bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU107 A Case Of Primary Histiocytic Sarcoma Of Pituitary Gland Presenting With Central Diabetes Insipidus
Authors: Ahn Seong Hee , Kim Youngjoon , Cho Yongin , Seo Da Hea , Kim So Hun , Cho Jinhyun , Choi Suk Jin , Kim Kyung Min , Kim Eun-Young , Hong Seongbin 
Published: October 2023

Abstract
Disclosure: S. Ahn: None. Y. Kim: None. Y. Cho: None. D. Seo: None. S. Kim: None. J. Cho: None. S. Choi: None. K. Kim: None. E. Kim: None. S. Hong: None.
Introduction: Histiocytic sarcoma is a rare and aggressive hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system. Here, we reported the first case of primary histiocytic sarcoma involving pituitary gland. Methods: Medical records were reviewed. Results: A 53 years old Korean men presented with general weakness, polydipsia, polyuria, and abnormal thyroid function test suspicious for secondary hypothyroidism. Laboratory examinations showed growth hormone deficiency, hypogonadotropic hypogonadism, and central diabetes insipidus. The magnetic resonance imaging showed a well-enhanced mass involving entire posterior pituitary gland with stalk thickening. The biopsy of pituitary mass was identified as a malignant tumor consistent with histiocytic sarcoma. This malignant tumor inoperably increased within a short duration and hormone deficiency such as secondary hypothyroidism and adrenal insufficiency additionally developed. Therefore, the patient started radiation therapy with desmopressin, levothyroxine, and hydrocortisone replacement. Conclusion: The biopsy is not regarded as the mandatory procedure for diagnosing patients with central diabetes insipidus with posterior pituitary lesion since in many cases, this is the result of hypophysitis. However, since there is still the possibility of primary malignancy and metastasis involving pituitary gland, an appropriate decision for performing biopsy should be made according to the patient’s clinical situations.
Presentation: Thursday, June 15, 2023
THU113 Psychopathological Characteristics In Patients With Arginine Vasopressin Deficiency (Central Diabetes Insipidus) And Primary Polydipsia
Authors: Beck Julia , Atila Cihan , Refardt Julie , Erlic Zoran , Drummond Juliana Beaudette , Soares Beatriz Santana , Beuschlein Felix , Winzeler Bettina Felicitas , Christ-Crain Mirjam 
Published: October 2023

Abstract
Disclosure: J. Beck: None. C. Atila: None. J. Refardt: None. Z. Erlic: None. J.B. Drummond: None. B.S. Soares: None. F. Beuschlein: None. B.F. Winzeler: None. M. Christ-Crain: None.
Introduction The differential diagnosis between arginine vasopressin deficiency (AVP-D), formally known as central diabetes insipidus, and primary polydipsia (PP) is challenging. In clinical routine, psychopathologic findings are often used as a hallmark for diagnosing PP; thus, it is often referred to as psychogenic polydipsia. Yet, psychopathologic characteristics are barely assessed in patients with AVP-D, and to date, no data exist comparing AVP-D and PP with regard to these features. Therefore, in this study, we aimed to compare levels of anxiety, depression, alexithymia, and overall mental health in patients with AVP-D and PP. Methods This study combined data from two diagnostic studies conducted at three tertiary medical centers. In total, 82 participants (n=39 with AVP-D, n=28 with PP, and n=15 healthy controls [HC]) underwent a psychological evaluation with standardized questionnaires at study inclusion. Anxiety levels were assessed using the State-Trait Anxiety Inventory, mood using the Beck’s Depression Inventory, alexithymia using the Toronto Alexithymia Scale, and overall physical and mental health using the Short Form 36 Health Survey (SF-36). Higher STAI, BDI, and TAS scores indicate higher anxiety, depression, and alexithymia levels. Higher SF-36 scores indicate better health and less disability. Results Compared with HC, patients with AVP-D and PP showed increased levels of anxiety (HC 28 points [24, 31] vs. AVP-D 36 points [31, 45], p&lt;0.01; vs. PP 38 points [33, 46], p&lt;0.01), depression (HC one point [0, 2] vs. AVP-D 7 points [4, 14], p&lt;0.01; vs. PP 7 points [3, 13], p&lt;0.01), and alexithymia (HC 30 points [29, 37] vs. AVP-D 43 points [35, 54], p&lt;0.01; vs. PP 46 points [37, 55], p&lt;0.01). Levels of anxiety, depression, and alexithymia showed no difference between patients with AVP-D and PP (p=0.58, p=0.90, p=0.50). Compared with HC, patients with AVP-D and PP reported comparable reduced self-reported mental health scores (HC 84 [68, 88] vs. AVP-D 60 [52, 80], p=0.05; vs PP 60 [47, 74], p&lt;0.01). Conclusion This is the first study demonstrating comparable increased levels of anxiety, depression, alexithymia, and overall reduced mental health in patients with AVP-D and PP. Based on these data, psychopathological findings should not be used as a hallmark to differentiate between both conditions.
Presentation: Thursday, June 15, 2023
THU118 Prefrontal-Medullary Circuit Is Necessary For Chronic Stress-Induced Neuroendocrine And Behavioral Outcomes
Authors: Pace Sebastian A , Lukinic Ema , Barrette Paige , Wallace Tyler , Myers Brent 
Published: October 2023

