bluuebunny/crossref_metadata_2025_split huggingface dataset:
12353 Differential Gene Expression And Pathway Analysis In Growth Hormone Secreting Pituitary Tumors According To Granulation Pattern
Authors: Shin Hyeju 
Published: October 2024

Abstract
Disclosure: H. Shin: None.
Differential gene expression and pathway analysis in growth hormone-secreting pituitary tumors according to granulation pattern. Hye Ju Shin [1], Kyung Won Kim[2], Chan Woo Kang[2], Eun Jig Lee[2], Cheol Ryong Ku[2]. [1]Department of Clinical Drug Discovery & Development, Yonsei University College of Medicine, Seoul, Republic of Korea, [2]Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea Objective: The purpose of this research is to explain clinical variations in patients with acromegaly by exploring gene expression differences according to granulation patterns in growth hormone (GH)-secreting pituitary tumors. Materials & methods: Transcriptome analysis was conducted on 6 normal pituitary tissues and 15 GH-secreting pituitary tumors, including 9 densely granulated somatotroph tumors (DGSTs) and 6 sparsely granulated somatotroph tumors (SGSTs). Results: The median age at diagnosis was 50 years, with a predominance of female patients (60%). We identified 3111 differentially expressed genes (DEGs) in tumors compared to normal pituitaries, with 1117 DEGs unique to a specific granulation within tumors. SGST showed enriched the pathways involved in neuronal development (axon development, axonogenesis, axon guidance, synapse and presynapse organization, gliogenesis, glial cell differentiation, nerve development, synaptic membrane adhesion, semaphorin-plexin signaling pathway involved in neuron projection guidance) and acute inflammatory response. No pathways were significantly downregulated in SGST compared with those in DGST. Three signaling pathways (JAK-STAT, phosphatidylinositol 3-kinase, and MAP cascade) and three neuronal development processes (generation of neurons, nerve development, and neurogenesis) were significantly enriched in both GO and GSEA analysis. The PPI networks constructed with the up- and downregulated DEGs consisted of 128 and 132 PPI pairs, respectively. There were 10 hub proteins, top highly connected DEGs: ANLN, TLE3, TLE2, DMD, ADRA1A, RBFOX1, MMP2, LMO1, RUNX1T1, and NPPA. Conclusion: The results indicate that granulation-specific gene expression may underpin diverse clinical characteristics in acromegaly. Overall, this study emphasizes the potential for further investigation into these transcriptomic variations and their roles in disease pathology, particularly the involvement of genes linked to neuronal development, inflammatory response, and JAK-STAT signaling in SGST.
Presentation: 6/3/2024
7141 Disruption of Transient Receptor Potential Channel 5 Causes Obesity and Maladaptive Behavior
Authors: LI Y , Cacciottolo T , Farooqi I S , Xu Y 
Published: October 2024

Abstract
Disclosure: Y. Li: None. T. Cacciottolo: None. I.S. Farooqi: None. Y. Xu: None.
The global surge in obesity over recent decades poses formidable challenges to public health and economic well-being. Transient Receptor Potential Channel 5 (TRPC5) emerges as a pivotal membrane-spanning cation channel implicated in energy homeostasis, pain modulation, and fear responses. Here, we identified microdeletions on chromosome Xq23 disrupting TRPC5 in boys with food-seeking, obesity, anxiety and autism. Significantly, these microdeletions were inherited from mothers grappling with a constellation of health issues, including obesity and anxiety, suggesting a potential intergenerational aspect to TRPC5-related conditions. We examined approximately 450,000 individuals with exome sequence data from the UK Biobank and found that the TRPC5 gene is the most strongly associated X-linked gene for human body mass index. Moreover, we identified 7 rare TRPC5 variants in patients with severe obesity underscores the potential role of TRPC5 in shaping the obesity phenotype. Functional experiments with HEK293 cells demonstrated that these variants led to a loss of Trpc5 function. Knock-in male mice harboring a human loss-of-function (LOF) TRPC5 variant developed obesity, anxiety, reduced social exploratory behavior and increased aggression; female mice homozygous for the same variant showed similar deficits with reduced severity. We found approximately 91% proopiomelanocortin (Pomc) neurons in arcuate nucleus of the hypothalamus (ARH) express Trpc5 in wild-type male mice. Utilizing the TRPC5 agonist benzothiadiazide derivative (BTD), we found that BTD (i.p., 10 mg/kg) reduced food intake and increased c-Fos expression in Pomc neurons in wild-type mice compared to the vehicle injection group. Importantly, the activation of Trpc5 using BTD did not induce toxicity or aversive effects. Importantly, chemogenetic inactivation using designer receptor exclusively activated by designer drugs (DREADD) of hM4Di-expressing Pomc neurons with clozapine N-oxide (CNO; i.p., 1 mg/kg) effectively blocked BTD-induced anorexia and c-Fos expression in Pomc neurons. Furthermore, we found that BTD-induced anorexia and c-Fos expression in Pomc neurons were blocked in mice with a LOF TRPC5 variant. This suggesting that the effects of BTD on food intake are mediated through Trpc5 in Pomc neurons. In conclusion, our study provides compelling evidence for the involvement of TRPC5 in the intricate regulation of human appetite, body weight, and maladaptive behaviors. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying TRPC5 variants. We suggest that TRPC5 should be included in diagnostic gene panels for severe childhood-onset obesity.
Presentation: 6/1/2024
7433 Distribution of Kisspeptin Neurons in the Adult Sheep Amygdala
Authors: Igler A , Amodei R , Roselli C E 
Published: October 2024

