Vasopressin Research Articles

Investigation of Fibrillar Aggregates Formed by Pathogenic Pre-Pro-Vasopressin Mutants that Cause ADNDI.

Aggregations of unfolded or misfolded proteins, both inside and outside cells, are implicated in numerous diseases, collectively known as amyloidosis. Particularly, Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare disease caused by mutations in the AVP-NPII gene, leading to the inability to secrete arginine vasopressin (AVP). These misfolded proteins accumulate within the endoplasmic reticulum (ER), causing cellular dysfunction. This study aimed to investigate the formation of amyloid-like aggregates within the cell resulting from misfolded mutant precursor proteins, which induce disulfide-linked oligomers due to the G45C, 207_209delGGC, G88V, C98X, C104F, E108D-1, E108D-2 and R122H mutations identified by our group in the AVP-NPII gene of ADNDI patients. De-glycosylation studies were performed to analyze the glycosylation patterns of mutant protein precursors. The involvement of these precursors in the ER-related degradation pathway was studied by conducting protease inhibition experiments. Disulfide-linked oligomer analysis determined the oligomerization status of the mutant precursors. Immunofluorescence and electron microscopy studies provided evidence of aggregate structures in the ER lumen. In vitro studies involving bacterial expression and fibril formation in E. coli. Our findings demonstrated that the N-glycan structure of mutant precursors remains intact within the ER. Protease inhibition experiments indicated the involvement of these precursors in the ER-related degradation pathway. Disulfide-linked oligomer analysis revealed homo-oligomer structures in mutations. Immunofluorescence and electron microscopy studies confirmed the presence of aggregate structures in the ER lumen. In vitro studies showed that mutant precursors could form fibril structures in E. coli. Our study may support the idea that ADNDI belongs to the group of neurodegenerative diseases due to the formation of fibrillar amyloid aggregates in the cell.

63 Utilization of vasopressin and norepinephrine in neonates with cardiorespiratory compromise: A multicenter retrospective cohort study in Canada

Abstract Background Data regarding neonatal clinical experience with Vasopressin (VA) and Norepinephrine (NE) are limited to small studies. The lack of large-scale studies with safety and efficacy data is preventing the widespread adoption of these agents. Objectives To describe epidemiological data on utilization of NE and VA in neonates including their indications, effectiveness and overall outcomes across 3 tertiary Neonatal Intensive Care Units (NICU) in Canada. Design/Methods This retrospective cohort study involved neonates who received NE or VA between January 1, 2015-December 31, 2020 at 3 tertiary NICUs. Data regarding demographic information, indications of use, dosing details, and clinical outcomes were described using mean, standard deviations (SD), frequencies and percentages. When appropriate, a comparative analysis was performed using Mann-Whitney U tests or the chi-square test as appropriate. Post-initiation changes in physiological variables and laboratory parameters over time were analyzed using repeated measure ANOVA. Results 133 neonates (VA:70, NE:63) were included in this study. Baseline demographic features, clinical characteristics at initiation, indication of use, dosing details and clinical response in neonates exposed to both agents are summarized in Table 1. VA was commonly used for oxygenation failure due to persistent pulmonary hypertension of the newborn (PPHN), while NE was commonly used for hypotension due to septic shock. NE was frequently used as a 1st line inotropic agent, whereas VA was used more as an additive agent [30 (47.6%) vs 12 (18.6%); p=<0.001]. During treatment, lower sodium levels were recorded in the VA group vs the NE group [126.5 (8.6) vs 132 (7); p=.035], but other safety parameters were similar. The time to reach predefined stability parameters were similar in both groups. Significant improvement in physiological parameters were seen over time with both agents (Figure 1). Mortality within 7 days of use was high in the cohort, but comparable between VA and NE groups [18 (25.7%) vs 22 (34.9%), p=0.206]. Other neonatal morbidities were comparable between groups (Table 1). Conclusion This multicenter study provides pragmatic insights into the current use of NE and VA in neonates. Our study reports the effective use of each agent in distinct patient subgroups. This cohort represented neonates with high illness severity; however, exposure to either agent did not independently increase the risk of mortality or adverse outcomes. Further prospective studies exploring its optimal use and cardiopulmonary effects would be interesting.

