{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:38:23Z","timestamp":1786639103881,"version":"build-2736575974"},"reference-count":40,"publisher":"Bioscientifica","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The desmopressin stimulation test (DesST) is used to identify Cushing disease (CD). Reportedly, most healthy people and patients with non-neoplastic hypercortisolism lack a significant response. We aimed to evaluate and improve DesST specificity (Sp).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Prospective evaluation of four DesST protocols in healthy volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty healthy volunteers underwent four DesST protocols in a randomized order. Protocols involved fluid restriction with desmopressin 10 \u00b5g (10NPO; \u2018standard\u2019), 4 \u00b5g (4NPO), and 10 \u00b5g preceded by dexamethasone 1 mg (10+DexNPO); and desmopressin 10 \u00b5g without fluid restriction (10H2O). We evaluated Sp for each protocol, using established response criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Previous criteria of relative increases of 35% and\/or 20% for ACTH and cortisol, respectively, had low Sp: 50% (95% CI: 28\u201372%; 10NPO) to 85% (95% CI: 69\u2013100%; 10+DexNPO). Using absolute ACTH increase &amp;gt;8.1 pmol\/L (37 pg\/mL) improved Sp to 100% across all protocols. Compared with 10NPO, median ACTH and cortisol were lower throughout during 10+DexNPO and also at +15 min during 4NPO (ACTH: 4.4 vs 4.9 pmol\/L (19.9 vs 22.1 pg\/mL), P = 0.06; cortisol: 248 vs 284 nmol\/L (9.0 vs 10.3 \u00b5g\/dL), P = 0.01). 10H2O and 10NPO results were similar. Adverse events were mild; hyponatremia occurred after 5\/80 tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>After desmopressin, healthy volunteers have small absolute increases in ACTH and cortisol that equate to large relative changes from baseline. Optimized response criteria should likely incorporate absolute values. Fluid restriction did not impact Sp, but using a lower desmopressin dose and dexamethasone pre-treatment are promising ways to improve diagnostic accuracy, if sensitivity is maintained in CD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance statement<\/jats:title>\n                    <jats:p>Half of healthy volunteers had a response consistent with Cushing disease (CD) during a commonly used 10 \u00b5g desmopressin stimulation test, interpreted using relative ACTH and\/or cortisol increases. This puts the test\u2019s reliability for excluding CD in question, particularly in settings of mild hypercortisolism. These situations include differentiating CD from non-neoplastic hypercortisolism, identifying cyclic ectopic ACTH-producing tumors during nadir phases, and establishing early CD recurrence. Optimized response criteria likely require absolute ACTH and\/or cortisol cutoffs. Using a reduced 4 \u00b5g dose of desmopressin or pre-treatment with 1 mg dexamethasone improved test specificity, offering promising ways to improve test performance if sensitivity is maintained in CD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration number<\/jats:title>\n                    <jats:p>NCT06635629.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-26-0270","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:37:48Z","timestamp":1785494268000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of desmopressin stimulation test specificity in healthy volunteers"],"prefix":"10.1530","volume":"15","author":[{"given":"Henrik","family":"Elenius","sequence":"first","affiliation":[{"name":"Diabetes and Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 , , ,","place":["Bethesda, Maryland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brielle M","family":"Brown","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 , , ,","place":["Bethesda, Maryland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raven","family":"McGlotten","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 , , ,","place":["Bethesda, Maryland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Moore","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 , , ,","place":["Bethesda, Maryland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0534-8025","authenticated-orcid":true,"given":"Lynnette K","family":"Nieman","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1 , , ,","place":["Bethesda, Maryland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2026081311364457800_bib1","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/S0140-6736(23)01961-X","article-title":"Cushing's syndrome","volume":"402","author":"Gadelha","year":"2023","journal-title":"Lancet"},{"key":"2026081311364457800_bib2","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1001\/jama.1993.03500170062035","article-title":"Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. A new test to distinguish Cushing\u2019s syndrome from pseudo-Cushing\u2019s states","volume":"269","author":"Yanovski","year":"1993","journal-title":"JAMA"},{"key":"2026081311364457800_bib3","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1210\/jc.2017-00115","article-title":"Regulation of pulsatile and entropic ACTH secretion under fixed exogenous secretagogue clamps","volume":"102","author":"Roelfsema","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib4","doi-asserted-by":"crossref","first-page":"e182","DOI":"10.1210\/clinem\/dgad454","article-title":"Ovine CRH stimulation and 8 mg dexamethasone suppression tests in 323 patients with ACTH-dependent Cushing\u2019s syndrome","volume":"109","author":"Elenius","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1365-2265.1993.tb00341.x","article-title":"The