Diagnostic Utility of Copeptin in Pediatric Patients with Polyuria-Polydipsia Syndrome: A Systematic Review and Meta-Analysis.

Pediatric patients with polyuria polydipsia syndrome (PPS) represent a diagnostic challenge for clinicians because of the technical difficulties in performing the gold standard water deprivation test (WDT). Copeptin, a stable biomarker representing the C-terminal portion of the polypeptide chain of the antidiuretic hormone, is a reliable diagnostic tool. To assess the diagnostic accuracy of baseline copeptin dosing, arginine/hypertonic saline copeptin stimulation tests, and WDT. This study aimed to establish the diagnostic utility of copeptin in pediatric patients by distinguishing between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia. Comparative and non-comparative primary studies published between January 2018 and August 2024 focusing on children were searched and included in PubMed, Cochrane Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. The QUADAS-2 tool was used to assess the risk of bias and applicability. Meta-analyses used fixed effects models because of low heterogeneity and the HSROC model. Eleven studies were included with an overall low bias and no significant applicability concerns. The mean pooled sensitivity = 0.98 (95% CI: 0.936-1.025), pooled specificity = 0.947 (95% CI: 0.920-0.973), and AUC = 0.972 (95% CI: 0.952-0.992), indicating excellent diagnostic accuracy. Stimulation methods for copeptin dosing represent an effective and less invasive diagnostic test for children with PPS, and future development of standard copeptin testing protocols is needed.

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

OBJECTIVE: 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 antagonizing AVP, upon copeptin stimulation tests. DESIGN: Post hoc secondary analysis of a multi-centric cross-over diagnostic study (NCT03572166). SETTING: Outpatients included at the University Hospital Basel. PARTICIPANTS: Patients with AVP-D and PP. INTERVENTIONS: Copeptin stimulation tests with hypertonic saline and arginine infusion. OUTCOMES AND MEASURES: The primary outcome was the absolute difference in apelin between baseline and peak of copeptin stimulation tests. Secondary objectives included the diagnostic ability of apelin. RESULTS: 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 = .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 = .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 = .007). CONCLUSIONS AND RELEVANCE: Our findings suggest that apelin decreases to a greater extent in PP compared with AVP-D upon copeptin stimulation tests. However, copeptin remains the best marker to differentiate AVP-D from PP.

Primary Polydipsia in a Toddler: A Rare Case.

Primary polydipsia (PP) is a rare but significant clinical entity in pediatric patients. Here, we present the case of a 16-month-old female referred to our center due to recurrent episodes of electrolyte imbalances. Initially admitted for management of a viral illness, she experienced unexplained electrolyte disturbances, prompting subsequent admissions marked by similar disruptions. Despite stabilization and discharge, her condition persisted. Pre-referral laboratory findings revealed significant electrolyte abnormalities alongside polyuria symptoms. Investigations unveiled a history of frequent heavy wet diapers and increased thirst. Further tests including a water deprivation test excluded diabetes insipidus. Following the restriction of water intake and careful monitoring, her condition markedly improved. This case emphasizes the importance of thorough evaluation in persistent electrolyte imbalances in toddlers, highlighting the role of polyuria as a contributing factor and the efficacy of targeted interventions in managing such cases.

Chronic Schizophrenia Presenting With Psychogenic Polydipsia Concealing Stage IV Uterine Adenocarcinoma: A Case Report.