Abstract
Disclosure: A. Igler: None. R. Amodei: None. C.E. Roselli: None.
Kisspeptin (Kiss1) neurons are primarily recognized for their role in regulating reproductive function by stimulating the release of hormones that control puberty and fertility. While these neurons are more commonly associated with the hypothalamus, recent research has suggested their presence in other brain regions, including the amygdala. The amygdala, a complex brain structure integral to emotional processing and social behaviors, encompasses various nuclei, yet the specific distribution and potential functional implications of Kiss1 neurons within this region remain to be elucidated. Studies in rodent models have indicated the presence of Kiss1-expressing neurons in the posterodorsal medial nucleus of the amygdala and implicated them in the modulation of sexual partner preference and anxiety in male mice. Understanding the distribution of Kiss1 neurons in the sheep amygdala could provide valuable insights into the potential roles of Kiss1 in modulating not only reproductive functions but also emotional and social behaviors in a species more closely related to humans. In this study, RNAscope® was performed to survey the distribution pattern of Kiss1 neurons within various nuclei of the amygdala in the adult sheep brain. In addition, duplex RNAscope® was used to examine co-localization of Kiss1 with estrogen receptor-α (ESR1) mRNA. We found widespread distribution of Kiss1 neurons within the major nuclei of the amygdala in adult male and luteal-phase female sheep. The density of Kiss1 neurons was highest in the cortical nucleus and ventral portion of the basal nucleus. Intermediate densities were observed in the medial, basal and lateral nuclei, while the lowest density was found in the central nucleus. There was extensive co-expression of Kiss1 and ERα mRNA throughout the amygdala. In the medial nucleus where co-localization was quantified, approximately 80% of Kiss1 neurons co-expressed ESR1; whereas only about 60% of ESR1 neurons co-expressed Kiss1. Notably, immunofluorescence histochemistry using antibody #AC564 (from A. Caraty) revealed that kisspeptin fibers were concentrated in the medial nucleus and sparsely distributed throughout other nuclei. These results are the first to establish a map of Kiss1-expressing neurons in different subregions of the amygdala, which provides a useful foundation for investigations into their potential involvement in the neurobiological mechanisms underpinning emotional processing, social and sexual behaviors. Supported by NIH Grant OD11047 to CER.
Presentation: 6/3/2024
6939 Do an empty sella and a partial empty sella affect the modeling and displacement of the optic chiasm?
Authors: Kaluza Bernadetta , Furmanek Mariusz , Domanski Jan , Zuk-Lapan Aleksandra , Babula Emilia , Iga Poprawa , Landowska Malgorzata , Jarzabek Karolina , Popczynska Justyna , Filipowicz Paulina , Wielgolewska Malgorzata , Walecki Jerzy , Franek Edward M 
Published: October 2024

