{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T19:35:31Z","timestamp":1774294531694,"version":"3.50.1"},"reference-count":28,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2023-0390_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Although AVP and its surrogate, copeptin, are mainly regulated by osmotic and volume stimuli, their secretion is also elicited by stress and growth hormone (GH) stimulating agents. The aim of this report is to describe unusual patterns of copeptin response in a subset of children undergoing GH stimulation tests (GH-ST).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2023-0390_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a secondary analysis of a cohort of 93 healthy short children with no polydipsia, polyuria or fluid\/electrolyte abnormalities, undergoing GH-ST with intravenous arginine, insulin, oral clonidine, or L-Dopa\/carbidopa in various combinations. Serum copeptin concentrations were measured 1\u20133\u202fmin after phlebotomy (0\u202fmin) and at 60, 90, 120\u202fmin during GH-ST.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2023-0390_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In 85 subjects (normal response group, NRG) serum copeptin concentrations increased from a 0\u202fmin median of 9\u202fpmol\/L (IQR 6, 11.5) (all values\u00a0\u226421) to a median peak between 60 and 120\u202fmin of 22 (IQR15, 38)\u202fpmol\/L, which varied depending on the stimulating agent. Conversely, in the eight outliers, copeptin concentrations decreased gradually from a median of 154 (IQR 61, 439)\u202fpmol\/L (all\u00a0\u226540\u202fpmol\/L) to values as low as 14\u202f% of the basal value, by 120\u202fmin. Test-associated anxiety was described in 17 subjects in the NRG (20\u202f%) and five of the outliers (63\u202f%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2023-0390_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A distinctive pattern of very elevated serum copeptin concentrations occurred in 9\u202f% of children undergoing GH-ST, similar to reports in previous pediatric studies. Etiology may include pain or stress of phlebotomy. This phenomenon should be recognized for proper interpretation of copeptin values in children.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2023-0390","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T12:31:08Z","timestamp":1700656268000},"page":"8-14","source":"Crossref","is-referenced-by-count":5,"title":["Very elevated serum copeptin concentrations occur in a subset of healthy children in the minutes after phlebotomy"],"prefix":"10.1515","volume":"37","author":[{"given":"Shruti","family":"Sastry","sequence":"first","affiliation":[{"name":"Department of Pediatrics , University of Pittsburgh , Pittsburgh , PA , USA"},{"name":"Division of Pediatric Endocrinology , UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh , PA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine A.","family":"March","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , University of Pittsburgh , Pittsburgh , PA , USA"},{"name":"Division of Pediatric Endocrinology , UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh , PA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"McPhaul","sequence":"additional","affiliation":[{"name":"Quest Diagnostics , San Juan Capistrano , CA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi R.","family":"Garibaldi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , University of Pittsburgh , Pittsburgh , PA , USA"},{"name":"Division of Pediatric Endocrinology , UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh , PA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"2024010910115249335_j_jpem-2023-0390_ref_001","doi-asserted-by":"crossref","unstructured":"Szczepanska-Sadowska, E, Zera, T, Sosnowski, P, Cudnoch-Jedrzejewska, A, Puszko, A, Misicka, A. Vasopressin and related peptides; potential value in diagnosis, prognosis and treatment of clinical disorders. Curr Drug Metab 2017;18:306\u201345. https:\/\/doi.org\/10.2174\/1389200218666170119145900.","DOI":"10.2174\/1389200218666170119145900"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_002","doi-asserted-by":"crossref","unstructured":"Kloter, M, Gregoriano, C, Haag, E, Kutz, A, Mueller, B, Schuetz, P. Risk assessment of sepsis through measurement of proAVP (copeptin): a secondary analysis of the TRIAGE study. Endocr Connect 2021;10:995\u20131005. https:\/\/doi.org\/10.1530\/ec-21-0211.","DOI":"10.1530\/EC-21-0211"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_003","doi-asserted-by":"crossref","unstructured":"Jochberger, S, Morgenthaler, NG, Mayr, VD, Luckner, G, Wenzel, V, Ulmer, H, et al.. Copeptin and arginine vasopressin concentrations in critically ill patients. J Clin Endocrinol Metab 