bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU049 Growth Hormone Treatment Reverses Deficits In POU1F1 Gene Mutation
Authors: Al-Samerria Sarmed , Phelan Joseph , Xu Huiting , Negron Ariel , Wondisford Fredric , Radovick Sally 
Published: October 2023

Abstract
Disclosure: S. Al-Samerria: None. J. Phelan: None. H. Xu: None. A. Negron: None. F. Wondisford: None. S. Radovick: None.
Mutations in the Pit 1 gene, also known as POU1F1, have been linked to the deficient development of somatotrophs and the synthesis of growth hormone (GH) in the anterior pituitary gland. In a previous study, we reported a point mutation in the PIT1 gene caused by a substitution of a lysine (K) with a glutamic acid (E) at position 216 (K216E) on one allele in a patient presenting with combined pituitary hormone deficiency (CPHD). This patient had undetectable levels of GH, TSH, very low PRL, and severe mental retardation associated with short stature (SS). To study the effects of GH treatment on growth and metabolism in CPHD, we created a unique mouse model with the K216E mutation in the PIT1 gene using the CRISPR/Cas9 genome editing system. In this study, 4-week-old male and female homozygous mice were randomly divided into two groups. The treatment group received subcutaneous injections of GH (5 mg/g/day) for 5 consecutive days per week for 4 weeks, while the control group received saline injections on the same schedule. GH treatment significantly improved the growth and body composition of male and female mice bearing the K216E. GH treatment also increased metabolism as measured by oxygen consumption, carbon dioxide production, and energy expenditure. These effects were observed both during treatment and 4 weeks post-treatment, although some reversal of the changes in body composition was observed 4 weeks post-treatment. Our findings demonstrate the utility of this mouse model in studying the effects of GH deficiency and treatment on growth and metabolism. This model holds great promise in advancing our understanding of the underlying mechanisms of hypopituitarism and CPHD, potentially serving as a valuable tool in identifying metabolic biomarkers for these conditions.
Presentation: Thursday, June 15, 2023
THU079 Danio Rerio (Zebrafish): A New Model Of AIP Loss Of Function
Authors: Wang Xian , Leggieri Adele , Anagianni Sofia , Brennan Caroline H , Korbonits Marta 
Published: October 2023

Abstract
Disclosure: X. Wang: None. A. Leggieri: None. S. Anagianni: None. C.H. Brennan: None. M. Korbonits: None.
Background: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene account for 10% of cases with familial isolated pituitary adenoma (FIPA). The main features of patients carrying heterozygous AIP mutations include young-onset, large and invasive growth hormone and/or prolactin-secreting pituitary tumours, although a milder spectrum of presentation has been also described. In several animal models (mouse, fruit fly, round worm), homozygous deletion of AIP results in embryonic mortality. In mice abnormal cardiac development has been observed. Objective: The aim of this study was to generate a zebrafish loss-of-function model to explore the cellular biological processes affected by heterozygous or homozygous aip mutations. Methods: Zebrafish homologue of human AIP was identified by EMBOSS Needle program. We used CRISPR/Cas9 to generate a line of fish carrying loss-of-function mutations targeting zebrafish aip exon 2. aip RNA expression was examined using in situ hybridisation. The growth rate and cardiac function were assessed using a stereo microscope with an integrated camera. The videos and pictures were analysed in ImageJ. Antisense in situ hybridisation with probes to growth hormone 1 (gh1), prolactin (prl) and proopiomelanocortin a (pomca) was used to assess pituitary phenotypes. Results: Zebrafish aip shows 78.8% of homology to human AIP. aip mRNA is expressed throughout the developing zebrafish embryo until 28 hours post fertilisation (hpf) stage when it becomes more strongly expressed in the head. We generated a 29 bp deletion in exon 2 of the zebrafish aip gene. These mutant animals showed reduced aip expression. No significant gross morphology differences were observed at 3 to 7 days post fertilisation (dpf) between wildtype (WT) and heterozygote (Het) animals. At 5dpf, WTs showed an increased heart rate than Hets (P=0.033). Conclusion: We have generated an aip loss of function zebrafish line that provides an ideal opportunity to analyse the role of aip in development.
Presentation: Thursday, June 15, 2023
THU084 Corticotroph Tumor Type Influences Clinical Presentation In Patients With Nonfunctioning Pituitary Neuroendocrine Tumors
Authors: Al-Shamkhi Nasrin , Engström Britt Edén , Gudjonsson Olafur , Wikström Johan , Casar-Borota Olivera , Rask Eva 
Published: October 2023