Psychogenic polydipsia (PPD) may be commonly seen in patients suffering from schizophrenia. It remains unknown how often psychiatric illness can mask other more serious conditions. The patient is a 58-year-old female with chronic schizophrenia and PPD presenting to the emergency department (ED) with abdominal pain over a seven-year period from 2016 to 2022 with her symptoms attributed to a schizophrenia exacerbation with minimal to no diagnostic follow-up. After several ED admissions, in 2022, tumor marker tests were collected yielding concerning results for underlying cancer including CA125 85.9/50.1, CA19-9 >10, and CEA 0.3. A pelvic ultrasound was completed in 2022 after another three ED visits, revealing an infiltrative uterine mass measuring up to 5.6 cm, which was confirmed by CT abdomen and pelvis to be stage IV uterine adenocarcinoma. Several potential opportunities for intervention were missed in this patient including (1) primary prevention, (2) inadequate physical exam and history acquisition, and (3) delayed diagnostic imaging from the onset of abdominal pain to diagnosis. This case highlights the shortcomings across disciplines in providing early intervention and the disparities of basic patient care in psychiatric patients.

Oral Levodopa Stimulates Copeptin Secretion in Children and Adolescents with Intact Posterior Pituitary Function.

BACKGROUND: Copeptin stimulation tests can be used in the differential diagnosis of polyuria-polydipsia syndrome. Current stimulation methods rely on intravenous or subcutaneous administration. Oral stimulus can further simplify the diagnostic approach. The levodopa stimulation test is widely used in the evaluation of growth hormone deficiency, and the dopamine pathway was reported to be associated with arginine vasopressin secretion. This study aims to investigate the effect of oral levodopa on copeptin secretion. METHODS: This study was a prospective observational single-center cohort study. Patients <18 years old with short stature and no symptoms of polyuria or polydipsia undergoing the levodopa stimulation test for suspected growth hormone deficiency were recruited from May 2023 to Nov 2023. Copeptin and growth hormone were measured at 0, 30, 60, 90, and 120 min during the levodopa test. The insulin tolerance test with copeptin and growth hormone measured at the same time points was conducted in part of patients. RESULTS: Forty-four participants were included in the final analysis. In the levodopa stimulation test, the median (interquartile range) copeptin concentration increased from 5.20 (3.51, 8.25) pmol/L to a maximum of 19.36 (8.97, 108.08) pmol/L (P < .001), 3.94 (1.41, 13.88) times that of the baseline (P < .001). Compared with the insulin tolerance test, peak copeptin in the levodopa test was significantly higher (34.61 [13.67, 98.96] vs 8.88 [7.14, 15.42] pmol/L, P = .009). Higher copeptin was associated with a larger dose of levodopa. CONCLUSIONS: Oral levodopa could be used to stimulate copeptin.

Copeptin as a diagnostic and prognostic biomarker in pediatric diseases.

Arginine vasopressin (AVP) plays a main role in maintaining the homeostasis of fluid balance and vascular tone and in regulating the endocrine stress response in response to osmotic, hemodynamic and stress stimuli. However, the difficulty in measuring AVP limits its clinical application. Copeptin, the C-terminal part of the AVP precursor, is released in an equimolar concentration mode with AVP from the pituitary but is more stable and simple to measure. Therefore, copeptin has emerged as a promising surrogate marker of AVP with excellent potential for the diagnosis, differentiation and prognosis of various diseases in recent decades. However, its application requires further validation, especially in the pediatric population. This review focuses on the clinical value of copeptin in different pediatric diseases and the prospects for its application as a potential biomarker.

Hyponatremia Secondary to Psychogenic Polydipsia and Schizophrenia: A Case Report.

Psychogenic polydipsia is characterized by excess thirst, followed by the overconsumption of liquids. This condition is seen in an array of mental illnesses, especially schizophrenia. Psychogenic polydipsia can lead to hyponatremia, which can lead to neurologic sequelae, such as seizures, cerebral edema, and death. In the case under study, the patient presents with schizophrenia, fatigue, weakness, and dizziness during psychiatric follow-up. A comprehensive metabolic panel (CMP) was ordered, which indicated hyponatremia. This patient was treated with salt tablets and behavioral therapy, which led to the normalization of his serum sodium and symptom improvement. The patient has a history of psychogenic polydipsia with hyponatremia, treated on and off for years with salt replacement and water restriction. Management of psychogenic polydipsia is a difficult task. It is important to understand the available management options so that water intoxication and the consequences of hyponatremia do not occur.

