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Rinsho Shinkeigaku = Clinical Neurology Jun 2024A 78-year-old man complained of subacute general fatigue and anorexia, following diplopia and gait disturbance. He demonstrated wide-based and small-stepped gait without...
A 78-year-old man complained of subacute general fatigue and anorexia, following diplopia and gait disturbance. He demonstrated wide-based and small-stepped gait without objectively abnormal ocular movements. Brain MRI showed enlargement of the pituitary stalk and gland with uniform contrast enhancement. PET-CT showed FDG uptake in the pituitary gland, mediastinal lymph nodes, and left hilar lymph nodes. Blood investigations revealed panhypopituitarism and high serum IgG4 levels up to 265 mg/dl. Histopathological examination revealed no IgG4-positive cell infiltration in the biopsied mediastinal lymph nodes. However, we suspected IgG4-associated hypophysitis based on the clinical symptoms and MRI findings, which were markedly resolved with steroid. Central masked diabetes insipidus was manifested, but was improved with oral desmopressin. We should pay close attention to the fact that IgG4-related hypophysitis may present with various symptoms regarded as indefinite complaints related to aging or underlying diseases, especially in elderly patients with multimorbidity.
Topics: Humans; Male; Aged; Hypopituitarism; Diabetes Insipidus, Neurogenic; Immunoglobulin G; Deamino Arginine Vasopressin; Magnetic Resonance Imaging; Autoimmune Hypophysitis; Positron Emission Tomography Computed Tomography; Hypophysitis; Biomarkers; Immunoglobulin G4-Related Disease; Treatment Outcome
PubMed: 38797688
DOI: 10.5692/clinicalneurol.cn-001934 -
Ethiopian Journal of Health Sciences Jul 2023Enuresis, defined as involuntary nocturnal urination without any underlying organic disorder in a child expected to control urination, poses a common problem. This study... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Enuresis, defined as involuntary nocturnal urination without any underlying organic disorder in a child expected to control urination, poses a common problem. This study evaluated the effectiveness of Tolterodine and Oxybutynin in children presenting with primary desmopressin-resistant enuresis.
MATERIALS AND METHODS
A randomized clinical trial was undertaken involving 68 participants aged between 5 and 16 years, all suffering from primary enuresis. These patients were randomly assigned to one of two treatment groups for a three-month period: Group 1, treated with Oxybutynin and Desmopressin, and Group 2, treated with Tolterodine and Desmopressin. Data on demographics, clinical and laboratory findings, and subjective responses to treatment were gathered. The response was measured based on the frequency of wetting incidents per night and week and compared with pre-treatment data.
RESULTS
Patients were divided into two groups (30 patients in Group 1 and 38 patients in Group 2). The mean age of the patients was 88.97±27.09 months. In the first treatment group, 6 out of 30 patients (20%) experienced a complete treatment response, as did 5 out of 38 patients (13.2%) in the second treatment group. This difference between the groups was not statistically significant. Seven patients (23%) in the Oxybutynin group and 13 patients (34%) in the Tolterodine group reported a lack of response to treatment, a difference that also lacked statistical significance.
CONCLUSION
For patients resistant to Desmopressin, the addition of anticholinergic drugs elicited a significant response in over half of the patients. However, no benefit was observed in using either Oxybutynin or Tolterodine in the treatment of Desmopressin-resistant enuresis.
Topics: Humans; Tolterodine Tartrate; Child; Mandelic Acids; Male; Female; Deamino Arginine Vasopressin; Adolescent; Treatment Outcome; Child, Preschool; Nocturnal Enuresis; Muscarinic Antagonists; Antidiuretic Agents; Urological Agents; Enuresis; Drug Resistance
PubMed: 38784212
DOI: 10.4314/ejhs.v33i4.7 -
Brain and Behavior May 2024One of the most serious complications associated with antiplatelet agents is antiplatelet-associated intracranial hemorrhage (AA-ICH). Desmopressin is a synthetic... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of desmopressin (DDAVP) in preventing hematoma expansion in intracranial hemorrhage associated with antiplatelet drugs use: A systematic review and metaanalysis.
INTRODUCTION
One of the most serious complications associated with antiplatelet agents is antiplatelet-associated intracranial hemorrhage (AA-ICH). Desmopressin is a synthetic antidiuretic hormone (ADH) analog. It has been linked to improving patient outcomes in antiplatelet-induced intracranial hemorrhage. The secondary outcomes included the incidence of thrombotic complications and neurological outcomes.