Abstract
Disclosure: N. Al-Shamkhi: None. B. Edén Engström: None. O. Gudjonsson: None. J. Wikström: None. O. Casar-Borota: None. E. Rask: None.
Introduction: According to the current World Health Organization classification of endocrine tumors the classification of non-functioning pituitary neuroendocrine tumors (NF-PitNET) is based on pituitary cell lineages, defined by immunohistochemical expression of anterior pituitary hormones and pituitary specific transcription factors. The second most common NF-PitNET type, after silent gonadotroph tumors, are silent corticotroph tumors that are regarded as a potentially more aggressive type. If there is indication for treatment, the first-line treatment is transsphenoidal surgery. Some, but not all studies have shown a higher degree of preoperative pituitary failure or more frequent postoperative pituitary failure in patients with silent corticotroph tumors compared to the other NF-PitNET. Objectives: We compared patients with silent corticotroph and silent gonadotroph tumors, and explored whether tumor type and radiological findings were associated with pre- or postoperative pituitary failure. Design and method: One hundred patients who underwent surgery for NF-PitNET at the same tertiary center were included. Data regarding age at surgery, sex, pre- and postoperative pituitary function and tumor type, were collected after chart review. Preoperative MRI examinations were revised regarding tumor volume and Knosp classification. Results: The majority, 72% (72/100) were classified as silent gonadotroph tumors followed by 18% (18/100) silent corticotroph tumors. Patients with silent corticotroph tumors were younger at surgery, P=0.003. There were no differences regarding sex, preoperative tumor volume, invasive growth on MRI, defined as Knosp grade &gt; 3, pituitary failure or prolactin elevation between the two tumor types. Binary logistic regression showed that having a silent corticotroph tumor, P=0.04, odds ratio 5.7 (CI: 1.06-30.71), higher age at surgery, P=0.003, odds ratio 1.07 (CI: 1.02-1.13), and a larger preoperative tumor volume, P=0.01, odds ratio 1.18 (CI: 1.04-1.33), were all factors associated with an increased likelihood of having postoperative pituitary failure. Sex, invasive growth and preoperative prolactin elevation were not significant predictors of postoperative pituitary failure in the binary logistic regression. Conclusion: The results indicate that silent corticotroph tumors influence the clinical presentation of NF-PitNET. Patients with silent corticotroph tumors were significantly younger at surgery, and demonstrated an increased likelihood of postoperative pituitary failure.
Presentation: Thursday, June 15, 2023
THU122 Effects Of A GLP-1 Agonist On Consumption Of Alcohol In Patients Treated For Smoking Cessation
Authors: Probst Leila Sofia , Monnerat Sophie , Lengsfeld Sophia , Bathelt Cemile , Meienberg Andrea , Burkard Thilo , Christ-crain Mirjam , Winzeler Bettina Felicitas 
Published: October 2023

Abstract
Disclosure: L.S. Probst: None. S. Monnerat: None. S. Lengsfeld: None. C. Bathelt: None. A. Meienberg: None. T. Burkard: None. M. Christ-crain: None. B.F. Winzeler: None.
Introduction: Alcohol use disorder causes high socio-economic costs and has a detrimental impact on health globally, being considered a key factor contributing to non-communicable diseases. In Switzerland four substances are currently approved for treatment of alcohol use disorder with only limited to moderate effects. Thus, the need for new treatment options in alcohol and substance use disorder is evident. Recent research has shed light on a new potential target for treatment of addiction: a body of preclinical studies provide evidence for the attenuating effects of GLP-1 agonists on addictive behavior in rodents and non-human primates. A few studies have shown a link between GLP-1 receptors and reward related processes in humans, and a trial from denmark examined the effect of exenatide in patients treated for alcohol use disorder, however clinical data are scarce and results remain inconclusive. Methods: This is a secondary analysis of the SKIP study, a double-blind, randomized, placebo-controlled trial to evaluate treatment with the GLP-1 agonist dulaglutide (Trulicy®) as a new therapy for smoking cessation. In the present analysis, the primary objective was to assess differences in alcohol consumption after 12 weeks of treatment with dulaglutide compared to placebo in alcohol-consuming smokers willing to quit smoking. We selected patients out of the cohort (n=255) who consumed alcohol at baseline and completed 12 weeks of treatment (n= 151). The independent effect of dulaglutide on alcohol consumption was analysed by fitting a multivariate generalized linear regression model with quasipoisson distribution and adjustment for baseline alcohol consumption. Preliminary Results: One hundred and fifty-one patients (placebo n=75, dulaglutide n=76) were included in the primary analysis. Baseline patient characteristics were well balanced between groups. The median age was 42 [IQR 33, 53] years with 61% (n=92) females. At baseline, patients in both treatment groups consumed 3 [IQR 2, 7] standard glasses of alcohol per week on average. At week 12, patients in the dulaglutide group drank an estimated 29% (IRR = 0.71; 95% CI 0.52, 0.97; p=0.04) less compared to the placebo group. For each additional glass consumed at baseline, alcohol consumption at week 12 increased by 6% (95% CI 5, 7; p&lt;0.001). Conclusion: These preliminary findings suggest that in patients who drink, alcohol intake tends to increase during smoking cessation. In the present analysis we were able to show that this increase was attenuated by the addition of a 12-week treatment with dulaglutide to standard smoking cessation therapy.
Presentation: Thursday, June 15, 2023
THU123 Knockout Of Renal Glut2 Gene Activates The Hypothalamic-pituitary-adrenal Axis To Increase Glucose Production In Mice
Authors: Faniyan Tumininu S , Robles Jorge , Zhang Xinyi , Bathina Siresha , Brookes Paul S , Perry Rachel J , Chhabra Kavaljit H 
Published: October 2023