desmopressin stimulation test in the differential diagnosis of Cushing\u2019s syndrome","volume":"38","author":"Malerbi","year":"1993","journal-title":"Clin Endocrinol"},{"key":"2026081311364457800_bib6","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1007\/s40618-023-02113-4","article-title":"Shortage of hCRH for the diagnosis of endogenous CS: the end of an era or the beginning of a new journey?","volume":"46","author":"Ceccato","year":"2023","journal-title":"J Endocrinol Investig"},{"key":"2026081311364457800_bib7","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1210\/jcem-59-6-1103","article-title":"Human corticotropin-releasing factor in man: pharmacokinetic properties and dose-response of plasma adrenocorticotropin and cortisol secretion","volume":"59","author":"Schurmeyer","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib8","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.3390\/ijms23126469","article-title":"The role of glucocorticoid receptor in the pathophysiology of pituitary corticotroph adenomas","volume":"23","author":"Regazzo","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026081311364457800_bib9","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1046\/j.1365-2265.1997.1330954.x","article-title":"Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess","volume":"46","author":"Colombo","year":"1997","journal-title":"Clin Endocrinol"},{"key":"2026081311364457800_bib10","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1507\/endocrj.44.687","article-title":"Desmopressin stimulation test for diagnosis of ACTH-dependent Cushing\u2019s syndrome","volume":"44","author":"Sakai","year":"1997","journal-title":"Endocr J"},{"key":"2026081311364457800_bib11","first-page":"1646","article-title":"The desmopressin and combined CRH-desmopressin tests in the differential diagnosis of ACTH-dependent Cushing\u2019s syndrome: constraints imposed by the expression of V2 vasopressin receptors in tumors with ectopic ACTH secretion","volume":"87","author":"Tsagarakis","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib12","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1046\/j.1365-2265.1999.00830.x","article-title":"Assessment of cortisol and ACTH responses to the desmopressin test in patients with Cushing\u2019s syndrome and simple obesity","volume":"51","author":"Tsagarakis","year":"1999","journal-title":"Clin Endocrinol"},{"key":"2026081311364457800_bib13","first-page":"176","article-title":"A combined test using desmopressin and corticotropin-releasing hormone in the differential diagnosis of Cushing\u2019s syndrome","volume":"82","author":"Newell-Price","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib14","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1507\/endocrj.EJ20-0837","article-title":"The usefulness of the combined high-dose dexamethasone suppression test and desmopressin stimulation test in establishing the source of ACTH secretion in ACTH-dependent Cushing\u2019s syndrome","volume":"68","author":"Qiao","year":"2021","journal-title":"Endocr J"},{"key":"2026081311364457800_bib15","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s11102-016-0729-y","article-title":"Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome","volume":"19","author":"Barbot","year":"2016","journal-title":"Pituitary"},{"key":"2026081311364457800_bib16","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1507\/endocrj.K08E-353","article-title":"Evaluation of diagnostic tests for ACTH-dependent Cushing\u2019s syndrome","volume":"56","author":"Suda","year":"2009","journal-title":"Endocr J"},{"key":"2026081311364457800_bib17","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1046\/j.1365-2265.2001.01260.x","article-title":"The limited value of the desmopressin test in the diagnostic approach to Cushing\u2019s syndrome","volume":"54","author":"Terzolo","year":"2001","journal-title":"Clin Endocrinol"},{"key":"2026081311364457800_bib18","doi-asserted-by":"crossref","first-page":"243","DOI":"10.14310\/horm.2002.1204","article-title":"The response of corticotropin and adrenal steroids to desmopressin stimulation in patients with various forms of hypercortisolism","volume":"7","author":"Marova","year":"2008","journal-title":"Hormones"},{"key":"2026081311364457800_bib19","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1210\/clinem\/dgaa409","article-title":"Non-invasive diagnostic strategy in ACTH-dependent Cushing\u2019s syndrome","volume":"105","author":"Frete","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib20","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1530\/eje.1.02278","article-title":"Ectopic ACTH syndrome: our experience with 25 cases","volume":"155","author":"Salgado","year":"2006","journal-title":"Eur J Endocrinol"},{"key":"2026081311364457800_bib21","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1007\/BF03345640","article-title":"The role of non-invasive dynamic tests in the diagnosis of Cushing\u2019s syndrome","volume":"31","author":"Vilar","year":"2008","journal-title":"J Endocrinol Investig"},{"key":"2026081311364457800_bib22","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1172\/JCI118547","article-title":"The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome","volume":"97","author":"de Keyzer","year":"1996","journal-title":"J Clin Investig"},{"key":"2026081311364457800_bib23","first-page":"2233","article-title":"Cortisol and adrenocorticotropin response to desmopressin in women with Cushing\u2019s disease compared with depressive