Abstract
Disclosure: B. Kaluza: None. M. Furmanek: None. J. Domanski: None. A. Zuk-Lapan: None. E. Babula: None. P. Iga: None. M. Landowska: None. K. Jarzabek: None. J. Popczynska: None. P. Filipowicz: None. M. Wielgolewska: None. J. Walecki: None. E.M. Franek: None.
An empty sella and a partial empty sella are a result of the bulging of the subarachnoid space into the sella turcica. Primary empty sella has no tangible cause, while secondary empty sella is due to a pathology in the central nervous system, which may be manifested as visual disorders occurring via optic chiasm modeling or displacement. The aim of the study was to determine whether an empty sella and a partial empty sella, both primary and secondary, were the risk factors for modeling the optic chiasm. In order to conduct the study, the hospital database was analyzed and 891 patients who had undergone pituitary and CNS MRI were selected. An empty sella and a partial empty sella were confirmed in 212 patients, of which 157 patients had a primary and 55 had a secondary form. Compression and modeling of the optic chiasm were found in 29 patients. Univariate logistic regression showed that the predictors of compression and modeling of the optic chiasm included: the presence of a pituitary adenoma (OR 2.275, 95% Cl 1.083-4.779, p=0.03) - especially macroadenoma (OR 29.472, [10.751-80.789], p=0.0001) and a status post CNS surgery (OR 10.226, [1.031-101.418], p=0.047). Conversely, an empty and partial empty sella (OR 1.02, [0.429-2.422], p=0.965) - both primary (0.741, [0.254-2.161], p= 0.584) and secondary (1.193, [0.353-4.034], p=0.776), as well as Rathke cleft cyst (OR 0.517,[0.121-2.206], p=0.373) and a pituitary cyst (OR 0.789, [0.184-3.383], p=0.749) were not found to play such a role. An empty and partial empty sella do not affect the modeling and displacement of the optic chiasm, so they may not contribute to visual symptoms such as the narrowing the visual field and diplopia.
Presentation: 6/3/2024
12408 Efnb2 Controls Pituitary Gland Development By Regulating Proliferation Of Pituitary Stem Cells
Authors: Gualtieri A , Gomez-Corral L , Nicholson J , Tan R , Guasti L , Gaston-Massuet C 
Published: October 2024

Abstract
Disclosure: A. Gualtieri: None. L. Gomez-Corral: None. J. Nicholson: None. R. Tan: None. L. Guasti: None. C. Gaston-Massuet: None.
Efnb2 encodes for the ligand Ephrinb2 that binds to its cognate Eph receptor, which plays an integral role in angiogenesis, stem cell regulation and tumorigenesis. Using a pituitary-specific Cre-driver (Hesx1Cre), we conditionally deleted Efnb2 from the early pituitary stem/progenitor cells (PSCs) of the developing pituitary gland. We found that Efnb2 is expressed in PSCs both during embryogenesis and adulthood, suggesting its involvement in PSCs maintenance. Here we show that genetic ablation of Efnb2 (Efnb2fl/fl;Hesx1Cre/+) results in severe pituitary hyperplasia, abnormal gland morphogenesis and delay in the terminal differentiation of hormone-producing cells. In order to understand the underlying molecular mechanisms by which Efnb2 deletion leads to pituitary abnormalities during embryogenesis, we performed transcriptomic analyses using mRNA-Seq at early stages of pituitary development on Efnb2+/+ and Efnb2−/− cell populations. Interestingly, unsupervised gene set enrichment analyses of the transcriptomic results identified Efnb2 as a key negative regulator of PSCs proliferation, whilst involved in the regulation of epithelial integrity and epithelial to mesenchymal transition (EMT). Functional assays performed to validate transcriptomic analyses revealed that Efnb2-null PSCs hyper-proliferate both in vitro and in vivo and downregulate the expression of genes involved in EMT, indicating a role of Efnb2 in these two developmental pathways. Indeed, whilst Efnb2-null PSCs within the marginal zone hyper-proliferate, they downregulate genes of epithelial integrity, resulting in an abnormal EMT transcriptomic profile. Additionally, these events lead to a significant delay of the pituitary cell lineage commitment program, leading to severe reduction in the expression of Pit1, Pomc1 and Gsu commitment markers. Taken together, our results reveal a novel role for Efnb2 (Ephrinb2) as key regulator of pituitary gland development. Efnb2 negatively regulates the proliferation of pituitary stem/progenitor cells controlling pituitary organ size while controlling the epithelial integrity of the stem cell niche.
Presentation: 6/2/2024
8719 Epidermal Inclusion Cyst Masquerading as Obstructive Craniopharyngioma
Authors: Murugesh M , Thelmo F , Watari J 
Published: October 2024

