bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR22-3 Uterine TGFβ Signaling Controls Endometrial Cell Homeostasis And Regeneration
Authors: Monsivais Diana 
Published: November 2022

Abstract
The transforming growth factor beta (TGFβ) signaling pathway has critical roles in the transduction of paracrine and autocrine signals that control development, reproduction, and cancer. To study the tissue-specific contribution of TGFβ signaling in the endometrium, we developed mice with conditional deletion SMAD2 and SMAD3 in the endometrial epithelium (using Lactoferrin-cre, "Ltf-cre"). We identified that double conditional deletion of SMAD2 and SMAD3 in the endometrial epithelium resulted in endometrial hyperplasia by 12-weeks of age, with myometrial invasion, metastasis, and death by 6-9-months of age. Smad2/3-Ltf-cre mice also lost epithelial progesterone receptor expression in the endometrium by 12 weeks of age. To study the signaling mechanism that controlled the malignant transformation of the glandular epithelium in Smad2/3-Ltf-cre mice, we developed 3-dimensional (3D) endometrial organoid cultures from the uterine epithelial tissues of control and mutant mice. To test how suppression of TGFβ signaling affected endometrial regeneration, 3D endometrial organoids from WT or Smad2/3-Ltf-cre mice were grown in the presence or absence of the TGFβ receptor inhibitor, A83-01. Using these conditions, we identified that WT endometrial organoids cultured with the SB505124 inhibitor or from Smad2/3-Ltf-cre mice, developed abnormal morphology. Histological analysis of the endometrial organoids showed that organoids cultured with A83-01 or from Smad2/3-Ltf-cre mice, developed increased secretory-like cells with increased mucin-1 expression. RNA-sequencing of the endometrial organoids revealed that a large number of differentially expressed genes were conserved between the WT organoids cultured with A83-01 and those from Smad2/3-Ltf-cre mice. Gene ontology analysis of the differentially expressed genes indicated that pharmacological or genetic inhibition of TGFβ signaling, resulted in over-representation of gene families related to BMP/SMAD1/5 signaling and retinoic acid signaling, with decreased enrichment of WNT/β-catenin signaling. These studies indicate that TGFβ-mediated signals are critical to endometrial function and that perturbation of this balance results in endometrial cancer. Funding support NICHD grants R00-HD096057 (to DM) and R01-HD032067 (to MMM), and grants NGP10125 and 1016187 from the Burroughs Wellcome Fund (to DM).
Presentation: Monday, June 13, 2022 11:30 a.m. - 11:45 a.m.
OR22-5 Effect of Melatonin Receptor 1 on Glucose and Lipid Metabolism in Melatonin-proficient (c3hf+ ∕+) Female Mice
Authors: Goyal Varunika 
Published: November 2022

Abstract
Various functions of the pineal gland hormone melatonin are mediated via receptors, MT1 and MT2. Both receptors are known to regulate glucose metabolism in mice and humans. In addition, the MT1 receptor also controls lipid metabolism in mice. Light exposure, jet lag and shift work often cause the inhibition of melatonin production and hence the action of its receptors. So far, the loss of melatonin signaling was studied in male mice only. Here, we analyze the effect of removal of MT1 receptor in female mice under a control diet (CD)/high fat diet (HFD) regimen. Female C3H-f+∕+ (WT) and C3H-f+∕+ MT1 KO (MT1KO) mice (n=9-12/group) at six weeks of age were housed singly and exposed to CD (D12450H, 10% kcal/fat) or HFD (D12451, 45% kcal/fat) for 14 weeks. Weight, food intake and fasting blood glucose level (FBG) of each mouse was measured weekly. Insulin (ITT) and glucose tolerance tests (GTT) were performed after 14 weeks. At the end of experiment, mice were euthanized and liver and blood samples were collected to assess the lipid profile in these samples. RNA-seq was performed on the liver tissue. No difference was seen in weight gain by WT and MT1KO female mice on a CD while MT1KOs tend to gain more weight on HFD than WT mice (16.94g vs 17.26g). WT and MT1KOs consumed same amount of food on CD, but MT1 KOs on HFD ate significantly more food than WT (283.16g vs 323.06g, P&lt;0.05). Under HFD, FBG in MT1KOs was significantly increased with respect to WTs (107.71mg/dL vs 158.50 mg/dL, P&lt;0.05). While no difference in CD mice was seen with IIT and GTT, HFD negatively affected GTT and ITT in MT1 KOs. No difference was observed in the lipid profile (e.g., total cholesterol, triglycerides, phospholipids and free fatty acids) of WT and MT1KO mice under CD, while HFD significantly increased the cholesterol (149.5 vs 225.2 mg/dL, P&lt;0.05) and phospholipids (287.8 vs. 358.6 mg/dL P&lt;0.05) levels in MT1KOs. Finally, HFD leads to a significant increase in lipid deposition in the liver of MT1KOs when compared to other groups (34.46 vs 54.88 mg/g tissue, P&lt;0.05). RNA-seq revealed a higher number (644) of differentially regulated genes and increase in lipid and glucose-related pathways in MT1KO mice with HFD. Our data show that C3H-f+∕+ female mice are protected from diet-induced obesity and its detrimental effects on glucose and lipid metabolism. However, under HFD conditions, removal of MT1 receptor abolishes such a protection. Lack of MT1 also leaded to an increase in lipid deposition in the liver. In conclusion, our data indicate that that melatonin (MT1) signaling is crucial for protection of females from diet induced obesity and its consequences.
Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.
PMON29 A Comparative Analysis of Musashi-Dependent Control of Mouse and Human Pituitary mRNA Translation
Authors: Banik Jewel , Childs Gwen , Hardy Linda , MacNicol Angus , MacNicol Melanie , Tomlinson Sophia 
Published: November 2022

