Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome – revisiting the direct and indirect water deprivation tests

2010 ◽  
Vol 118 (08) ◽  
Author(s):  
W Fenske ◽  
D Lorenz ◽  
U Haagen ◽  
J Papassotiriou ◽  
M Fassnacht ◽  
...  
1981 ◽  
Vol 98 (2) ◽  
pp. 244-246 ◽  
Author(s):  
S. Anne Hendricks ◽  
Barbara Lippe ◽  
Solomon A. Kaplan ◽  
W-N. Paul Lee

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Emily K Brooks ◽  
Caroline Bachmeier ◽  
Juanita Vorster ◽  
Jane Sorbello ◽  
Faseeha C Peer ◽  
...  

Abstract Differentiating between primary polydipsia and central diabetes insipidus (DI) can be challenging. The water deprivation test has traditionally been used to diagnosis DI, however has poor diagnostic accuracy (1). Direct measurement of anti-diuretic hormone (ADH) is limited clinically. Copeptin is the C-terminal glycoprotein moiety of ADH prohormone, and correlates well with plasma ADH. Unlike ADH, copeptin is easy to measure (2). Hypertonic saline stimulated copeptin measurements have recently been described for the diagnosis of central DI. A copeptin cut-off of >4.9 pmol/L has a diagnostic accuracy of 96.5% for distinguishing primary polydipsia from central DI (3). A copeptin assay has recently been established in our laboratory. Validation of hypertonic saline-stimulated copeptin concentrations in our local population is needed before this test can be used with confidence in patients presenting to our institution with polyuria-polydipsia syndrome. The aim of this study was to develop a local reference range for hypertonic saline-stimulated copeptin in healthy volunteers. Twenty healthy volunteers (10 male and 10 female) were recruited. Subjects underwent a hypertonic saline test, as previously described (3). Hypertonic saline (3%) was administered as an initial 250 mL bolus followed by 0.15 mL/kg/minute until a target serum sodium of ≥150 mmol/L was reached. At this time, blood was drawn for copeptin. Twelve healthy volunteers (7 females; 5 males) have undergone the study to date. Median age was 28 years (range 26-50); median body weight 75.7 kg (range 57.9 -94.5); median baseline plasma sodium 138 mmol/L (range 136 - 140) and median serum osmolality 289.5 (range 281-297). Median peak sodium was 152 mmol/L (range 150-154) with osmolality 314.5 mmol/kg (range 306-320). Median volume of hypertonic saline infused was 1583 mL (1230-2177) and median hypertonic saline stimulated copeptin was 29.2 pmol/L (9.6-167.4). Overall symptom burden was 5/10 (range 3/10-9/10). There were no serious adverse events. Development of a local reference range for hypertonic saline stimulated copeptin measurements will assist in interpretation of the test in our local population of patients presenting with polyuria-polydipsia syndrome. References 1. Fenske W, Quinkler M, Lorenz D, Zopf K, Haagen U, Papassotiriou et al. Copeptin in the differential diagnosis of the polyuria-polydipsia syndrome- revisiting the direct and indirect water deprivation tests. JCEM. 2011;96:1506-1515 2. Timper K, Fenske W, Kuhn F, Frech N, Arici B, Rutishauser J et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. JCEM. 2015;100:2268-2274 3. Fenske, W, Refardt J, Chifu I, Schnyder I, Winzeler B, Drummond J. A copeptin-based approach in the diagnosis of diabetes insipidus. NEJM. 2018;379:428-439


2019 ◽  
Vol 181 (1) ◽  
pp. R11-R21 ◽  
Author(s):  
Mirjam Christ-Crain

Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since decades, the gold standard for differentiation has been the water deprivation test, which has limitations leading to an overall unsatisfying diagnostic accuracy. Furthermore, it is cumbersome for patients with a long test duration. Clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. The direct test including vasopressin (AVP) measurement upon osmotic stimulation was meant to overcome these limitations, but failed to enter clinical practice mainly due to technical constraints of the AVP assay. Copeptin is secreted in equimolar amount to AVP but can easily be measured with a sandwich immunoassay. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation and has led to a ‘revival’ of the direct test in the differential diagnosis of DI. We have shown that a baseline copeptin, without prior thirsting, unequivocally identifies patients with nephrogenic DI. In contrast, for the differentiation between central DI and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is superior to the water deprivation test. Close sodium monitoring during the test is a prerequisite. Further new test methods are currently evaluated and might provide an even simpler way of differential diagnosis in the future.


2011 ◽  
Vol 96 (5) ◽  
pp. 1506-1515 ◽  
Author(s):  
Wiebke Fenske ◽  
Marcus Quinkler ◽  
Daniela Lorenz ◽  
Kathrin Zopf ◽  
Ulrike Haagen ◽  
...  

2015 ◽  
Vol 100 (6) ◽  
pp. 2268-2274 ◽  
Author(s):  
Katharina Timper ◽  
Wiebke Fenske ◽  
Felix Kühn ◽  
Nica Frech ◽  
Birsen Arici ◽  
...  

Context: The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic “gold standard” is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging. Objective: The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome. Design, Setting, and Patients: This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia. Measurements: A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response. Results: Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity. Limitation: This study was limited by incorporation bias from including AVP levels as a diagnostic criterion. Conclusion: Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary Funding Sources: Swiss National Science Foundation, University of Basel.


Author(s):  
Bruce Mackay

The broadest application of transmission electron microscopy (EM) in diagnostic medicine is the identification of tumors that cannot be classified by routine light microscopy. EM is useful in the evaluation of approximately 10% of human neoplasms, but the extent of its contribution varies considerably. It may provide a specific diagnosis that can not be reached by other means, but in contrast, the information obtained from ultrastructural study of some 10% of tumors does not significantly add to that available from light microscopy. Most cases fall somewhere between these two extremes: EM may correct a light microscopic diagnosis, or serve to narrow a differential diagnosis by excluding some of the possibilities considered by light microscopy. It is particularly important to correlate the EM findings with data from light microscopy, clinical examination, and other diagnostic procedures.


2011 ◽  
Vol 21 (2) ◽  
pp. 59-62
Author(s):  
Joseph Donaher ◽  
Christina Deery ◽  
Sarah Vogel

Healthcare professionals require a thorough understanding of stuttering since they frequently play an important role in the identification and differential diagnosis of stuttering for preschool children. This paper introduces The Preschool Stuttering Screen for Healthcare Professionals (PSSHP) which highlights risk factors identified in the literature as being associated with persistent stuttering. By integrating the results of the checklist with a child’s developmental profile, healthcare professionals can make better-informed, evidence-based decisions for their patients.


1968 ◽  
Vol 11 (4) ◽  
pp. 842-852 ◽  
Author(s):  
H. N. Wright

Previous findings on the threshold for tones as a function of their duration have suggested that such functions may be systematically affected by sensori-neural hearing losses of cochlear origin. The present series of investigations was designed to explore this relation further and to determine also whether the amount of hearing loss present has any effect upon the results which are obtained. Preliminary studies were also carried out on a conductively impaired listener to indicate whether hearing losses of this type affect the threshold-duration function. The results indicate that the threshold-duration function is systematically affected by sensori-neural hearing losses of cochlear origin. This effect is manifested by a progressive shortening of the time constant relating threshold to duration and is not uniquely related to the amount of hearing loss present. The results obtained from the conductively impaired listener suggested that this type of hearing loss has no effect on the threshold-duration function, thereby implying that such functions may contribute significantly to the differential diagnosis of auditory disorders.


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