Abstract
Disclosure: M. Murugesh: None. F. Thelmo: None. J. Watari: None.
The most common cause of a sellar mass is notably pituitary adenoma (84.6%), followed by craniopharyngioma (3.2%), cystic nonneoplastic lesion (2.8%), inflammatory lesion (1.1%), meningioma (0.94%). Epidermoid cysts are benign congenital inclusion cysts that can occur anywhere in the body, with about 7% percent occurring in the head and neck region. Very rarely, they can present intracranially, accounting for about 0.3-1.8% of primary tumors. We present a rare case of epidermoid cyst growing as a suprasellar mass causing hypopituitarism.A 58-year-old female presented to the emergency department with dizziness in the setting of an ear infection. CT head showed 2.8 cm complex suprasellar mass, with adjacent 1 cm nodule at the cerebellopontine angle. MRI showed 2.7 x 2.4 x 2.7 cm suprasellar mass along with “a lobular component along the left posterior aspect extending to the cerebellopontine angle which measures about 1.3 cm, causing mass effect on the midbrain, pons, and optic chiasm”. The differential included craniopharyngioma, macroadenoma and meningioma. Notably, she denied any vision changes. She was evaluated by neurosurgery and after extensive multidisciplinary discussion with ENT and ophthalmology, the patient proceeded with endoscopic surgery for mass resection. Intra-operatively, the mass was noted to be densely adherent to the basilar artery, and sub-total resection was performed. Surprisingly on pathology the mass was identified as an epidermoid cyst, as evidenced by debris with cholesterol clefts and no lesional cells. The patient was started empirically on hydrocortisone 50mg three times a day post-resection. Endocrinology was consulted postoperatively with initial concerns of diabetes insipidus in the setting of hypernatremia, however, the patient’s sodium levels normalized. Pituitary panel at this time was concerning for central hypothyroidism (TSH 0.53 and FT4 0.8) and central adrenal insufficiency (ACTH &lt;9 and AM cortisol 0.9). She was ultimately discharged on prednisone 5mg and levothyroxine 75 mcg with outpatient follow-up. While epidermoid cysts are present in the head and neck region about 7% of the time, they rarely occur in intracranial regions, with about 1.5% of intracerebral epidermoid cysts occurring intracranially. They tend to be slow growing and are often found only when they grow large enough to become symptomatic, as seen in our presented case. Our case highlights the importance of recognizing epidermoid cysts as a rare cause of sellar masses.
Presentation: 6/1/2024
7917 Bilateral Adrenal Hemorrhages As The Initial Presentation Of Poorly Differentiated Bronchogenic Carcinoma
Authors: Malapur Bina , Jakoby Michael G , Williams Vanessa 
Published: October 2024

Abstract
Disclosure: B. Malapur: None. M.G. Jakoby: None. V. Williams: None.
Introduction: Bilateral adrenal hemorrhage is rare, and most cases occur in the setting of bacterial sepsis, coagulopathies such as antiphospholipid antibody syndrome, treatment with anticoagulants, surgery, or trauma. We present a patient with asynchronous bilateral adrenal hemorrhages that resulted in an eventual diagnosis of poorly differentiated bronchogenic carcinoma. Case: A 65-year-old female smoker was found to have a large right adrenal hematoma on computed tomography (CT) obtained for evaluation of acute onset right flank pain. No hemorrhage or anatomic abnormalities of the left adrenal gland were apparent, and the patient was discharged home after her pain was controlled. Approximately one month later, she returned to hospital with bilateral flank pain, and bilateral adrenal hemorrhages were diagnosed on repeat CT imaging. An 8 cm left upper lobe lung mass was revealed on a chest CT scan, and cytology from a bronchoscopic biopsy confirmed poorly differentiated bronchogenic carcinoma. The patient had no recent surgeries, abdominal trauma, or treatment with anticoagulants, serologic evaluation for coagulopathies and disseminated intravascular coagulation was unremarkable, blood cultures failed to grow bacterial pathogens, and acid-fast staining of lung tissue was negative. The patient was discharged from her second hospital admission on hydrocortisone and fludrocortisone. Discussion: Adrenal hemorrhage in the setting of malignancy is usually a complication of adrenal metastases. The prevalence of adrenal metastases in advanced stage cancer is approximately 3%, with lung and breast cancers and melanoma showing the highest predilection for adrenal metastases. This case is unusual because the patient had no focal masses or disruption of left adrenal contour on CT to indicate adrenal metastases at the time of right adrenal hemorrhage, and she did not have other established risk factors for pathologic bleeding in the setting of malignancy such as thrombocytopenia or treatment with chemotherapy agents, anticoagulants, or nonsteroidal anti-inflammatory drugs. Adrenal hemorrhage is also a rare inciting event resulting in the diagnosis of lung cancer; to date, there are only 29 published cases of spontaneous adrenal hemorrhage as the initial presentation of lung cancer. This case illustrates the importance of careful evaluation for malignancy in patients with spontaneous adrenal hemorrhage and no clear etiology for adrenal bleeding.
Presentation: 6/1/2024
12525 Feline Hypersomatotropism In The USA And Canada: Demographics Of 4620 Cats With Presumed Acromegaly
Authors: Egbert Rebecca J , Fowkes Robert C , Niessen Stijn J M , Petroff Brian K 
Published: October 2024

