bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMON63 The Impact of Protein-Energy Malnutrition on Outcomes of Adult Hospitalizations for SIADH: A Nationwide Analysis
Authors: Ojemolon Pius , Olafimihan Ayobami , Awoyomi Moyosoluwa , Kwei-Nsoro Robert , Shaka Hafeez 
Published: November 2022

Abstract

Introduction
Protein-energy malnutrition (PEM) is a leading cause of morbidity and mortality, particularly in developing countries. Via multiple mechanisms, there is an association between PEM and hyponatremia, but not much is known about concomitant PEM and the syndrome of inappropriate anti-diuretic hormone secretion (SIADH) or the effect of PEM on the outcomes of patients admitted with SIADH.

Methods
We extracted data from the US Nationwide Inpatient Sample (NIS) for 2019. The NIS contains hospital discharge information estimating yearly US hospitalizations. We included hospitalizations with a principal discharge diagnostic code for SIADH using the ICD-10-CM code (E22.2). Hospitalizations of patients less than 18 years of age were excluded from the study. This cohort was divided based on the secondary diagnosis of PEM.
Outcomes analyzed included comparing inpatient mortality rates, mean length of hospital stay (LOS), mean hospitalization cost (THC), and rates of septic shock, acute myocardial infarction (AMI), acute respiratory failure (ARF), acute renal failure (AKI), acute pulmonary edema (PE) between the subgroups. Adjustments were made for age, sex, race, primary payer, median household income by zip code, Charlson Comorbidity Index (CCI), hospital location, bed-size, and teaching status using multivariate regression analysis. Statistical significance was set at a p-value &lt; 0.05.

Results
There were 39,110 hospitalizations involving patients with SIADH as the reason for the admission in 2019, and 13.2% of them had comorbid PEM. While both cohorts had a higher proportion of females, the subgroup with comorbid PEM had a lower proportion of females comparatively (57.8 vs 62.3%, p=0.006). There was no significant difference in mean age (72.7±13.6 vs 72.1±12.2 years, p=0.113), but the cohort with PEM had a higher proportion of CCI &gt;2 and more ethnic minorities.
In patients with SIADH, PEM was associated with higher adjusted odds ratio (aOR) for mortality (2.53 vs 0.9%, aOR: 2.1, p=0.004), increased LOS (6.6 vs 4.7 days, p&lt;0.001) increased THC (13,884 vs 10,223 US$, p &lt;0.001), and higher odds of comorbid septic shock (8.7 vs 2.8%, aOR: 2.69, p=0.014), CVA (14.6 vs 6.5%, aOR: 2.02, p=0.042), PE (8.7 vs 2.5%, aOR: 2.8, p=0.023) and ARF (13 vs 6.5%, aOR: 1.97, p&lt;0.001), with no significant difference in AKI or AMI odds.

Conclusions
Comorbid PEM was associated with increased odds of mortality, LOS, THC, septic shock, CVA, PE, and ARF in hospitalizations for SIADH. The mechanism of this association is unclear, but further studies are necessary to better understand this potentially important relationship.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON79 Supraphysiologic Vasopressin-Induced Receptor Desensitization: A Case Report
Authors: Rabiei Samaneh , Jaffa Matthew , Kantorovich Vitaly 
Published: November 2022

Abstract

Background
Arginine vasopressin (AVP) is a nonapeptide released from the neurohypophysis in response to increases in plasma osmolality, hypovolemia, hypotension, and angiotensin II. V2 receptors, expressed on the basolateral membrane of the renal collecting ducts coupled to the adenylyl cyclase-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway. PKA increases the synthesis and shuttling of aquaporin 2 water channel containing vesicles (AQMCV) from cytoplasmic vesicles to the luminal surface of the renal collecting ducts (and inhibits the endocytosis of the vesicles), where they are inserted into the apical cell membrane. As a result, AVP increases free water reabsorption from the filtrate and decreases serum osmolality. There are different protocols for CDI management in post neurosurgical patient, including IV or SQ injections as well as continuous vasopressin drip. Here we discussed a case where prolonged IV drip could probably have caused loss of response to IV DDAVP injections.