Arginine vasopressin induces analgesic effects and inhibits pyramidal cells in the anterior cingulate cortex in spared nerve injured mice.

Neuropathic pain (NP) is a severe disease caused by a primary disease or lesion affecting the somatosensory nervous system. It`s reported that NP is related to the increased activity of glutamatergic pyramidal cells and changed neural oscillations in the anterior cingulate cortex (ACC). Arginine vasopressin (AVP), a neurohypophyseal hormone, has been shown to cause pain-alleviating effects when applied to peripheral system. However, the extent to which, and the mechanisms by which, AVP induces analgesic effects in the central nervous system remain unclear. In the present study, we observed that intranasal delivery of AVP inhibited mechanical pain, thermal pain and spontaneous pain sensitivity in mice with spared nerve injury. Meanwhile, AVP application exclusively reduced the FOS expression in the pyramidal cells but not interneurons in the ACC. In vivo electrophysiological recording of the ACC further showed that AVP application not only inhibited the theta oscillation in local field potential analysis, but also reduced the firing rate of spikes of pyramidal cells in the ACC in neuropathic pain mice. In summary, AVP induce analgesic effects by inhibiting neural theta oscillations and the spiking of pyramidal cells of the ACC in mice with neuropathic pain, which should provide new potential noninvasive methods for clinical treatment of chronic pain.

Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement.

The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.

International expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus (arginine vasopressin resistance).

Congenital nephrogenic diabetes insipidus (NDI; also known as arginine vasopressin resistance) is a rare inherited disorder of water homeostasis, caused by insensitivity of the distal nephron to arginine vasopressin. Consequently, the kidney loses its ability to concentrate urine, which leads to polyuria, polydipsia and the risk of hypertonic dehydration. The diagnosis and management of NDI are very challenging and require an integrated, multidisciplinary approach. Here, we present 36 recommendations for diagnosis, treatment and follow-up in both children and adults, as well as emergency management, genetic counselling and family planning, for patients with NDI. These recommendations were formulated and graded by an international group of experts in NDI from paediatric and adult nephrology, urology and clinical genetics from the European Rare Kidney Disease Reference Network and the European Society of Paediatric Nephrology, as well as patient advocates, and were validated by a voting panel in a Delphi process. The goal of these recommendations is to provide guidance to health care professionals who care for patients with NDI and to patients and their families. In addition, we emphasize the need for further research on different aspects of this potentially life-threatening disorder to support the development of evidence-based guidelines in the future.

Impact of Hyponatremia and ADH Secretion in MIS-C and COVID-19: An Integrative Approach of Prognostic and Diagnostic Markers

The COVID-19 pandemic has introduced challenges in pediatric care, especially due to the emergence of Multisystem Inflammatory Syndrome in Children (MIS-C), a severe condition associated with SARS-CoV-2 infection. This study investigated the impact of hyponatremia and antidiuretic hormone (ADH) secretion corelated to clinical outcomes in these patients. We conducted a retrospective cohort study, including 118 pediatric patients, with a detailed sub-cohort analysis of 53 patients for ADH secretion markers. Hyponatremia, defined by age-specific sodium thresholds, was present in 47.22% of MIS-C cases and 28.04% of COVID-19 cases. Ordinal logistic regression analysis revealed that severe hyponatremia significantly increased the likelihood of more severe clinical outcomes (β = 3.514, p < 0.001). A significant correlation was found between hyponatremia and prolonged hospitalization. For ADH secretion, a predictive model using ridge regression was analysed, which demonstrated that serum sodium level, U/P ratio, and hospitalization duration are key predictors of SIADH. This model fit was assessed using the ROC curve with an AUC of 0.96, indicating reliable model performance. Our findings underscore the significant role of hyponatremia on the clinical severity and hospitalization outcome of COVID-19 and MIS-C in pediatric patients.

