bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU069 Growth Hormone Secretion And Serum High-sensitivity C-reactive Protein Levels In Adult Patients With Non-functioning Pituitary Tumors
Authors: Seki Yasufumi , Morimoto Satoshi , Bokuda Kanako , Watanabe Daisuke , Watanabe Satoshi , Yamashita Kaoru , Takano Noriyoshi , Ichihara Atsuhiro 
Published: October 2023

Abstract
Disclosure: Y. Seki: None. S. Morimoto: None. K. Bokuda: None. D. Watanabe: None. S. Watanabe: None. K. Yamashita: None. N. Takano: None. A. Ichihara: None.
Background: Growth hormone (GH) deficiency, which causes visceral obesity and non-alcohol fatty liver disease, increases cardiovascular event risks. Serum high-sensitivity C-reactive protein (hs-CRP) levels has been reported to estimate those risks. GH supplementation therapy was reported to decrease the serum hs-CRP levels in GH deficient patients, however, the association between GH secretion and serum hs-CRP levels have been unclear. Patients and Methods: We retrospectively reviewed charts of the patients with non-functioning pituitary adenoma and Rathke’s cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests to assess GH secretion, and investigated the association between GH secretion and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases, or received GH supplementation therapy were excluded. Results: Among 171 patients (100 NFPA and 71 Rathke’s cysts), 55 (32%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (754 [393—1330] vs 249 [113—537] ng/mL, P &lt; 0.001). Serum hs-CRP levels were significantly correlated with logarithm of peak GH response to GHRP-2 (r = -0.50, P &lt; 0.001), but not with IGF-1 SD score (r = -0.10, P = 0.21). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0.001) after adjustment with age, sex, BMI, smoking habit, alcohol consumption, hypertension, diabetes mellitus, dyslipidemia, abnormal liver function, and other pituitary hormone deficiencies. Severe GH deficiency were significantly associated with for serum hs-CRP levels higher than 1000 ng/mL (Odds ratio, 2.58 ;95% Confidence interval 1.15-5.78) when adjusted for obesity and abnormal liver function. Conclusion: GH secretion was significantly and negatively associated with serum hs-CRP levels independent of atherosclerotic risk factors, metabolic complications of GH deficiency, and other anterior pituitary hormone secretions.
Presentation: Thursday, June 15, 2023
SAT670 Is Myostatin A Biomarker Of Skeletal Muscle Mass?
Authors: Orioli Laura , Samaras Sofia , Lause Pascale , de Barsy Marie , Thissen Jean-Paul Mathieu , Loumaye Audrey 
Published: October 2023

Abstract
Disclosure: L. Orioli: None. S. Samaras: None. P. Lause: None. M. de Barsy: None. J.M. Thissen: None. A. Loumaye: None.
Rationale: Our study aims to determine whether myostatin is a biomarker of muscle mass in cancer cachexia and obesity. Methods: The ACTICA study included cancer patients with and without cachexia. The MYDIASECRET study included obese patients evaluated before and 3 months after bariatric surgery. Body composition was assessed using bioelectrical impedance analysis (BIA101 device, Akern). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen’s and Sergi’s equations, respectively. Results were expressed as indexes (kg/m²). Myostatin plasma concentrations were determined using ELISA. Spearman’s coefficient was used to correlate muscle mass indexes and myostatin. Results: The ACTICA study included 143 patients of whom 70 with cachexia. SMM index (SMMI) and ASMM index (ASMMI) were lower in patients with cachexia compared to those without cachexia (SMMI: 8.0 kg/m² [6.7-9.5] vs 9.0 kg/m² [7.8-10.1], p=0.004; ASMMI: 6.2 kg/m² [5.5-7.1] vs 7.2 kg/m² [6.4-7.8], p&lt;0.001). Myostatin was also lower in patients with cachexia (1434 pg/mL [999-2118] vs 2149 pg/mL [1551-2984], p&lt;0.001). Myostatin was positively correlated with SMMI and ASMMI (SMMI: R=0.500, p&lt;0.001; ASMMI: R=0.479, p&lt;0.001). The MYDIASECRET study included 62 patients. SMMI and ASMMI were decreased after surgery (SMMI: -0.8 kg/m², p&lt;0.001; ASMMI: -1.1 kg/m², p&lt;0.001). Myostatin was also decreased after surgery (1773 pg/mL [1440-2309] vs 2582 pg/mL [1708-3522], p&lt;0.001). Myostatin was positively correlated with SMMI before (R=0.388, p=0.002) and after surgery (R=0.435, p&lt;0.001). Change in myostatin after surgery was also positively correlated with change in SSMI (R=0.287, p=0.023). Conclusion: Myostatin is positively correlated with muscle mass indexes in different conditions, suggesting its potential role as a biomarker of muscle mass.
