Arginine Vasopressin Secretion Research Articles

The Relationship Between Copeptin Level and Enuresis in Children Aged 5 - 15 Years

Background: Enuresis is bedwetting that occurs during sleep in children over five years old. If left untreated, it can lead to social and psychological problems for children and their parents. The role of copeptin in patients with primary monosymptomatic nocturnal enuresis (PMNE) has been reported in several studies. Due to the favorable structural properties of copeptin and the reflection of arginine vasopressin (AVP) concentration, it can be used as an alternative marker for AVP secretion. Objectives: This study aims to compare the levels of copeptin in healthy and enuresis children aged 5 - 15 years. Methods: This case-control study was performed on 42 children with primary monosymptomatic enuresis and 42 children without enuresis who were referred to the clinic of Taleghani hospital in Gorgan in 2020. Copeptin levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. Results: Out of 84 patients, an equal proportion of girls (21 patients) and boys (21 patients) participated in both the case and control groups. The age of the children was 8.05 ± 2.46 years, and there was no statistically significant difference between the two groups (P = 0.16). The mean level of copeptin in the case and control groups were 6.7 ± 4.27 and 6.87 ± 8.52 pg/mL, respectively, significantly lower in the case group (P = 0.03). There was a statistically significant difference in the level of copeptin between the boys in the two groups (P = 0.03). Although the mean level of copeptin in the girls in the patient group was lower than that in the control group, this difference was not statistically significant (P = 0.35). Conclusions: In this study, the mean level of copeptin in PMNE was significantly lower than that in the control group, which suggests it may be considered as a probable biomarker for the prediction of response to treatment with desmopressin, but further study is required to confirm this hypothesis.

Hyponatremia and Cancer: From Bedside to Benchside

Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. This applies also to cancer patients. Multiple causes can lead to hyponatremia, but most frequently this electrolyte disorder is due to the syndrome of inappropriate antidiuresis. In cancer patients, this syndrome is mostly secondary to ectopic secretion of arginine vasopressin by tumoral cells. In addition, several chemotherapeutic drugs induce the release of arginine vasopressin by the hypothalamus. There is evidence that hyponatremia is associated to a more negative outcome in several pathologies, including cancer. Many studies have demonstrated that in different cancer types, both progression-free survival and overall survival are negatively affected by hyponatremia, whereas the correction of serum [Na+] has a positive effect on patient outcome. In vitro studies have shown that cells grown in low [Na+] have a greater proliferation rate and motility, due to a dysregulation in intracellular signalling pathways. Noteworthy, vasopressin receptors antagonists, which were approved more than a decade ago for the treatment of euvolemic and hypervolemic hyponatremia, have shown unexpected antiproliferative effects. Because of this property, vaptans were also approved for the treatment of polycystic kidney disease. In vitro evidence indicated that this family of drugs effectively counteracts proliferation and invasivity of cancer cells, thus possibly opening a new scenario among the pharmacological strategies to treat cancer.

Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency.

The symptoms of diabetes insipidus may be masked by the concurrence of adrenal insufficiency and emerge after the administration of hydrocortisone, occasionally at high doses. To elucidate the mechanism underlying polyuria induced by the administration of high-dose corticosteroids in the deficiency of arginine vasopressin (AVP), we first examined the secretion of AVP in three patients in whom polyuria was observed only after the administration of high-dose corticosteroids. Next, we examined the effects of dexamethasone or aldosterone on water balance in wild-type and familial neurohypophyseal diabetes insipidus (FNDI) model mice. A hypertonic saline test showed that AVP secretion was partially impaired in all patients. In one patient, there were no apparent changes in AVP secretion before and after the administration of high-dose corticosteroids. In FNDI mice, unlike dexamethasone, the administration of aldosterone increased urine volumes and decreased urine osmolality. Immunohistochemical analyses showed that, after the administration of aldosterone in FNDI mice, aquaporin-2 expression was decreased in the apical membrane and increased in the basolateral membrane in the collecting duct. These changes were not observed in wild-type mice. The present data suggest that treatment with mineralocorticoids induces polyuria by reducing aquaporin-2 expression in the apical membrane of the kidney in partial AVP deficiency.