The biology of water homeostasis.

Water homeostasis is controlled by a brain-kidney axis that consists of central osmoreceptors, synthesis and secretion of arginine vasopressin (AVP) and AVP-responsive aquaporin-2 (AQP2) water channels in kidney collecting duct principal cells that facilitate water reabsorption. In addition to AVP, thirst represents a second line of defense to maintain water balance. Water balance disorders arise because of deficiency, resistance or inappropriate secretion of AVP or disturbances in thirst sensation (hypodipsia, polydipsia). People with water balance disorders are prone to develop hyponatremia or hypernatremia, which expose cells to osmotic stress and activate cell volume regulation mechanisms. This review covers several recent insights that have expanded our understanding of central osmoregulation, AQP2 regulation and cell volume regulation. This includes the role of with-no-lysine kinase 1 (WNK1) as a putative central osmolality sensor and, more generally, as an intracellular crowding sensor that coordinates the cell volume rescue response by activating sodium and potassium cotransporters. Furthermore, several new regulators of AQP2 have been identified, including for AVP-dependent AQP2 regulation (yes-associated protein, nuclear factor of activated T-cells, microRNAs) and AVP-independent AQP2 regulation (epidermal growth factor receptor, fluconazole, prostaglandin E2). It is also becoming increasingly clear that long-term cell volume adaptation to chronic hypotonicity through release of organic osmolytes comes at the expense of compromised organ function. This potentially explains the complications of chronic hyponatremia, including cognitive impairment, bone loss and vascular calcification. This review will illustrate why these new insights derived from basic science are also relevant for developing new approaches to treat water balance disorders.

Apelin levels in patients with polyuria-polydipsia syndrome upon copeptin stimulation tests.

Differentiating between arginine vasopressin deficiency (AVP-D) and primary polydipsia (PP) requires a copeptin-stimulation test. We aimed to characterize changes in apelin, an endogenous hormone antagonising AVP, upon copeptin-stimulation tests. Post-hoc secondary analysis of a multicentric cross-over diagnostic study (NCT03572166). Apelin levels were measured in patients included at the University Hospital Basel. The primary outcome was the absolute difference in apelin between baseline and peak of copeptin-stimulation tests with hypertonic saline and arginine infusion. Secondary objectives included the diagnostic ability of apelin. Thirty-eight patients were analysed, 23 (60%) had PP and 15 (40%) had AVP-D. No difference was seen between baseline median [IQR] apelin levels in PP and AVP-D (1079 [912, 1225] and 910 [756, 1039] pmol/l, respectively). Upon hypertonic saline, apelin decreased by -241 [-326, -124] pmol/l in PP and -47.2 [-198, 5.86] pmol/l in AVP-D (p=0.022). The area under the curve (AUC) to differentiate PP from AVP-D was 97.1% (95%CI: 90.5, 100) for copeptin and 49.3% (95%CI: 30.4, 68.1) for apelin (p<.001). Upon arginine, apelin decreased by -39.2 [-96.4, 39.8] pmol/l in PP and increased by 25.8 [2.8, 113.0] pmol/l in AVP-D (p=0.1). The AUC was 97.1% [95%CI: 79.6, 98.0] for copeptin and 60.5% [95%CI: 39.8, 80.0] for apelin (p=0.007). Our findings suggest that apelin decreases to a greater extent in PP compared to AVP-D upon copeptin-stimulation tests. However, copeptin remains the best marker to differentiate AVP-D from PP.

A Study of Hydroelectrolytic and Acid-Base Disturbances in MIS-C Patients: A Perspective on Antidiuretic Hormone Secretion.

COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) is a rare autoimmune disorder characterized by a range of polymorphic manifestations, similar to but distinct from other well-known inflammatory syndromes in children. We conducted a retrospective-descriptive study in which we summarized the clinical presentation of, biomarker variations in, and complications occurring in patients diagnosed with MIS-C, admitted to the Emergency Clinical Hospital for Children "Sf. Ioan", Galati, between July 2020 and June 2024. A total of 36 children met the MIS-C classification criteria according to the WHO-approved case definitions. A total of 41.7% (n = 15) were male and 58.3% (n = 21) were female. The median age of the study group was 4 years (IQR: 1.75-9.25 years). Surgical involvement was suspected in 16.7% (n = 6) of the patients, while 52.8% (n = 19) required intensive care. Clinically, fever was the most common symptom present in 89% (n = 32) of the cases. Gastrointestinal disorders were also common, with 50% (n = 18) presenting with inappetence, 42% (n = 15) with vomiting, and 39% (n = 14) with abdominal pain from admission, which worsened over time. Paraclinically, all patients exhibited signs of inflammation, and 86.1% (n = 31) had hydroelectrolytic and acid-base imbalances. The median hospital stay was 10 days (IQR: 7-12 days), with a stagnant clinical course in most cases. The inflammatory mechanisms in MIS-C, which can affect the secretion of antidiuretic hormone (ADH), were correlated with hydroelectrolytic disturbances and may lead to severe complications. For this reason, it is imperative to evaluate hydroelectrolytic disorders in the context of MIS-C and use diagnostic and prognostic biomarkers to develop effective therapeutic management strategies, ultimately improving the quality of life of affected children.

Methylene blue therapy in addition to standard treatment for acute-phase septic shock: a pilot randomized controlled trial.

Methylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase. To determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to the Control group. This was a 1:1 randomized clinical trial of two groups (MB and Control). Forty-two patients were included in the present study; 23 patients were allocated to the Control group, and 19 were randomized to the MB group. Both groups had access to standard treatment, consisting of fluid replacement, vasopressors, and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 h. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 min (T2), 2 h (T3), 24 h (T4), 48 h after the infusion started (T5) and 24 h after weaning (T6). MB therapy was started together with the indication of vasopressin (VAS) as a second vasopressor. The MB group showed an immediate reduction in NOR dosage, an earlier reduction in VAS dosage, and higher IL-10 levels compared to the Control group. Early administration of MB in combination with standard treatment for septic shock might be reduce vasopressors dose. Continuous infusion of MB for 48 h was considered safe and there was no adverse events. These results highlight the potential of MB as a safe adjuvant therapeutic option in the treatment of septic shock. https://clinicaltrials.gov/, identifier RBR-96584w4.

Severe Hyponatremia Caused by Sertraline-Induced Syndrome of Inappropriate Antidiuretic Hormone Secretion: A Complication With Critical Implications for Patient Safety

Severe Hyponatremia Caused by Sertraline-Induced Syndrome of Inappropriate Antidiuretic Hormone Secretion: A Complication With Critical Implications for Patient Safety

L'enuresi notturna: in quadramento e gestione

Enuresis is the involuntary discharge of urine during sleep. It is a fairly common problem in paediatric age: approximately 1 child out of 5 is affected at 5 years of age, with a potential significant impact on their quality of life and family. Pathogenesis is multifactorial, resulting in a combination of genetic factors, delayed maturation of the central nervous system, night-time anti-diuretic hormone deficiency and, in case, coexisting conditions such as sleep and behavioural disorders. Adequate diagnosis and management can speed up resolution, which usually occurs spontaneously, and identify those cases underlying an organic cause. Diagnosis is clinical. Instrumental investigation (such as ultrasound or urodynamic tests) is reserved to selected cases. Treatment mainly involves behavioural approach alongside, in those in which this approach fails, nocturnal alarm and/or pharmacological therapy. Assessment of associated comorbidities is crucial (ex. constipation, sleep and behavioural disorders).

Clinical characteristics and management of adipsic arginine vasopressin deficiency in children and adolescents with sellar germ cell tumors.