Case
Patient is a 46-year-old male admitted with AMS with imaging revealed ruptured anterior communicating artery aneurysm associated with subarachnoid and intra parenchymal hemorrhage. The patient underwent emergent aneurysm coiling and EVD placed. The patient was subsequently started on heparin infusion due to a large frontal lobe clot which was found on cerebral angiogram. The next day, the patient developed acute diabetes insipidus with hypernatremia and polyuria. Repeat head CT demonstrated increased cerebral edema around the frontal clot. The patient underwent right frontal craniotomy for clot evacuation. He patient was subsequently started on vasopressin infusion (ranging from 0.5-6 units/hour) by neurosurgery team for urinary output less than 200 mL/hour. ​Urinary output and sodium level improved and remained stable on infusion. When endocrinology attempted transition to DDAVP IV injections patient responded with severe polyuria to initial 0.5 mcg injection. Eventually patient required 1 mcg IV every 4 hours dosing to maintain normal urine output and required a slow wean off to the standard dose of 0.5 mcg every 8 hours over 14 days.

Discussion
we are presenting a case of CDI associated to SAH who was started on IV infusion of vasopressin, required slow weaning. phenomenon called for slow re-sensitization of the receptors with gradual decreasing of DDAVP dosing. Animal studies have shown that V1 and V2 receptors levels are sensitive to hormone-induced downregulation of hormone receptors. Hypervasopressinemia in rats whose blood vasopressin concentration was experimentally elevated by IV infusion to extraphysiologic levels caused significant desensitization of kidney vasopressin receptors. In another study, IM injection of DDAVP to rats led to a total loss of kidney V receptors. Thus, it is likely that administration of high dose DDAVP IV in this patient induced downregulation of kidney V2 receptors.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON88 A Rare Case of Composite Paraganglioma in the Bladder
Authors: Kreit Helen , Chary Priyanka Kesavan , Bright Tamis , Rehman Aziz U 
Published: November 2022

Abstract

Background
Paragangliomas are neuroendocrine tumors that arise from embryonic neural crest cells; they are essentially extra-adrenal pheochromocytomas most frequently found in the head and neck. Composite tumors are rare and consist of the presence of two histologically distinct tissues within a single tumor. Additionally rare is the presence of a composite paraganglioma in the retroperitoneum and urinary bladder, of which there are few reported cases.

Case Report
We present a case of a 57 year old female who was found to have an incidental pelvic mass noted to progressively increase in size over the years on subsequent imaging. The patient had a cystoscopy and retrograde pyelogram that were both unremarkable. MRI Pelvis showed a 1.8×1.8×1.9 cm rounded, well-circumscribed lesion at the left posterior lateral bladder extending exophytically from the serosa at the ureterovesicular junction. As she had associated hypertension, palpitations, and anxiety, the patient was evaluated for pheochromocytoma.Laboratory workup showed elevated plasma levels of free Metanephrines at 130 (&lt;57 pg/mL), free Normetanephrines at 247 (&lt;148 pg/mL), and a free Total level at 377 (&lt;205 pg/mL). 24-hour urine collection was consistent with mild elevation of Metanephrines at 330 (90-315 mcg/24 h), normal levels of Normetanephrines at 469 (122-676 mcg/24 h), and normal levels of Total urine Metanephrines of 799 (224-832 mcg/24 h). 24-hour urine free Catecholamines showed: Epinephrine of 6 (2-24 mcg/24 h), Norepinephrine of 77 (15-100 mcg/24 h), and a Total (Epi+NE) of 83 (26-121 mcg/24 h), with Dopamine of 220 (52-480 mcg/24 h).Due to mildly elevated metanephrine levels, the patient was started on the alpha-blocker doxazosin. She ultimately underwent a laparoscopic removal of the bladder mass, with pathology reports confirming presence of a composite paraganglioma with atypical features. Additionally, further immunohistochemistry was negative for the SDHB gene mutation in the tissue samples obtained.

