{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:08:25Z","timestamp":1781276905340,"version":"3.54.1"},"reference-count":116,"publisher":"Walter de Gruyter GmbH","issue":"7","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["1K23135800"],"award-info":[{"award-number":["1K23135800"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypotonic polyuria, also known as the polyuria-polydipsia syndrome (PPS), caused by primary polydipsia (PP), arginine vasopressin deficiency (AVP-D or central diabetes insipidus), or uncommonly by AVP resistance (AVP-R), is diagnostically challenging due to overlapping symptoms and the need to conclusively diagnose or exclude AVP-D caused by serious organic lesions of the central nervous system. Diagnostic tests that stimulate AVP secretion by increasing plasma osmolality include the water deprivation test (WDT) and the hypertonic saline test (HST). The WDT, considered the gold standard for evaluating PPS in children, has suboptimal diagnostic accuracy, is burdensome, and requires hospitalization. The HST has been used rarely in children due to safety concerns and need for intensive monitoring. The finding that some anterior pituitary stimulating agents also stimulate the posterior pituitary, and the availability of a robust serum\/plasma assay for copeptin as a reliable surrogate of AVP, has allowed development of nonosmotic, copeptin\/AVP stimulation tests. In the present review, we focus on these new copeptin stimulation tests, which include single stimuli with intravenous (IV) arginine, IV insulin, intramuscular glucagon, oral levodopa, and double stimuli (IV arginine-insulin or AITT; IV arginine and oral Levodopa\/carbidopa or ALD-ST), which we have previously shown to induce very robust copeptin secretion. Specifically, the ALD-ST differentiated AVP-D from PP in 20 children with high diagnostic accuracy at a cutoff stimulated copeptin of 9.3\u202fpmol\/L. We propose the utilization of the outpatient ALD-ST in the early stages of PPS evaluation in children, given its safety, cost-effectiveness, and limited side effects.<\/jats:p>","DOI":"10.1515\/jpem-2025-0046","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T03:20:34Z","timestamp":1747884034000},"page":"703-717","source":"Crossref","is-referenced-by-count":3,"title":["The changing landscape in the evaluation of hypotonic polyuria in children and adolescents: the role of the new copeptin stimulation tests"],"prefix":"10.1515","volume":"38","author":[{"given":"Luigi R.","family":"Garibaldi","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology , UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh , PA , USA"},{"name":"Department of Pediatrics , 6614 University of Pittsburgh , Pittsburgh , PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Sastry","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology , UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh , PA , USA"},{"name":"Department of Pediatrics , 6614 University of Pittsburgh , Pittsburgh , PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"McPhaul","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute , San Juan Capistrano , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"March","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology , UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh , PA , USA"},{"name":"Department of Pediatrics , 6614 University of Pittsburgh , Pittsburgh , PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"2025071812031900322_j_jpem-2025-0046_ref_001","doi-asserted-by":"crossref","unstructured":"Christ-Crain, M. 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Approach to the patient: \u201cutility of the copeptin assay\u201d. J\u00a0Clin Endocrinol Metab 2022;107:1727\u201338. https:\/\/doi.org\/10.1210\/clinem\/dgac070.","DOI":"10.1210\/clinem\/dgac070"},{"key":"2025071812031900322_j_jpem-2025-0046_ref_024","doi-asserted-by":"crossref","unstructured":"Fenske, WK, Schnyder, I, Koch, G, Walti, C, Pfister, M, Kopp, P, et al.. Release and decay kinetics of copeptin vs AVP in response to osmotic alterations in healthy volunteers. J\u00a0Clin Endocrinol Metab 2018;103:505\u201313. https:\/\/doi.org\/10.1210\/jc.2017-01891.","DOI":"10.1210\/jc.2017-01891"},{"key":"2025071812031900322_j_jpem-2025-0046_ref_025","doi-asserted-by":"crossref","unstructured":"Balanescu, S, Kopp, P, Gaskill, MB, Morgenthaler, NG, Schindler, C, Rutishauser, J. Correlation of plasma copeptin and vasopressin concentrations in hypo-iso-and hyperosmolar States. 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