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known •Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. •There are few reports on aAVP-D, most of which focus on adult patients. •The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New •Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. •Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. •Early recognition and structured management of ADI lowered the risk of complications.

Arginine vasopressin deficiency (central diabetes insipidus) with partial empty sella: a case report

BackgroundArginine vasopressin deficiency (central diabetes insipidus) is defined as a reduction in the release of arginine vasopressin (AVP) resulting in a variable degree of polyuria. Partial empty sella refers to an enlarged sella turcica that is not completely filled by pituitary gland. It can be either primary or secondary and its manifestation ranges from asymptomatic cases to isolated posterior pituitary, isolated anterior pituitary or both anterior and posterior pituitary dysfunctions. Diabetes insipidus caused by a partially empty sella is rare.Case presentationThe patient, an 18-year-old Ethiopian woman who presented with long standing headache, increased urination, increased thirst, absence of menses and weight loss. Urine and serum osmolality was done and suggested diabetes insipidus. On further workup, brain magnetic resonant imaging was done and partially empty sella was diagnosed.ConclusionDiabetes insipidus secondary to partially empty sella is uncommon. In patients presenting with headache and anterior or posterior pituitary dysfunction, empty sella should be considered, whether partial or complete.

A smart lab on a wearable microneedle patch with convolutional neural network‐enhanced colorimetry for early warning of syndrome of inappropriate antidiuretic hormone secretion

AbstractFrequent nocturia‐induced nighttime visits aggravate falls in seniors, requiring synthetic antidiuretic drugs that risk the dangerous syndrome of inappropriate antidiuretic hormone secretion (SIADH), thus the detection of sodium ion and uric acid alterations during treatment is obligatory for drug‐safe management. Herein, we design a convolutional neural network (CNN)‐enhanced smart wearable microneedle array‐based colorimetric (WMNC) sensor to independently detect in vivo interstitial fluid (ISF) sodium ions and uric acid alterations. The WMNC sensor is composed of a vacuum tube‐driven microneedle array patch and a built‐in colorimetric sensing paper, enabling an efficient ISF extraction and rapid colorimetric assay. Furthermore, leveraging self‐designed CNNs, the WMNC sensor efficiently eliminates the influence of ambient light on colorimetric outcomes, facilitating a rapid and accurate colorimetric result classification. This study provides an ISF‐based rapid, intuitionistic, user‐friendly, wearable point‐of‐care technique for the elderly suffering from nocturia in monitoring their health status for early warnings of SIADH.

Desmopressin use in major cardiac surgery is associated with renal impairment: a retrospective single-center analysis

BackgroundDesmopressin acetate (1-deamino-8-d-arginine vasopressin—DDAVP) is a analogue of the antidiuretic hormone vasopressin. DDAVP is suggested to reduce bleeding after cardiac surgery using cardiopulmonary bypass. The aim of this study was to determine if DDAVP has any negative impact on renal function leading to acute kidney injury (AKI) and therefore increases the need for renal replacement therapy (RRT).MethodsWe performed a retrospective single institutional cohort analysis of 2,179 patients undergoing elective and urgent cardiac surgery with CPB from 2017 to 2021. Logistic regression analysis was used to investigate any association between DDAVP, the incidence of AKI KDIGO class 3 and the need for RRT, respectively. The model was adjusted for relevant covariates, including preexisting renal impairment, pharmacological hemodynamic support with vasopressors, complexity of the surgery and postoperative lactate. Secondary outcomes included, in hospital mortality and the need for allogenic blood transfusion.ResultsA total of 992 (45.5%) patients received DDAVP intraoperatively during surgery or shortly thereafter. The use of DDAVP was associated with a significant increase in in AKI KDIGO class 3 (OR 2.27; 95% CI 1.46–3.55; p < 0,001) and the need for RRT (OR 2.19; 95%CI 1.48–3.24; p < 0,001). Both findings persisted after covariate adjusting. No increased in-hospital mortality was associated with DDAVP.ConclusionIn cardiac surgery, the use of DDAVP was associated with an increased rate of server AKI and the requirement for RRT. Given the severity of the potential harm associated with DDAVP, an evidence-based reevaluation is needed to enable an accurate risk and benefit assessment.