Limited Role of Endogenous Vasopressin/Copeptin in Stimulation of ACTH-Cortisol Secretion during Glucagon Stimulation Test in Humans.

Copeptin is a stable part of a vasopressin precursor that closely mirrors arginine vasopressin (AVP) secretion. It is known that AVP/copeptin is also released in response to nonosmotic stimuli, such as stress evoked during anterior pituitary dynamic testing. In order to examine the role of AVP in challenging the hypothalamo-pituitary-adrenal axis, we assessed adrenocorticotropic hormone (ACTH), cortisol, copeptin and growth hormone (GH) during a glucagon stimulation test (GST) in 10 patients with satisfactory initial cortisol concentrations (mean ± SD: 20.34 ± 5.10 µg/dL) and failure to show any further cortisol increment on stimulation. For comparison, we measured copeptin in two subjects during an insulin tolerance test (ITT). During GST, there was an increase in copeptin (p = 0.02, average individual increase of 98%, range 10% to 321%). There was a robust increase in GH (p = 0.002, average increase 3300%), a decline in cortisol (p = 0.02, average decline 21.8%) and a fall in ACTH (p = 0.06). The relative increase in copeptin during ITT (176% and 52.2%) overlapped with increments observed during GST; however, here there was an increase in cortisol (20.45→24.26 µg/dL and 4.23→29.29 µg/dL, respectively). There was a moderate correlation between copeptin and GH concentrations (r = 0.4235, p = 0.0007). These results confirm that AVP is not crucial for ACTH-cortisol stimulation, though it might be an important factor in GH secretion.

ODP325 Inverse Relationship Between IL-6 and Sodium Levels in Patients With COVID-19 and Other Respiratory Tract Infections

Abstract Background Hyponatremia is highly prevalent in patients with COVID-19. One of the most common causes of hyponatremia in these patients is the syndrome of inadequate antidiuresis (SIAD). Interleukin 6 (IL-6) is a key mediator of inflammation in COVID-19. We hypothesized that hyponatremia in COVID-19 is due to IL-6 mediated non-osmotic arginine vasopressin (AVP) secretion, and that the inverse association between IL-6 and plasma sodium concentration is stronger in COVID-19 compared to other respiratory infections. METHODS This is a secondary analysis of a prospective, observational, cohort study including patients with COVID-19 suspicion admitted to the Emergency Department, University Hospital of Basel, Switzerland, between March and July 2020. We included patients with PCR-confirmed COVID-19 and patients without COVID-19 but similar symptoms, further subclassified in bacterial and other viral respiratory infections. The primary objective was to investigate the association between plasma sodium levels and IL-6 levels. Results 500 patients were included, of whom 184 (37%) with COVID-19, 92 (18%) with bacterial respiratory infections, 224 (45%) with other viral respiratory infections. Hyponatremia prevalence was higher in patients with COVID-19 compared to patients with other viral respiratory infections (28% vs 12%, p<0. 01), and similar to patients with bacterial respiratory infections (28% vs 30%, p<0.41). In all three groups, median [IQR] IL-6 levels were significantly higher in hyponatremic compared to normonatremic patients (COVID-19: 43.4 [28.4, 59.8] vs 9.2 [2.8, 32.7] pg/ml, p<0. 0001; bacterial: 122.1 [63. 0, 282. 0] vs 67.1 [24.9, 252. 0] pg/ml, p<0. 05; viral: 14.1 [6.9, 84.7] vs 4.3 [2.1, 14.4] pg/ml, p<0. 05). IL-6 levels were negatively correlated with plasma sodium levels in COVID-19, whereas the correlation in bacterial and other viral infections was weaker (COVID-19: ρ = − 0.52, p < 0. 001; bacterial: ρ = − 0.24, p = 0. 056, viral: ρ = − 0.24, p < 0. 001). Conclusion IL-6 levels were inversely correlated with plasma sodium levels, with a stronger correlation in patients with COVID-19 compared to patients with bacterial and other viral infections. IL-6 might stimulate AVP secretion and lead to higher rates of hyponatremia due to the syndrome of inadequate antidiuresis in these patients. Presentation: No date and time listed

Disorders of Salt and Water Balance After Pituitary Surgery.