2006;91:4381\u20136. https:\/\/doi.org\/10.1210\/jc.2005-2830.","DOI":"10.1210\/jc.2005-2830"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_004","doi-asserted-by":"crossref","unstructured":"Ahmed, TAN, Johny, JS, Abdel-Malek, MY, Fouad, DA. The additive value of copeptin for early diagnosis and prognosis of acute coronary syndromes. Am J Emerg Med 2021;50:413\u201321. https:\/\/doi.org\/10.1016\/j.ajem.2021.08.069.","DOI":"10.1016\/j.ajem.2021.08.069"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_005","doi-asserted-by":"crossref","unstructured":"Bonnet, L, Marquant, E, Fromonot, J, Hamouda, I, Berbis, J, Godefroy, A, et al.. Copeptin assays in children for the differential diagnosis of polyuria-polydipsia syndrome and reference levels in hospitalized children. Clin Endocrinol 2022;96:47\u201353. https:\/\/doi.org\/10.1111\/cen.14620.","DOI":"10.1111\/cen.14620"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_006","doi-asserted-by":"crossref","unstructured":"Binder, G, Weber, K, Peter, A, Schweizer, R. Arginine-stimulated copeptin in children and adolescents. Clin Endocrinol 2023;98:548\u201353. https:\/\/doi.org\/10.1111\/cen.14880.","DOI":"10.1111\/cen.14880"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_007","doi-asserted-by":"crossref","unstructured":"March, CA, Sastry, S, McPhaul, MJ, Wheeler, SE, Garibaldi, L. Combined arginine and insulin stimulation elicits a robust and consistent copeptin response in short children. Horm Res Paediatr 2023;96:395\u2013403. https:\/\/doi.org\/10.1159\/000528661.","DOI":"10.1159\/000528661"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_008","doi-asserted-by":"crossref","unstructured":"Winzeler, B, Cesana-Nigro, N, Refardt, J, Vogt, DR, Imber, C, Morin, B, et al.. Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. Lancet 2019;394:587\u201395. https:\/\/doi.org\/10.1016\/s0140-6736(19)31255-3.","DOI":"10.1016\/S0140-6736(19)31255-3"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_009","doi-asserted-by":"crossref","unstructured":"Rothballer, AB. Changes in the rat neurohypophysis induced by painful stimuli with particular reference to neurosecretory material. Anatomical Rec 1953;115:21\u201341. https:\/\/doi.org\/10.1002\/ar.1091150103.","DOI":"10.1002\/ar.1091150103"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_010","doi-asserted-by":"crossref","unstructured":"Morgenthaler, NG, Struck, J, Jochberger, S, Dunser, MW. Copeptin: clinical use of a new biomarker. Trends Endocrinol Metab 2008;19:43\u20139. https:\/\/doi.org\/10.1016\/j.tem.2007.11.001.","DOI":"10.1016\/j.tem.2007.11.001"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_011","doi-asserted-by":"crossref","unstructured":"Mirsky, IA, Paulisch, G, Stein, M, Jinks, R. The antidiuretic activity of the plasma of adrenalectomized, hypophysectomized and adrenalectomized-hypophysectomized rats. Endocrinology 1954;54:691\u20137. https:\/\/doi.org\/10.1210\/endo-54-6-691.","DOI":"10.1210\/endo-54-6-691"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_012","doi-asserted-by":"crossref","unstructured":"Ueta, Y, Dayanithi, G, Fujihara, H. Hypothalamic vasopressin response to stress and various physiological stimuli: visualization in transgenic animal models. Horm Behav 2011;59:221\u20136. https:\/\/doi.org\/10.1016\/j.yhbeh.2010.12.007.","DOI":"10.1016\/j.yhbeh.2010.12.007"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_013","doi-asserted-by":"crossref","unstructured":"Kendler, KS, Weitzman, RE, Fisher, DA. The effect of pain on plasma arginine vasopressin concentrations in man. Clin Endocrinol 1978;8:89\u201394. https:\/\/doi.org\/10.1111\/j.1365-2265.1978.tb02156.x.","DOI":"10.1111\/j.1365-2265.1978.tb02156.x"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_014","doi-asserted-by":"crossref","unstructured":"Haas, M, Glick, SM. Radioimmunoassayable plasma vasopressin associated with surgery. Arch Surg 1978;113:597\u2013600. https:\/\/doi.org\/10.1001\/archsurg.1978.01370170059011.","DOI":"10.1001\/archsurg.1978.01370170059011"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_015","doi-asserted-by":"crossref","unstructured":"Deveci, OS, Ozmen, C, Karaaslan, MB, Celik, AI, Rahimova, H, Akray, A, et al.. Increased circulating copeptin levels are associated with vaso-occlusive crisis and right ventricular dysfunction in sickle cell anemia. Med Princ Pract 2022;31:47\u201353. https:\/\/doi.org\/10.1159\/000521216.","DOI":"10.1159\/000521216"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_016","doi-asserted-by":"crossref","unstructured":"Christ-Crain, M, Refardt, J, Winzeler, B. Approach to the patient: \u201cutility of the copeptin assay\u201d. J Clin Endocrinol Metab 2022;107:1727\u201338. https:\/\/doi.org\/10.1210\/clinem\/dgac070.","DOI":"10.1210\/clinem\/dgac070"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_017","doi-asserted-by":"crossref","unstructured":"Chortis, V, Bancos, I, Crowley, RK, Arlt, W. Supine or sitting plasma metanephrine screening? A unifying solution