illness","volume":"81","author":"Malerbi","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.20452\/pamw.65","article-title":"[The desmopressin test in the diagnosis of Cushing\u2019s disease]","volume":"117","author":"Gasi\u0144iska","year":"2007","journal-title":"Pol Arch Med Wewn"},{"key":"2026081311364457800_bib25","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1046\/j.1365-2265.1999.00850.x","article-title":"ACTH and cortisol release following intravenous desmopressin: a dose-response study","volume":"51","author":"Scott","year":"1999","journal-title":"Clin Endocrinol"},{"key":"2026081311364457800_bib26","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/S0006-3223(98)00232-7","article-title":"Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers","volume":"45","author":"Scott","year":"1999","journal-title":"Biol Psychiatry"},{"key":"2026081311364457800_bib27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/j.1552-4604.1976.tb01529.x","article-title":"Effect of 1-deamino-5-D-arginine vasopressin (DDAVP) on plasma cortisol (hydrocortisone)","volume":"16","author":"Rado","year":"1976","journal-title":"J Clin Pharmacol"},{"key":"2026081311364457800_bib28","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1365-2141.1981.tb02789.x","article-title":"Response of factor VIII\/von Willebrand factor to DDAVP in healthy subjects and patients with haemophilia A and von Willebrand\u2019s disease","volume":"47","author":"Mannucci","year":"1981","journal-title":"Br J Haematol"},{"key":"2026081311364457800_bib29","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/cen.12661","article-title":"Evaluation of the DDAVP test in the diagnosis of Cushing\u2019s disease","volume":"82","author":"Rollin","year":"2015","journal-title":"Clin Endocrinol"},{"key":"2026081311364457800_bib30","first-page":"3569","article-title":"The desmopressin test in the differential diagnosis between Cushing\u2019s disease and pseudo-Cushing states","volume":"85","author":"Moro","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib31","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1365-2265.2006.02717.x","article-title":"The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo-Cushing\u2019s states","volume":"66","author":"Pecori Giraldi","year":"2007","journal-title":"Clin Endocrinol"},{"key":"2026081311364457800_bib32","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1210\/jc.2009-1146","article-title":"Use of the desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing\u2019s disease","volume":"95","author":"Tirabassi","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib33","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1210\/clinem\/dgae250","article-title":"European Society of endocrinology and endocrine society joint clinical guideline: diagnosis and therapy of Glucocorticoid-induced adrenal insufficiency","volume":"109","author":"Beuschlein","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081311364457800_bib34","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1007\/s40618-023-02099-z","article-title":"Second-line tests in the differential diagnosis of neoplastic and non-neoplastic hypercortisolism: a systematic review and meta-analysis","volume":"46","author":"Mondin","year":"2023","journal-title":"J Endocrinol Investig"},{"key":"2026081311364457800_bib35","doi-asserted-by":"crossref","first-page":"R205","DOI":"10.1530\/EJE-16-0946","article-title":"Diagnosis of endocrine disease: differentiation of pathologic\/neoplastic hypercortisolism (Cushing\u2019s syndrome) from physiologic\/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing\u2019s syndrome)","volume":"176","author":"Findling","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"2026081311364457800_bib36","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1515\/cclm-2016-0559","article-title":"Comparison of ex vivo stability of copeptin and vasopressin","volume":"55","author":"Heida","year":"2017","journal-title":"Clin Chem Lab Med"},{"key":"2026081311364457800_bib37","first-page":"R635","article-title":"Glucocorticoid inhibition of neurohypophysial vasopressin secretion","volume":"252","author":"Raff","year":"1987","journal-title":"Am J Physiol"},{"key":"2026081311364457800_bib38","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1530\/EC-14-0086","article-title":"Role of endogenous ACTH on circadian aldosterone rhythm in patients with primary aldosteronism","volume":"3","author":"Sonoyama","year":"2014","journal-title":"Endocr Connect"},{"key":"2026081311364457800_bib39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1172\/JCI9516","article-title":"Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP","volume":"106","author":"Kaufmann","year":"2000","journal-title":"J Clin Investig"},{"key":"2026081311364457800_bib40","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1055\/s-0043-100113","article-title":"Coagulation profile in patients with different etiologies for cushing syndrome: a prospective observational study","volume":"49","author":"Tirosh","year":"2017","journal-title":"Horm Metab Res"}],"container-title":["Endocrine Connections"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0270\/523011\/ec-26-0270.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0270\/523011\/ec-26-0270.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:04:51Z","timestamp":1786637091000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article\/15\/8\/e260270\/77922\/Evaluation-of-desmopressin-stimulation-test"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1530\/ec-26-0270","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"article-number":"e260270"}}