Transsphenoidal surgery is the first-line treatment for many clinically significant pituitary tumors and sellar lesions. Although complication rates are low when performed at high-volume centers, disorders of salt and water balance are relatively common postoperatively. Both, or either, central diabetes insipidus (recently renamed arginine vasopressin deficiency - AVP-D), caused by a deficiency in production and/or secretion of arginine vasopressin, and hyponatremia, most commonly secondary to the syndrome of inappropriate antidiuresis, may occur. These conditions can extend hospital stay and increase the risk of readmission. This article discusses common presentations of salt and water balance disorders following pituitary surgery, the pathophysiology of these conditions, and their diagnosis and management.

Nephrogenic syndrome of inappropriate antidiuresis – a case report in pediatric age

Syndrome of inappropriate antidiuresis (SIAD) results in hyponatremia, low plasma osmolality, euvolemia and inappropriately concentrated urine with high sodium excretion. In most cases, there is an inappropriate secretion of arginine vasopressin (AVP); however, in a minority of cases, there is a gain-of-function mutation in the AVP receptor 2 -nephrogenic SIAD

Inverse relationship between IL-6 and sodium levels in patients with COVID-19 and other respiratory tract infections: data from the COVIVA study.

ObjectiveHyponatremia in COVID-19 is often due to the syndrome of inadequate antidiuresis (SIAD), possibly mediated by interleukin-6 (IL-6)-induced non-osmotic arginine vasopressin (AVP) secretion. We hypothesized an inverse association between IL-6 and plasma sodium concentration, stronger in COVID-19 compared to other respiratory infections.DesignSecondary analysis of a prospective cohort study including patients with COVID-19 suspicion admitted to the Emergency Department, University Hospital of Basel, Switzerland, between March and July 2020.MethodsWe included patients with PCR-confirmed COVID-19 and patients with similar symptoms, further subclassified into bacterial and other viral respiratory infections. The primary objective was to investigate the association between plasma sodium and IL-6 levels.ResultsA total of 500 patients were included, 184 (37%) with COVID-19, 92 (18%) with bacterial respiratory infections, and 224 (45%) with other viral respiratory infections. In all groups, median (IQR) IL-6 levels were significantly higher in hyponatremic compared to normonatremic patients (COVID-19: 43.4 (28.4, 59.8) vs 9.2 (2.8, 32.7) pg/mL, P < 0.001; bacterial: 122.1 (63.0, 282.0) vs 67.1 (24.9, 252.0) pg/mL, P < 0.05; viral: 14.1 (6.9, 84.7) vs 4.3 (2.1, 14.4) pg/mL, P < 0.05). IL-6 levels were negatively correlated with plasma sodium levels in COVID-19, whereas the correlation in bacterial and other viral infections was weaker (COVID-19: R = −0.48, P < 0.001; bacterial: R = −0.25, P = 0.05, viral: R = −0.27, P < 0.001).ConclusionsIL-6 levels were inversely correlated with plasma sodium levels, with a stronger correlation in COVID-19 compared to bacterial and other viral infections. IL-6 might stimulate AVP secretion and lead to higher rates of hyponatremia due to the SIAD in these patients.

Dex modulates the balance of water-electrolyte metabolism by depressing the expression of AVP in PVN.