METHODS
A systematic search was conducted on three databases (PubMed, Cochrane, and ClinicalTrials.gov) to find eligible literature that compares desmopressin (DDAVP) versus controls in patients with AA-ICH. The Mantel-Haenszel statistic was used to determine an overall effect estimate for each outcome by calculating the risk ratios and 95% confidence intervals (CI). Heterogeneity was measured using the I test. The risk of bias in studies was calculated using the New Castle Ottowa Scale.
RESULTS
Five studies were included in the analysis with a total of 598 patients. DDAVP was associated with a nonsignificant decrease in the risk of hematoma expansion (RR = .8, 95% CI,.51-1.24; p = .31, I = 44%). It was also associated with a non-significant decrease in the risk of thrombotic events (RR,.83; 95% CI,.25-2.76; p = .76, I = 30%). However, patients in the DDAVP group demonstrated a significant increase in the risk of poor neurological outcomes (RR, 1.31; 95% CI, 1.07-1.61; p = .01, I = 0%). The risk of bias assessment showed a moderate to low level of risk.
CONCLUSION
DDAVP was associated with a nonsignificant decrease in hematoma expansion and thrombotic events. However, it was also associated with a significantly poor neurological outcome in the patients. Thus, until more robust clinical trials are conducted, the use of DDAVP should be considered on a case-to-case basis.
Topics: Deamino Arginine Vasopressin; Humans; Platelet Aggregation Inhibitors; Intracranial Hemorrhages; Hematoma; Hemostatics
PubMed: 38778788
DOI: 10.1002/brb3.3540 -
Thrombosis and Haemostasis Jun 2024Desmopressin (DDAVP) is used in patients with moderate/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However,...
BACKGROUND
Desmopressin (DDAVP) is used in patients with moderate/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However, its effectiveness varies between individuals. The GIDEMHA study aims to investigate the influence of gene variants.
MATERIAL AND METHODS
The study collected the trajectory of FVIII levels from therapeutic intravenous DDAVP tests in four French hemophilia treatment centers. A pharmacological analysis was performed associated with efficacy scores according to variants: absolute and relative responses, as well as new scores: absolute duration (based on duration with FVIII ≥ 0.50 IU.mL) and relative duration (based on half-life).
RESULTS
From enrolled 439 PWMHs, 327 had a hot-spot variant (with ≥5 PWMHs). For these, the median (min-max) basal and peak FVIII were 0.20 (0.02-0.040) and 0.74 (0.14-2.18) IU.mL respectively, with FVIII recovery being 3.80 IU.ml (1.15-14.75). The median FVIII half-life was 3.9 hours (0.7-15.9 hours). FVIII was normalized (≥0.50 IU.mL) in 224/327 PWMHs (69%) and the median time with normalized FVIII was 3.9 hours (0.0-54.1 hours). Following the response profiles to DDAVP defined by the four efficacy scores, four groups of variants were isolated, and then compared using survival curves with normalized FVIII ( < 0.0001): "long-lastingly effective" [p.(Glu739Lys), p.(Ser2030Asn), p.(Arg2178His), p.(Gln2208Glu), and T-stretch deletion in intron 13]; "moderately effective" [p.(Ser112Phe), p.(Ala219Thr), p.(Thr2105Ile), p.Phe2146Ser), and p.(Asp2150Asn)]; "moderately ineffective" [p.Ala81Asp), p.(Gln324Pro), p.(Tyr492His), p.(Arg612Cys), p.(Met701Val), p.(Val2035Asn), and p.(Arg2178Cys)]; and "frequently ineffective" [c.-219C > T, p.(Cys2040Tyr), p.(Tyr2169His), p.(Pro2319Leu), and p.(Arg2326Gln)].
CONCLUSION
In view of our data, we propose indications for DDAVP use in PWMH based on variants for minor and major invasive procedures.
PubMed: 38759975
DOI: 10.1055/a-2329-3375 -
PloS One 2024Loss-of-function mutations in the type 2 vasopressin receptor (V2R) are a major cause of congenital nephrogenic diabetes insipidus (cNDI). In the context of partial...