Conclusion
Composite paragangliomas of the urinary bladder are very rare. Certain genetic pathologic variants carry an increased risk for malignancy and possible metastasis; therefore, these neuroendocrine tumors usually require targeted mutation testing. At this time, the pathogenesis of composite paragangliomas is still largely unknown, with little information available about treatment options and clinical outcomes.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF01 | PMON44 Absence of Kisspeptin in KNDy Neurons of Mice Causes Sexually Dimorphic Metabolic Dysfunction on a High-Fat Diet
Authors: Nandankar Nimisha , Negrón Ariel , Al-Samerria Sarmed , Levine Jon , Radovick Sally 
Published: November 2022

Abstract
Kisspeptin neurons in the arcuate nucleus (ARC) of the hypothalamus are considered as the gonadotropin-releasing hormone (GnRH) pulse generator to control the cascade of hormone secretions that constitute the reproductive axis. These neurons typically co-express Neurokinin B and Dynorphin and are thus dubbed KNDy neurons. In addition, KNDy neuron kisspeptin is hypothesized to be a major sensor and regulator of metabolic homeostasis while relaying energy status to the hypothalamic-pituitary-gonad (HPG) axis. However, the direct metabolic impact of KNDy neuron kisspeptin has not been well-characterized. To explore this role, we examined the metabolic profile of our previously established KNDy neuron-specific kisspeptin knock-out mouse model (Pdyn-Cre/Kissfl/fl, or KO). To do so, we performed glucose tolerance tests, EchoMRI body composition analysis, and measured body weight in wild type (WT) control or KO mice fed with either regular chow or a high-fat diet (HFD, 60% kcal fat, Research Diets, New Brunswick, NJ) for 12 weeks post-weaning. At 4 weeks on the HFD, KO females weighed significantly more than HFD WT females, which continued through the remaining 8 weeks. Additionally, we found significantly decreased glucose tolerance and increased fat mass in HFD KO females compared to HFD WT females. However, KO males exhibited no significant differences in body weight, body composition, or glucose tolerance between the genotypes on either diet. This data suggests that KNDy neuron kisspeptin is critical for metabolic homeostasis and preventing metabolic dysfunction when challenged with a high-fat diet. Our findings further suggest a sexual dimorphism whereby KNDy neuron kisspeptin performs this action predominantly in females.
Presentation: Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF01 | PMON45 Urocortin 3 Interaction with GABA and Glutamate in the Posterodorsal Subnucleus of The Medial Amygdala Mediates Suppression of GnRH Pulse Generator Frequency in Female Mice
Authors: Ivanova Deyana , Li Xiao-Feng , McIntyre Caitlin , Xu HongBei , O’Byrne Kevin 
Published: November 2022

Abstract
Stress exerts a profound impact on reproductive function and disrupts pulsatile luteinizing hormone (LH) secretion. The posterodorsal subnucleus of the medial amygdala (MePD) is an upstream modulator of the hypothalamus pituitary gonadal axis. Stress alters neuronal activity within the MePD, increasing the expression of Urocortin3 (Ucn3) while enhancing the inhibitory output from the MePD to key hypothalamic reproductive centres. Designer receptor exclusively activated by designer drugs (DREADDs) inhibition of MePD Ucn3 neurons prevents psychological stress-induced suppression of LH pulses in female mice. The neurochemical pathways in the MePD responsible for regulating the GnRH pulse generator in the presence of stress remain unknown. We investigate the neurotransmission involved in the neural circuitry responsible for the suppression of GnRH pulse generator activity by MePD Ucn3 neuronal activation. Ucn3-Cre-tdTomato female ovariectomised (OVX) mice were unilaterally injected with AAV-ChR2 and implanted with optofluid cannulae targeting the MePD. Firstly, we optically stimulated MePD Ucn3 neurons with blue light at 10 Hz, 10 mW and monitored the effect on LH pulses. Next, we combined optogenetic activation of MePD Ucn3 neurons with pharmacological antagonism of GABAA or GABAB receptors with bicuculline or CGP, respectively, and observed the effect on LH pulsatility. Finally, during optical activation of MePD Ucn3 neurons we administered a combination of NMDA and AMPA receptor antagonists, AP5 and CNQX respectively, and monitored the effect on pulsatile LH secretion. Optogenetic stimulation of MePD Ucn3 neurons suppressed pulsatile LH secretion compared to controls and administration of aCSF had no effect on LH pulse interval (MePD Ucn3 activation: 36.04 ± 2.49 vs. pre-treatment control period: 17.50 ± 0.67 vs control virus: 21.67 ± 1.67 min; mean ± SEM; p&lt;0.0001; n=12). Intra-MePD infusion of bicuculline (BIC) or CGP during optogenetic stimulation of MePD Ucn3 neurons completely blocked the suppressive effect of MePD Ucn3 neuronal activation on LH pulsatility (MePD Ucn3 activation and BIC: 20.50 ± 2.03 vs. pre-treatment control period: 17.58 ± 0.75 min; MePD Ucn3 activation and CGP: 16.30 ± 0.63 vs. pre-treatment control period: 17.50 ± 0.77 min; n=7-10). Intra-MePD infusion of AP5 + CNQX during optogenetic stimulation of MePD Ucn3 neurons similarly completely blocked the suppressive effect of MePD Ucn3 neuronal activation on LH pulsatility (MePD Ucn3 activation and AP5 + CNQX: 19.58 ± 1.42 min; n=6). Our findings show for the first time that optogenetic stimulation of MePD Ucn3 neurons inhibits GnRH pulse generator activity via GABA and glutamate signalling within the MePD.
Presentation: Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF01 | PMON46 Regulation of the Pituitary Cell Lineage Regulator Prop1 by the Stem Cell Determinant Musashi
Authors: Banik Jewel , Childs Gwen V , Hardy Linda L , Lim Juchan , MacNicol Angus M , MacNicol Melanie C , Tomlinson Sophia , Urbaniak Alicja 
Published: November 2022