Dexmedetomidine (Dex) is a highly selective α2 adrenergic agonist used in clinical anesthesia. Studies have shown that Dex can act on the collecting duct and reduce the body’s water reabsorption, thereby increasing water discharge. However, the specific mechanism of Dex on water homeostasis remains unclear. The hypothalamus is the regulatory center of water and salt balance and secretes related neurochemical hormones, such as arginine vasopressin (AVP), to regulate the discharge of water and salt. The paraventricular nucleus (PVN) and supraoptic nucleus (SON) in the hypothalamus are also considered to be the key targets of the thirst loop. They are responsible for the secretion of AVP. The suprachiasmatic nucleus (SCN) is also one of the brain regions where AVP neurons are densely distributed in the hypothalamus. This study used C57BL/6J mice for behavior, immunofluorescence, and blood analysis experiments. Our results showed that Dex could not only depress the expression of AVP in the PVN but also reduce serum AVP concentration. The animal water intake was decreased without impairing the difference in food consumption and the urine excretion was enhanced after the intraperitoneal injection of Dex, while AVP supplementation restored the water intake and inhibited the urine excretion of mice in the Dex group. In addition, the renin-angiotensin-aldosterone system is vital to maintaining serum sodium concentration and extracellular volume. We found that serum sodium, serum chloride, serum aldosterone (ALD) concentration, and plasma osmolality were decreased in the Dex group, which inhibited water reabsorption, and the plasma osmolarity of mice in the Dex group supplemented with AVP was significantly higher than that in Dex group. We also found that Dex significantly increased the concentration of blood urea nitrogen and decreased the concentration of creatinine within the normal range of clinical indicators, indicating that there was no substantive lesion in the renal parenchyma. These results showed that Dex could modulate the balance of water-electrolyte metabolism by depressing the expression of AVP in PVN without impairing renal function.

Diagnosis and Management of Central Diabetes Insipidus in Adults.

Central diabetes insipidus (CDI) is a clinical syndrome which results from loss or impaired function of vasopressinergic neurons in the hypothalamus/posterior pituitary, resulting in impaired synthesis and/or secretion of arginine vasopressin (AVP). AVP deficiency leads to the inability to concentrate urine and excessive renal water losses, resulting in a clinical syndrome of hypotonic polyuria with compensatory thirst. CDI is caused by diverse etiologies, although it typically develops due to neoplastic, traumatic, or autoimmune destruction of AVP-synthesizing/secreting neurons. This review focuses on the diagnosis and management of CDI, providing insights into the physiological disturbances underpinning the syndrome. Recent developments in diagnostic techniques, particularly the development of the copeptin assay, have improved accuracy and acceptability of the diagnostic approach to the hypotonic polyuria syndrome. We discuss the management of CDI with particular emphasis on management of fluid intake and pharmacological replacement of AVP. Specific clinical syndromes such as adipsic diabetes insipidus and diabetes insipidus in pregnancy as well as management of the perioperative patient with diabetes insipidus are also discussed.

Bile Duct Ligation Changes the Inhibitory Control of Vasopressin Neurons in Male Rats