Abstract
Specialized cell lineages within the anterior pituitary produce specific hormones which, in turn, regulate diverse biological processes ranging from growth, metabolism, and reproduction to stress. Interestingly, these specialized cell lineages exhibit a high degree of cellular plasticity, readily altering their differentiation state to produce different hormones in response to organismal demand. Underlying molecular mechanisms controlling cellular plasticity in the pituitary are not fully defined but appear to involve post-transcriptional regulation exerted by the Musashi family of sequence-specific RNA binding proteins. Musashi is a bifunctional regulator of target mRNAs and can exert either repression or activation of translation in a context-dependent manner. Our recent work has implicated a role for Musashi-dependent repression of key pituitary mRNAs in the mouse, including a lineage-specific transcription factor (Pou1f1), the gonadotropin releasing hormone receptor (Gnrhr), and two anterior pituitary hormones (Prl and Tshb). In this study, we look to determine the potential relevance of Musashi-dependent mRNA translational control to the human pituitary. Reflecting our findings in the adult mouse, a re-analysis of published human fetal pituitary single cell RNA sequencing data revealed Musashi1 (MSI1) and Musashi2 (MSI2) expression in both stem/progenitor cell populations as well as in all hormone-producing cell lineages of the anterior pituitary. We further report that the human homologs of identified Musashi-target mRNAs in the mouse pituitary also possess Musashi binding elements (MBEs) in their 3' untranslated regions (UTRs). In the case of the human Pou1f1 3' UTR, we were able to verify Musashi-dependent mRNA translational repression in reporter assays as seen with the murine Pou1f1 3' UTR. Interestingly, a germline Pou1f1 mutation identified in human patients, disrupts a consensus MBE in the human Pou1f1 3' UTR and abolishes Musashi-dependent repression. We developed a bioinformatic pipeline to characterize pathogenic human mutations catalogued in the Geno2MP database for disruption or creation of consensus MBEs in pituitary-specific mRNA 3' UTRs. Our findings suggest an evolutionarily conserved role for Musashi in the post-transcriptional regulation of pituitary mRNAs in both mice and humans and identify several human mutations which may perturb Musashi regulation of human pituitary function.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON33 Non-Syndromic SRY Negative 46 XX Testicular Disorder of Sex Development (DSD): A Rare Cause of Infertility
Authors: Riaz Aiman , Barua Nabonita , Gordner Chelsea 
Published: November 2022