Abstract
The pituitary gland controls responses to changing physiological requirements during growth, pregnancy, puberty, and stress. Synthesis and secretion of appropriate pituitary hormones in response to changing organismal demands is mediated through a remarkable capacity for cellular plasticity of the distinct hormone-producing cells. The mechanisms governing pituitary cellular plasticity are not fully understood. We hypothesize that plasticity in the adult tissue is mediated through similar mechanisms to those that occur during embryonic and postnatal pituitary development. The Prophet of Pit1(Prop1), a paired-like homeodomain transcription factor, is the earliest pituitary-specific transcription factor and is highly expressed in pituitary progenitor cells where it controls lineage commitment to the distinct hormone-producing cell types. Our recent work has identified post-transcriptional regulation of pituitary gene expression in the adult tissue via the stem cell determinant, mRNA binding protein, Musashi. The full-length mouse Prop1 (mProp1) mRNA 3' untranslated region (UTR) contains 24 consensus binding elements for Musashi (MBEs) and demonstrates Musashi1-dependent translational activation in vitro. Specifically, the terminal mProp1 3' UTR MBE directs 40% of Musashi1-mediated translation activation, and mutational disruption of this terminal MBE abolishes all Musashi1-dependent translational activation. Immunoprecipitation of Musashi-mRNA complexes from adult mouse pituitaries confirmed Musashi1-mProp1 mRNA association in adult tissue. The gene sequence data for the human Prop1 (hPROP1) mRNA 3' UTR is incomplete in the Ensembl and RefSeq databases. Using published RNA sequencing datasets, we identified an expressed full-length hPROP1 mRNA 3' UTR of 6996 nucleotides with 54 predicted consensus MBEs, suggesting that the human PROP1 mRNA, like the murine Prop1 mRNA, may be subject to Musashi-dependent translational control. Our findings are consistent with the hypothesis that the Musashi protein exerts evolutionarily conserved control of Prop1 mRNA translation to facilitate plasticity of anterior pituitary function.
Presentation: Saturday, June 11, 2022 1:31 p.m. - 1:36 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBMON186 Beta-agonist Profiling Reveals Novel Biased Signaling Phenotypes For The Beta 2-adrenergic Receptor With Implications In The Treatment Of Asthma
Authors: Pascali Francesco D , Ippolito Michael , Wolfe Emily , Komolov Konstantin E , Hopfinger Nathan , Lemenze Douglas , Kim Nicholas , Armen Roger S , An Steven S , Scott Charles P , Benovic Jeffrey L 
Published: November 2022

Abstract
Asthma involves chronic airway inflammation and airway smooth muscle (ASM) cell contraction. Treatment include agonists of the beta 2-AR, a GPCR that induces the Gs/cAMP pathway leading to ASM relaxation. These agonists can also promote severe side effects which have been correlated with beta-arrestins (barr) activation. Therefore, biased ligands selective for the Gs/cAMP pathway over the barr-induced side effects should be beneficial. To test this, we have used high-throughput screening to identify Gs-biased agonists. The initial lead candidates were further analyzed for their ability to modulate Gs and Gi interaction, cAMP production, and barr interaction. We identified three compounds which showed minimal barr recruitment as well as decreased barr-mediated outputs including receptor internalization and ERK activation. They also showed reduced GRK-mediated phosphorylation of the receptor as well as decreased agonist-promoted receptor desensitization in human ASM cells. These Gs-biased agonists may contribute to develop more effective drugs for asthma and may help to determine the structure determinants of receptor mediated biased signaling.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBSMON194 Diagnosing Adrenal Insufficiency In Children: A Survey Among Pediatric Endocrinologists In North America
Authors: Silva Carolina , Patel Trisha , Lam Carol 
Published: November 2022