Approach to the patient with suspected hypotonic polyuria.

Investigation and management of hypotonic polyura is a common challenge in clinical endocrinology. The three main causes, recently renamed to arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus), AVP-resistance (AVP-R, formerly nephrogenic diabetes insipidus), and primary polydipsia (PP) require accurate diagnosis as management differs for each. This new nomenclature more accurately reflects pathophysiology, and has now been adopted by the Systemised Nomenclature of Medicine (SNOMED). Advances in diagnosis over the last few years have centered around the use of copeptin measurement. Here, we use three patient case histories to highlight the use of this approach, and to demonstrate how it can succeed where other approaches, such as the water deprivation test, sometimes fail. We discuss the overall approach to each type of patient and the strengths and limitations of diagnostic strategies, illustrating the use of the new nomenclature.

A novel AVPR2 gene mutation in a Chinese pedigree with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.

Transient severe hypotonic hyponatraemia in children - presentation of three cases.

Hyponatraemia, defined as sodium concentration below 135 mmol/l, is one of the most common electrolyte imbalances. Differential diagnosis of hyponatraemia is difficult. We describe 3 cases of children with transient, severe hyponatraemia (< 125 mmol/l). While diagnosing hyponatraemia, it is of major importance to carefully ask in the anamnesis about habits related to the amount of fluid intake and the type of consumed fluids. It should also be noted that a frequent procedure during an infection is to increase fluid ingesting as a prevention of dehydration. One, however, should remember about the possibility of inducing water poisoning in a patient consuming excessive amounts of hypotonic fluids, especially when exposed to non-osmotic antidiuretic hormone stimulus, such as an acute infection or stress, and/or reduced renal excretory capacity. Only the presence of polyuria does not justify a diagnosis of arginine vasopressin deficiency (AVP-D), and especially the implementation of desmopressin treatment before all diagnostic procedures are completed, specifically in the case of hyponatraemia. Desmopressin can be used simultaneously with intravenous 3% saline solution only in the treatment of a very severe hyponatraemia, to avoid overcorrection of natraemia. In patients after profound hyponatraemia, polyuria can be observed after normalisation of fluid intake, but it is temporary.

A challenging diagnosis of Langerhans' cell histiocytosis with hypothalamic-pituitary and mandibular involvement: case report and literature review.

Background: Langerhans cell histiocytosis (LCH) is a rare bone marrow derived neoplasm that mainly affects children. It is a multiorgan disorder and hypothalamic-pituitary involvement is uncommon. LCH reveals a wide spectrum of indications; thus, the diagnosis and treatment are usually challenging. Case Report: A 22-year-old male presented with polydipsia, polyuria with nonspecific radiological findings, later on, developed a mandibular lesion and a biopsy was conducted which led to LCH diagnosis. After many improper treatments due to unclear diagnosis, the patient was finally placed on chemotherapy and is now under surveillance. Discussion: LCH is a rare disease with diverse clinical manifestations affecting various organs. Associated mutations, such as BRAF V600E, contribute to its complexity. In adults, initial symptoms include pain, weight loss, and fever, with potential pituitary involvement leading to Arginine vasopressin (AVP) deficiency. Commonly affected organs include bone, skin, and the pituitary gland. The disease can be categorized into single-system and multisystem. Pathological diagnosis involves electron microscopy or immunohistochemical staining. Treatment options vary; the presented case utilized Desmopressin acetate and prednisolone before transitioning to cyclophosphamide for multisystemic LCH. Conclusion: AVP deficiency can suggest hypothalamic-pituitary LCH, and a biopsy, if possible, is recommended to confirm the diagnosis.

Characterization in the rat of the individual tendency to rely on alcohol to cope with distress and the ensuing vulnerability to drink compulsively.