Dilutional hyponatremia typically is caused by increased Arginine Vasopressin (AVP) secretion. This increases the risk of complications and mortality in patients with liver cirrhosis. Liver cirrhosis in male rats increases AVP release but the underlying mechanisms are still under investigation. In other models of chronic AVP release, changes in chloride homeostasis alters the inhibitory control of AVP neurons in the supraoptic nucleus (SON) causing GABA mediated excitation instead of inhibition. In the bile duct ligation (BDL) model of cirrhosis, changes in either intracellular chloride concentration or cell firing activity have not been directly tested. We hypothesize that liver cirrhosis increases intracellular chloride concentration leading to a decrease in GABA‐mediated inhibition of SON neurons from male rats.To test this hypothesis, we injected an adeno‐associated virus with a vasopressin promoter and a ratiometric chloride indicator, AAV2‐0VP1‐ClopHensorN into the SON of adult male Sprague‐Dawley rats. The rats either received BDL surgery, which was used to model liver cirrhosis, or a sham ligation surgery. All BDL rats had significantly higher liver weight to body weight ratio (n = 10‐20, p &lt; 0.05), lower plasma osmolality (n = 10‐20, p &lt; 0.001) and lower hematocrit (n = 10‐20, p &lt; 0.05) as compared to sham rats. All rats were anesthetized with isoflurane (2‐3%), their brains were collected, and slices containing the SON were prepared. Loose‐cell patch recordings were made at 31±1oC using standard artificial cerebrospinal fluid. Labeled AVP cells and unlabeled SON cells were tested with focal application of muscimol (100µM), a GABAA receptor agonist.Cells from BDL rats showed impaired GABAA‐mediated inhibition in response to muscimol, as compared to those from sham rats. All putative AVP SON neurons from sham rats (4/4) showed decreased activity following muscimol while half of the putative AVP SON neurons (7/14) from BDL rats were excited (p &lt; 0.001). Similar results were observed in experiments were the injections missed the SON. In these experiments, all SON neurons from sham rats were inhibited by muscimol (26/26) while thirty‐five percent of SON neurons from BDL rats (16/45) were excited by muscimol (p = 0.001). ClopHensorN based chloride imaging showed that muscimol application was associated with decreased intracellular chloride concentrations in putative AVP cells from BDL rats as compared to sham rats (n = 31‐32, p = 0.001). The results show that liver cirrhosis impairs the normal inhibitory response of SON neurons to GABAA receptor activation which could contribute to increased cell activity and dilutional hyponatremia in male rats.

Copeptin Levels Before and After Transsphenoidal Surgery for Cushing Disease: A Potential Early Marker of Remission.

Arginine-vasopressin and CRH act synergistically to stimulate secretion of ACTH. There is evidence that glucocorticoids act via negative feedback to suppress arginine-vasopressin secretion. Our hypothesis was that a postoperative increase in plasma copeptin may serve as a marker of remission of Cushing disease (CD). Plasma copeptin was obtained in patients with CD before and daily on postoperative days 1 through 8 after transsphenoidal surgery. Peak postoperative copeptin levels and Δcopeptin values were compared among those in remission vs no remission. Forty-four patients (64% female, aged 7-55 years) were included, and 19 developed neither diabetes insipidus (DI) or syndrome of inappropriate anti-diuresis (SIADH). Thirty-three had follow-up at least 3 months postoperatively. There was no difference in peak postoperative copeptin in remission (6.1 pmol/L [4.3-12.1]) vs no remission (7.3 pmol/L [5.4-8.4], P = 0.88). Excluding those who developed DI or SIADH, there was no difference in peak postoperative copeptin in remission (10.2 pmol/L [6.9-21.0]) vs no remission (5.4 pmol/L [4.6-7.3], P = 0.20). However, a higher peak postoperative copeptin level was found in those in remission (14.6 pmol/L [±10.9] vs 5.8 (±1.4), P = 0.03]) with parametric testing. There was no difference in the Δcopeptin by remission status. A difference in peak postoperative plasma copeptin as an early marker to predict remission of CD was not consistently present, although the data point to the need for a larger sample size to further evaluate this. However, the utility of this test may be limited to those who develop neither DI nor SIADH postoperatively.

Aetiological diagnosis of hyponatraemia in non-critical patients on total parenteral nutrition: A prospective multicentre study