Abstract
Disclosure: S.A. Pace: None. E. Lukinic: None. P. Barrette: None. T. Wallace: None. B. Myers: None.
Chronic stress exposure is a major risk factor for psychiatric and cardiometabolic diseases. Although the pathologies associated with chronic stress are well-documented, the biological mechanisms underlying these physiological changes remain unknown. Human imaging studies indicate the prefrontal cortex is a key site for processing stress-related information. Within the rat prefrontal cortex, the infralimbic area (IL) is critical for regulating physiological stress reactivity in a sex-specific fashion. Here we examined the necessity of an IL downstream circuit for neurogenic regulation of neuroendocrine susceptibility after chronic stress. We focused on an IL to rostral ventrolateral medulla (RVLM) circuit due to the ability of the RVLM to initiate the sympatho-adrenomedullary stress responses and influence HPA axis activity. Critically, the IL-RVLM circuit is structurally positioned to underlie a crucial link between stress appraisal and sympathetic reactivity. To determine the role of the IL-RVLM circuit during chronic stress, an intersectional viral strategy was used to express a light-chain variant of Tetanus Toxin (TeLC) in RVLM-projecting IL neurons, thereby disrupting IL-RVLM signaling. TeLC-expressing IL neurons had less synaptobrevin-2 protein located on terminals and fewer synaptic appositions in the RVLM. This chronic circuit disruption approach was evaluated in the context of a 2-week chronic variable stress (CVS) paradigm in male and female rats. In males, CVS-exposed TeLC rats displayed decreased corticosterone levels in response to a novel stressor compared to control rats. CVS-naïve males showed no significant changes. In females, we similarly observed no differences in unstressed rats. However, CVS TeLC female rats had increased glycemic and corticosterone stress responses compared to CVS control animals. Additionally, female CVS TeLC rats had increased behavioral avoidance indicated by less time spent in the center of an open field arena compared to CVS control rats. This behavioral effect was not present in males. These results suggest that the IL-RVLM circuit is essential for preventing chronic stress outcomes in female rats, but not males. Further, this circuit regulation is necessary only after chronic stress exposure. Future studies will be aimed at determining sex differences in chronic stress effects on IL-RVLM signaling.
Presentation: Thursday, June 15, 2023
THU119 Screening Publicly Available Data To Identify Candidate Genes For Congenital Hypopituitarism
Authors: Brinkmeier Michelle L , Martínez Mayer Julián Jorge , Ellsworth Buffy Sue , Raetzman Lori Therese , Cheung Leonard , Perez-Millan Maria Ines , Camper Sally Ann , Davis Shannon William 
Published: October 2023

