{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T19:00:17Z","timestamp":1767034817708,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Traditionally, low-dose dexamethasone suppression test (LDDST) was used to confirm the diagnosis of Cushing\u2019s syndrome (CS), and high-dose dexamethasone suppression test (HDDST) was used to differentiate Cushing\u2019s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS), but some studies suggested that HDDST might be replaced by LDDST. For the differential diagnosis of CS, dexamethasone suppression test was usually combined with other tests such as bilateral petrosal sinus sampling (BIPSS) and pituitary magnetic resonance imaging, but the optimal pathway to incorporate these tests is still controversial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To develop an optimized pathway for the differential diagnosis of CD and EAS based on LDDST.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Setting<\/jats:title><jats:p>Single-center retrospective study (2011\u20132019).<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Two hundred sixty-nine CD and 29 EAS patients with pathological diagnosis who underwent consecutive low- and high-dose DST.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For the differential diagnosis of CD and EAS, the area under curve (AUC) of LDDST using urine free cortisol (0.881) was higher than that using serum cortisol (0.685) (p &amp;lt; 0.001) in head-to-head comparison among a subgroup of 108 CD and 10 EAS. The AUC of LDDST (0.883) was higher than that of HDDST (0.834) among all the included patients. With the cutoff of &amp;lt;26%, the sensitivity and specificity of LDDST were 39.4% and 100%. We designed a new pathway in which BIPSS was only reserved for those patients with unsuppressed LDDST and adenoma &amp;lt;6mm, yielding an overall sensitivity of 97.7% and specificity of 86.7%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>LDDST had similar value to HDDST in differentiating CD and EAS using the specific cutoff point. The pathway that combined LDDST and BIPSS could differentiate CD and EAS accurately.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.720823","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T02:45:27Z","timestamp":1630723527000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["An Optimized Pathway for the Differential Diagnosis of ACTH-Dependent Cushing\u2019s Syndrome Based on Low-Dose Dexamethasone Suppression Test"],"prefix":"10.3389","volume":"12","author":[{"given":"Kang","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anli","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaolin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61375-1","article-title":"Cushing\u2019s Syndrome","volume":"386","author":"Lacroix","year":"2015","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-20-12-1539","article-title":"Tests of Pituitary-Adrenal Suppressibility in the Diagnosis of Cushing\u2019s Syndrome","volume":"20","author":"Liddle","year":"1960","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030871","article-title":"Diagnosis and Complications of Cushing\u2019s Syndrome: A Consensus Statement","volume":"88","author":"Arnaldi","year":"2003","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.19.5.0346","article-title":"The Diagnosis and Differential Diagnosis of Cushing\u2019s Syndrome and Pseudo-Cushing\u2019s States","volume":"19","author":"Newell-Price","year":"1998","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-116-3-211","article-title":"Urine Free Cortisol in the High-Dose Dexamethasone Suppression Test for the Differential Diagnosis of the Cushing Syndrome","volume":"116","author":"Flack","year":"1992","journal-title":"Ann Intern Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.78.2.8106630","article-title":"A Comparison of the Standard High Dose Dexamethasone Suppression Test and the Overnight 8-Mg Dexamethasone Suppression Test for the Differential Diagnosis of Adrenocorticotropin-Dependent Cushing\u2019s Syndrome","volume":"78","author":"Dichek","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030510","article-title":"Discriminatory Value of the Low-Dose Dexamethasone Suppression Test in Establishing the Diagnosis and Differential Diagnosis of Cushing\u2019s Syndrome","volume":"88","author":"Isidori","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-73-2-408","article-title":"Routine Inferior Petrosal Sinus Sampling in the Differential Diagnosis of Adrenocorticotropin (ACTH)-Dependent Cushing\u2019s Syndrome: Early Recognition of the Occult Ectopic ACTH Syndrome","volume":"73","author":"Findling","year":"1991","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.82.6.3991","article-title":"Effectiveness