bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatostatin, as a Bridge Between the GH-Axis and the Gth-Axis
Authors: Mizrahi Naama , Hollander-Cohen Lian , Levavi-Sivan Berta 
Published: May 2021

Abstract
Somatostatin (SST) is a 14-amino acid peptide produced in the hypothalamus of vertebrates, including fish. It regulates many physiological processes such as growth development and metabolic processes in the animal’s body. Negative control of growth hormone in vivo and in vitro was characterized in several fish species such as salmon, goldfish, rainbow trout and tilapia. Although very important, the SST/SST-R system in Nile tilapia (Oreochromis niloticus) was not deeply characterized. The somatostatin system in tilapia possess two ligands (Somatostatin1b and Somatostatin 2), and five receptors (SST-R 1-5). Unlike mammals, in fish, FSH and LH are secreted from different cell populations in the pituitary. By performing cell specific transcriptome analysis of double-labelled transgenic tilapia expressing GFP and RFP in LH or FSH cells, respectively, we identified genes specifically enriched in each cell type. Analysis of the RNA-seq discovered 4 types of SST-Rs: sstr2, sstr3, sstr5 and sstr5x3. The specific localization of each SST-R was identified by In Situ hybridization with specific probes for each of the SST-Rs. SST-R2 and SST-R5x3 were expressed on LH and FSH cells, while SST-R5 was exclusively expressed on LH cells. Interestingly, SST-R3, which was expressed on GH secreting cells, was also expressed on both gonadotropin-secreting cells. Transactivation assays, using COS7 cell line transfected with tilapia SST-Rs together with the reporter plasmid CRE-luc, demonstrated an effect through the cAMP/PKA pathway. Signal transduction analysis demonstrated that SST agonist (Octreotide; IC50 = 0.8-60nM) decreased the cAMP/PKA pathway, while an opposite effect was found when SST antagonist (Cyclosomatostatin; EC50 = 0.1 - 188 nM) was used. To understand the physiological effects of somatostatin on gonadotropins and GH release, we examined the effect of ip injection (100 μg/kg BW) of somatostatin agonist and antagonist on plasma FSH, LH and GH levels. SST agonist decreased plasma GH and FSH levels, as fast as two hours post injection and their levels remained low until the end of the experiment. On the other hand, SST antagonist increased LH and FSH levels two hours post injection, but while FSH levels remained high during the entire experiment, LH levels went back to basal levels afterwards. Our results show - for the first time in fish - a direct effect of SST on gonadotropin release, that could serve as a bridge between the GH-axis and the GTH-axis. The research was funded by the Israel Science Foundation (ISF) no. 1540/17.
Sirtuin 1 Regulates Synapsin 1 in POMC-Producing N43-5 Neurons via FOXO1
Authors: Teaney Nicole A , Cyr Nicole E 
Published: May 2021

Abstract
The nutrient-sensor protein Sirtuin 1 (Sirt1; silent mating type information regulation 2 homolog 1) has been shown to have significant and opposing effects on insulin resistance, leptin resistance, and body weight in the periphery and the brain. In the hypothalamic arcuate nucleus (ARC) of the brain, Sirt1 increases in the obese state and acts to promote weight gain as well as insulin and leptin resistance by increasing the orexigenic neuropeptides Agouti-related protein (AgRP) and neuropeptide Y (NPY), and in a distinct set of ARC neurons, by decreasing POMC and thus its anorexigenic derivative alpha-melanocyte stimulating hormone (alpha-MSH) (1). Sirt1’s actions on these neuropeptides are mediated at least in part by the deacetylation of the transcription factor forkhead box O1 (FOXO1). Another mechanism by which Sirt1 regulates body weight appears to be through mediating changes in the synapses of these neuropeptide-producing ARC neurons. For example, a previous study demonstrated that Sirt1 inhibition with the specific Sirt1 inhibitor, Ex-527, decreased AgRP-NPY inhibitory synaptic input on POMC neurons, which suggests that the obesity-induced increase in ARC Sirt1 would increase AgRP-NPY inhibition of POMC neurons thus promoting weight gain (2). The present study investigated how Sirt1 regulates synapses specifically in POMC-producing N43-5 neurons. Results reveal that inhibition of Sirt1 with Ex-527 significantly increased the presynaptic marker Synapsin 1 (Syn1) in N43-5 neurons. Furthermore, we investigated whether the Sirt1 target, FOXO1, mediates these synaptic changes. FOXO1 overexpression significantly decreased Syn1 and transfection of mutant FOXO1 significantly increased Syn1. Overall, our results suggest that Sirt1 regulates synapses of POMC neurons and does so in a manner that differs from Sirt1’s regulation of AgRP-NPY neuronal synapses. Future work will elucidate the mechanisms and consequences of Sirt1 and FOXO1 regulation of POMC neuron synapses under different nutritional conditions in vitro and in vivo.
