bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP322 Impact of Mifepristone on Liver Function and Resolution of Liver Steatosis in Patients with Cushing Syndrome – A Case Study
Authors: East Honey E , Moraitis Andreas G , Belanoff Joseph K 
Published: November 2022

Abstract

Background
Hypercortisolism is a recognized cause of non-alcoholic fatty liver disease (NAFLD). Mifepristone (Korlym®, Corcept Therapeutics), a glucocorticoid receptor (GR) antagonist, is FDA-approved for the treatment of hyperglycemia in patients with endogenous Cushing syndrome (CS). Mifepristone has also shown beneficial effects in preclinical models of fatty liver disease, including reduced liver injury, improved insulin sensitivity, and increased plasma adiponectin concentrations. Here, we report the case of a patient with CS and liver steatosis who was treated intermittently with mifepristone.

Clinical Case
A 36-year-old woman with CS associated with uncontrolled type 2 diabetes mellitus, obesity, major depressive disorder, hyperlipidemia, hypertension, and liver steatosis was intermittently treated with mifepristone for 3 years. Abdominal imaging was performed several times for abdominal pain. Before treatment with mifepristone was initiated, the patient had a body weight of 198 lbs, BMI of 32kg/m 2, HbA1c of 11.5%, and liver steatosis as noted on abdominal imaging with normal liver function tests (ALT: 40 U/L [normal: 6-42 U/L], AST: 30 U/L [normal: 8-36 U/L]). After 16 months, treatment with mifepristone was discontinued secondary to abnormal uterine bleeding. Imaging performed around the time of discontinuation showed resolution of liver steatosis, which was accompanied by significant reductions in LFTs to levels typically seen in healthy volunteers without liver steatosis (ALT: 10 U/L, AST: 17 U/L). The patient's HbA1c had decreased to 6.8%. Imaging performed 7months after mifepristone discontinuation showed recurrence of liver steatosis, LFTs had returned to pre-treatment values (ALT: 42 U/L, AST: 31U/L), and HbA1c had increased to 9.3%. The patient underwent hysterectomy and restarted mifepristone treatment. One year after resumption of mifepristone, imaging showed that liver steatosis had resolved once again, along with a similar reduction in LFTs as observed before (ALT: 16 U/L, AST: 12 U/L). Fourteen months after restart, mifepristone was discontinued again. Labs and imaging performed 10 months after discontinuation showed, as previously, recurrence of liver steatosis along with elevated LFTs (ALT: 100 U/L, AST: 56 U/L). Data from mifepristone's prospective pivotal study (SEISMIC, NCT00569582) of 50 patients with CS also showed a similar reduction in ALT throughout the study, which was reversed during the 6-week discontinuation follow-up phase of the study. This was followed by a repeat reduction when mifepristone was restarted in the extension study (NCT00936741).

Conclusion
These results suggest that mifepristone is effective in improving liver function and decreasing liver steatosis in patients with endogenous CS, a trend that is also accompanied by improvement in insulin resistance and glycemic control.
Presentation: No date and time listed
ODP326 Isolated Abducens Palsy as a Presenting Feature of Pituitary Apoplexy
Authors: Alam Mustafa , Alam Mustafa , Abdelrahim Baha , Alam Mahad , Horani Mohamed Hosam 
Published: November 2022

Abstract

Case Presentation
A 27-year-old female with a history of T1DM presented to the ED for continued visual changes onset the past 10 days. The patient states that she was driving from Wisconsin to Arizona when she developed blurry vision localized to her right eye. She was previously evaluated by outpatient ophthalmology where she was diagnosed with R abducens palsy with no evidence of retinopathy. Associated symptoms included nausea, dizziness, and right sided HA localized behind her right eye and the base of her head. This HA was not relieved by Excedrin or Tylenol. Over the past 3 months, her menstrual periods have been lighter and irregular. Additionally, she has been lactating ever since the birth of her child 2.5 years ago. Hospital Course: Pt had stable vitals: T: 36.4 C, HR: 97, BP: 130/76, RR: 23, SPO2: 100%. Physical exam was WNL other than CN6 palsy. Lab workup was notable for: Na: 138, Cr: 1. 02. FT4 0.94, TSH 3.281, AM Cortisol 8.5, Random Cortisol 7.5, FSH 3.4, FG Glucose 329, and Prolactin 60.4. An MR Brain with and without contrast revealed an enlarged pituitary with a posterior 7mm lesion with small amount of hemorrhage given the high T1 signal. The patient was admitted for concerns of apoplexy and started on Hydrocortisone 50mg IV q12 x2 followed by Hydrocortisone 15mg qAM and 5mg qPM. 18 units of Lantus were started q24 hours along with Cabergoline 0.5mg tabs qhs Wednesday and Sunday.