Versus Efficacy: The Limited Value in Clinical Practice of High Dose Dexamethasone Suppression Testing in the Differential Diagnosis of Adrenocorticotropin-Dependent Cushing\u2019s Syndrome","volume":"82","author":"Aron","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1159\/000091830","article-title":"The Discriminatory Value of the Low-Dose Dexamethasone Suppression Test in the Investigation of Paediatric Cushing\u2019s Syndrome","volume":"65","author":"Dias","year":"2006","journal-title":"Horm Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e328305082f","article-title":"Work-Up and Management of Paediatric Cushing\u2019s Syndrome","volume":"15","author":"Savage","year":"2008","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4158\/EP161721.RA","article-title":"An Individualized Approach to the Evaluation of Cushing Syndrome","volume":"23","author":"Sharma","year":"2017","journal-title":"Endocr Pract"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(86)90113-3","article-title":"The Corticotropin-Releasing-Hormone Test Versus the High-Dose Dexamethasone Test in the Differential Diagnosis of Cushing\u2019s Syndrome","volume":"2","author":"Hermus","year":"1986","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-016-0729-y","article-title":"Second-Line Tests in the Differential Diagnosis of ACTH-Dependent Cushing\u2019s Syndrome","volume":"19","author":"Barbot","year":"2016","journal-title":"Pituitary"},{"key":"B15","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1056\/NEJM199109263251301","article-title":"Petrosal Sinus Sampling With and Without Corticotropin-Releasing Hormone for the Differential Diagnosis of Cushing\u2019s Syndrome","volume":"325","author":"Oldfield","year":"1991","journal-title":"N Engl J Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1818","article-title":"Treatment of Cushing\u2019s Syndrome: An Endocrine Society Clinical Practice Guideline","volume":"100","author":"Nieman","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz194","article-title":"The Optimal Cut-Off of BIPSS in Differential Diagnosis of ACTH-Dependent Cushing\u2019s Syndrome: Is Stimulation Necessary","volume":"105","author":"Chen","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1054\/jocn.2002.1141","article-title":"Clinical Implications of Dynamic MRI for Pituitary Adenomas: Clinical and Histologic Analysis","volume":"9","author":"Kanou","year":"2002","journal-title":"J Clin Neurosci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1148\/radiology.150.1.6316418","article-title":"Petrosal Sinus Sampling for Cushing Syndrome: Anatomical and Technical Considerations. Work in Progress","volume":"150","author":"Doppman","year":"1984","journal-title":"Radiology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1950)3:1<32::aid-cncr2820030106>3.0.co;2-3","article-title":"Index for Rating Diagnostic Tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0125","article-title":"The Diagnosis of Cushing\u2019s Syndrome: An Endocrine Society Clinical Practice Guideline","volume":"93","author":"Nieman","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.2.440","article-title":"Diagnosis and Management of Cushing\u2019s Syndrome: Results of an Italian Multicentre Study","volume":"84","author":"Invitti","year":"1999","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1530\/eje-16-0967","article-title":"Diagnostic Tests for Cushing\u2019s Syndrome Differ From Published Guidelines: Data From ERCUSYN","volume":"176","author":"Valassi","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B24","article-title":"Ectopic Cushing\u2019s Syndrome in Light of Modern Diagnostic Techniques and Treatment Options","volume":"36","author":"Witek","year":"2015","journal-title":"Neuro Endocrinol Lett"},{"key":"B25","doi-asserted-by":"publisher","first-page":"E5","DOI":"10.3171\/2014.11.FOCUS14766","article-title":"The Role of Inferior Petrosal Sinus Sampling in ACTH-Dependent Cushing\u2019s Syndrome: Review and Joint Opinion Statement by Members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology","volume":"38","author":"Pecori Giraldi","year":"2015","journal-title":"Neurosurg Focus"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.720823\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T02:45:30Z","timestamp":1630723530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.720823\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,2]]},"references-count":25,"alternative-id":["10.3389\/fendo.2021.720823"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.720823","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2021,9,2]]},"article-number":"720823"}}