{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:30:48Z","timestamp":1785180648016,"version":"3.55.0"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K16370"],"award-info":[{"award-number":["21K16370"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21KK0149"],"award-info":[{"award-number":["21KK0149"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)\u2010independent and ACTH\u2010dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH\u2010independent hypercortisolemia. ACTH is derived from pro\u2010opiomelanocortin, and its processing involves prohormone convertase 1\/3. High\u2010molecular\u2010weight ACTH is generally found in ACTH\u2010producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high\u2010molecular\u2010weight ACTH alternation during ACTH\u2010independent Cushing's syndrome remain unclear. A 40\u2010year\u2010old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH\u2010independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non\u2010suppressed ACTH (18.1\u2009pg\/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high\u2010molecular\u2010weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high\u2010molecular\u2010weight ACTH levels was observed. Histological findings revealed cortisol\u2010producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high\u2010molecular\u2010weight ACTH. The observed decline in high\u2010molecular\u2010weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic\u2013pituitary\u2013adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH\u2010related molecules warrants further exploration to enhance our understanding of the hypothalamic\u2013pituitary\u2013adrenal axis feedback mechanism.<\/jats:p>","DOI":"10.1111\/jne.13438","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T04:09:08Z","timestamp":1723522148000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Understanding negative feedback: Changes in high\u2010molecular\u2010weight adrenocorticotropic hormone in adrenocorticotropic hormone\u2010independent Cushing's syndrome"],"prefix":"10.1111","volume":"36","author":[{"given":"Yuto","family":"Ichinose","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine Kobe University Hospital  Kobe 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