Abstract

Introduction
Male infertility can be categorized as endocrine and systemic disorders, primary testicular defects in spermatogenesis, sperm transport disorders and idiopathic male infertility. Chromosomal abnormalities are one of the primary testicular defects. The overall incidence of chromosome abnormalities in infertile men is estimated to be around 5.8%. XX male is a rare sex chromosomal disorder in infertile men. We present case of a young patient with infertility, azoospermia, hypergonadotropic hypogonadism and classical (46, XX) karyotype with negative FISH and SRY gene. Case report: 28-Year-old gentleman was referred to adult endocrinology clinic as part of work up for infertility. Initial work up included 2 semen analyses which were consistent with azoospermia. Examination revealed height 180 cm, weight 77 kg, a body mass index 24 kg/m2, normal phenotypic male without gynecomastia and had normal male pattern hair distribution. Genital examination showed normal male phallus without hypospadias, a hypoplastic scrotum, bilateral firm testes, with no varicocele or hydrocele. Labs were suggestive of compensated primary hypogonadism (FSH 47.9 mIU/ml, LH 20.4 mIU/ml, total testosterone 397.9 ng/dl by LC/MS, free testosterone 15.76 ng/dl by equilibrium dialysis, Inhibin B &lt; 10 pg/ml, and anti-Mullerian hormone 0.390 ng/ml. Given normal testosterone levels, he was not started on testosterone replacement. Karyotype analysis revealed 46 XX and FISH was negative for SRY gene. CT imaging of abdomen and pelvis did not reveal any Mullerian structures, prostrate and seminal vesicles reported as normal. Patient met with a Urologist and was informed that testicular sperm extraction will not be a possibility for him. Patient had a detailed consultation with a geneticist for genetic and family counseling. Chromosome microarray analysis was obtained and was normal. Invitae Disorders of sex development (DSD) panel obtained for genetic sequencing of 53 genes including SOX-9, DHH, WNT4, WT1, was found to be non-diagnostic.

Conclusion and Discussion
SRY negative 46 XX male is a DSD and a rare genetic cause of male factor infertility, with a discrepancy between genotype and phenotypic sex. In the case presented, genetic work up for potential etiologies has been unrevealing. Further studies are needed to identify the genetic causes of the SRY negative 46 XX male phenotype. Physicians involved in care of these patients should orient with clinical management and prognosis. For Classical 46 XX Males seeking fertility, the current options include invitro-fertilization with donor sperm or adoption only. Testosterone replacement should be considered to correct hypogonadism for physical and sexual well-being. Genetic consultation should be sought in all these cases.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF30 | PSAT136 Gitelman Syndrome and Primary Hyperparathyroidism, a Case Report
Authors: Alnahas Zeinab , Markov Marko , Horani Mohamad H 
Published: November 2022

Abstract

Introduction
Gitelman syndrome, also known as familial hypokalemia-hypomagnesemia, is a rare autosomal recessive disorder that impairs the sodium chloride cotransporter (NCC) and magnesium channels in the renal distal convoluted tubule, causing salt-losing tubulopathy. It is characterized by hypokalemia, hypomagnesemia, hypocalciuria, and secondary hyperaldosteronism. Although hypocalciuria is a distinctive characteristic of Gitelman syndrome, it seldom can cause any change in the total plasma calcium level. Thus, the occurrence of hypercalcemia would need further investigation.

Case presentation
We reported a case of a 36-year-old normotensive man with a past medical history significant for bipolar depression disorder and a history of chronic atrial fibrillation secondary to chronic hypokalemia, hypomagnesemia, and mild hypercalcemia. He was diagnosed with Gitelman syndrome. However, he was noncompliant with spironolactone, potassium, and magnesium supplementation. He suffered a motor vehicle accident, and on presentation to the emergency room, he was found with a serum potassium of 2.5 mEq/L (reference value 3.5-5.1), serum magnesium of 0.8 mEq/L (reference value 1.6-2.6), total serum calcium of 11.3 mEq/L (reference value 8.4-10.2), and serum phosphorus of 2.7 (reference value 2.5-4.5 mg/dl). Random urine potassium was 122.1 mEq/L, and intact parathyroid hormone was 144 pg/mL (reference value 14-65). His CT neck scan showed a 1.5 cm nodule inferior to the right thyroid lobe pole consistent with an inferior parathyroid adenoma. However, a parathyroid radionuclide scan using technetium-99m MIBI showed no radiopharmaceutical localization for parathyroid adenoma.