Discussion
Pituitary Apoplexy is an endocrine emergency characterized by cortisol levels insufficient for normal body homeostasis. However, not all presentations of Apoplexy are typical. This case highlights isolated abducens palsy as the presenting feature of pituitary apoplexy. Due to the nature of the anatomy of the cavernous sinus, ocular palsies can be a simple physical findings that may have important clinical correlates that should be investigated further.
Presentation: No date and time listed
ODP334 Must we Wait for the Development of Metastasis to be Able to Distinguish Dopamine Resistant Aggressive Prolactinoma from Prolactin Producing Pituitary Carcinomas? Case Report and Literature Review
Authors: Rios Paola , Iragorry Corina , Jara Mark , Hannoush Zeina 
Published: November 2022

Abstract

Background
Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. In the vast majority of cases, these are benign tumors with excellent clinical response to medical therapy with dopamine agonist agents such as bromocriptine and cabergoline. Rarely medical treatment fails to normalize prolactin levels and/or decrease the size of the tumor, posing a challenge to the clinician.

Case presentation
40-year-old man who underwent resection of a 7.4 cm pituitary prolactinoma via frontal craniotomy followed by radiotherapy. He developed panhypopituitarism and was placed on chronic hormonal replacement therapy plus high dose cabergoline. Two years later he presented with recurrence of his disease and was diagnosed with an unresectable 4.9 cm pituitary adenoma showing cortical breakthrough of the sellar floor, invasion into the optic chiasm, erosion of the posterior sphenoid walls, extension into the sphenoid sinuses and posteriorly into the pons, midbrain and third ventricle, as well as complete encasement of the distal, superior cerebellar and posterior cerebral arteries. The patient underwent endoscopic trans sphenoidal partial tumor resection and CSF leak repair. Pathology revealed a pituitary prolactinoma with Ki-67 of up to 8% and positive p53 immunostaining. His cabergoline dose was adjusted to 0.5 mg PO daily and he was also started on Sandostatin 20 mg IM monthly as well as appropriate hormonal replacement of the other deficient pituitary hormonal axes. Follow up imaging revealed stability of the lesion. The patient continues to do clinically well and actively follows with endocrinology and neurosurgery with serial brain MRIs and laboratory workup.

Discussion
The histological and biochemical characteristics of aggressive prolactin secreting tumors has been reported to be of minimal utility in distinguishing benign from malignant lesions. Tumors can only be diagnosed as carcinomas after they have metastasized and they can only be classified as aggressive after treatment failure or unusual growth, which creates a disadvantage for the prognosis and management of these patients. Clinicians are in need of better guidelines that can help them identify the rare cases that might warrant more aggressive clinical interventions beyond dopamine agonists such as surgery, radiation, temozolomide, somatostatin receptor agonists and others, with the hope of delaying or preventing the development of metastasis. Case reports of atypical presentations of aggressive prolactinomas such as the one here presented, can help broaden our understanding of the predictable signs of poor prognosis.
Presentation: No date and time listed
ODP341 Pachydermia lesions identified on imaging in a cohort of acromegaly patients
Authors: Roque Joao , Marques Pedro 
Published: November 2022

Abstract

Introduction
Pachydermia is a clinical term derived from the former taxonomic order of mammals pachydermata, and it corresponds to a benign thickening and furrowing of the skin. It is classically associated with pachydermoperiostosis, but it can emerge in another conditions, including in acromegaly. These lesions may be distributed throughout the body. When they are mainly located to the scalp and forehead, resembling cerebral gyri, they receive the designation of cutis verticis gyrata (CVG). These are seldomly reported in acromegaly patients. Therefore, with this study we aimed to assess the prevalence of these pachydermia lesions in the patients with acromegaly followed at our center.