for patients and doctors. Clin Endocrinol 2015;82:776\u20137. https:\/\/doi.org\/10.1111\/cen.12659.","DOI":"10.1111\/cen.12659"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_018","doi-asserted-by":"crossref","unstructured":"Darr, R, Pamporaki, C, Peitzsch, M, Miehle, K, Prejbisz, A, Peczkowska, M, et al.. Biochemical diagnosis of phaeochromocytoma using plasma-free normetanephrine, metanephrine and methoxytyramine: importance of supine sampling under fasting conditions. Clin Endocrinol 2014;80:478\u201386. https:\/\/doi.org\/10.1111\/cen.12327.","DOI":"10.1111\/cen.12327"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_019","doi-asserted-by":"crossref","unstructured":"Eisenhofer, G, Deutschbein, T, Constantinescu, G, Langton, K, Pamporaki, C, Calsina, B, et al.. Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma. Clin Chem Lab Med 2020;59:353\u201363. https:\/\/doi.org\/10.1515\/cclm-2020-0904.","DOI":"10.1515\/cclm-2020-0904"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_020","doi-asserted-by":"crossref","unstructured":"Eijkelenkamp, K, van Geel, EH, Kerstens, MN, van Faassen, M, Kema, IP, Links, TP, et al.. Blood sampling for metanephrines comparing venipuncture vs. indwelling intravenous cannula in healthy subjects. Clin Chem Lab Med 2020;58:1681\u20136. https:\/\/doi.org\/10.1515\/cclm-2020-0022.","DOI":"10.1515\/cclm-2020-0022"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_021","doi-asserted-by":"crossref","unstructured":"Eichler, I, Eichler, HG, Rotter, M, Kyrle, PA, Gasic, S, Korn, A. Plasma concentrations of free and sulfoconjugated dopamine, epinephrine, and norepinephrine in healthy infants and children. Klin Wochenschr 1989;67:672\u20135. https:\/\/doi.org\/10.1007\/bf01718028.","DOI":"10.1007\/BF01718028"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_022","unstructured":"Sastry, S, March, C, Garibaldi, L, McPhaul, M, Wheeler, S, editors. The effect of phlebotomy and placement of an intravenous catheter on plasma catecholamine and serum copeptin concentrations. Hormone research in paediatrics. Allschwilerstrasse 10, Ch-4009 Basel, Switzerland: Karger; 2022."},{"key":"2024010910115249335_j_jpem-2023-0390_ref_023","doi-asserted-by":"crossref","unstructured":"Aykanat Girgin, B, Gol, I. Reducing pain and fear in children during venipuncture: a randomized controlled study. Pain Manag Nurs 2020;21:276\u201382. https:\/\/doi.org\/10.1016\/j.pmn.2019.07.006.","DOI":"10.1016\/j.pmn.2019.07.006"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_024","doi-asserted-by":"crossref","unstructured":"Siegenthaler, J, Walti, C, Urwyler, SA, Schuetz, P, Christ-Crain, M. Copeptin concentrations during psychological stress: the PsyCo study. Eur J Endocrinol 2014;171:737\u201342. https:\/\/doi.org\/10.1530\/eje-14-0405.","DOI":"10.1530\/EJE-14-0405"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_025","doi-asserted-by":"crossref","unstructured":"Urwyler, SA, Schuetz, P, Sailer, C, Christ-Crain, M. Copeptin as a stress marker prior and after a written examination--the CoEXAM study. Stress 2015;18:134\u20137. https:\/\/doi.org\/10.3109\/10253890.2014.993966.","DOI":"10.3109\/10253890.2014.993966"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_026","doi-asserted-by":"crossref","unstructured":"Fenske, W, Refardt, J, Chifu, I, Schnyder, I, Winzeler, B, Drummond, J, et al.. A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med 2018;379:428\u201339. https:\/\/doi.org\/10.1056\/nejmoa1803760.","DOI":"10.1056\/NEJMoa1803760"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_027","doi-asserted-by":"crossref","unstructured":"Tuli, G, Munarin, J, Tessaris, D, Einaudi, S, Matarazzo, P, de Sanctis, L. Distribution of plasma copeptin levels and influence of obesity in children and adolescents. Eur J Pediatr 2021;180:119\u201326. https:\/\/doi.org\/10.1007\/s00431-020-03777-3.","DOI":"10.1007\/s00431-020-03777-3"},{"key":"2024010910115249335_j_jpem-2023-0390_ref_028","doi-asserted-by":"crossref","unstructured":"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\u2013polydipsia syndrome: a prospective multicenter study. J Clin Endocrinol Metab 2015;100:2268\u201374. https:\/\/doi.org\/10.1210\/jc.2014-4507.","DOI":"10.1210\/jc.2014-4507"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2023-0390\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2023-0390\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T10:12:26Z","timestamp":1704795146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2023-0390\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,11,23]]},"published-print":{"date-parts":[[2024,1,29]]}},"alternative-id":["10.1515\/jpem-2023-0390"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2023-0390","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"value":"0334-018X","type":"print"},{"value":"2191-0251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,23]]}}}