Abstract
Disclosure: M.L. Brinkmeier: None. J.J. Martínez Mayer: None. B.S. Ellsworth: None. L.T. Raetzman: None. L. Cheung: None. M.I. Perez-Millan: None. S.A. Camper: None. S.W. Davis: None.
Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia and holoprosencephaly, are midline defects that cause significant morbidity for affected people. Variants in 44 genes are associated with CH, but most cases of CH are caused by unknown variants. Whole exome (WES) and whole genome sequencing (WGS) of CH patient DNA identifies variants in genes known to cause CH and variants of uncertain significance (VUS) in genes that are not currently associated with CH. The functional significance of VUS in CH candidate genes can be established using mouse models. Many of the human CH genes were first discovered in mice, and in most cases the mouse phenotype was an excellent predictor of the human phenotype. The International Mouse Phenotyping Consortium (IMPC) is an invaluable resource of phenotyping data generated by the international effort to determine function of all protein coding genes in the mouse genome through targeted disruption. Using the mouse phenotyping data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to characterize targeted alleles that cause embryonic lethality or subviability, we have identified 51 genes that cause embryonic pituitary malformations. The malformations range in severity and include absent adenohypophysis, absent neurohypophysis, hypoplasia, and hyperplasia. Using the GenePaint RNA in situ hybridization data for mouse embryos and single cell RNA sequencing (scRNAseq) data from e14.5 dissected pituitary glands, we confirmed expression for all candidate genes in the tissues that contribute to the developing pituitary gland. Using gene ontology (GO) terms associated with these 51 genes, we identified molecular pathways not previously associated with pituitary gland organogenesis, including cilia formation, amino acid metabolism, and epigenetic regulation. We present here the candidate gene list, scRNAseq expression data, GO term analysis, select images from GenePaint, and select images of the observed malformations. These genes associated with mouse pituitary malformations significantly expand the list of candidate genes for screening in WES and WGS in human cases of CH.
Presentation: Thursday, June 15, 2023
SAT672 Dulaglutide Might Reduce Visceral Fat In Patients With Metabolic Syndrome
Authors: Kim Yu Na 
Published: October 2023

Abstract
Disclosure: Y. Kim: None.
Liraglutide was shown to reduce visceral fat irrespective of T2DM status. However, due to cost and insurance coverage, dulaglutide has been prescribed more often than liraglutide in the clinical setting. This retrospective study aimed to evaluate the effect of dulaglutide on visceral fat among patients with metabolic syndrome. We reviewed medical records of patients aged ≥ 50 with metabolic syndrome and seen at a frailty clinic, where we measured body and visceral fat and BMI by bioelectrical impedance analysis and assessed frailty. One hundred ninety-six patients (average age 69.9, men 100, women 96) were seen from 12/1/2021 to 11/30/2022, and 53 patients were excluded due to missing data. Among 143 patients, five were taking dulaglutide when seen at the frailty clinic. We constructed a control group using matching sampling, but one patient was excluded because the matching pair was unavailable. We compared data between patients taking dulaglutide(study group) and the matched control group using a paired sample t-test. The % visceral fat of the dulaglutide group was lower than the control group (dulaglutide mean 10.75, control mean 11, P= 0.39). Three patients in the study group had the same % visceral fat as their paired control, and 2 out of 4 patients gained weight after starting dulaglutide. In this study, our study group was found to have lower % visceral fat on average than their paired control, although two patients gained weight. Given the small sample size, further studies with larger cohorts are needed to investigate this further.
Presentation: Saturday, June 17, 2023
THU126 SARS-CoV-2 Infection And Vaccination In Patients With Pituitary Diseases: A Pilot Study
Authors: da Silva Marcela Cunha , Del Corso Leticia Marinho , Boguszewski Cesar Luiz 
Published: October 2023