Materials and methods
We retrospectively reviewed the head magnetic resonance imaging (MRI) of 42 patients with acromegaly followed at our center. We inspected the composition, thickness and shape of the scalp, and those cases with more than 1 unequivocal furrow on the skin/connective tissue of the scalp region visible on the MRI were considered as a patient displaying pachydermia lesions. Demographic data and IGF-I levels at diagnosis were also registered.

Results
Six out of the 42 (14%) acromegaly patients displayed pachydermia lesions identifiable on MRI. Of the 6 patients, 4 had pachydermia lesions in the parietal area, while the occipital and the temporo-occipital regions were each involved in 1 patient. The mean age of these six patients were 51±10yr, and there were 4 males and 2 females. Their serum IGF-1 levels at the diagnosis of acromegaly were 1125±326ng/mL (minimum and maximum IGF-1 levels were respectively 517 and 1358), and 5 of the six patients were identified with a pituitary macroadenoma at diagnosis, while only one patient had a microadenoma.

Discussion
Pachydermia lesions are uncommonly reported in patients with acromegaly, although their prevalence might be significant in this setting, particularly in male patients, as demonstrated in this study. Pachydermia lesions may be depicted on imaging studies, thus clinical examination together with careful inspection of the scalp and skin on radiological studies may be important to identify such lesions, which in turn may contribute for an earlier diagnosis of acromegaly or facilitate the investigation of other etiologies.
Presentation: No date and time listed
OR08-4 Endocrine Mechanisms of an Orphan G Protein-Coupled Receptor Regulating Metabolic Homeostasis
Authors: Ren Hongxia 
Published: November 2022

Abstract
G protein-coupled receptors (GPCRs) are the largest protein family and amenable for pharmacological manipulation. GPCRs in the neuroendocrine and enteroendocrine systems respond to various biological cues and in turn exert crucial roles in maintaining whole body metabolic homeostasis. For example, GPCRs in the gastrointestinal tract are involved in maintaining glucose and energy homeostasis by regulating the release of gut hormones in response to luminal dietary nutrients as well as microbial metabolites. We recently identified that an orphan GPCR, Gpr17, was co-expressed in glucagon-like peptide-1 (GLP-1)-expressing EECs in human and rodent intestinal epithelium. We reported that acute genetic ablation of Gpr17 in intestinal epithelium (iKO) improved oral glucose tolerance and glucose-stimulated insulin secretion (GSIS) in female and male mice through increased secretion of incretin hormone in response to nutrient ingestion (Cell Reports, 2022). In the neuroendocrine system, we previously identified Gpr17 as the transcription target of Forkhead box protein O1 (FoxO1) in the hypothalamus and generated hypothalamic neuron specific Gpr17 knockout animals (Cell, 2012). Our results demonstrated that agouti-related peptide (AgRP) neuron Gpr17 knockout mice had increased satiety during fasting-refeeding challenge (Diabetes, 2015) and that proopiomelanocortin (POMC) neuron Gpr17 knockout mice had increased alpha-melanocyte stimulating hormone (aMSH) processing and increased firing of POMC neurons (Nutrition & Diabetes, 2019). However, how Gpr17 may regulate energy balance especially regarding leptin hormone signaling is unclear. To address this question, we used genetic knockout approach to generate Gpr17 conditional knockout in leptin receptor expressing neurons in the brain. We found Gpr17 deficiency in leptin receptor expressing neurons increased leptin sensitivity in animals and resulted in reduced food intake, which corresponded with reduced inflammatory response in the hypothalamus. Moreover, male Gpr17 whole body knockout mice have improved intraperitoneal glucose tolerance, and increased insulin sensitivity in hyperinsulinemic-euglycemic clamp studies. In conclusion, our collective body of work showed that ablation of Gpr17 signaling in the neuroendocrine and enteroendocrine systems led to improved neurohormonal regulation to maintain metabolic homeostasis, indicating functionally targeting this GPCR may lead to better therapeutic outcome of diabetes and obesity.
Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.
ODP030 Autoimmune Adrenalitis Following mRNA Covid- 19 Immunization In A Patient Without A Known Diagnosis Of Adrenal Insufficiency.
Authors: Jamal Yusra , Camacho Yudi , Mullally Jamie 
Published: November 2022