Abstract
Disclosure: T.S. Faniyan: None. J. Robles: None. X. Zhang: None. S. Bathina: None. P.S. Brookes: None. R.J. Perry: None. K.H. Chhabra: None.
We recently reported the contribution of renal GLUT2 (glucose transporter 2) to systemic glucose homeostasis using a mouse model in which we can knockout renal Glut2 gene at a desired time. Renal Glut2 knockout mice have improved glucose tolerance and are protected from high-fat diet or streptozocin-induced diabetes because they excrete excess blood glucose in urine. Interestingly, despite the profound loss of glucose in urine, renal Glut2 knockout mice have normal fasting blood glucose levels. These findings indicate that an increase in endogenous glucose production may be compensating for the loss of glucose in urine. To determine the mechanisms responsible for evoking the increase in endogenous glucose production, we focused on studying the hypothalamic-pituitary-adrenal (HPA) axis because of its established role in elevating blood glucose levels. We used ELISA to measure circulating adrenocorticotrophic hormone (ACTH) and corticosterone, which are major hormones of the HPA axis. Moreover, we used fluorescence in situ hybridization to assess the expression of hypothalamic corticotropin releasing hormone gene (Crh). We also performed in vitro metabolomics analysis of the mouse liver using mass spectrometry. Finally, we measured glucose production from pyruvate in vivo in the liver and kidney using mass isotopomer distribution analysis. Renal Glut2 knockout mice had increased (p&lt;0.05) levels of hypothalamic Crh (100 ±13 vs 142 ±9 %, control vs experimental), circulating ACTH (120 ±8 vs 213 ±12 pg/ml), and corticosterone (30.4 ±5.5 vs 115 ±15.2 ng/ml). In addition, we found that metabolites such as hepatic glucose-6-phosphate (19.2 ±1.5 vs 15 ±1 arbitrary unit, control vs experimental), glucose-1-phosphate (20 ±1.5 vs 15.5 ±1), and fructose-6-phosphate (16 ±1.2 vs 12.4 ±0.8) were decreased in renal Glut2 knockout mice. We further observed that glucose production was increased in both the liver (15.1 ±0.4 vs 18.4 ±0.5 mg/kg/min) and kidney (1.7 ±0.2 vs 2.6 ±0.3 mg/kg/min) in renal Glut2 knockout mice. Our results demonstrate that loss of renal Glut2 causes hyperactivation of the HPA axis coupled with decrease in hepatic glucose metabolism and increase in hepatic as well as renal glucose production. These findings may explain how the renal Glut2 knockout mice prevent hypoglycemia despite massive glycosuria. Altogether, our study identifies a novel crosstalk between the kidneys, hypothalamus, and adrenal glands to regulate systemic glucose homeostasis. This information may be useful in either optimizing the efficacy of drugs that enhance glycosuria to treat diabetes or addressing the side effects of such drugs on the HPA axis.
Presentation: Thursday, June 15, 2023
FRI288 Single-Cell Transcriptomics Identifies Pituitary Gland Cell Type Population Changes In Diet Induced Obesity
Authors: Ruggiero-Ruff Rebecca Elizabeth , Le Brandon , Lainez Nancy , Coss Djurdjica 
Published: October 2023