8067 AVP Gene Mutation: A Rare Cause of Diabetes Insipidus

Abstract Disclosure: N. Navrange: None. M. Williams: None. P. Madhavan: None. Introduction: Arginine vasopressin deficiency (AVP-D), also known as neurohypophyseal or central diabetes insipidus (DI), is marked by a reduced secretion of arginine vasopressin (AVP), resulting in polyuria and polydipsia. AVP-D is a rare disorder, with a prevalence of 1 in 25,000. Typically, the disorder is acquired. However, in less than 5% of cases, it has a genetic etiology. The majority of mutations in the AVP gene are autosomal dominant. Normally, AVP encodes vasopressin, also known as antidiuretic hormone (ADH). It plays a key role in the reabsorption of water in the kidney, the regulation of blood pressure, and controlling the body’s osmotic balance. However, a mutation in this gene leads to a deficient release of ADH, leading to reduced reabsorption of water in the collecting duct and decreased ability to concentrate urine. This results in increased urine output and excessive thirst. The onset and severity of symptoms varies between individuals. Case Report: In this report, we discuss the case of a 40-year-old Caucasian female with familial neurohypophyseal diabetes insipidus. The patient presented to the clinic for follow-up care of DI and hyponatremia. She received her DI diagnosis before the age of 5 and has multiple family members with the condition including her maternal grandfather, mother, and 2 siblings. Additionally, she suspected one of her children was exhibiting excessive urination. Past medical history is also significant for seizure disorder, postpartum cardiomyopathy, Chiari malformation type I and remote history of substance abuse. Vitals were stable with blood pressure of 122/86 mmHg, heart rate of 93 bpm, body mass index of 31.8. Physical exam was unremarkable except for obesity. She is currently managed with DDAVP 0.05 mg twice daily. Previously, imaging was performed to rule out pituitary abnormalities. The patient was referred for genetic testing due to her family history and was found to have a previously described rare autosomal dominant mutation of the AVP protein. The single nucleotide polymorphism in exon 1 results in a missense mutation substituting an alanine nucleotide for threonine (c.55G&amp;gt;A). The patient was counseled to share these results with her children’s pediatrician, as they could benefit from testing for the mutation. Discussion: Our patient has a pathogenic variant in AVP, specifically a missense mutation from Alanine to Threonine at codon 19 of the AVP protein. This mutation is associated with autosomal dominant neurohypophyseal diabetes insipidus. This case provides an example of a rare cause of neurohypophyseal diabetes insipidus and emphasizes the necessity of obtaining detailed family history in patients who have DI and considering genetic testing for patients with suspicion for familial involvement. Presentation: 6/2/2024