(1) Cyr, N. E., Steger, J. S., Toorie, A. M., Yang, J. Z., Stuart, R., Nillni, E. A. (2014). Central Sirt1 Regulates Body Weight and Energy Expenditure Along With the POMC-Derived Peptide α-MSH and the Processing Enzyme CPE Production in Diet-Induced Obese Male Rats, Endocrinology, 155(7), 2423–2435.
(2) Dietrich, M. O., Antunes, C., Geliang, G., Liu, Z., Borok, E., Nie, Y., . . . Horvath, T. L. (2010). Agrp neurons mediate Sirt1’s action on the melanocortin system and energy balance: Roles for Sirt1 in neuronal firing and synaptic plasticity. The Journal of Neuroscience, 30(35), 11815–11825.
A Case of Pituitary Germinoma With Complete Recovery of Visual Field
Authors: Alameri Majid , Boharoon Hessa , Alnuaimi Abdulla Mohamed , Wernig Florian , Seckl Michael , Gonzales Michael 
Published: May 2021

Abstract
Central nervous system germ cell tumours (GCTs) are rare, accounting for 0.1-3.4% of all primary brain malignancies. Intracranial GCTs (ICGCTs) usually arise within the pineal recess (50-65%), sellar-suprasellar region (25-35%) and rarely in the basal ganglia-thalamus (5-10%). A peakonset occurs during the second decade of life with a median age at diagnosis between10-12 years and a male predominance. Histologically, ICGCTs are classified into germinomas accounting for two thirds of cases and non-germinomatous GCTs. ICGCTs present with clinical features dependent on their location and tumour size. Symptoms most often arise from compressed optic structures, increased intracranial pressure and central endocrine abnormalities, particularly diabetes insipidus (DI). Clinical findings combined with elevated tumour marker levels within the serum and/or cerebrospinal fluid (CSF) can be diagnostic.
Case: A 30-year-old lady who survived a childhood leukaemia presented as an emergency with a two-month history of headaches, dizziness and near-complete visual loss. Cranial MRI identified a large sellar mass with suprasellar extension compressing the optic chiasma and hypothalamus. Biochemical and endocrine profiles confirmed diabetes insipidus, hypocortisolaemia and hypothyroidism all requiring hormone replacement. Visual field examination revealed total left visual loss and a right temporal hemianopia. Cerebrospinal fluid analysis identified an elevated human chorionic gonadotropin (HCG) level at 16 IU/L (normal &lt;2), with a normal alpha-fetoprotein (AFP) level. Both tumour markers were normal in the serum. Emergency Etoposide-Cisplatin (Em-EP) chemotherapy was initiated for a suprasellar GCT followed by the EPOMB-ITMTX regimen [Etoposide-Cisplatinwith intrathecal Methotrexate (ITMTX) alternating with Vincristine-Methotrexate-Bleomycin]. After four cycles EPOMB-ITMTX, the vision was fully restored, brain MRI demonstrated an excellent radiological response and the CSF HCG normalised. Our patient received volumetric-modulated arc cranial radiotherapy (VMAT) with a total 54 Gy in 16 fractions. She remains well without disease recurrence for 14 months. Tumour markers are normal with stable MRI brain and whole-spine. Endocrine follow-up confirms recovery in all pituitary axes except the gonadotrophins for which she remains on hormone replacement therapy. Conclusion: This case demonstrates an excellent outcome for a young adult diagnosed with a suprasellar GCT treated with chemotherapy followed by stereotactic radiotherapy. It highlights the importance in keeping a high clinical index of suspicion in young adults presenting with a midline intracranial tumour, visual dysfunction and an endocrinopathy. CSF analysis identified an elevated tumour marker level, which bypasses the need for a histological diagnosis.