Abstract
Disclosure: M.C. Silva: None. L.M. Del Corso: None. C.L. Boguszewski: None.
Introduction: The COVID-19 pandemic caused by the SARS-CoV-2 virus brought several questions globally. Among patients with pituitary diseases, there are few data in the literature about prevalence of SARS-CoV-2 infection, vaccination and their possible consequences and adverse events. Aim: To evaluate the prevalence and characteristics of SARS-CoV-2 infection, and the prevalence, efficacy and safety of vaccination in adult patients with pituitary diseases. Methods: Observational, cross-sectional study of adult patients with pituitary diseases followed in a reference center. Clinical data were collected and a questionnaire about SARS-CoV-2 infection, vaccination and its possible adverse effects was applied. The severity definitions used for COVID-19 disease were based on the World Health Organization: Mild – symptoms of infection without pneumonia; Moderate – presence of pneumonia; Severe – severe pneumonia (respiratory rate greater than 30 breaths per minute, severe respiratory distress or oxygen saturation less than 90% on room air). Results: We have studied 116 consecutive patients, 59 women (50.9%), with a median age of 47.5 years (range 39-59). The cause of pituitary disease was tumoral in 82 cases (70.7%) and non-tumoral in 34 (29.3%), the most prevalent etiologies were prolactinoma (n=31; 26.7%), idiopathic hypopituitarism (n=30; 25.9%) and acromegaly (n=23; 19.8%). Among hypopituitary patients (n=65; 56%), thirty (46.2%) had ACTH deficiency and all were on glucocorticoid replacement. The median time of pituitary disease was 14 years (range 6-23) and the median age at diagnosis was 32 years (range 18.5-45). SARS-CoV-2 infection was confirmed in 33 patients [28.4%; 17 before vaccination; 21 women; prolactinoma (n=12), acromegaly (n=9), non-tumoral disease (n=8); ACTH deficiency (n=6)]. The median age of infected patients was 47.5 years (range 29.5-57). In 20 cases (60.6%) the infection was mild, in 8 (24.2%) was moderate and in 5 (15.2%) was severe. All severe cases required hospitalization, although one patient refused. All but one of the participants were vaccinated against COVID-19, mostly Oxford-AstraZeneca (41.7%) and Pfizer-BioNTech (35.8%). Among those vaccinated, 64 (55.7%) reported on some adverse events, the most common pain at the site of vaccine shot (28.3%), fever (19.5%) and headache (9.7%), with a median duration of 1.5 days (range 1-3). In 61 cases, the reversal of symptoms was spontaneous (95.3%), two patients required outpatient care, and in one permanent alopecia developed. Conclusions: The prevalence of SARS-CoV-2 infection in patients with pituitary diseases was 28.4%, with 5% of severe cases requiring hospitalization. The vaccination was almost universal among our patients, being safe and effective in preventing severe cases of SARS-CoV-2 infection.
Presentation: Thursday, June 15, 2023
FRI282 Sexually Dimorphic Responses Of Kisspeptin Expression To Neonatal Exposure To Estrogen In Rats
Authors: Marzbanabbasabadi Behrokh , Lin PoChing , Park ChanJin , Ko Chemyong 
Published: October 2023

Abstract
Disclosure: B. Marzbanabbasabadi: None. P. Lin: None. C. Park: None. C. Ko: None.
Kisspeptin neurons (Kiss1 neurons) are located mainly in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) of hypothalamus and play a key role as regulators of GnRH secretion in all mammalian species. In both females and males, ARC contains more Kiss1 neurons than AVPV. Importantly, unlike ARC, AVPV displays sexual dimorphism; female AVPV contains significantly more Kiss1 neurons than males’. Recent studies showed that neonatal exposure to estrogen decreased Kiss1 expression in the hypothalamus, impacting fertility, in both sexes. However, whether such impact was driven by decreased number of Kiss1 neurons or expression of Kiss1 gene is not known. In this study, we tested our hypothesis that neonatal estrogen exposure decreases both the number of Kiss1 neurons and the Kiss1 gene expression in AVPV, in a gender-dependent manner. This hypothesis was tested in rats by treating them with estradiol benzoate (EB, a prodrug that is converted to estradiol) and measuring the effect by counting the number of Kiss1 neurons (Kiss1 mRNA expressing cells) and comparing Kiss1 mRNA expression levels between EB-exposed and control hypothalami. Male and female rat pups were injected, on postnatal day 1, subcutaneously with 0.3 mg EB via microsphere that was designed to release EB for 2 weeks; unexposed age matching pups were used as controls (n=6-7/group). Male rats were euthanized at 2.5 months of age and their entire brains were collected. Female brains were also sampled at 2.5 months of age, but after synchronizing their estrous cycle by injecting them with PMSG and hCG following an established superovulation protocol. The brains were serially sectioned and the sections from AVPV and caudal region of ARC where Kiss1 neurons most highly populated were identified and used for localizing Kiss1 neurons and quantitating Kiss1 mRNA expression level, using RNAscope. Results showed that in the AVPV, EB-exposed rats had less Kiss1 neurons both in males (8.7±1.9 vs. 42.2±7.9 Kiss1 neurons/section in control, p=0.02) and females (26.0±5.65 vs. 141.6±15.8 Kiss1 neurons/section in control, p=0.03) and showed lower Kiss1 mRNA expression in males (0.33 folds, p=0.03) and in females (0.44 folds, p=0.04) as well. In the ARC, EB-exposed rats had less Kiss1 neurons in females (27.5±4.3 vs. 56.0±2.4/section in control, p=0.00), but had same number in males (31.7±2.3 vs. 42.8±7.6 kiss1 neurons/section in control, p=0.22). EB exposure increased Kiss1 mRNA expression in both males (2.39 folds, p=0.00) and females (1.55 folds, p=0.05). In conclusion, this study showed that neonatal exposure to estrogen alters the number of Kiss1 neurons and Kiss1 mRNA expression in AVPV in a gender-dependent manner. In addition, neonatal estrogen exposure also alters Kiss1 neuron numbers and Kiss1 gene expression in the ARC as well.
Presentation: Friday, June 16, 2023
FRI283 Fragile X Gene Mutations Alter GnRH Neuron And Ovarian Innervation With Consequences On Reproductive Function
Authors: Villa Pedro A , Lainez Nancy , Jonak Carrie R , Berlin Sarah , Ethell Iryna , Coss Djurdjica 
Published: October 2023