8142 Endocrine Considerations Prior to Pituitary Tumor Resection

Abstract Disclosure: P. Einafshar: None. T. Delibasi: None. Endocrine Considerations in Pituitary Tumor Resection Introduction: Diabetes Insipidus (DI) is an endocrine condition involving a disturbance to the action of Anti-Diuretic Hormone (ADH) resulting in polyuria, and polydipsia with complications such as severe water and electrolyte disturbances. It can be classified into Central DI which affects the secretion of ADH or Nephrogenic DI which affects peripheral ADH receptors in Distal Convoluted Tubules (DCTs) in the renal system. Both subtypes however present similarly and are usually known to be transient. It is important to consider the most common etiologies contributing to both central and nephrogenic DI as severe complications may arise if not diagnosed and treated promptly. The most important step is to monitor and manage water and electrolytes and avoid excessive water loss which can lead to irreversible complications. This can be accomplished by introducing synthetic ADH called DDAVP or Desmopressin. Case Description: A 57-year-old female was admitted in preparation for a supra-orbital resection of a suprasellar mass. Two hours post-procedure, she was found to have an increase in urine output with her labs notable for a significant acute increase in serum sodium and a decrease in urine osmolality. Upon emergent Endocrinology evaluation, due to concerns of Acute Diabetes Insipidus in the setting of insult to the pituitary stalk, she was started on emergent treatment with IV DDAVP. Her course was complicated with persistent DI resulting in a case of permanent DI requiring out-patient daily treatments with DDAVP. Discussion: Injury to the pituitary stalk resulting in various endocrine abnormalities has been studied involving a trans-sphenoidal resection of pituitary tumors, but there is a paucity of cases reported when patients undergo a supra-orbital surgical approach. It is vital for Endocrinology and Neurosurgical services to be aware of this phenomenon, and a multi-disciplinary approach to patient management should be considered. Furthermore, close follow-up of pituitary hormones in the post-operative setting is imperative in order to avoid severe complications, such as brain damage or poor mental status. We hope to educate residents and fellows about this phenomenon that is rarely reported in the literature but can have profound effects on patient’s quality of life if not considered by the consulting Endocrinology team. References Christ-Crain, M., Winzeler, B., &amp; Refardt, J. (2021). Diagnosis and management of diabetes insipidus for the internist: an update. Journal of internal medicine, 290(1), 73-87. Mutter, C. M., Smith, T., Menze, O., Zakharia, M., &amp; Nguyen, H. (2021). Diabetes insipidus: pathogenesis, diagnosis, and clinical management. Cureus, 13(2). Presentation: 6/1/2024

12237 Monosynaptic Gabaergic Signaling From Suprachiasmatic Nucleus Neuromedin S Neurons To Preoptic Area Kisspeptin Neurons In Mice

Abstract Disclosure: W.I. Abdulmajeed: None. B.B. Jamieson: None. S.X. Thomas: None. Y. Rim: None. A.G. Novak: None. R.E. Campbell: None. R. Piet: None. In female rodents, projections from suprachiasmatic nucleus (SCN) neurons relay timing cues to the gonadotropin-releasing hormone (GnRH) neuronal network for the preovulatory surge. Kisspeptin (KISS1) neurons of the rostral periventricular area of the third ventricle (RP3V) are thought to integrate these cues with estradiol positive feedback to drive GnRH neuron activity, the gonadotropin surge and ovulation. We recently reported that SCN neuron projections release arginine vasopressin (AVP), thereby stimulating female RP3VKiss[1] neuron action potential firing in an estrous cycle stage-dependent manner. In the SCN, AVP is expressed in a subset of neuromedin S (NMS) neurons, a neuronal population essential for circadian rhythms. Moreover, a previous report indicates that exogenous NMS stimulates LH secretion in female rodents. SCNNMS neurons might, therefore, play a role in timing the preovulatory surge. However, whether SCNNMS neurons project to and regulate the activity of RP3VKISS[1] neurons is currently unknown. To address this question, we combined anterograde viral tract-tracing and channelrhodopsin-2 (ChR2)- assisted circuit mapping. Female mice expressing Cre recombinase in NMS cells (NMS-Cre) received stereotaxic injections in the SCN of adeno-associated viral vectors (AAVs) carrying the Cre-dependent sequence for mCherry. Fluorescence immunohistochemistry revealed that mCherry-expressing fibers come in close apposition with the great majority (&amp;gt;80%) of KISS1-immunoreactive neurons in the RP3V, suggesting a SCNNMS-to-RP3VKISS[1] neuron circuit. To interrogate this circuit, we next injected AAVs carrying Cre-dependent channelrhodopsin (ChR2) in the SCN of female NMS-Cre mice that also express the green fluorescent protein in KISS1 cells. Blue LED light (460-487 nm) activation of ChR2-expressing SCNNMS neuronal fibers in the RP3V evoked postsynaptic currents (PSCs) in most KISS1 neurons recorded in whole-cell voltage clamp (-60 mV) in brain slices. Evoked PSCs had short latencies and were blocked by bath application of 0.5 µM tetrodotoxin (TTX), indicating that they were generated by action potential-dependent release. Addition of 100 µM 4-Aminopyridine (4-AP, a potassium channel blocker) to TTX rescued these responses, indicating the existence of a monosynaptic SCNNMS-to-RP3VKISS[1] connection. In addition, evoked PSCs were suppressed by 5 µM gabazine, a GABAA receptor antagonist, but not by 20 µM NBQX and 50 µM D-AP5, AMPA- and NMDA-type glutamate receptor antagonists, respectively, revealing that SCNNMS projections release GABA onto RP3VKISS[1] neurons. Together, our findings are consistent with SCNNMS neurons extending monosynaptic GABAergic projections to RP3VKISS[1] neurons. Further studies are needed to determine the impact of these projections on RP3VKISS[1] neuron activity and the role they might play in the preovulatory surge. Presentation: 6/1/2024