Conclusion
Hypercalcemia is extremely rare in Gitelman syndrome, offset by the action of concomitant hypomagnesemia. Our case shows the importance of investigating other causes of hypercalcemia, such as primary hyperparathyroidism in patients with Gitelman syndrome. To our knowledge, Gitelman syndrome and primary hyperparathyroidism are an extremely rare association that is present in our case.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:48 p.m. - 12:53 p.m.
LBMON137 Don't Be Fooled By Normotension Pheo Could Be The Potential
Authors: Idriss Setana , Shaikhoun Mazin , Ahmad Rehan 
Published: November 2022

Abstract

Introduction
Sustained or proximal hypertension is the most common sign of pheochromocytoma, but approximately 5-15% of pts present with normal blood pressure. We report a case of a patient incidentally found to have a catecholamines secreting adrenal tumor, but was normotensive on admission.

Case
30-year-old morbidly obese woman incidentally found to have a 4.8 cm left adrenal gland mass while being worked up for sepsis secondary to atypical pneumonia. Initially, the patient presented with dyspnea, chest pain, palpitation, nausea, and vomiting. Her past medical history is significant for preeclampsia, 200 lb wt loss in 1 year, NSTMI a few months prior to admission discharged on dual antiplatelet and metoprolol which she couldn't tolerate due to hypotensive episodes. On arrival to the ED the patient was afebrile, normotensive SBP 90-110 DBP 57-70 mmHg, HR 86 BPM, RR 20, saturating 98% on room air. Her laboratory workup was significant for leukocytosis, elevated D-dimer, hyperkalemia 5.9 mmol/L, mildly elevated liver enzymes, and mildly elevated troponin. MRI abdomen 4.8×4.4×5. 0 cm complex enhancing mass with eccentric necrosis and/or fibrosis arising from the left adrenal gland. Ur Normetanephrine 5867 mcg/24h, Ur Metanephrine 3017 Mcg/24hr, urine dopamine and norepinephrine were within normal limits. Serum Metanephrine 2.64 nmol/L normetanephrine 13.50 nmol/L, aldosterone, renin, and cortisol levels were normal.

Discussion
Sustained or proximal hypertension is the most common sign of pheochromocytoma, but approximately 5-15% of pts present with normal blood pressure. Other signs and symptoms that may occur include orthostatic hypotension, visual blurring, papilledema, weight loss, polyuria, polydipsia, constipation, increased ESR, insulin resistance, hyperglycemia, leukocytosis, psychiatric disorders, and, rarely, secondary erythrocytosis due to overproduction of erythropoietin. The beta-adrenergic blocker should never be started first because a blockade of vasodilatory peripheral beta-adrenergic receptors with unopposed alpha-adrenergic receptor stimulation can lead to a further elevation in blood pressure. Our patient was normotensive throughout the hospitalization, and before admission was on metoprolol for NSTMI, however, she was unable to tolerate it due to hypotensive episodes.

Conclusion
Most patients with pheochromocytoma present with hypertension, however, few cases could present with normotension or even hypotension.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBMON139 A Case of Adipsic Diabetes Insipidus In Patient With Third Ventricular Tumor And Right Frontal Craniotomy.
Authors: Thambuluru Sirisha Reddy , Caraccio Donald 
Published: November 2022

Abstract

Introduction
Adipsic diabetes insipidus (ADI) is a rare hypothalamic disorder consisting of central diabetes insipidus (CDI) and loss of thirst. In hyperosmolar state, signals from osmosensors integrate in the central thirst center resulting in stimulatory signals between subfornical-oragan, organum-vasculosm of lamina terminalis and median preoptic nucleus increasing thirst and release of vasopressin. Disruption in this mechanism leads to adipsia.