Presentation: Saturday, June 17, 2023
FRI295 Prolactin Exerts Anti- And Pro-inflammatory Actions In Joint Tissues That Are Cytokine-Dependent
Authors: García Rodrigo José Fernando , Ortiz Georgina , Martínez Díaz Oscar Fernando , Herrera Xarubet Ruiz , Ledesma Colunga María Guadalupe , de la Escalera Gonzalo Martínez , Clapp Carmen 
Published: October 2023

Abstract
Disclosure: J.F. García Rodrigo: None. G. Ortiz: None. O. Martínez Díaz: None. X. Ruiz Herrera: None. M. Ledesma Colunga: None. G. Martínez de la Escalera: None. C. Clapp: None.
The close association between rheumatoid arthritis (RA), sex, reproductive state, and stress have long-linked the sexually dimorphic, reproductive, stress-related hormone prolactin (PRL) to disease progression. However, this role is questioned by the fact that PRL has both pro-inflammatory and anti-inflammatory outcomes in RA with mechanisms that are unclear. Here, we show that PRL modifies in an opposite manner the inflammatory action of IL-1β and TNF-α in mouse synovial fibroblasts (SF) in culture and in joints in vivo. SF isolated from the knee joint of male C57BL/6 mice were incubated with or without IL-1β (1 ng/mL) or TNF-α (10 ng/mL) in the presence or absence of PRL (2.3 μg/mL). Both, IL-1β and TNF-α upregulated the metabolic activity (MTT assay) and the RT-qPCR expression of pro-inflammatory mediators (IL-1β, IL-6, iNOS) via the activation of the NF-κB signaling pathway (immunocytofluorescence, Western blot). However, IL-1β increased and TNF-α decreased the levels of the long PRL receptor isoform (RT-qPCR, Western blot) and this opposite action associated with contrasting effects of PRL in these cells. PRL decreased the IL-1β upregulation of metabolic activity and expression of pro-inflammatory mediators by blocking the degradation of NF-κB inhibitors kB-beta (Iκ-Bβ) and alpha (Iκ-Bα) and, thereby, interfering with the nuclear translocation of NF-κB. By contrast, PRL increased TNF-α-induced stimulation of metabolic activity and expression of pro-inflammatory mediators by promoting the nuclear translocation of NF-κB led by the increased degradation of Iκ-Bβ and Iκ-Bα. The double-faceted regulatory role of PRL against the two cytokines also manifested in vivo. IL-1β (80 ng) or TNF-α (300 ng) with or without PRL (2 μg) were injected into the intra-articular space of the knee joint of mice and, after 24 h, joint inflammation was monitored through the expression of pro-inflammatory mediators (IL-1β and iNOS). Both IL-1β and TNF-α upregulated the expression of IL-1β and iNOS in the joint. However, PRL inhibited the joint proinflammatory effect of IL-1β on IL-1β and iNOS, but not that of TNF-α. We conclude that the outcome of PRL actions on joint inflammation is dependent on its interaction with specific inflammatory cytokines, the level of the PRL receptor, and the activation of NF-κB signaling. We speculate that the opposite effects of PRL help balance joint inflammation in RA and that determining the mechanisms underlying dual actions provide insights into the pathophysiology of RA and the development of new treatments. Supported by UNAM (DGAPA-PAPIIT IN202321).