Only some vulnerable individuals who recreationally drink alcohol eventually develop the compulsive drinking pattern that characterizes alcohol use disorder. A new frontier in biomedical research lies in understanding the neurobehavioural mechanisms of this individual vulnerability, a necessary step towards developing novel effective therapeutic strategies. Translational research has been hindered by the lack of valid, reliable and robust approaches that enable the study of the influence of the reliance on alcohol to cope with stress or self-medicate negative emotional states on the subsequent transition to alcohol use disorder. We have therefore developed a behavioural task in the rat that enables the investigation of the neural and cellular basis of the exacerbation of the vulnerability to develop compulsive alcohol drinking by the use of alcohol to develop an adjunctive, anxiolytic, polydipsic drinking behaviour in a schedule-induced polydipsia procedure. Hence, in our task, alcohol is introduced in the schedule-induced polydipsia context after several weeks of training with water so that rats are exposed to alcohol for the first time in a distressing context and learn to drink alcohol as a coping strategy. Capitalizing on this protocol, we have consistently been able to identify a subpopulation of rats that were unable to learn to cope with negative states by drinking water and relied on alcohol to do so. This maladaptive reliance on alcohol drinking to cope with distress has been shown to be associated with an exacerbation of the subsequent transition to compulsive drinking. Furthermore, these vulnerable rats reached blood alcohol levels comparable to that of intoxication in humans, thereby developing two key features of alcohol use disorder, namely excessive alcohol intake and compulsive drinking. Altogether, this behavioural task provides a novel and unique tool for the investigation of the neurobehavioural mechanisms underlying the exacerbation of the individual vulnerability to developing compulsive alcohol drinking by the use of alcohol as a strategy to cope with distress, and for the evaluation of the efficacy of potential therapeutic strategies in a personalized medicine approach. This procedure, which focuses on an understudied but key factor of the development of alcohol use disorder, may become widely used as it benefits the fields of alcohol, emotion regulation and stress, the interest in which has substantially increased since the evidence of a profound exacerbation of alcohol use and alcohol-related negative consequences by the distress and social isolation engendered by the various measures implemented worldwide in response to the COVID-19 pandemic.

Severe Hyponatremia (96 mmol/L) Secondary to Primary Polydipsia and Pneumonia.

A 63-year-old man who presented to the hospital with altered mental status and decreased responsiveness was found to have severe symptomatic hyponatremia with a sodium level of 96 mmol/L and pneumonia. The patient was admitted to the medical intensive care unit for septic shock and acute severe hyponatremia. He was intubated for airway protection, and treated with 3% hypertonic saline bolus and antibiotics. After four days, sodium levels were corrected to 128 mmol/L, and the patient was extubated and downgraded to the medical floor. This case demonstrates one of the lowest recorded sodium lab values ever and the patient was successfully treated and discharged home with appropriate outpatient appointments.

Copeptin Stimulation by Combined Intravenous Arginine and Oral LevoDopa/Carbidopa in Healthy Short Children and Children with the Polyuria-Polydipsia Syndrome.

INTRODUCTION: Stimulated copeptin may provide an alternative to water deprivation testing (WDT) in the evaluation of polyuria-polydipsia syndrome (PPS). Though best studied, arginine stimulation alone produces a modest copeptin response in children. We investigated the effectiveness of the arginine + LevoDopa/Carbidopa stimulation test (ALD-ST) for copeptin. METHODS: 47 healthy short children (controls), 10 children with primary polydipsia, and 10 children with AVP deficiency received arginine hydrochloride (500 mg/kg intravenously over 30 min) and Levodopa/carbidopa (10:1 ratio; 175 mg of l-Dopa/m2 BSA) orally. Serum copeptin was measured at 0, 60, 90, and 120 min. RESULTS: In controls, ALD-ST increased copeptin from a median of 7.0 pmol/L (IQR 5.0-10.0) to a peak of 44.0 pmol/L (IQR 21.4-181.0) between 60 and 120 min (p < 0.001). Copeptin peak was higher in subjects who experienced nausea or vomiting (57%) than in those who did not (131.0 pmol/L [IQR 42.5-193.8] vs. 22.7 pmol/L [IQR 16.0-33.7], p < 0.001). While subjects with primary polydipsia had similar baseline (8.5 pmol/L [IQR 8.0-11.0]) and stimulated (125.2 pmol/L [IQR 87.6-174.0]) copeptin levels as controls, subjects with AVP deficiency had lower baseline (2.5 pmol/L [IQR 2.0-3.1]) and peak levels (4.6 pmol/L [IQR 2.4-6.0]). A peak copeptin of ≥9.3 pmol/L best predicted absence of complete or partial AVP deficiency with a sensitivity of 100% and specificity of 80%. CONCLUSIONS: ALD-ST induced a robust peak copeptin in healthy short children and children with primary polydipsia. Nausea/vomiting, a side effect of ALD-ST, amplified the copeptin response. The ALD-ST may be a suitable initial screening test in children with PPS.