Abstract
A 45-year-old female with a past medical history of Hashimoto thyroiditis and celiac disease presented after a syncopal episode that resulted in a motor vehicle accident. The patient had symptoms of fatigue, nausea, and anorexia for three weeks following the second dose of the Pfizer-BioNTech COVID-19 Vaccine. Initial laboratory tests revealed hyponatremia with serum sodium (Na) of 123mEq/L that worsened to 111mEq/L after receiving the normal saline infusion. Serum potassium was 3.4mEq/l, Thyroid-stimulating hormone level was 6.350mIU/l, free thyroxine level was 1.1 ng/dl and glucose were 85mg/dl. The PCR test for COVID-19 was negative. Vitals were unremarkable except for a low blood pressure of 90/60. On physical examination, the patient was alert and communicative and there was no hyperpigmentation of the skin. The patient denied personal and family history of adrenal insufficiency. She denied prior use of any steroid medications. Her prior outpatient serum Na levels were normal (138-140 mEq/L). The patient was admitted to the ICU for severe hyponatremia, where she was treated with fluid restriction and hypertonic saline. However, she remained hypotensive, and serum sodium failed to improve above 118mEq/l. Serum cortisol at 8: 00 am and 10: 00 am were 4.5 and 5.8 mcg/dl, respectively. She was started on stress doses of hydrocortisone 100 mg intravenous (IV) followed by hydrocortisone 50 mg IV every 8 hours and serum Na improved to 130m Eq/l. Steroids were tapered gradually to physiological doses. The levothyroxine dose was also increased from the home dose of 75mcg to 88 mcg daily due to the elevated TSH. Hormonal workup showed aldosterone of 0.3ng/dl, plasma renin activity of 20, and adrenocorticotropic hormone(ACTH) levels of &gt;1250pg/ml. Gonadotropins, insulin-like growth factor-1, and prolactin were within normal limits. Cosyntropin stimulation test after holding steroids for 24 hours was abnormal, with pre-cosyntropin cortisol level 7. 0mcg/dl, and the 60-minute post-cosyntropin cortisol level 7.1mcg/dl. The diagnosis of autoimmune adrenalitis was confirmed with a positive 21-hydroxylase antibody test. The patient had an uneventful recovery and was discharged on oral hydrocortisone.
Presentation: No date and time listed
PMON155 Intraoperative, confocal laser endomicroscopy in pituitary surgery
Authors: Schlaffer Sven-Martin , Buchfelder Michael , Coras Roland 
Published: November 2022

Abstract

Introduction
Fluorescence imaging, such as confocal laser endomicroscopy (CLE) is a fast modality of image acquisition, which offers the possibility of early intraoperatively diagnosis and may be used to improve surgical decision making.

Objective
Within a 3-month prospective trail we used the Zeiss CONVIVO CLE in transspehnoidal surgery for different sellar pathologies. CLE is a miniaturized portable, handheld, fiber optic-based, confocal laser scanning microscope used in conjunction with a 488-nm excitable fluorophore. During the trial period we investigated feasibility, diagnostic accuracy and usability in terms of differential diagnosis in transsphenoidal surgeries of various pituitary tumours (15 pituitary adenomas, 2 craniopharyngiomas, 1 sellar metastasis).
Method: Patients were randomly selected. Inclusion criteria were a pituitary macroadenoma or a sellar mass lesion exceeding 10 mm in diameter. A transsphenoidal approach was used and fluorescin was injected upon opening the sellar floor. CLE was carried out immediately after dural opening and during tumour resection, whenever possible. Additionally, the microprobe was used ex vivo with the resected tumor material. Histopathologic features of CLE images and H&E-stained permanent sections were assessed and compared postoperatively.
Result: We were able to obtain CLE in-vivo images in all cases. Using the microscopic approach, no problems occurred regarding space for the microprobe. To obtain in-vivo images we had to rest the probe within a mount. Wiggling of the surgeon's hand, pulse synchronous movements of the mass and mild intraoperative venous bleeding led to inexact images. To overcome these problems, we used CLE as early as possible at the beginning of tumor resection to avoid bleeding interferences.
Additionally we investigated resected tumor specimens ex-vivo within the OR. Since no bleeding and no interference with movements occurred image quality and acquisition time improved.
Histopathologic features of CLE images and H&E-stained permanent sections showed, that except for the sellar metastasis, a diagnosis could be made on the basis of the intraoperative CLE images, whereas the ex-vivo images were more precise.