Presentation: Friday, June 16, 2023
FRI305 Impulse Control Disorders In Patients With Prolactinomas And Non-Functioning Pituitary Adenomas Treated With Dopamine Agonists
Authors: Kolitz Tamara , Shemesh Elad , Nathan Alexandra , Eldor Roy , Izkhakov Elena , Greenman Yona 
Published: October 2023

Abstract
Disclosure: T. Kolitz: None. E. Shemesh: None. A. Nathan: None. R. Eldor: None. E. Izkhakov: None. Y. Greenman: None.
Objective Impulse control disorder (ICD) is a well-recognized side effect of dopamine agonist (DA) treatment in patients with Parkinson’s disease and restless leg syndrome. The available data on the incidence of ICD in patients treated with DA for pituitary tumors are sparse. This study aimed to assess the occurrence of ICD among patients with prolactinomas or NFPA treated with DA compared to patients with prolactinomas or NFPA not treated with DA and to patients with non-pituitary endocrine disorders. Methods Patients attending the general endocrine and pituitary clinics at the Institute of Endocrinology in our medical center were invited to fill in an anonymous validated questionnaire on hypersexuality, pathologic gambling, compulsive shopping, and punding. Associated relevant clinical information was also obtained. Results In total, 174 patients consented to participate. Those with pituitary disorders other than prolactinomas and NFPA were excluded. The final study cohort consisted of 67 patients with NFPA (31 DA-treated) and 40 with prolactinomas (35 DA-treated). The control group consisted of 67 non-DA-treated subjects with other endocrine disorders. The entire cohort was comprised of 77 men and 97 women (mean age 56±17 years). ICDs were reported by 19/66 (29%) DA-treated patients with prolactinomas or NFPA, 3/41 (7%) non-DA-treated patients with prolactinomas or NFPA and 8/108 (7.5%) non-DA-treated patients with prolactinomas, NFPA or other endocrine disorders (p&lt;0.001). There were no significant differences in ICD rates between DA-treated patients with prolactinomas compared to those with DA-treated NFPA, or between non-DA-treated patients with either prolactinomas or NFPA and controls. The ICD rate among DA-treated women was significantly higher than that of non-DA-treated women (34.5% and 7.5%, respectively. p&lt;0.001). No comparable differences were observed in DA-treated versus non-DA-treated men or between all participating men and women. Conclusion ICD rates are significantly higher among patients treated with DA for prolactinomas or NFPA compared to non-DA-treated patients with prolactinomas, NFPA or other non-pituitary endocrine disorders. Patients being treated with DA for any pituitary lesion should be informed of the greater risk of associated ICD.
Presentation: Friday, June 16, 2023
SAT679 Telehealth And Metabolic Health: Unraveling The Effects Of A 12-week Low-starch Diet On Homa2B IR In Overweight Women
Authors: Erta Gita , Gersone Gita , Tretjakovs Pēteris 
Published: October 2023

Abstract
Disclosure: G. Erta: None. G. Gersone: None. P. Tretjakovs: None.