Abstract
Disclosure: R.E. Ruggiero-Ruff: None. B. Le: None. N. Lainez: None. D. Coss: None.
Obesity is a worldwide growing public health concern, with a current prevalence of 43% in the United States and projected future increase. Obesity is associated with type 2 diabetes, cardiovascular disease, stroke, and endocrine abnormalities. The pituitary gland is the master gland that responds to metabolic perturbations and regulates homeostasis via hormone secretion. Thyrotrophic, gonadotropic, somatotropic, lactotropic and corticotropic dysfunctions may occur as a consequence of obesity and perpetuate pathophysiologic conditions since pituitary hormones regulate metabolic function in return. Previous work from our lab determined that mice fed high fat diet have reduced levels of gonadotropin hormones, indicating that diet-induced obesity may play a role in pituitary hormone production. We postulate that diet-induced obesity alters the pituitary transcriptome and/or select population changes. To determine the effect of diet-induced obesity on pituitary gland population plasticity, we performed single-cell RNA-sequencing (scRNA-seq) of pituitary glands from control and high-fat diet-fed mice and characterized population changes and gene expression changes in each population. While gonadotrope population changes levels of gene expression that results in the lower gonadotropin levels, somatotrope and lactotrope populations, on the other hand, change at the population level with alterations in the cell numbers that result in altered levels of growth hormone and prolactin in the circulation. In summary, we defined diet-induced changes in pituitary hormone production and population shifts that may play a role in altered hormone production in obese patients and consequently dysregulation of homeostasis.
Presentation: Friday, June 16, 2023
FRI298 Serum Prolactin To Tumor Size Ratio As An Effective Parameter To Accurately Distinguish Prolactinoma From NFPT
Authors: Mishra Ipsita , Pradhan Amrita , Baliarsinha Anoj Kumar 
Published: October 2023

Abstract
Disclosure: I. Mishra: None. A. Pradhan: None. A.K. Baliarsinha: None.
Preoperative diagnosis of prolactinomas is critical because dopamine agonists therapy have been regarded as a primary treatment. Multiple studies have compared serum prolactin levels in clinically nonfunctioning (NF) tumors and prolactinomas to identify cutoffs that may distinguish primary tumoral secretion from stalk effect. Prolactin levels are correlated with the size of prolactinomas but are not associated with tumor size in non prolactin-secreting lesions or the degree of stalk deviation and compression. By using the tumor size, we investigated an effective parameter for the discrimination between prolactinoma and NFPT. 33 patients with pituitary lesion of histological diagnosis were retrospectively recruited for this study. The data obtained was entered into Microsoft Excel Worksheet and analysed using Statistical Package for Social Sciences (SPSS, IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.).The Prolactinoma group (n=16) showed higher serum prolactin (mean=418 ng/mL) than those in the NFPT group (n=17) (mean=33.34 ng/mL, p-values &lt; 0.001).Using receiver operating curve analyses, we compared diagnostic performances of serum prolactin (PRL)/ tumor volume ratio in both groups. Unlike NFPT, serum prolactin values significantly correlated with tumor volume in Prolactinoma group. At a cut off of 12.2ng/ml/cm3,serum PRL/tumor volume was found to have a sensitivity of75.8% in diagnosing prolactinomas. However the specificity was 24.2%. Burke et al and Wright et al studied significantly smaller groups of patients and reported a linear relationship between prolactin levels and prolactinoma volume as estimated by a simplified ellipsoid volume equation. Our study demonstrates that the assessment of prolactin secretory density, based on a calculation of serum prolactin per unit tumor volume, can be used as a potential method to distinguish prolactinomas from hyperprolactinemia secondary to stalk effect and could be valuable in guiding patient management in equivocal or challenging patient cases wherein the etiology of hyperprolactinemia is uncertain.
Reference: (1) Burke WT, Penn DL, Castlen JP, et al. Prolactinomas and nonfunctioning adenomas: preoperative diagnosis of tumor type using serum prolactin and tumor size. J Neurosurg. 2019:1e8.(2) Wright K, Lee M, Escobar N, et al. Tumor volume improves preoperative differentiation of prolactinomas and nonfunctioning pituitary adenomas.Endocrine.2021;74(1):138e145
Presentation: Friday, June 16, 2023
FRI301 Prolactin And Obesity: Analysis Off Weight Oscillation In The Follow-up Of Macroprolactinomas
Authors: Oliveira Miriam C , Côrtes Aguiar Diego Paixão , Brand Corso Eduardo R , Rech Carolina G S L , Pereira Lima Julia F S 
Published: October 2023