Abstract

Accurately diagnosing adrenal insufficiency (AI) is of vital importance, but it can be challenging, particularly in children. While the ACTH stimulation test remains the gold standard test for diagnosing AI, its protocols and interpretation of results remain controversial. There are no international recommendations specific for the pediatric age group.

Objective
to understand current practices of North American pediatric endocrinologists, regarding the diagnosis of AI in children, with focus in interpreting results of ACTH stimulation tests.

Methods
an anonymous, electronic survey was sent to members of the Pediatric Endocrine Society in February of 2022. Email reminders were sent over the following month, and the survey was closed after 6 weeks. RedCap was used to administer the survey and store data.

Results
221 survey responses were included. 52% of participants had more than 10 years of clinical experience, and 78% practiced in academic centers. All respondents ordered ACTH stimulation tests for the diagnosis of AI; 82% also used morning cortisol levels, 77% used cortisol levels during stress, and 14% used random cortisol. For the diagnosis of primary AI, 85% chose high-dose ACTH stimulation tests (HDST). For secondary AI, 62% ordered low-dose ACTH stimulation tests (LDST), 22% HDST, and the remainder used both. The most frequently used time points for the HDST were 0 and 60 minutes, and for the LDST, 0, 30 and 60 minutes. For interpretation of ACTH stimulation test results, 95% considered peak cortisol levels, 70% also took into context the clinical picture, and 48% considered the relative increase in cortisol levels from baseline. 17% of respondents used different cutoff values for LDST vs. HDST; 18% used specific cutoffs for newborns. Median (IQR) cortisol levels after ACTH stimulation tests for diagnosing AI was 18 (15.5-18) ug/L; 54% of participants used 18 ug/dL, 40% considered levels between 10 and 18 ug/L, and 7% used cutoffs between 18 and 20 ug/L. Finally, 43% of providers did not know what type of cortisol assay was used in their laboratory.

Discussion
In North America, pediatric endocrinology providers use ACTH stimulation protocols variably, including decisions about HDST vs. LDST, time points for cortisol measurement, and interpretation of results. Notably, there was a wide distribution of responses concerning cortisol cutoffs. Also, a significant proportion of providers who ordered and interpreted results of ACTH stimulation tests did not know which biochemical assay was employed. These exploratory results highlight the need for pediatric-specific recommendations on ACTH stimulation protocols, based on the best available evidence.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP374 Abdominal Distention as a Unique Sign of Congenital Hypothyroidism
Authors: Antezana Vania Lizzeth Escobar , Dorado Juan Pablo Hayes , Justiniano Walter Montero , Colque Doris Maribel Totola , Parada Valeria Urizar , Arias Paola Andrea Colque 
Published: November 2022

Abstract

Background
Most neonates with congenital hypothyroidism have a normal appearance at birth. Infrequent clinical presentations have been reported, including abdominal distention as the only sign, which remit with the initiation of levothyroxine therapy.

Clinical Case
Female newborn, full-term, appropriate weight for gestational age, six days old, who presented abdominal distension, without vomiting and with normal meconium elimination. No visceromegaly or abdominal masses were palpated. With the diagnosis of sepsis, treatment was started with ampicillin and amikacin, decompressive nasogastric tube and intravenous fluids. Abdominal X-ray showed intestinal distension. The requested cultures were negative. On the seventh day of life a TSH level of 89 mlU/L was reported; the free T4 value was analyzed and was found to be low. With the diagnosis of congenital hypothyroidism, levothyroxine therapy was indicated, and the abdominal distension remitted one week after initiation of therapy.

Conclusion
Most cases of congenital hypothyroidism are asymptomatic; abdominal distension, as the only sign of congenital hypothyroidism, is caused by the lower intestinal motility frequently observed in congenital hypothyroidism.
Presentation: No date and time listed