Background: Telehealth has emerged as a promising approach for delivering health care interventions remotely, allowing increased access and convenience, especially in the context of lifestyle interventions for metabolic health. In this study, our aim was to investigate the effects of a 12-week low-starch diet on HOMA2B IR (Homeostatic Model As-sessment for Beta Cell Function Insulin Resistance) in overweight women using tele-health consultations. Methods: A prospective single arm intervention study was conducted among 14 overweight women aged 18-48 years with a body mass index (BMI) of 25-29,9 kg/m^2. Participants received weekly telehealth consultations via video conference with an endocrinologist and were prescribed a low-starch diet for 12 weeks. The dietary intervention focused on reducing the intake of high-starch foods, such as refined grains, potatoes, and bread, while promoting the consumption of non-starchy vegetables, lean protein, and healthy fats. HOMA2B IR, a widely used surrogate marker of insulin resistance, was measured at baseline and after 12 weeks. Results: After 12 weeks of the low-starch diet intervention, there was a significant reduction in HOMA2B IR in overweight women (Mean ± SD: Baseline HOMA2B IR data (2.126 ± 1.909) improved to 1.522 ± 1.468 at 12 weeks (p &lt; 0.05)), indicating improved beta cell function and decreased insulin resistance. Participants also showed reductions in bodyweight, waist circumference, and fasting blood glucose levels. The compliance with the low starch diet was generally high. Conclusion: Our findings suggest that a 12-week low-starch diet administered through telehealth consultations may have positive effects on HOMA2B IR, as well as bodyweight and fasting blood glucose levels, in overweight women. These results highlight the potential of telehealth as a convenient and effective mode of delivering lifestyle interventions to improve metabolic health. More research with larger sample sizes and longer follow-up periods is warranted to confirm these findings and explore the long-term effects of telehealth-based interventions on metabolic health outcomes.
Presentation: Saturday, June 17, 2023
SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues
Authors: Lim Juchan 
Published: October 2023

Abstract
Disclosure: J. Lim: None.
In mammals, the control of cell fate is imperative to the development of multicellular organisms as well as tissue homeostasis/regeneration in the adult. The anterior pituitary (AP) controls growth, metabolism, reproduction, and stress responses through the synthesis and secretion of specific hormones by distinct AP cell lineages. Interestingly, the anterior pituitary exhibits a high level of adult cell plasticity that allows committed hormone-producing cells to alter their cell fate and produce different hormones to meet altered organismal demands. The molecular mechanisms underlying this adult cell plasticity have not been fully characterized. To investigate the mechanism(s) of pituitary cell transdifferentiation, our lab has employed a rat GH3 cell culture model that undergoes somatotrope to lactotrope conversion in response to a cocktail of 3 growth factors (EGF, estradiol and insulin). Upon stimulation of lactotrope transdifferentiation, we confirmed a significant reduction of Growth hormone (Gh1) and reciprocal elevation of Prolactin (Prl) protein and transcript levels in the treated group compared to untreated controls. Proteomic and transcriptomic analyses from the same samples detected upregulation of 124 proteins and 553 transcripts and downregulation of 28 proteins and 556 transcripts respectively. Gene ontology analyses identified a number of upregulated proteins involved in autophagy (e.g. autolysosome), MTORC1 signaling, and a number of upregulated transcripts involved in the regulation of cell proliferation and apoptosis. A number of the upregulated proteins and transcripts are involved in Epithelial-to-mesenchymal transition (EMT) and metabolic change (i.e. glycolysis, hypoxia), while downregulated transcripts involved in neurogenesis (i.e. Notch1, Notch2, Sox2, Sox5). Further, differential expression analyses comparing the proteomic and transcriptomic levels of the treated vs. control GH3 cells identified a number of upregulated proteins with no change in their corresponding transcripts related to MTORC1 signaling and glycolysis as well as a number of unchanged proteins with corresponding upregulated transcripts involved in mitochondrial activity suggesting a broad role for post-transcriptional regulation during transdifferentiation. In a complementary in vivo study, we assessed pituitary cell fate changes in response to hypothyroidism, using a similar integrated proteogenomic profiling. Together, we identify a number of altered molecular pathways that underlie distinct pituitary cell plasticity responses to physiological cues.
Presentation: Saturday, June 17, 2023
SAT605 Growth Hormone Action In Somatostatin Neurons Regulates Anxiety And Fear Memory
Authors: dos Santos Willian O , Juliano Vitor A L , Vieira Henrique R , Frazao Renata , Munhoz Carolina Demarchi , Donato Jose 
Published: October 2023

Abstract
Disclosure: W.O. dos Santos: None. V.A. Juliano: None. H.R. Vieira: None. R. Frazao: None. C.D. Munhoz: None. J. Donato: None.