Case presentation
27 yr old male with history of prediabetes, 4.6cm third ventricular epidermoid cyst s/p endoscopic ventriculosmoy, hypogonadotropic hypogonadism, central hypothyroidism, and CDI underwent right frontal craniotomy for residual third ventricular cyst. Developed worsening DI, new onset hyperglycemia, and secondary adrenal insufficiency. Discharged with oral DDAVP 300mcg oral twice daily for CDI. 1 week later presented to ED with weakness. BP 132/112, HR 139, RR 38, SPO2 94%. Labs significant for corrected sodium of 172 (136-145mmol/L), glucose 699 (70-99mg/dl), calcium 11.8 (8.3-10.6 mg/dl). Discharged after 3 weeks with intranasal DDAVP 10mcg twice daily (BID). Again presented 1 week after for weakness. Vitals BP 105/64, HR 134, F 37.3 C, RR 31, SPO2 96%. Corrected sodium of 174 (136-145mmol/L) and glucose 708 (70-99mg/dl). Denied missing medication. Reported no increased water intake. Patient was diagnosed with adipsic DI based on subjective lack of thirst during period of significant hyperosmolar hypernatremia state. Overtime switched to 10mcg BID intranasal DDAVP and started on 4L fixed water intake. Had 5L urine output daily. Sodium levels ranged from 132-137. Discharged on intranasal DDAVP 10mcg AM/20mcg PM, 4L daily fixed water intake, and twice weekly sodium checks as outpatient. Goal sodium 135-140. DDAVP adjusted after sodium rose to 145. At recent clinic visit continued fixed 4L fluid intake with extra 500-1L intake for increased sweating/exercise, and sodium level 134. A1c 10% on insulin, and weight gain of 70lbs since surgery (8mon piror), BMI of 45. Started on GLP-1RA and sleep study. Learning points: Less than 100 cases of ADI reported worldwide and associated with increased morbidity/mortality1. This patient likely developed ADI due to disruption of central thirst center from epidermoid cyst and trans frontal craniotomy. We must be hypervigilant for ADI in patients with third ventricular tumors who undergo frontal craniotomy. Management is complex and requires patients are followed closely with weekly labs, either fixed water intake or fixed DDAVP dose and adjustment depending on labs. Important to screen these patients for obesity and sleep apnea given increased likelihood of hypothalamic dysfunction1. Reference: Cuesta, M., Hannon, M. J. & Thompson, C. J. Adipsic diabetes insipidus in adult patients. Pituitary 20, 372-380 (2017). https://doi.org/10.1007/s11102-016-0784-4
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP072 Squamous Cell Carcinoma Or Fungal Infection? An Unusual Presentation Of Anterior Hypopituitarism
Authors: Kapoor Ashutosh , Shaikh Sheeba , Lewis Alexander 
Published: November 2022

Abstract

Introduction
Intracranial squamous cell carcinomas are rare tumours with a poor prognosis. Lack of specific imaging characteristics mandates a high index of clinical suspicion and ultimately histopathological confirmation. Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from Sino nasal squamous cell carcinomas (SNSCC) in clinical practice. Our case draws attention to the fact that biopsy results are necessary in discriminating between the two entities, due to the diagnostic conundrum in context of Anterior Hypopituitarism. Case detailsWe report a case of 78-year-old lady who presented with a 3-month history of increasing headache, lethargy and confusion. There was no change in urinary habit. On examination she had right sided ptosis and restricted eye movements with a reported 4-week duration. Primary care physicians referred her for ophthalmic assessment. Past medical history was significant for absent vision in the affected eye due to Ischaemic optic neuropathy since 2018. A CT Angiogram was organised which revealed a large soft tissue mass that could not be differentiated from the optic chiasma. Differentials included chondrosarcoma, chordoma, invasive pituitary macroadenoma and skull base Plasmacytoma. Subsequent MRI imaging suggested appearances could be consistent with aggressive fungal sinusitis. Endocrine investigations showed partial anterior hypopituitarism. ManagementEmpiric treatment was started with Intravenous anti-fungals and steroids, alongside appropriate pituitary hormone replacement. Her case was discussed in the Skull Base Multi-disciplinary Team (MDT) meeting. She was then transferred to the regional tertiary centre for surgical intervention, where she underwent debridement of the Ethmoid sinus, Sphenoid Sinus and Anterior base of skull for presumed chronic invasive fungal sinusitis. Post-operative imaging displayed satisfactory debulking of the central skull base tumour. Histopathology from sphenoid sinus reported invasive squamous cell carcinoma. The post-operative imaging and histopathology results were discussed in the regional MDT and considering the advanced stage a decision was made for best supportive care. Within 2 months neurological symptoms progressed and further imaging demonstrated radiological tumour progression.

Discussion
Sinonasal Squamous cell carcinoma (SNSCC) is a rare tumour and thus pose difficulty in detection. Presentation usually occurs at an advanced stage since initial symptoms are nonspecific and the tumour remains indolent for many months to years. There is limited evidence in relation to detection and follow up of these cases. Clinical presentation and radiological appearance can be varied. This case highlights the need for histological confirmation of the diagnosis to guide appropriate treatment pathways and ensure compassionate, appropriate care.
Presentation: No date and time listed