8431 Triphasic response of pituitary stalk post anoxic injury in a mechanically ventilated patient

Abstract Disclosure: P. Henriquez Feliz: None. H. Neizer: None. E. Alshdifat: None. F. Abdulkarim: None. T. Mazhude: None. T. Zahra: None. Introduction: A phenomenon may manifest wherein the pituitary undergoes a triphasic response following an inciting event. Phases include diabetes insipidus (DI) followed by Syndrome of inappropriate Antidiuretic Hormone (ADH), and finally a recurrence of DI. Research has established that this is a common complication to neurosurgical interventions but there are limited reports following anoxic brain injury. This case demonstrates a potential pituitary stalk injury after an anoxic brain injury. Case: Unknown 30 year old male found by EMS with pulseless electrical activity cardiac arrest likely from polysubstance use. Returned of spontaneous circulation after 30 minutes in the emergency department. Total downtime unknown. Managed by Intensive Care Unit. Scans were negative. Initial blood work showed eunatremia with a specific gravity (sg) 1.068 and serum osmolarity (Sosm) 311. Eventually, developed hypernatremia, 163 mmol/L, and a urine osmolarity (Uosm) of 428 mosm, raising concern for central DI (CDI). Responded to hypotonic fluids not requiring desmopressin at that time. On day 10, developed severe hyponatremia 113 mmol/L with a Uosm of 774, suggesting ADH mediated response or excessive free water intake. Sodium normalized after managed with fluid restriction. On day 16, patient developed hypernatremia, 178 mmol/L, and Uosm of 869 mosm. Suggestive of CDI recurrence. Treated with desmopressin and hydrocortisone. Discussion: Changes in water-electrolyte balances may occur after anoxic brain injury. The mechanism is believed to arise from axonal shock due to disruptions in vascular supply leading to unregulated release of ADH from degenerating posterior pituitary, causing oliguria and hyponatremia, and subsequent permanent DI from loss of neurons. These stages may last 5-7 days on initial phase, and the second phase can extend anywhere from 2-14 days. In this case, phases one and two lasted four and three days, respectively. It is important to acknowledge that timelines may vary based on management initiation and recognition of transition between stages. CDI treatment involves hypotonic fluids with desmopressin. Our patient was initially managed with free water due to low suspicion for CDI. During shift towards suspected second phase, Uosm increased, urine output and sodium dropped significantly. However, it is uncertain whether this was due to axonal injury causing SIADH or a consequence of hypotonic fluids causing increased response of ADH. As predicted during triphasic response, patient became oliguric with a net negative fluid balance of &amp;gt;10L and Uosm of 869. Therefore, desmopressin was started with good response. Further follow up was unattainable as neurological status deteriorated preceding to brain death. Most cases reported showed hypoattenuation lesion of posterior pituitary on MRI; MRI would have been required to determine if there was injury to the pituitary in this case. Presentation: 6/2/2024