Abstract
Disclosure: P.A. Villa: None. N. Lainez: None. C.R. Jonak: None. S. Berlin: None. I. Ethell: None. D. Coss: None.
Mutations in the Fragile X messenger ribonucleoprotein 1 gene (FMR1) cause Fragile X syndrome, the most common cause of inherited mental disability, attributed to the loss of the Fragile X messenger ribonucleoprotein (FMRP). FMR1 mutations also comprise a majority of the genetic causes of premature ovarian failure (POF) in women, mechanisms of which are unknown. We utilized the Fmr1KO mouse model to determine the role of the FMR1 gene in the reproductive system in females. Similarly to what occurs in women harboring the mutation, our data demonstrate that Fmr1KO female mice experienced premature reproductive senescence, where reproductive function stopped at p163; in contrast, wild type controls stopped reproducing at p263. Since POF in women can occur due to either an insufficient pool of primordial follicles or early depletion of follicles, we quantified primordial follicles in 3 week old females and determined there was no difference between KO and controls. We then determined that Fmr1KO females had a higher number of corpora lutea at 8 weeks of age and gave birth to larger litters, suggesting that KO females recruit more follicles in each estrus cycle. Given that follicle stimulating hormone (FSH) and luteinizing hormone (LH) are essential in ovarian function, we analyzed gonadotropin levels in Fmr1KO females and determined they have higher serum LH and FSH. Inhibin b, progesterone, and testosterone levels were also higher, suggesting that high gonadotropins do not result from the lack of feedback. Ovariectomy determined that the hypothalamus drives high LH in KO females, while increased FSH is dependent on the ovaries. Increased vasculature in the corpora lutea and higher sympathetic innervation of developing follicles may increase steroid hormone production and drive increased serum FSH levels. To investigate the hypothalamic role in increased LH, we determined that a majority of gonadotropin-releasing hormone (GnRH) neurons express FMRP, which also have a higher number of GABAergic synapses in Fmr1KO females. Given that GABA is excitatory to GnRH neurons, alterations in afferent synaptic input can affect GnRH and LH secretion. LH pulsatile analysis determined higher LH pulse frequency in both unmodified and ovariectomized females, indicating an increase in GnRH neuron activity. In summary, our results reveal hypothalamic and ovarian contributions to the reproductive phenotype of Fragile X mutation carriers that may lead to early menopause.
Presentation: Friday, June 16, 2023
FRI297 Hemoglobin Decline As A Signal For Hyperprolactinemia Onset Prior To Prolactinoma Diagnosis In Hypogonadal Men
Authors: Rudman Yaron , Duskin-Bitan Hadar , Richter Ilan , Tsvetov Gloria , Masri-Iraqi Hiba , Akirov Amit , Shimon Ilan 
Published: October 2023

Abstract
Disclosure: Y. Rudman: None. H. Duskin-Bitan: None. I. Richter: None. G. Tsvetov: None. H. Masri-Iraqi: None. A. Akirov: None. I. Shimon: None.
Background: Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and non-specific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration. Methods: We retrospectively evaluated the pre-diagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded. Results: Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dl at diagnosis. We identified 25 patients with “informative” HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/ml; median follow-up, 14.0 years), demonstrating an obvious pre-diagnosis HB decrease (greater than 1.0 g/dl), from a pre-diagnosis baseline HB of 14.4±0.3 g/dl to 12.9±0.5 g/dl at diagnosis. The median “low-HB duration” (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between “low-HB duration” and patient-reported sexual dysfunction duration (n=17, R=0.502, p=0.04). The “low-HB duration” was significantly longer than the reported sexual dysfunction duration (7.0±4.5 vs 2.9±2.5 years, p=0.01). Conclusions: In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.
Presentation: Friday, June 16, 2023