Dysfunctions in growth hormone (GH) secretion increase the prevalence of anxiety and depression. Furthermore, GH receptor (GHR) signaling in the amygdala has been associated with fear memory, a key feature of post-traumatic stress disorder. However, it is currently unknown which neuronal population is targeted by GH action to influence neuropsychiatric diseases. Here we showed that approximately 60% of somatostatin (SST)-expressing neurons in the extended amygdala are directly responsive to GH. GHR ablation in SST-expressing cells (SSTΔGHR mice) led to increased anxiety in the light-dark box and elevated plus maze tests, whereas SSTΔGHR females showed no changes in anxiety, compared to control animals. Using auditory Pavlovian fear conditioning, both male and female SSTΔGHR mice exhibited a significant reduction in fear memory. In contrast, GHR ablation in SST neurons did not affect memory in the novel object recognition test. The gene expression was analyzed in a bilateral micropunch comprising the central nucleus of the amygdala and basolateral complex of male mice. Increased mRNA expression of Gabbr2 (GABAB2 receptor), Syp (synaptophysin), and Bdnf were observed in the amygdala of SSTΔGHR mice. In conclusion, GHR expression in SST neurons is necessary to regulate anxiety in males, but not in female mice. GHR ablation in SST neurons also decreases fear memory and affects the gene expression in the amygdala. Our findings identified for the first time a specific neuronal population responsible for mediating the effects of GH on behavioral aspects associated with neuropsychiatric diseases.
Presentation: Saturday, June 17, 2023
SAT616 Differentiating Resistant Prolactinoma From Macroprolactinemia
Authors: Lacount Steven , Belany Paul 
Published: October 2023

Abstract
Disclosure: S. Lacount: None. P. Belany: None.
Introduction: Prolactinomas are the most common secretory tumor of the pituitary gland. Hyperprolactinemia can present as hypogonadism, infertility, galactorrhea, or it may remain asymptomatic. In asymptomatic hyperprolactinemia, macroprolactinemia and other secondary causes should be considered and ruled out. Prolactinomas treated with dopamine agonists typically respond well, with decreasing tumor size and prolactin level reduction. We present a case of a prolactinoma not responding biochemically or anatomically to maximum doses of dopamine agonists, concerning for resistant prolactinoma versus macroprolactinemia. Clinical Case: A 62 y.o. male with PMH of HTN, HLD and CAD who presented with fatigue and headaches in 2009. Initial work-up showed an elevated prolactin level to 178 ng/mL (reference range 2.0-18.0 ng/mL). MRI pituitary showed a 1.8 x 1.9 x 1.5 cm mass but without optic chiasmal compression. Patient refused medications and opted to pursue endoscopic endonasal approach (EEA), which was completed in March 2009. Pathology and hormonal immunostains confirmed prolactinoma. Due to persistently elevated prolactin levels following EEA, cabergoline was started. Follow-up MRI Pituitary in November 2012 showed stable heterogeneous residual tissue without tumor recurrence. Despite escalating cabergoline doses (up to 8 mg weekly), his prolactin levels remained slightly elevated (50 ng/mL) after surgery with unchanged symptoms from presentation. Due to the association of cabergoline and cardiac valve disease development, his dose was decreased back down to 0.5 mg twice weekly. Given his persistent asymptomatic hyperprolactinemia that was nonresponsive to high-dose cabergoline, there was consideration for macroprolactinemia causing a falsely high level. Screening polyethylene glycol (PEG) precipitation test in November 2022 was normal. MRI pituitary in December 2022 showed a progressive sellar lesion with increased size and cavernous sinus invasion near the carotid artery. Patient was referred to neurosurgery in January 2023 for further evaluation of potential resistant prolactinoma. Due to the MRI findings and persistently elevated prolactin levels, he will undergo repeat EEA in May 2023 for treatment of resistant prolactinoma. Conclusion: Dopamine agonists are very effective in treating prolactinomas. In asymptomatic hyperprolactinemia, PEG precipitation is an inexpensive test to screen for macroprolactinemia. Once macroprolactinemia and other secondary causes are ruled out, resistant prolactinoma can be considered. Resistant prolactinoma is defined by failure to achieve normoprolactinemia and at least 50% reduction in tumor size on maximum-tolerated therapy. Risk factors for resistant prolactinoma include larger tumor volume and male gender. Treatment options include different or increased dopamine agonist doses, radiotherapy and resection.