Clozapine Prescripers-Dogmatic or Pragmatic?

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.

Avian Diabetes Mellitus: A Review.

Diabetes mellitus (DM) is an uncommon, poorly documented metabolic disorder of birds. Extrapolating knowledge from DM in mammals is challenging because of marked differences in avian physiology and metabolism. A literature review from December 1991 to January 2022 identified 14 publications covering 16 diabetic birds, 63% (10/16) of which belonged to the order Psittaciformes with Ara as the predominant genus. No sex predilection was noted, but males generally presented at a younger age. Commonly reported clinical signs included polyuria 94% (15/16), polydipsia 88% (14/16), weight loss 75% (12/16), lethargy 63% (10/16), and polyphagia 38% (6/16). Diagnosis of DM was based on the presence of clinical signs and persistent hyperglycemia 100% (16/16), often with glucosuria 93% (13/14), response to insulin therapy 80% (8/10), and pancreatic pathology 90% (9/10). Specific treatment for DM was initiated in 14 patients, but blood glucose regulation for 6 months or longer was only achieved in 6 birds. Five of the regulated birds were managed with injectable long-acting insulin and 1 with oral glipizide combined with dietary modifications. However, glipizide yielded poor results in other cases, likely attributable to a lack of functional beta cells. Three diabetic birds progressed to remission. Treatment proved unsuccessful for 7 patients with a mean survival time of 36 days from diagnosis. One patient was lost to follow-up, and 2 were euthanized immediately following diagnosis. Histological examination of the pancreas frequently (90%, 9/10) revealed abnormalities including atrophy, fibrosis, and vacuolization of the endocrine islets with or without lymphoplasmacytic pancreatitis. Comorbidities, including hemosiderosis and infection, were common. This review suggests that birds diagnosed with DM are primarily affected by a type I diabetes as observed in dogs and humans. In contrast to mammalian species, avian DM is often associated with underlying disease and a complete clinical workup is essential to diagnose and address secondary disease conditions prior to initiating long-term insulin therapy.

Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia compared to healthy controls.