Loss-of-function mutations in the type 2 vasopressin receptor (V2R) are a major cause of congenital nephrogenic diabetes insipidus (cNDI). In the context of partial cNDI, the response to desmopressin (dDAVP) is partially, but not entirely, diminished. For those with the partial cNDI, restoration of V2R function would offer a prospective therapeutic approach. In this study, we revealed that OPC-51803 (OPC5) and its structurally related V2R agonists could functionally restore V2R mutants causing partial cNDI by inducing prolonged signal activation. The OPC5-related agonists exhibited functional selectivity by inducing signaling through the Gs-cAMP pathway while not recruiting β-arrestin1/2. We found that six cNDI-related V2R partial mutants (V882.53M, Y1283.41S, L1614.47P, T2736.37M, S3298.47R and S3338.51del) displayed varying degrees of plasma membrane expression levels and exhibited moderately impaired signaling function. Several OPC5-related agonists induced higher cAMP responses than AVP at V2R mutants after prolonged agonist stimulation, suggesting their potential effectiveness in compensating impaired V2R-mediated function. Furthermore, docking analysis revealed that the differential interaction of agonists with L3127.40 caused altered coordination of TM7, potentially contributing to the functional selectivity of signaling. These findings suggest that nonpeptide V2R agonists could hold promise as potential drug candidates for addressing partial cNDI.
Topics: Receptors, Vasopressin; Humans; HEK293 Cells; Diabetes Insipidus, Nephrogenic; Mutation; Signal Transduction; Cyclic AMP; Deamino Arginine Vasopressin; beta-Arrestins; Animals
PubMed: 38748623
DOI: 10.1371/journal.pone.0303507 -
Wiener Klinische Wochenschrift Jul 2024This guideline is intended to provide practical guidance for the diagnosis and treatment of haemophilia in Austria. Few randomized controlled interventional trials are...
This guideline is intended to provide practical guidance for the diagnosis and treatment of haemophilia in Austria. Few randomized controlled interventional trials are available addressing the treatment of haemophilia, therefore recommendations are usually based on low level of evidence and represent expert consensus.This guideline is based on the WFH guideline, published in 2020, and adapted according to the national circumstances and experience.It includes recommendations and suggestions for diagnosis and follow-up visits and pharmacological therapies for treatment and prophylaxis. Further topics comprise special aspects in children and adults with severe haemophilia, outcome measurement, and management of trauma, special bleedings and interventions, including dental procedures, inhibitors, management of haemophilia carriers, and psychosocial aspects.
Topics: Hemophilia A; Humans; Austria; Child; Adult; Practice Guidelines as Topic
PubMed: 38743098
DOI: 10.1007/s00508-024-02370-0 -
American Journal of Physiology. Renal... Jun 2024We have previously shown that kidney collecting ducts make vasopressin. However, the physiological role of collecting duct-derived vasopressin is uncertain. We...
We have previously shown that kidney collecting ducts make vasopressin. However, the physiological role of collecting duct-derived vasopressin is uncertain. We hypothesized that collecting duct-derived vasopressin is required for the appropriate concentration of urine. We developed a vasopressin conditional knockout (KO) mouse model wherein Cre recombinase expression induces deletion of arginine vasopressin () exon 1 in the distal nephron. We then used age-matched 8- to 12-wk-old fl/fl;-Cre(-) [wild type (WT)] and fl/fl;-Cre(+) mice for all experiments. We collected urine, serum, and kidney lysates at baseline. We then challenged both WT and knockout (KO) mice with 24-h water restriction, water loading, and administration of the vasopressin type 2 receptor agonist desmopressin (1 µg/kg ip) followed by the vasopressin type 2 receptor antagonist OPC-31260 (10 mg/kg ip). We performed immunofluorescence and immunoblot analysis at baseline and confirmed vasopressin KO in the collecting duct. We found that urinary osmolality (UOsm), plasma Na, K, Cl, blood urea nitrogen, and copeptin were similar in WT vs. KO mice at baseline. Immunoblots of the vasopressin-regulated proteins Na-K-2Cl cotransporter, NaCl cotransporter, and water channel aquaporin-2 showed no difference in expression or phosphorylation at baseline. Following 24-h water restriction, WT and KO mice had no differences in UOsm, plasma Na, K, Cl, blood urea nitrogen, or copeptin. In addition, there were no differences in the rate of urinary concentration or dilution as in WT and KO mice UOsm was nearly identical after desmopressin and OPC-31260 administration. We conclude that collecting duct-derived vasopressin is not essential to appropriately concentrate or dilute urine. Hypothalamic vasopressin is required for appropriate urinary concentration. However, whether collecting duct-derived vasopressin is involved remains unknown. We developed a novel transgenic mouse model to induce tissue-specific deletion of vasopressin and showed that collecting duct-derived vasopressin is not required to concentrate or dilute urine.