Abstract
Disclosure: M.C. Oliveira: None. D. Paixão Côrtes Aguiar: None. E.R. Corso: None. C.G. Rech: None. J.F. Lima: None.
Introduction: Prolactin can be a modulator of body composition and weight and has been associated with obesity. However, the data, especially regarding weight behavior when normalizing hyperprolactinemia, are controversial. Methods: We retrospectively reviewed our data on a large sample of patients with treated macroprolactinomas, with or without normalization of PRL levels. Results: The sample consisted of 73 patients, 35 F, 38 M, and 15 to 86 years. In 42 cases (57.5%), the MRI showed suprasellar extension of the tumor, and in 37 (50.6%) some sort of invasion. In the presentation, the patients' weight varied between 49 and 156 kg, and the BMI (n=69) was between 18 and 52. Obesity was present in 39 patients (56.5%) and overweight in 19 (27.5%). Obesity was classified as class 1 in 19 cases (48.7% of obese patients), class 2 in 7 (17.9%), and class 3 in 13 cases (33.3%). The occurrence of obesity showed no significant difference between gender (p= 0,627) or the presence of suprasellar tumor extension. Of the patients with invasion (38/68), 92% were obese or overweight, with a significant association between both (p= 0,05). The obesity/overweight did not show an association (p= 0.716) with hypopituitarism or with specific deficiencies: GH, ACTH, and TSH, all with p= 1,000, and hypogonadism, p= 0,649. There was no correlation between initial weight and PRL levels (r= -0.033; p= 0.783). The follow-up ranged from 6 and 202 months. All patients used, at some point, bromocriptine or cabergoline. In 51 cases (69.9%) the PRL normalized. Of those who did not normalize, 19 had a reduction in the PRL level superior to 50%, in 14 cases in a percentage greater than 90%. There was a correlation between the initial weight and the percentage reduction in PRL at the last visit: higher initial weights correlated with smaller reductions in PRL (r= -0.470; p= 0.042). The last weight (n 64) was 89 ± 23,8 kg and the last BMI was 31,4 ± 6,9. In 36 cases (56.3%) the weight decreased: 18 of them with significant loss (reduction &gt;5% of initial weight). Another 27 patients (42.2%) had weight gain: 18 of them with significant gain (&gt;5% of the initial). In 12 patients, there was a class change in weight rating, 5 cases for a better classification and 7 for a worse. Significant weight loss was not associated with PRL normalization, p= 0.149. Conclusion: The prevalence of obesity and overweight in patients with macroprolactinomas far exceeds that found in the general population. In one-third of the cases, obesity is class 3. A meaningful association between obesity and tumor invasion was observed. There was no correlation between initial weight and PRL levels, and significant weight loss was also not associated with PRL normalization.
Presentation: Friday, June 16, 2023
FRI302 Umar Durrani
Authors: Durrani Umar Safwaan , Paracha Awais , Vasireddy Satvik , Waheed Fatima , Thomure Michael 
Published: October 2023

Abstract
Disclosure: U.S. Durrani: None. A. Paracha: None. S. Vasireddy: None. F. Waheed: None. M. Thomure: None.
Prolactinomas are tumors of the pituitary gland that induce hyperprolactinemia. Symptoms at presentation can include growth delay, infertility, neurologic deficits and bothersome galactorrhea. Dopamine suppresses prolactin production; therefore, dopamine agonists are first-line treatment for prolactinomas. However, hyperdopaminergia is also associated with psychiatric disorders. The dopamine hypothesis states that cerebral hyperdopaminergia can contribute to symptoms of schizophrenia. Thus, psychiatric disorders are commonly treated with dopamine antagonists. Almost 1 in 8 people in the world have a psychiatric condition. It is almost inevitable that the medical system will have to treat patients with both a psychiatric condition and a prolactinoma; thus, it is essential to identify treatment regimens for these patients. In order to identify potential treatments, we conducted a PubMed literature search focusing on patients with prolactinomas and co-existing psychiatric diagnoses. Our inclusion criteria helped us focus on patients who presented with concurrent prolactinoma and psychiatric condition which were confirmed by brain imaging, serologic prolactin levels, and reports of psychiatric conditions/episodes in their medical history (or chart). Our search yielded 30 studies representing a total of 54 patients with both conditions. We found that four key themes emerged from the literature: 1) discontinuing risperidone in exchange for other atypical antipsychotics such as aripiprazole, olanzapine or ziprasidone, 2) discontinuing thioridazine, thiothixene and remoxipride in exchange for clozapine, 3) dopamine agonist therapy cessation to abate psychiatric symptoms, and 4) surgery and/or radiation after pharmacotherapy. In conclusion, we would recommend focusing on specific antipsychotics (aripiprazole, olanzapine, ziprasidone, or clozapine) while shying away from (risperidone, thioridazine, thiothixene, and remoxipride). We would also recommend ceasing dopamine agonist therapy at least until symptoms improve. If these two methods are not yielding sufficient results, then pursuing surgical options or radiation therapy may be considered.
Presentation: Friday, June 16, 2023