OBJECTIVE: Distinguishing arginine vasopressin deficiency (AVP-D; central diabetes insipidus) from primary polydipsia (PP), commonly referred to as psychogenic polydipsia, is challenging. Psychopathologic findings, commonly used for PP diagnosis in clinical practice, are rarely evaluated in AVP-D patients, and no comparative data between the two conditions currently exist. DESIGN: Data from two studies involving 82 participants [39 AVP-D, 28 PP, and 15 healthy controls (HC)]. METHODS: Psychological evaluations were conducted using standardized questionnaires measuring anxiety [State-Trait Anxiety Inventory (STAI)], alexithymia [Toronto Alexithymia Scale (TAS-20)], depressive symptoms (Beck's Depression Inventory-II (BDI-II), and overall mental health [Short Form-36 Health Survey (SF-36)]. Higher STAI, TAS-20, and BDI-II scores suggest elevated anxiety, alexithymia, and depression, while higher SF-36 scores signify better overall mental health. RESULTS: Compared to HC, patients with AVP-D and PP showed higher levels of anxiety (HC 28 points [24-31] vs AVP-D 36 points [31-45]; vs PP 38 points [33-46], P < .01), alexithymia (HC 30 points [29-37] vs AVP-D 43 points [35-54]; vs PP 46 points [37-55], P < .01), and depression (HC 1 point [0-2] vs AVP-D 7 points [4-14]; vs PP 7 points [3-13], P < .01). Levels of anxiety, alexithymia, and depression showed no difference between both patient groups (P = .58, P = .90, P = .50, respectively). Compared to HC, patients with AVP-D and PP reported similarly reduced self-reported overall mental health scores (HC 84 [68-88] vs AVP-D 60 [52-80], P = .05; vs PP 60 [47-74], P < .01). CONCLUSION: This study reveals heightened anxiety, alexithymia, depression, and diminished overall mental health in patients with AVP-D and PP. The results emphasize the need for careful interpretation of psychopathological characteristics to differentiate between AVP-D and PP.

[Consensus recommendations on the diagnosis and treatment of hyponatremia from the Austrian Society for Nephrology 2024]. / Konsensusempfehlungen zur Diagnose und Therapie der Hyponatriämie der Österreichischen Gesellschaft für Nephrologie 2024.

Hyponatremia is a disorder of water homeostasis. Water balance is maintained by the collaboration of renal function and cerebral structures, which regulate thirst mechanisms and secretion of the antidiuretic hormone. Measurement of serum-osmolality, urine osmolality and urine-sodium concentration help to diagnose the different reasons for hyponatremia. Hyponatremia induces cerebral edema and might lead to severe neurological symptoms, which need acute therapy. Also, mild forms of hyponatremia should be treated causally, or at least symptomatically. An inadequate fast increase of the serum sodium level should be avoided, because it raises the risk of cerebral osmotic demyelination. Basic pathophysiological knowledge is necessary to identify the different reasons for hyponatremia which need different therapeutic procedures.

The diagnostic performance of copeptin in clinical practice: A prospective study.

OBJECTIVE: Plasma copeptin is a relatively new biomarker for evaluation of arginine vasopressin (AVP) secretion. The aim of this study was to test the diagnostic performance of copeptin in patients with polyuria-polydipsia syndrome. DESIGN, PATIENTS AND MEASUREMENTS: This was a prospective study where 88 patients with polyuria-polydipsia syndrome were evaluated with a water deprivation test (WDT). Weight, urine osmolality, urine specific gravity, and plasma copeptin were collected at baseline, after 8 h, and at termination of the WDT when one of the following had been reached: (i) >3% weight reduction, (ii) urine specific gravity >1.017 or urine osmolality >600 mOsm/kg, or (iii) intolerable adverse symptoms. RESULTS: Of 88 patients (57 women), 21 (24%) were diagnosed with central diabetes insipidus (cDI), 5 (6%) with nephrogenic DI (nDI), and 62 (71%) with primary polydipsia (PP). Median (interquartile range) copeptin at baseline was 1.7 (1.4-2.5) pmol/L in cDI, 22 (18-65) pmol/L in nDI, and 2.7 (2-4) pmol/L in PP. After 8 h of WDT, the highest copeptin in patients with cDI was 4.0 pmol/L. In patients with PP: (i) 41 had urine osmolality <600 mOsm/kg, 7 (17%) of these had copeptin >4.0 pmol/L, (ii) 21 had urine osmolality ≥600 mOsm/kg, 14 (67%) of these had copeptin >4.0 pmol/L. CONCLUSIONS: Copeptin >4.0 pmol/L after an overnight WDT can be used to rule out cDI and copeptin ≥21 pmol/L at baseline to diagnose nDI. The diagnostic performance of copeptin in the context of the WDT is otherwise limited in the diagnostic work-up of patients with polyuria-polydipsia syndrome.