Abstract
Disclosure: R.J. Egbert: None. R.C. Fowkes: None. S.J. Niessen: None. B.K. Petroff: None.
Spontaneous models of endocrinopathies are powerful tools to understand disease etiology. Endocrine diseases in companion animals are particularly useful to study, as they share their environment with humans and typically present with clinical disease that phenocopies human symptoms. One such disease in domestic cats, hypersomatotropism (HST, feline acromegaly), is a disorder of excessive growth hormone and increased IGF-1 (Insulin like Growth Factor 1), usually caused by hyperplasia or neuroendocrine tumors of the pars distalis of the pituitary gland. This retrospective study used serum IGF-1 results to investigate population characteristics for domestic cats with HST in the United States and Canada. Laboratory records from 1Jan06 to 31Dec22 were reviewed and animals with a circulating IGF-1 hormone concentration of 190 nmol/L (1,450 ng/mL) or greater were presumed to have acromegaly. This review identified 4,620 such cats with a mean age (n=4,351) of 11.2 years (median: 11.2, range: .5-20.3yr) and mean weight (n=2,086) of 6.03 Kg (median: 5.91, range: 2.27-15.0 Kg). Males outnumbered females in the database, which included 3,048 males and 1,181 females. Domestic Short/Medium/Longhair cats were the most prevalent breed (n=3,563; 77%), followed by Maine Coon cats (n=120; 2.6%) and Siamese cats (n=111, 2.4%). Just under half of the animals (n=2,037, 44%) had a history of diabetes mellitus on the submission form. Most submissions were from the US (n=4,347, 94%) with the most hypersomatotropic cats from California (n=841, 18.2%), New York (n=604, 13.1%), Massachusetts (n=402, 8.7%), Colorado (225, 4.9%), and Texas (200, 4.3%). The mean serum IGF-1 concentration of these animals was 358 nmol/mL (median: 345, range 190-761 nmol/mL). For comparison, an age and sex matched control group of 95 animals with residual samples previously submitted for unrelated testing was selected. The mean IGF-1 concentration for the control group was 97 nmol/mL (median: 85, range 0-311 nmol/mL). In summary, HST is diagnosed most frequently in older male cats in urbanized North America, and potentially displays some breed disposition, suggesting both a genetic and environmental component to the disease etiology.
Presentation: 6/2/2024
8168 From Salt to the Sella- Discovering Empty Sella Syndrome as a Rare Cause of Severe Hyponatremia
Authors: Vemparala Pranathi , Challagulla Sabita 
Published: October 2024

Abstract
Disclosure: P. Vemparala: None. S. Challagulla: None.
Introduction: Hyponatremia is a common electrolyte disorder with potentially life-threatening consequences. Careful evaluation of hyponatremia can uncover significant underlying conditions. We present an interesting case of a patient who presented with symptoms of severe hyponatremia and a workup led us to the discovery of empty sella syndrome as the etiology. Case Presentation: A 54-year-old male with hypertension presented with 2 days of left-sided headache, blurred vision, generalized weakness, and vomiting. Pertinent medication history revealed the use of thiazide diuretic, bupropion and varenicline. Physical examination was unremarkable. Laboratory data showed severe hyponatremia with a serum sodium of 118 meq/L. Initial improvement with fluids was followed by a decline (106-112 meq/L). CT head without contrast showed a prominent empty sella turcica. Workup revealed urine osmolality and elevated urine sodium. A low AM cortisol level of 1.0 mcg/dl (reference range- AM- 7.0 - 25.0 mcg/dl), and decreased adrenocorticotropic hormone (ACTH) level of 5.2 pg/ml (reference range- 7.2 - 63.3 pg/ml) suggested secondary adrenal insufficiency. All other anterior pituitary hormones were normal. Brain magnetic resonance imaging (MRI) confirmed the diagnosis of partial empty sella. Treatment with hypertonic saline, fluid restriction, and steroids led to symptom resolution. Conclusion: Empty sella syndrome is a rare pituitary condition that can be primary- characterized by herniation of the subarachnoid space within the sella, or secondary- which occurs when the sella is empty due to damage to the pituitary gland by tumor, radiation, etc. It can cause potential hypopituitarism, be asymptomatic, or present with symptoms of raised intracranial pressure. In patients with hypopituitarism, deficiencies of ACTH and TSH are rarer and appear to be more common with a complete empty sella. This case emphasizes the need for a comprehensive hyponatremia workup, awareness of secondary adrenal insufficiency, and recognition of the life-threatening potential of even partial empty sella syndrome when untreated.
Presentation: 6/1/2024