterization Of A Novel Immortalized Ovine Neuronal KNDy Cell Line
Authors: Toyoizumi Rebekka , Markgraf Christopher Y , Starman Alia , Rodriguez Emily , Lee Blake L , Bahn-Bales Roxanne , Stricklin Olivia , Estill Charles , Roselli Charles E , Chappell Patrick E 
Published: October 2023

Abstract
Disclosure: R. Toyoizumi: None. C.Y. Markgraf: None. A. Starman: None. E. Rodriguez: None. B.L. Lee: None. R. Bahn-Bales: None. O. Stricklin: None. C. Estill: None. C.E. Roselli: None. P.E. Chappell: None.
The multiphenotypic hypothalamic KNDy neurons play a critical role in the neuroendocrine regulation of reproduction, and via their stimulation of GnRH release, are requisite for fertility and pubertal progression. In vivo evidence has accumulated identifying this more caudal population of Kisspeptin neurons in mediating predominantly negative feedback effects of gonadal steroids, and their ability to synthesize and secrete kisspeptin (KP), neurokinin B (NKB/Tac3), and dynorphin (Dyn) implicates them as crucial regulators of GnRH pulse generation. We have previously generated murine immortalized arcuate KNDy neuronal cell lines to explore molecular mechanisms underlying the steroid hormone regulation of these cells, and in the current study, we characterize a novel immortalized ovine neuronal cell line model of KNDy (oKNDy) cells derived from fetal female sheep brain (∼133 days of fetal development). Clonal lines were derived from isolated mediobasal hypothalamic explants using lentiviral infection of neurons with plasmids encoding SV40 large T-antigen. These neurons express ovine kiss1, tac3, and pdyn, as well as steroid receptors esr1, esr2, and pgr. Similar to KNDy neurons in vivo, receptors for Tac3 (tacr3) and Dyn (oprk1) were also found to be expressed in our oKNDy cells. Further, low physiological concentrations (5-50pM) of 17β-estradiol (E2) were found to significantly repress kiss1 and tac3 expression, while having no effect on tacr3. Concentrations of E2 and progesterone (P4) approximating proestrous levels maximally repressed kiss1 and tac3 after 24h, with elevations in pdyn noted under the same conditions. While cells exposed to higher E2 levels exhibited greater kiss1/tac3 repression, P4 exposure alone revealed stimulation of expression with increasing P4. Since these neurons were derived from the short-day seasonally breeding sheep, they can also be used to explore how circannual timing cues derived from the pituitary pars tuberalis may exert gating signals on the reproductive axis as previously modeled in vivo. Consistent with this, we have found high levels of thyroid hormone receptor α (thra) expression in our oKNDy neurons, suggesting they can respond to locally-synthesized T3. We are continuing to characterize these oKNDy neuronal cells in culture in order to provide insight into GnRH pulse generation and construct molecular models of neuronal responsiveness to steroids and other regulatory inputs.
Presentation: Friday, June 16, 2023