Conclusion
CLE is a potential imaging modality for transnasal assessment of skull base and pituitary lesions. It may help to establish an early diagnosis, to identify pituitary microadenomas, especially in cushing´s disease and to distinguish the various sellar pathologies.
CLE is a fascinating possibility to verify a suspected diagnoses already intraoperatively.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON54 Exosomes Isolated from Conditioned Media of Immortalized Kisspeptin Neurons Exert Diverse Effects on Central and Peripheral in Vitro Cell Models.
Authors: Chappell Patrick , Ewton Jessica , James Teagan , Karthikeyan Varsha , Starman Alia 
Published: November 2022

Abstract
Previous work in our laboratory explored the proteomic contents of exosome-like extracellular vesicles (EVs) released into the media in vitro from immortalized Kisspeptin (KP) neuronal cell lines KTaV-3 (derived from female mouse AVPV) and KTaR-1 (derived from KNDy neurons in the ARC). EVs were isolated from conditioned media via ultracentrifugation or filtration kit and validated using a NanoCyte, and LCMS-MS analysis revealed that relative abundance of exosomal cargo varied dependent upon estrogen (E2) exposure in vitro, with ∼150-170 proteins up-regulated and ∼200-220 proteins downregulated by E2 in EVs of KTaR-1 and KTaV-3 KP neurons.
Since E2-regulated KP exosomal proteins included candidates implicated in the regulation of synaptic plasticity and signaling (i.e. annexins, semaphorins, connexins), we investigated the effects of exposure to purified EVs on gene expression in immortalized GnRH neurons (GT1-7 cells). Notably, EVs from 24h E2-treated KTaV-3 neurons induced increased expression of kiss1r in GT1-7 cells, in contrast to KTaV-3 neurons not exposed to E2, suggesting that AVPV KP neurons may signal an increase in KP receptivity in GnRH neurons in vivo via non-neuronal communication. Additionally, increases in expression of the synaptic scaffolding protein PSD-95 (dlg4) were seen in GT1-7 cells treated with E2-treated KTaV-3 EVs, suggesting AVPV KP neurons may use extracellular vesicles to modulate GnRH neuronal synaptic plasticity over the estrous cycle. While EVs isolated from KTaR-1 conditioned media did not alter GT1-7 kiss1r or dlg4 levels, treatment (24h) resulted in induction of selective gap junction hemichannel expression in GT1-7 cells. KTaR-1 (but not KTaV-3) EVs increased expression of Cx26 (gjb2) irrespective of E2 exposure, while induction of Cx43 (gja1) expression in GT1-7 cells was only observed following treatment with E2-deprived KTaR-1 EVs.
Further, we found that KTaR-1 media and EVs can affect osteoblast function in vitro, including increases in sp7 and runx2 expression, E2-dependent modulation of wnt10b, and formation of bone matrix (evaluated by Alizarin Red assay) in cultured osteoblast lines, supporting recent studies implicating ARC KP neurons in bone remodeling. Lastly, we found significant levels of immunomodulatory pentraxins (PTX3) in KP EVs, with abundance dependent upon prior E2 exposure in KTaR-1 KP neurons, as revealed by ELISA. Together, results from these studies suggest that EVs may represent additional intercellular communication pathways utilized by Kiss-1 neurons to elicit changes in nearby neuronal populations and potentially even in the periphery, affecting inflammation and bone remodeling. Future studies will address mechanisms involved in the E2 regulation of exosomal cargo in these critical neuronal populations.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.