{"id":17496,"date":"2019-07-26T05:34:29","date_gmt":"2019-07-25T21:34:29","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=17496"},"modified":"2019-08-06T11:21:12","modified_gmt":"2019-08-06T03:21:12","slug":"lancet%e5%8f%91%e8%a1%a8%e8%bf%b0%e8%af%84","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=17496","title":{"rendered":"[Lancet\u53d1\u8868\u8ff0\u8bc4]: \u4f4e\u5f20\u6027\u591a\u5c3f\u65b0\u7684\u68c0\u67e5\u65b9\u6cd5"},"content":{"rendered":"\n

COMMENT|ONLINE FIRST<\/a><\/p>\n\n\n\n

Testing the waters: a new test for hypotonic polyuria<\/h1>\n\n\n\n

Ewout J Hoorn<\/h3>\n\n\n\n

Lancet Published: July 11, 2019 DOI:https:\/\/doi.org\/10.1016\/S0140-6736(19)31414-X<\/a><\/h3>\n\n\n\n

Three disorders can cause water diuresis (hypotonic polyuria): primary polydipsia, central diabetes insipidus, and nephrogenic diabetes insipidus. These causes of hypotonic polyuria are difficult to differentiate, especially the partial forms of central diabetes insipidus from primary polydipsia.1<\/a><\/sup> Yet this differentiation is crucial because the management for each disorder is quite different. For years, hypotonic polyuria was assessed with the water-deprivation test, with subsequent measurements of plasma vasopressin (the direct test) or urine osmolality (the indirect test).2<\/a><\/sup> Depending on the underlying disorder, water deprivation should increase plasma vasopressin and urine osmolality (primary polydipsia), increase only plasma vasopressin (nephrogenic diabetes insipidus), or increase neither plasma vasopressin nor urine osmolality (central diabetes insipidus). After water deprivation, the response to desmopressin can be tested for further differentiation.<\/p>\n\n\n\n

In the past few years, two modifications in the test for hypotonic polyuria have been proposed. The first was to replace plasma vasopressin with copeptin, the C-terminal segment of the vasopressin prohormone.3<\/a>, 4<\/a><\/sup> Copeptin has a better diagnostic performance in the water-deprivation test than plasma vasopressin and has fewer technical limitations. The second was to replace water deprivation with a more direct osmotic stimulus\u2014namely, the infusion of hypertonic saline.5<\/a><\/sup> When copeptin was stimulated with hypertonic saline, the diagnostic accuracy for hypotonic polyuria was much greater than when it was stimulated by water deprivation.<\/p>\n\n\n\n

In The Lancet<\/em>, Bettina Winzeler and colleagues6<\/a><\/sup> propose to modify the test for hypotonic polyuria once again by replacing hypertonic saline with arginine. Arginine is already of use as a provocative test for growth hormone release, and other growth hormone secretagogues like hexarelin have been shown to stimulate vasopressin secretion.7<\/a>, 8<\/a><\/sup> On the basis of these previous studies, Winzeler and colleagues hypothesised that arginine also stimulates the posterior pituitary and can therefore be used as a test for diabetes insipidus. Winzeler and colleagues used their new arginine stimulation test in a development cohort and a validation cohort of patients with central diabetes insipidus (21 in development cohort, 17 in validation cohort) or primary polydipsia (31 in development cohort, 27 in validation cohort) and a cohort of healthy adults (20 in development cohort, 30 validation cohort) and children (who had suspected growth hormone deficiency; 42 in development cohort).6<\/a><\/sup>As predicted, arginine increased copeptin concentrations 1\u00b78\u20132\u00b72 times in patients with primary polydipsia and the cohort of healthy adults and children, but only by 1\u00b72 times in the patients with central diabetes insipidus. The copeptin response to arginine was compared with the final diagnosis that, in the absence of a gold standard, was based on the results of the indirect water-deprivation test, patient characteristics, and treatment response. Overall, arginine-stimulated copeptin at a cutoff of 3\u00b78 pmol\/L reached a diagnostic accuracy of 93% (95% CI 86\u201397) for the differentiation between central diabetes insipidus and primary polydipsia.<\/p>\n\n\n\n

A clear advantage of arginine is that it is better tolerated than hypertonic saline.5<\/a>, 6<\/a><\/sup> Furthermore, it might be sufficient to measure copeptin only once 1 h after arginine stimulation, the timepoint with the highest diagnostic accuracy.6<\/a><\/sup> However, should endocrinology units invest in hypertonic saline or arginine? Two aspects should be considered before making this decision.<\/p>\n\n\n\n

First, most patients who were included in the studies with hypertonic saline and arginine were already known to have central diabetes insipidus or primary polydipsia.5<\/a>, 6<\/a><\/sup> Some of these patients might not have required a test for polyuria because they already had a diagnosis of hypopituitarism or because they presented with hyponatraemia or hypernatraemia.3<\/a>, 9<\/a><\/sup> Furthermore, those with central diabetes insipidus used desmopressin. Patients on chronic desmopressin treatment sometimes have hyponatraemia10<\/a><\/sup> that can suppress endogenous vasopressin synthesis,11<\/a><\/sup> which might blunt the response to arginine. Thus, whether the arginine stimulation test would reach the same diagnostic accuracy in a cohort of patients with unexplained hypotonic polyuria is unclear. Such a cohort would also include patients with nephrogenic diabetes insipidus, who were not included in the current study. However, the authors have shown previously that a single unstimulated copeptin measurement is sufficient to establish this diagnosis.3<\/a>, 4<\/a><\/sup><\/p>\n\n\n\n

\"\"\/<\/figure>\n\n\n\n

The second consideration is more specific to the use of a non-osmotic stimulus for vasopressin release. In 21 patients with central diabetes insipidus, Laczi and colleagues12<\/a><\/sup> found that a third had an increase in vasopressin after non-osmotic stimulation with histamine but not after osmotic stimulation with hypertonic saline. This observation suggests that these patients had adipsic diabetes insipidus, a subclass of central diabetes insipidus that is caused by impaired osmoreceptor function. However, adipsic diabetes insipidus is rare and usually presents with hypernatraemia,10<\/a><\/sup> which would render polyuria testing unnecessary.9<\/a><\/sup> Alternatively, in some patients with central diabetes insipidus, the osmoreceptor pathways to vasopressin release might be more affected than the non-osmotic pathways.<\/p>\n\n\n\n

Notwithstanding these considerations, the proof-of-concept study by Winzeler and colleagues offers the promise of a simple and well tolerated test for hypotonic polyuria. A definitive study would now be a head-to-head comparison of hypertonic saline versus arginine. Pending this study, one could envision a stepped approach in which the arginine stimulation test is done first, followed by the hypertonic saline-infusion test only when copeptin concentrations increased with arginine.<\/p>\n","protected":false},"excerpt":{"rendered":"

COMMENT|ONLINE FIRST Testing the waters: a new test for […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[24,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17496"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=17496"}],"version-history":[{"count":2,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17496\/revisions"}],"predecessor-version":[{"id":17500,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17496\/revisions\/17500"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=17496"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=17496"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=17496"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}