{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:30:47Z","timestamp":1785180647488,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JUSTICE Group 1 2023"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Case Reports in Endocrinology"],"published-print":{"date-parts":[[2024,3,25]]},"abstract":"<jats:p>Production of the high-molecular-weight forms of adrenocorticotropic hormone (big-ACTH) has been reported in a small number of ectopic ACTH syndrome and ACTH-producing pituitary macroadenoma. However, perioperative changes in big-ACTH in patients with subclinical Cushing\u2019s disease have not been reported. A 63-year-old woman presented 25\u2009\u00d7\u200920\u2009\u00d7\u200920-mm-sized macroadenoma in the pituitary gland. Her early morning plasma ACTH and cortisol levels were 111\u2009pg\/mL and 11.6\u2009\u03bcg\/dL, respectively. Cushingoid features and diurnal variation in plasma cortisol levels were not observed. The patient\u2019s urinary free cortisol (UFC) was 59.3\u2009\u03bcg\/day. The corticotropin-releasing hormone (CRH) test showed that plasma ACTH levels were 1.5 times higher than the preload value. The overnight dexamethasone suppression test (DST) showed that the plasma cortisol level was not suppressed by 0.5\u2009mg of dexamethasone (DEX) but was suppressed by 8\u2009mg of DEX. Inferior pyramidal sinus sampling was consistent with Cushing\u2019s disease. Taken together, the patient was clinically diagnosed with subclinical Cushing\u2019s disease caused by an ACTH-producing pituitary adenoma. Endoscopic transsphenoidal adenomectomy was performed. In the postoperative CRH test, plasma ACTH levels showed six-fold increase. The postoperative DST showed cortisol suppression at 0.5\u2009mg of DEX. The UFC levels decreased to 35.1\u2009\u03bcg\/day. Pituitary contrast-enhanced MRI revealed no residual tumor, and plasma ACTH and cortisol levels remained within normal ranges. Gel filtration of preoperative and postoperative plasma ACTH was performed, and a high molecular weight fraction of ACTH was detected, which markedly decreased postoperatively. The absence of Cushingoid features and the lack of significant cortisol hypersecretion in this case were thought to be due in part to big-ACTH, which has low bioactivity. By careful evaluation of laboratory and clinical findings, we identified it as a big-ACTH-producing adenoma. This is the first report of a case in which the big-ACTH transition was observed perioperative and is a valuable case.<\/jats:p>","DOI":"10.1155\/2024\/8721614","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T01:20:07Z","timestamp":1711416007000},"page":"1-6","source":"Crossref","is-referenced-by-count":3,"title":["Subclinical Cushing\u2019s Disease with High-Molecular-Weight Forms of Adrenocorticotropic Hormone Production"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5011-2652","authenticated-orcid":true,"given":"Takahiko","family":"Inukai","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5273-4602","authenticated-orcid":true,"given":"Nozomi","family":"Harai","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4850-9889","authenticated-orcid":true,"given":"Yukie","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7092-5913","authenticated-orcid":true,"given":"Tadatsugu","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0301-7672","authenticated-orcid":true,"given":"Airi","family":"Antoku","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6318-1500","authenticated-orcid":true,"given":"Yuko","family":"Muroi","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3590-9228","authenticated-orcid":true,"given":"Masakazu","family":"Ogiwara","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2863-4561","authenticated-orcid":true,"given":"Kyoichiro","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej15-0446"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.45.1809"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-65-6-1296"},{"key":"4","first-page":"51","article-title":"[A case of Silent corticotroph adenoma with dissociation of blood ACTH\/cortisol ratio and histopathologic changes during the course of several Hardy surgeries: morphology, function, and clinical picture.] Sukai ni wataru Hardy shujyutu no keikacyu, kecchyu ACTH\/cortisol hi no kairi to soshikisaibouzou no henka wo mitometa Silent corticotroph adenoma no ichirei: keitai\u30fbkinou\u30fbrinshouzou no kentou","volume":"20","author":"M. Tobita","year":"2010","journal-title":"ACTH Related Peptides"},{"key":"5","article-title":"[A Case of Ectopic ACTH-Producing Tumor Diagnosed by Big ACTH Measurement and PET\/CT.] Big ACTH sokutei to PET\/CT ga shindan ni yukou datta ishosei ACTH sanseishuyou no ichirei","volume":"85","author":"M. Konishi","year":"2009","journal-title":"Folia Endocrinologica Japonica"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1023\/b:pitu.0000011172.26649.df"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.51.97"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.3171\/2008.8.jns08154"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1258\/000456303322326371"},{"key":"10","first-page":"37","article-title":"[Development and clinical application of a highly sensitive immune complex transfer EIA (ICT-EIA) for big ACTH (POMC and proACTH) 2: investigation in macroACTHoma (macA) or ectopic ACTH syndrome (EAS). ] big ACTH (POMC to proACTH) ni taisuru koukando immune complex transfer EIA (ICT-EIA) no kaihatsu to rinshououyou2: kyodai ACTH sanseisenshu(macroACTHoma, macA)aruiha ishosei ACTH shoukougun (EAS) deno kentou","volume":"30","author":"H. 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