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Nature Reviews. Endocrinology Mar 2016Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and... (Review)
Review
Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of copeptin is undetermined. Quantification of AVP can be difficult, but copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.
Topics: Animals; Body Fluids; Glycopeptides; Homeostasis; Humans; Hyponatremia; Polydipsia; Polyuria; Vasopressins
PubMed: 26794439
DOI: 10.1038/nrendo.2015.224 -
Journal of Endocrinological... Jan 2020Copeptin is secreted in equimolar amount to Arginine Vasopressin (AVP) but can easily be measured with a sandwich immunoassay. Both peptides, copeptin and AVP, show a... (Review)
Review
COPEPTIN
Copeptin is secreted in equimolar amount to Arginine Vasopressin (AVP) but can easily be measured with a sandwich immunoassay. Both peptides, copeptin and AVP, show a high correlation. Accordingly, copeptin mirrors the amount of AVP in the circulation and its measurement provides an attractive marker in the differential diagnosis of diabetes insipidus.
THE POLYURIA POLYDIPSIA SYNDROME
Diabetes insipidus-either central or nephrogenic-has to be differentiated from primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since many decades, the "gold standard" for differential diagnosis has been the classical water deprivation test, which has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 hours and is cumbersome for patients. Clinical signs and symptoms as well as MRI characteristics overlap between patients with diabetes insipidus and primary polydipsia. Direct measurement of AVP upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay.
COPEPTIN AS DIAGNOSTIC TOOL IN THE POLYURIA POLYDIPSIA SYNDROME
We have recently shown that copeptin, without prior water deprivation, identifies patients with nephrogenic diabetes insipidus. On the other hand, for the more difficult differentiation between central diabetes insipidus and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these two entities with a high diagnostic accuracy, and is superior to the water deprivation test. It is important to note that close sodium monitoring during the hypertonic saline test is a prerequisite.
CONCLUSION
Therefore, we propose that copeptin upon hypertonic saline infusion should become the new standard test in the differential diagnosis of diabetes insipidus.
Topics: Biomarkers; Diagnosis, Differential; Glycopeptides; Humans; Polyuria
PubMed: 31368050
DOI: 10.1007/s40618-019-01087-6 -
Minerva Endocrinologica Dec 2018Diabetes insipidus, characterized by polyuria and polydipsia, is a rare disease during pregnancy. Nevertheless, its recognition is important to avoid complications due... (Review)
Review
Diabetes insipidus, characterized by polyuria and polydipsia, is a rare disease during pregnancy. Nevertheless, its recognition is important to avoid complications due to dehydration and hypernatremia. Its manifestation during pregnancy ranges from exacerbation of pre-existing central or nephrogenic diabetes insipidus to transient pregnancy-induced diabetes insipidus due to the increased metabolism of the antidiuretic hormone vasopressin (AVP) by the placental vasopressinase. Diagnosis can be challenging, as urinary frequency is common during pregnancy and primary polydipsia also needs to be excluded. Also, the standard water deprivation test is not recommended during pregnancy due to the increased risk of complications. Treatment depends upon the final diagnosis, with desmopressin (DDAVP) being the medication of choice in AVP-deficient diabetes insipidus, whereas nephrogenic diabetes insipidus requires treatment of the underlying disease and supportive measures.
Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypoglycemic Agents; Pregnancy; Pregnancy Complications
PubMed: 29463074
DOI: 10.23736/S0391-1977.18.02807-9 -
Journal of Psychosomatic Research Nov 2021Polydipsia is defined at the intake of excessive fluid (>3 L daily). Psychogenic polydipsia (PPD) presents without an identifiable medical cause and is often seen in... (Review)
Review
OBJECTIVE
Polydipsia is defined at the intake of excessive fluid (>3 L daily). Psychogenic polydipsia (PPD) presents without an identifiable medical cause and is often seen in patients with diagnoses of schizophrenia, OCD, anxiety, alcohol use disorder, and other psychotic disorders. The purpose of this systematic review is to assess the therapeutic effect of various non-antipsychotic medications on patients with a stable psychotic illness and concurrent PPD.