Skeletal Muscle Stromal Cells Derived From MuRF1 Knockout Mice Are Resistant to Adipogenesis
Authors: Norman Jennifer Elise , Marshall Andrea Gail , Rutledge John C , Bodine Sue C 
Published: May 2021

Abstract
Background: Intramuscular adipose tissue has been found to contribute to muscle dysfunction and is associated with a sedentary lifestyle, aging, and glucocorticoid treatment. Muscle ring finger 1 knockout (MuRF1 KO) mice have been shown to be protected from muscle loss following disuse, aging, and glucocorticoid treatment. In this study we used in vitro techniques to determine if MuRF1 KO muscle stromal cells are resistant to adipogenesis. Methods: Stromal cells were isolated from skeletal muscle tissue of MuRF1 KO and wild type mice. These cells were expanded in culture until 70–90% confluent, then differentiated in either a myogenic media formulation (myogenic cultures) or an adipogenic media formulation (adipogenic cultures). Gene expression was analyzed by qRT-PCR, protein content was measured by bicinchoninic acid assay, and triglyceride content was analyzed by colorimetric assay. We also analyzed isolated stromal cells, which had not been expanded in culture, by flow cytometry to identify myogenic satellite cells (SCs) and fibro-adipogenic progenitors (FAPs). Results: Wild type adipogenic cultures had higher expression of Trim63, the gene encoding MuRF1, when compared to wild type myogenic cultures. Adipogenic cultures had higher expression of adipogenic programing and lipid handling genes than myogenic cultures. These adipogenic cultures also had higher triglyceride content than myogenic cultures. The expression of adipogenic programing genes and lipid handling genes were lower in cultures derived from MuRF1 KO mice compared to wild type derived cultures; however, there was no statistically significant difference in the triglyceride content between the two genotypes. Analysis of stromal cell populations by flow cytometry indicated no difference in the FAP:SC ratio between wild type and MuRF1 KO mice. Conclusions: These results indicate that although there are no differences in the ratio of FAPs to SCs in wild type and MuRF1 KO mice, the MuRF1 KO cultures appear to be resistant to adipogenesis. The mechanism behind this resistance to adipogenesis remains to be elucidated.
A Rare Case of Nephrogenic Diabetes Insipidus From Tenofovir
Authors: Vasim Izzah , Amoakohene Peggy Nana Ama , McMillan Janice , Hong Gregory 
Published: May 2021

Abstract
Introduction: Diabetes insipidus (DI) is a clinical condition which manifests as excessive urine output, either because of impaired or inadequate antidiuretic hormone (ADH) secretion, or an inability of the kidneys to respond to ADH. Nephrogenic DI is more often drug induced. Recent clinical reports have shown that medications like tenofovir may result in nephrogenic DI as well. Tenofovir is a well-known nucleoside reverse transcriptase inhibitor analog of adenosine used in the management of both human immunodeficiency virus (HIV) and chronic hepatitis B. With its increased use, reports of adverse outcomes have been documented, mainly its effect on renal function including nephrogenic DI, renal failure and Fanconi syndrome. We present a case of nephrogenic DI whilst on Biktarvy (a combination of bictegravir, emtricitabine and tenofovir alafenamide). Case: A 59-year-old African American female with a history of HIV on Biktarvy, T2DM, HLD, HTN, MI, CAD, COPD presented to our hospital with weakness and falls for 1-2 months associated with polydipsia and polyuria. She had started Biktarvy for HIV about 2 months ago after which her symptoms got worse. Labs showed a serum Na of 151, potassium of 3.2 on admission with serum osmolality of 323 and urine osmolality of 134. During hospitalization, she was challenged with 100ug oral Desmopressin. Urine labs failed to correct after Desmopressin administration which was highly indicative of severe nephrogenic DI. The challenge was repeated with 200ug oral Desmopressin with similar results. Pituitary DI was considered given the patient’s falls; however urine osmolality did not improve following desmopressin challenge. Furthermore, her serum Co-peptin level was elevated at 36.1 that ruled out central DI. The patient’s hypokalemia was believed to be driving her nephrogenic DI which has been reported in various case reports with patients on Tenofovir, but has never been reported in patients taking Biktarvy (which includes Tenofovir Alafenamide). She was subsequently placed on fluid restriction during which time the patient’s serum Na and Cr increased while urine osmolality did not correct. HCTZ was ultimately started as a treatment for nephrogenic DI and patient was transitioned of biktarvy to lamivudine and dolutegravir. Her polyuria and polydipsia improved, however she developed hyponatremia likely because of HCTZ. Patient concentrating ability improved off biktarvy and HCTZ was discontinued on the day prior to discharge without issue. Her subsequent serum sodium and potassium levels were normal. Conclusions: Our case highlights a rare incidence of tenofovir induced hypokalemia leading to nephrogenic DI. This case illustrates the importance of monitoring patients on tenofovir for signs of renal [tubular] dysfunction. In a polyuric patient on tenofovir, there should be a high index of suspicion for nephrogenic diabetes insipidus.