BackgroundIn patients receiving total parenteral nutrition (TPN), the frequency of hyponatraemia is high. However, the causes of hyponatraemia in TPN have not been elucidated, although diagnosis is required for appropriate therapy. The aim of this study is to describe the aetiology of hyponatraemia in non-critical hospitalised patients receiving TPN. MethodsProspective multicentre study in 19 Spanish hospitals. Non-critically hyponatraemic patients receiving TPN and presenting hyponatraemia over a 9-month period were studied. Data collected included sex, age, previous comorbidities, and serum sodium levels (SNa) before and following TPN initiation. Parameters for study of hyponatraemia were also included: clinical volaemia, the presence of pain, nausea, gastrointestinal losses, diuretic use, oedema, renal function, plasma and urine osmolality, urinary electrolytes, cortisolaemia, and thyroid stimulating hormone. Results162 patients were included, 53.7% males, age 66.4 (SD13.8) years. Volume status was evaluated in 142 (88%): 21 (14.8%) were hypovolaemic, 96 (67.6%) euvolaemic and 25 (17.6%) hypervolaemic. In 111/142 patients the analytical assessment of hyponatraemia was completed. Hypovolaemic hyponatraemia was secondary to GI losses in 10/111 (9%), and to diuretics in 3/111 (2.7%). Euvolaemic hyponatraemia was due to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in 47/111 (42.4%), and to physiological stimuli of Arginine Vasopressin (AVP) secretion in 28/111 (25.2%). Hypervolaemic hyponatraemia was induced by heart failure in 19/111 (17.1%), cirrhosis of the liver in 4/111 (3.6%). ConclusionsSIADH was the most frequent cause of hyponatraemia in patients receiving TPN. The second most frequent cause was physiological stimuli of AVP secretion induced by pain/nausea.

A review of risk factors and prevention strategies for exercise associated hyponatremia.

Exercise-associated hyponatremia (EAH) is defined as a serum sodium concentration under 135mmol·L-1 during or within 24h of exercise. Increasing interest in endurance events has led to a higher number of athletes presenting with this potentially life-threatening condition. EAH is largely caused by the overconsumption of hypotonic fluids leading to weight gain during exercise. The primary risk factors include the inappropriate secretion of arginine vasopressin, longer exercise duration, smaller body mass, and to smaller extent ingestion of non-steroidal anti-inflammatory drugs. Accurate tracking of fluid intake and losses to prevent weight gain during exercise, sodium supplementation, and heat acclimatization may help attenuate declines in serum sodium concentration during exercise.

Transcriptional and Post-Transcriptional Regulation of Oxytocin and Vasopressin Gene Expression by CREB3L1 and CAPRIN2.

Water homoeostasis is achieved by secretion of the peptide hormones arginine vasopressin (AVP) and oxytocin (OXT) that are synthesized by separate populations of magnocellular neurones (MCNs) in the supraoptic and paraventricular (PVN) nuclei of the hypothalamus. To further understand the molecular mechanisms that facilitate biosynthesis of AVP and OXT by MCNs, we have explored the spatiotemporal dynamic, both mRNA and protein expression, of two genes identified by our group as being important components of the osmotic defence response: Caprin2 and Creb3l1. By RNA in situ hybridization and immunohistochemistry, we have characterized the expression of Caprin2 and Creb3l1 in MCNs in the basal state, in response to dehydration, and during rehydration in the rat. We found that Caprin2 and Creb3l1 are expressed in AVP and OXT MCNs and in response to dehydration expression increases in both MCN populations. Protein levels mirror the increase in transcript levels for both CREB3L1 and CAPRIN2. In view of increased CREB3L1 and CAPRIN2 expression in OXT neurones by dehydration, we explored OXT-specific functions for these genes. By luciferase assays, we demonstrate that CREB3L1 may be a transcription factor regulating Oxt gene expression. By RNA immunoprecipitation assays and Northern blot analysis of Oxt mRNA poly(A) tails, we have found that CAPRIN2 binds to Oxt mRNA and regulates its poly(A) tail length. Moreover, in response to dehydration, Caprin2 mRNA is subjected to nuclear retention, possibly to regulate Caprin2 mRNA availability in the cytoplasm. The exploration of the spatiotemporal dynamics of Creb3l1- and Caprin2-encoded mRNAs and proteins has provided novel insights beyond the AVP-ergic system, revealing novel OXT-ergic system roles of these genes in the osmotic defence response.