Presentation: Saturday, June 17, 2023
OR2803 Corticotroph Fate Weighted Cell Differentiation Paradigm For Human Induced Pluripotent Stem Cells
Authors: Elyse Moore M , Chen Kevin G , Park Kyeyoon , Asuzu David , Ramavenkat Nikhil , Walbridge Stuart , Mullaney Dustin , Arhin Martin , Maric Dragan , Mandal Debjani , Chittiboina Prashant 
Published: October 2023

Abstract
Disclosure: M.E. Moore: None. K.G. Chen: None. K. Park: None. D. Asuzu: None. N. Ramavenkat: None. S. Walbridge: None. D. Mullaney: None. M. Arhin: None. D. Maric: None. D. Mandal: None. P. Chittiboina: None.
Introduction: The vertebrate anterior pituitary gland is a highly conserved ‘master’ organ that controls hormonal milieu in real-time. Pituitary adenomas and their treatments (surgery, chemotherapy or radiation) can result in pituitary organ failure, specifically hypocortisolism, a challenging condition to manage. Here, we created an optimized paradigm (anterior pituitary corticotroph or APcor) to preferentially drive human induced pluripotent stem cells (hiPSCs) towards a pituitary corticotroph fate. Methods: We directed U112I hiPSCs towards terminally differentiated cell types using a combination of rho-associated kinase inhibitor (Y-27632), bone morphogenic protein 4 (BMP4), transforming growth factor β inhibitor (SB431542), sonic hedgehog (SHH), fibroblast growth factor 8b (FGF8b), fibroblast growth factor 10 (FGF10) and leukemia inhibitory factor (LIF). Markers for pluripotent stem cells, cranial placode (CP), Rathke’s Pouch (RP), anterior pituitary progenitors and mature cell types were assessed at 10-day intervals using quantitative qRT-PCR and multiplex immunocytochemistry (mICC) or immunohistochemistry (IHC). ACTH activity was measured using ELISA (MD Bio). Results: We tested initial differentiation conditions and found optimal CP initiation in presence of SB431542. We observed decrease in embryonic stem cell markers OCT4 and NANOG by day 10, with concomitant increase in CP/RP markers SIX1, PAX6 and SIX6 using mICC/IHC and qRT-PCR. Continuation of differentiation paradigm with LIF showed strong expression of anterior pituitary progenitor markers PITX1, TBX19 and POU1F1 at day 20. pRT-PCR analysis at this time point confirms differentiation towards pituitary cell types without needing enrichment for SIX1. At day 30, POMC expression was observed by IHC in 10-15% of cells as measured by quantitative analysis (Qupath 0.2.0), indicating mature corticotrophs. Corticotroph cell fate was confirmed with corticotropin releasing hormone (CRH) stimulation which led to up to 40x-fold increase in ACTH expression detected by ELISA (D30 w/CRH vs Pluripotent w/CRH). Conclusions: We found with the APcor paradigm, we can reliably drive towards corticotroph cell fate. We successfully differentiated hiPSCs into mature functioning corticotrophs with ability to recapitulate pituitary organ function. Our method is amenable to 3D organoid formation and pre-clinical implantation in animal models of hypophysectomy as a novel hormone replacement therapy.
Presentation: Sunday, June 18, 2023