METHODS
A systematic search was conducted using the following databases: PubMed, MEDLINE with Full Text, CINAHL complete, Cochrane database of systematic reviews, Cochrane methodology register, MasterFILE Premier, APA PsychArticles, APA PsychInfo, APA PsycBooks, APA PsycTests, TRIP, Nursing and Allied Health. The quality of each retained study was assessed using appropriate risk of bias tools based on study design.
RESULTS
The initial search resulted in 1422 articles from which 22 articles were included for qualitative synthesis. Study designs ranged from case reports to double blind, placebo controlled randomized trials and was interpreted uniquely based on study design. Acetazolamide was effective in improving some PPD outcomes. Fluoxetine at high doses was effective in reducing fluid intake and polydipsia. Other medications included in this review performed equivocally for reduction of numerous parameters evaluating PPD.
CONCLUSION
No one drug appeared to be the most efficacious; however, some did show promise in specific populations. Those in need of pharmacotherapeutic options for PPD may consider one of the included agents to assist with co-morbid state. Further high-quality research is needed to provide better treatment guidance for PPD.
PubMed: 34856427
DOI: 10.1016/j.jpsychores.2021.110674 -
Swiss Medical Weekly May 2020Polyuria-polydipsia syndrome consists of the three main entities: central or nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between these...
Polyuria-polydipsia syndrome consists of the three main entities: central or nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between these diagnoses is essential as treatment differs substantially, with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the classical water deprivation test had several pitfalls and clinicians were often left with uncertainity concerning the diagnosis. With the establishment of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of the polyuria-polydipsia syndrome has been newly evaluated. Whereas unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, two new tests using stimulated copeptin cutoff levels showed a high diagnostic accuracy in differentiating central diabetes insipidus from primary polydipsia. For the hypertonic saline infusion test, osmotic stimulation via the induction of hypernatraemia is used. This makes the test highly reliable and superior to the classical water deprivation test, but also requires close supervision and the availability of rapid sodium measurements to guarantee the safety of the test. Alternatively, arginine infusion can be used to stimulate copeptin release, opening the doors for an even shorter and safer diagnostic test. The test protocols of the two tests are provided and a new copeptin-based diagnostic algorithm is proposed to reliably differentiate between the different entities. Furthermore, the role of copeptin as a predictive marker for the development of diabetes insipidus following surgical procedures in the sellar region is described.
Topics: Diabetes Insipidus; Diabetes Mellitus; Diagnosis, Differential; Diagnostic Tests, Routine; Glycopeptides; Humans; Polyuria
PubMed: 32374887
DOI: 10.4414/smw.2020.20237 -
Best Practice & Research. Clinical... Jun 2015Central diabetes insipidus (CDI) is a complex and heterogeneous clinical syndrome affecting the hypothalamic-neurohypophyseal network and water balance. A recent... (Review)
Review
Central diabetes insipidus (CDI) is a complex and heterogeneous clinical syndrome affecting the hypothalamic-neurohypophyseal network and water balance. A recent national surveillance in Denmark showed a prevalence rate of twenty-three CDI patients per 100,000 inhabitants in five years. The differential diagnosis between several presenting conditions with polyuria and polydipsia is puzzling, and the etiological diagnosis of CDI remains a challenge before the identification of an underlying cause. For clinical practice, a timely diagnosis for initiating specific treatment in order to avoid central nervous system damage, additional pituitary defects and the risk of dissemination of germ cell tumor is advisable. Proper etiological diagnosis can be achieved via a series of steps that start with careful clinical observation of several signs and endocrine symptoms and then progress to more sophisticated imaging tools. This review summarizes the best practice and approach for the diagnosis and treatment of patients with CDI.
Topics: Antidiuretic Agents; Brain Injuries; Brain Neoplasms; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Disease Management; Histiocytosis, Langerhans-Cell; Humans; Magnetic Resonance Imaging; Neoplasms, Germ Cell and Embryonal
PubMed: 26051300
DOI: 10.1016/j.beem.2015.04.013 -
Psychopharmacology Bulletin Apr 2024Clozapine, amongst antipsychotics, has a unique composite mode of action that might translate into an expanded therapeutic potential on clinical grounds. Sorely,... (Review)
Review
Clozapine, amongst antipsychotics, has a unique composite mode of action that might translate into an expanded therapeutic potential on clinical grounds. Sorely, clozapine remains underutilized.