Topics: Animals; Kidney Tubules, Collecting; Mice, Knockout; Deamino Arginine Vasopressin; Kidney Concentrating Ability; Arginine Vasopressin; Male; Antidiuretic Hormone Receptor Antagonists; Mice; Aquaporin 2; Antidiuretic Agents; Receptors, Vasopressin; Mice, Inbred C57BL; Water Deprivation; Osmolar Concentration; Sodium; Vasopressins; Benzazepines
PubMed: 38695074
DOI: 10.1152/ajprenal.00057.2024 -
Nature Reviews. Endocrinology May 2024Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes... (Review)
Review
Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific for AVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.
PubMed: 38693275
DOI: 10.1038/s41574-024-00985-x -
Research and Practice in Thrombosis and... Mar 2024Desmopressin is frequently used perioperatively in persons with nonsevere hemophilia A. However, increase in factor (F)VIII:C after desmopressin use is interindividually...
BACKGROUND
Desmopressin is frequently used perioperatively in persons with nonsevere hemophilia A. However, increase in factor (F)VIII:C after desmopressin use is interindividually highly variable. Tachyphylaxis has only been reported in test setting for persons with hemophilia A, with a remaining response of approximately 70% after a second dose compared with that after a first dose.
OBJECTIVES
To study tachyphylaxis of FVIII:C response after multiple administration(s) of desmopressin in perioperative persons with nonsevere hemophilia A.
METHODS
We studied FVIII:C levels after desmopressin before (day 0 [D0]) and on days 1 (D1) and 2 (D2) after surgery in 26 patients of the DAVID and Little DAVID studies. We studied tachyphylaxis by comparing the responses at D1 and D2 with that at D0. We also assessed the reproducibility of the D0 response in comparison to an earlier performed desmopressin test.
RESULTS
The median absolute FVIII:C increase was 0.50 IU/mL (0.35-0.74; = 23) at D0, 0.21 IU/mL (0.14-0.28; = 17) at D1, and 0.23 IU/mL (0.16-0.30; = 11) at D2. The median percentage of FVIII increase after the second administration (D1) compared with the first (D0) was 42.9% (29.2%-52.5%; = 17) and that of the third (D2) compared with the first (D0) was 36.4% (23.7%-46.9%; = 11). The FVIII:C desmopressin response at D0 was comparable with the desmopressin test response in 74% of the patients.
CONCLUSION
Tachyphylaxis in the surgical setting was considerably more pronounced than previously reported, with FVIII:C at D1 and D2 of 36% to 43% of the initial response. Our results may have important implications for monitoring repeated desmopressin treatment when used perioperatively.
PubMed: 38660455
DOI: 10.1016/j.rpth.2024.102367 -
Scientific Reports Apr 2024Arginine-vasopressin (AVP), a cyclic peptide hormone composed of nine amino acids, regulates water reabsorption by increasing intracellular cyclic adenosine...
Arginine-vasopressin (AVP), a cyclic peptide hormone composed of nine amino acids, regulates water reabsorption by increasing intracellular cyclic adenosine monophosphate (cAMP) concentrations via the vasopressin V2 receptor (V2R). Plasma AVP is a valuable biomarker for the diagnosis of central diabetes insipidus (CDI) and is commonly measured using radioimmunoassay (RIA). However, RIA has several drawbacks, including a long hands-on time, complex procedures, and handling of radioisotopes with special equipment and facilities. In this study, we developed a bioassay to measure plasma AVP levels using HEK293 cells expressing an engineered V2R and a cAMP biosensor. To achieve high sensitivity, we screened V2R orthologs from 11 various mammalian species and found that the platypus V2R (pV2R) responded to AVP with approximately six-fold higher sensitivity than that observed by the human V2R. Furthermore, to reduce cross-reactivity with desmopressin (DDAVP), a V2R agonist used for CDI treatment, we introduced a previously described point mutation into pV2R, yielding an approximately 20-fold reduction of responsiveness to DDAVP while maintaining responsiveness to AVP. Finally, a comparison of plasma samples from 12 healthy individuals demonstrated a strong correlation (Pearson's correlation value: 0.90) between our bioassay and RIA. Overall, our assay offers a more rapid and convenient method for quantifying plasma AVP concentrations than existing techniques.
Topics: Humans; Arginine Vasopressin; HEK293 Cells; Cyclic AMP; Receptors, Vasopressin; Biosensing Techniques; Deamino Arginine Vasopressin; Animals; Biological Assay
PubMed: 38658606
DOI: 10.1038/s41598-024-60035-4