Central Diabetes Insipidus: A Case Series and Literature Review

Central diabetes insipidus (CDI) is a rare disorder of water homeostasis characterized by the excretion of a large volume of hypotonic urine resulting from deficient secretion of arginine vasopressin. It is the most common form of diabetes insipidus and manifests when more than 90% of the vasopresinergic magnocellular neurons have been destroyed. The correct diagnosis is always a challenge as it is not always possible to differentiate the different etiologies of CDI based on clinical, hormonal, and radiological examination alone. Histopathology may have to be resorted to at times to provide a definitive diagnosis. In this case series we describe five patients of CDI with varied aetioogies who presented to our tertiary centre. The case series describes and discusses the clinical presentation, evaluation and management of these patients who presented with diabetes insipidus. The aetiologies discussed are extremely rare and required histopathological examination for the final confirmation of diagnosis.

Betamethasone reverses AVP-induced dysfunction in trophoblast cells

Previously published data demonstrate that arginine vasopressin (AVP) secretion is elevated throughout gestation in pregnancies affected by preeclampsia. Additionally, chronic infusion of AVP in mice mimics human preeclampsia with pregnancy-specific hypertension, glomerular endotheliosis, proteinuria, and inflammation. In this AVP-infusion mouse model, betamethasone (BMTZ) has been shown to reverse the preeclampsia phenotype. Corticosteroids have previously been used to ameliorate human HELLP syndrome. Steroids have pleotropic therapeutic effects. The mechanism of BMTZ in reversing preeclampsia is unknown. The objective of this study is to determine if BMTZ improves AVP-induced placental dysfunction. Cell migration of HTR8/SVneo cells was analyzed via closure of a 500um gap over 48 hours (Ibidi). Cells were treated with saline, AVP + vasopressin receptor antagonists, and AVP + BMTZ. The area of migration was imaged and calculated (Olympus Cell Sens) and percent change from baseline area was calculated. MMP-9, a marker of inflammation, was measured in cultured media using a commercially available ELISA (Invitrogen). Statistical significance was determined by ANOVA (α=0.05). At 48 hours, AVP demonstrated lower cell migration in comparison to saline (23.8 vs. 32.3 percent change). This dysfunction was reversed with the addition BMTZ (53.8 vs. 32.3 percent change, p< 0.001). Administration of AVP + AVP antagonists (Conivaptan [29.4], Relcovaptan [32.5], Tolvaptan [35.4]) did not significantly affect migration (p >0.05). MMP-9 concentration was significantly lowered in the cell culture supernatant of cells treated with AVP+BMTZ vs. AVP alone (0.242 vs. 0.286 ng/mL, p=0.04). Treating HTR8/Svneo trophoblastic cells in vitro with AVP results in abnormal migration and cytokine expression. BMTZ reverses this AVP-induced dysfunction. In part, this effect may be due to a reversal of MMP-9 associated inflammation. Our results suggest that further investigation is warranted in the use of betamethasone as a novel therapeutic strategy for preeclampsia.

Diabetes insipidus

Diabetes insipidus (DI) is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of more than 3 liters a day [1,2]. Central DI results from inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland. Besides central DI further underlying etiologies of DI can be due to other primary forms (renal origin) or secondary forms of polyuria (resulting from primary polydipsia). All these forms belong to the Polyuria Polydipsia Syndrom (PPS). In most cases central and nephrogenic DI are acquired, but there are also congenital forms caused by genetic mutations of the AVP gene (central DI) [3] or by mutations in the gene for the AVP V2R or the AQP2 water channel (nephrogenic DI) [4]. Primary polydipsia (PP) as secondary form of polyuria includes an excessive intake of large amounts of fluid leading to polyuria in the presence of intact AVP secretion and appropriate antidiuretic renal response.Differentiation between the three mentioned entities is difficult [5], especially in patients with Primary polydipsia or partial, mild forms of DI [1,6], but different tests for differential diagnosis, most recently based on measurement of copeptin, and a thorough medical history mostly lead to the correct diagnosis. This is important since treatment strategies vary and application of the wrong treatment can be dangerous [7]. Treatment of central DI consists of fluid management and drug therapy with the synthetic AVP analogue Desmopressin (DDAVP), that is used as nasal or oral preparation in most cases. Main side effect can be dilutional hyponatremia [8].In this review we will focus on central diabetes insipidus and describe the prevalence, the clinical manifestations, the etiology as well as the differential diagnosis and management of central diabetes insipidus in the out- and inpatient setting.