A Rare Case of Recurrent Lymphocytic Hypophysitis Spanning 8 Years
Authors: Prahdan Aprajita , Mishra Sunil Kumar , Kuchay M Shafi , Singh Varindera Paul , Kumar Modi Jayesh Ashok 
Published: May 2021

Abstract
Background: Lymphocytic Hypophysitis (LH) is predominantly a self-limiting condition. Reports of recurrent LH have been limited to case series, predominantly within first two years of initial presentation (1). There is paucity of data on long term follow up of these cases and late recurrence of LH is considered very rare (2). Clinical Case: We describe the clinical course of a 47-year female, who first presented to us, 8 years back, with headache, visual disturbance and secondary amenorrhea. Her MRI pituitary was suggestive of a pituitary mass, which was removed by trans-sphenoidal surgery. Histopathology of the mass was suggestive of LH. Patient had symptomatic improvement, and remained well on out-patient follow-up, on hormone replacement therapy. She took replacement dose of glucocorticoid for 4 years after the initial surgery and then it was discontinued. However, she re-presented to us with headache and visual disturbance this time associated with xerostomia and xerophthalmia. In this presentation, due to presence of sicca symptoms a suspicion of autoimmune aetiology was kept. Her lab parameters were consistent with pan hypopituitarism along with new appearance of anti-TPO antibodies. She underwent two consecutive trans-sphenoidal surgeries for relief of pressure symptoms, and has been started immunosuppressive doses of glucocorticoids along with methotrexate. Other causes of recurrent hyophysitis, as IgG4 related Hypophysitis, were excluded by immunohistochemistry and normal serum IgG4 level (0.72g/l). She has since been discharged, and remains well on outpatient follow-up with no mass effect. MRI pituitary done at 2 months follow up is not suggestive of residual regrowth or mass effect. Conclusion: This case highlights the importance of long term follow up of LH patients. Other autoimmune aetiology maybe considered in cases unresponsive to standard treatment, necessitating titration of additional immunosuppressive therapy. References: 1.M.N. Joshi et al, Hypophysitis: diagnosis and treatment, European Journal of Endocrinology 2018, 179, R151-R1632.Honegger et al, Treatment of Primary Hypophysitis in Germany: Journal Clinical Endocrinology and Metabolism, September 2015, 100(9):3460 –3469
A Rare Case of Sellar Mass Composed of Primary Leiomyosarcoma and Pituitary Adenoma
Authors: Kim Young Ki , Goak In Sun , Kim Yu Ji , Jin Heung Yong , Park Tae Sun , Lee Kyung Ae 
Published: May 2021

Abstract
Background: Nonfunctioning pituitary adenomas (NFPAs) are most common pituitary tumors, and primary pituitary gland malignancies are extremely rare. Most malignant pituitary gland lesions metastasize from other sites. Primary malignant lesions, such as sarcomas, usually develop after radiotherapy or chemotherapy for other diseases. We report a rare case of primary sellar leiomyosarcoma (LMS) without prior therapy that arose concurrently with a pituitary adenoma. Clinical Case: A 56-year-old woman with ptosis of the right eye, headache, and progressive visual deficits visited our neurosurgery department. She had no medical history besides hypertension. Twelve months ago, she was referred to us because of decreased visual acuity and a 3.5×3.6-cm-sized pituitary mass detected on brain MRI. Normal pituitary functions with mild hyperprolactinemia suggested a nonfunctioning pituitary mass with stalk compression. After transsphenoidal surgery, histopathology revealed a pituitary adenoma; MRI immediately post-surgery revealed no grossly remnant lesion. However, during the current visit, sellar MRI revealed a re-growing mass in the pituitary fossa extending to the sphenoid sinus and compressing the optic chiasm with a suprasellar extension. Functional endoscopic sinus surgery was performed, and histopathology revealed a composite tumor, i.e., a mesenchymal tumor with a pituitary adenoma. On immunohistochemical staining, smooth muscle