Topics: Humans; Clozapine; Schizophrenia; Dyskinesia, Drug-Induced; Antipsychotic Agents
PubMed: 38601835
DOI: No ID Found -
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 -
Endocrine Connections Dec 2018The pathomechanism of primary polydipsia is poorly understood. Recent animal data reported a connection between fibroblast growth factor 21 (FGF-21) and elevated fluid...
The pathomechanism of primary polydipsia is poorly understood. Recent animal data reported a connection between fibroblast growth factor 21 (FGF-21) and elevated fluid intake independently of hormonal control by the hormone arginine-vasopressin (AVP) and osmotic stimulation. We therefore compared circulating FGF-21 levels in patients with primary polydipsia to patients with AVP deficiency (central diabetes insipidus) and healthy volunteers. In this prospective cohort study, we analyzed FGF-21 levels of 20 patients with primary polydipsia, 20 patients with central diabetes insipidus and 20 healthy volunteers before and after stimulation with hypertonic saline infusion targeting a plasma sodium level ≥150 mmol/L. The primary outcome was the difference in FGF-21 levels between the three groups. Baseline characteristics were similar between the groups except for patients with central diabetes insipidus being heavier. There was no difference in baseline FGF-21 levels between patients with primary polydipsia and healthy volunteers (122 pg/mL (52,277) vs 193 pg/mL (48,301), but higher levels in patients with central diabetes insipidus were observed (306 pg/mL (114,484); P = 0.037). However, this was not confirmed in a multivariate linear regression analysis after adjusting for age, sex, BMI and smoking status. Osmotic stimulation did not affect FGF-21 levels in either group (difference to baseline: primary polydipsia -23 pg/mL (-43, 22); central diabetes insipidus 17 pg/mL (-76, 88); healthy volunteers -6 pg/mL (-68, 22); P = 0.45). To conclude, FGF-21 levels are not increased in patients with primary polydipsia as compared to central diabetes insipidus or healthy volunteers. FGF-21 therefore does not seem to be causal of elevated fluid intake in these patients.
PubMed: 30592707
DOI: 10.1530/EC-18-0469 -
BMC Veterinary Research Jul 2023Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting...
BACKGROUND
Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting level of < 5% and high level of comfort there may be complacency and underestimation of the impact side effects of corticosteroids may have on a pet and pet owner.
OBJECTIVE
The objective of this clinical study was to describe the experience and perception of an owner who administered anti-inflammatory doses of oral prednisolone and prednisone to their dog for up to 14 days. We hypothesized dogs receiving anti-inflammatory doses of prednisone and prednisolone would experience much greater rates of side effects by day 14 then reported in current literature.
ANIMALS
There were 45 dogs initially enrolled in the study.
RESULTS
At each study point, 31 owners provided results. On day 5, 74% (23/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, polypnea and/or increased vocalization, with 11 individuals (35%) reporting these changes greatly increased. On day 14, 90% of owners (28/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, and/or polypnea as the most common changes noted. Overall, 61% (19/31) of owners reported an increase in filling of the water bowl over baseline and one-third (11/31) of pet owners reported cleaning up urinary accidents for pets who had been continent prior to the start of the study. Pet owner steroid satisfaction remained high through day 14 at 4.5/5 (1 = very unsatisfied, 5 = very satisfied).
CONCLUSION
This study highlights the impact short term anti-inflammatory doses of prednisone or prednisolone have on dog behaviour and confirms our hypothesis that by day 14, 90% of dogs experienced one or more behaviour changes, with polyuria and polydipsia most commonly reported. Adverse events were noted regardless of starting dosage or regimen. Although most pet owners expressed satisfaction with steroid treatment due to its high efficacy, 70% would select a more costly treatment if that treatment had fewer side effects.
Topics: Dogs; Animals; Prednisolone; Prednisone; Polyuria; Drug-Related Side Effects and Adverse Reactions; Hyperphagia; Polydipsia; Perception; Dog Diseases
PubMed: 37488543
DOI: 10.1186/s12917-023-03644-x