Vasopressin but Not Oxytocin Responds to Birth Stress in Infants.

ContextBirth triggers a large fetal neuroendocrine response, which is more pronounced in infants born vaginally than in those born by elective cesarean section (ECS). The two related peptides arginine vasopressin (AVP) and oxytocin (OT) play an essential role in peripheral and central stress adaptation and have a shared receptor mediating their function. Elevated cord blood levels of AVP and its surrogate marker copeptin, the C-terminal part of AVP prohormone, have been found after vaginal delivery (VD) as compared to ECS, while release of OT in response to birth is controversial. Moreover, AVP, copeptin and OT have not yet been measured simultaneously at birth.ObjectiveTo test the hypothesis that AVP but not OT levels are increased in infants arterial umbilical cord blood in response to birth stress and to characterize AVP secretion in direct comparison with plasma copeptin.MethodsIn a prospective single-center cross-sectional study, we recruited healthy women with a singleton pregnancy and more than 36 completed weeks of gestation delivering via VD or ECS (cesarean without prior uterine contractions or rupture of membranes). Arterial umbilical cord blood samples were collected directly after birth, centrifuged immediately and plasma samples were frozen. Concentrations of AVP and OT were determined by radioimmunoassay and that of copeptin by ultrasensitive immunofluorescence assay.ResultsA total of 53 arterial umbilical cord blood samples were collected, n = 29 from VD and n = 24 from ECS. Ten venous blood samples from pregnant women without stress were collected as controls. AVP and copeptin concentrations were significantly higher in the VD group than in the ECS group (both p < 0.001), median (range) AVP 4.78 (2.38–8.66) vs. 2.38 (1.79–3.88) (pmol/L), copeptin 1692 (72.1–4094) vs. 5.78 (3.14–17.97), respectively, (pmol/L). In contrast, there was no difference in OT concentrations (pmol/L) between VD and ECS, 6.00 (2.71–7.69) vs. 6.14 (4.26–9.93), respectively. AVP and copeptin concentrations were closely related (Rs = 0.700, p < 0.001) while OT did not show any correlation to either AVP or copeptin. In linear regression models, vaginal delivery and biochemical stress indicators, base deficit and pH, were independent predictors for both AVP and copeptin. OT was not linked to base deficit or pH.ConclusionVaginal birth causes a profound secretion of AVP and copeptin in infants. Whereas AVP indicates acute stress events, copeptin provides information on cumulative stress events over a longer period. In contrast, fetal OT is unaffected by birth stress. Thus, AVP signaling but not OT mediates birth stress response in infants. This unique hormonal activation in early life may impact neurobehavioral development in whole life.

Asymptomatic meningitis diagnosed by positron emission tomography in a patient with syndrome of inappropriate antidiuretic hormone secretion: a case report

BackgroundSyndrome of inappropriate antidiuretic hormone secretion can be caused by arginine-vasopressin-producing tumors or enhanced arginine vasopressin secretion from the posterior pituitary gland due to central nervous system disorders and intrathoracic diseases.Case presentationA 53-year-old Asian man was hospitalized with complaints of tremor and hiccups. Laboratory examination revealed findings suggestive of hypotonic hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion. The patient did not complain of headache or photophobia, and showed no signs of meningeal irritation. Positron emission tomography–computed tomography revealed 18F-fluoro-deoxy-glucose accumulation along the cervical spinal cord, based on which the patient was diagnosed as having aseptic meningitis. The hyponatremia was treated successfully by fluid restriction, and optimum plasma sodium concentration was maintained by tolvaptan administration.ConclusionsThis case underscores the need to consider the possibility of mild meningitis as the cause of syndrome of inappropriate antidiuretic hormone secretion in patients without other identifiable cause.