actin, synaptophysin, and chromagranin were positive; tumor cell mitosis was observed at 7/10 high-power fields. Finally, a composite tumor of myxoid leiomyosarcoma and pituitary adenoma was diagnosed. Hence, systemic chemotherapy with radiotherapy was planned for the remnant lesion. Hormonal replacement therapy with hydrocortisone and thyroxine was also started for subsequent hypopituitarism. Conclusion: NFPA is benign and has good prognosis if it is not grow in size or is completely resected. Conversely, primary sarcomas, such as LMS, show rapid extension and aggressive local invasion. Although their incidence is extremely rare, few primary pituitary sarcoma cases with or without pituitary adenoma have been reported. In the former case, initial diagnosis of pituitary adenoma may lead to delayed diagnosis of combined malignant lesions. Thus, clinicians should consider this possibility and high index of suspicion is required when diagnosing a pituitary mass.
A Rare Case of Sellar Metastastic Renal Cell Carcinoma Mimicking Pituitary Adenoma - a Case Report
Authors: Tambovtseva Anastasia , Gandhi Rima , Abdelmasih Randa , Monsour Elio Paul , Hamza Alan 
Published: May 2021

Abstract
Introduction: Metastatic sellar masses are very contributing to 2% of all sellar masses, and up to 0.87% of all metastases to the brain. Breast and lung cancer contribute for up to 60% of all sellar metastases but it is important to recognize other cancers that can also metastasize to pituitary gland. Renal Cell carcinoma (RCC) is number nine on that list. Here we present a case of rare RCC metastasis to pituitary which was mistaken as pituitary adenoma to emphasize early recognition and management of pituitary metastases which may result in better patient’s outcomes and prognosis. Case Presentation: 7 2 year-old male with a remote history of left sided RCC presented with worsening diplopia, blurry vision and headaches for 2 months. Physical exam was remarkable for right sided ptosis with right oculomotor, trochlear and abducens palsy. Computed Tomography Imaging (CT) of the brain showed hyperdense sellar/suprasellar fullness. Magnetic Resonance Imaging (MRI) with and without contrast of the brain showed 2.2 x 1.7 cm enhancing mass in the right cerebellopontine angle with local mass effect concerning for a pituitary tumor. Laboratory work-up was remarkable for hyperprolactinemia 36.5 ng/mL, low TSH &lt;0.015 mU/L, and normal ACTH, FSH and LH levels. Patient underwent endoscopic trans-nasal resection of pituitary tumor. Surgical pathology of the tumor was consistent with metastatic renal cell carcinoma. He was discharged with appropriate multidisciplinary outpatient follow up with endocrinology, oncology and radiology. Discussion: Pituitary metastasis is very rare and often mistaken for pituitary adenoma. Only 7% of Pitutary metastases are symptomatic. Symptom presentation depends on the location of metastases. They include diabetes insipidus (45.2%), visual field defects (27.9%), hypopituitarism (23.6%), ophthalmoplegia (21%), headache (15.8%) and hyperprolactinemia (6.3%). Although, there is no gold standard imaging for sellar masses, both thin-section CT and MRI are beneficial. CT is used for visualizing bony destruction and calcification, on the other hand MRI demarcates lesions in that area. Due to its rarity, there is no standardized guideline therapy for pituitary metastasis and it should be individualized based on patient’s presentation, but it should be multidisciplinary approach of surgical resection, postoperative stereotactic radiosurgery, chemotherapy, and hormone replacement therapy. Prognosis of metastases to pituitary is very poor, with reported six to twenty-two months post resection survival. Factors contributing to prolonged survival are younger age, single/small metastases, and locally guided radiation therapy. Conclusion: This case is to shed light on early recognition of sellar metastasis as a challenging diagnosis especially in patients with rapidly growing pituitary mass and neurological symptoms with history of malignancy for better outcomes.