{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:26:27Z","timestamp":1787765187906,"version":"build-2784847793"},"reference-count":17,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:p>A 36-year-old man with a 1-year history of diabetes mellitus was referred to the authors' hospital for further endocrinological evaluation of acromegaly. On physical examination, typical acromegalic features but no typical cushingoid features were observed. The clinical diagnosis of growth hormone (GH)\u2013producing pituitary adenoma was confirmed by MR imaging findings, nonsuppression of serum GH levels during a 75-g oral glucose tolerance test (trough GH 6.33 ng\/ml), and elevated serum insulin-like growth factor\u2014I levels (1361.3 ng\/ml). Moreover, autonomic adrenocorticotropic hormone (ACTH) secretion was suspected, based on inadequate suppression of ACTH or cortisol levels by an 0.5-mg overnight dexamethasone suppression test. Analysis of the patient's plasma by using the gel filtration method revealed the presence of a high-molecular-weight (HMW) form of ACTH known to exhibit low biological activity. Transsphenoidal adenomectomy was performed for the pituitary tumor. Immunohistochemical investigation of the resected specimen showed strong and diffuse immunoreactivity to GH and focal immunoreactivity to ACTH. Although there have been a few cases of pituitary adenoma that produced GH and ACTH concomitantly, this is the first report of the detection of HMW ACTH in patients with GH- and ACTH-producing adenomas. Furthermore, the previous cases also did not exhibit typical cushingoid features. It is suggested that the secretion of ACTH in patients with concurrent GH- and ACTH-secreting adenomas might consist of the HMW form and that the HMW ACTH is consequently associated with a subclinical Cushing state.<\/jats:p>","DOI":"10.3171\/2008.8.jns08154","type":"journal-article","created":{"date-parts":[[2008,11,7]],"date-time":"2008-11-07T16:48:10Z","timestamp":1226076490000},"page":"369-373","source":"Crossref","is-referenced-by-count":15,"title":["Combined acromegaly and subclinical Cushing disease related to high-molecular-weight adrenocorticotropic hormone"],"prefix":"10.3171","volume":"110","author":[{"given":"Kenji","family":"Oki","sequence":"first","affiliation":[{"name":"Departments of Molecular and Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiminori","family":"Yamane","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Oda","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomu","family":"Kamei","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwa Jeet","family":"Amatya","sequence":"additional","affiliation":[{"name":"Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Oki","sequence":"additional","affiliation":[{"name":"The Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuoki","family":"Kohno","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-1100369","series-title":"Endocrinol Jpn","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1507\/endocrj1954.38.271","article-title":"A case of pituitary adenoma producing both growth hormone (GH) and adrenocorticotropic hormone (ACTH)","volume":"38","author":"Arita","year":"1991"},{"key":"b2-1100369","series-title":"Am J Med Sci","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1097\/00000441-199211000-00005","article-title":"Case report: acromegaly and Cushing's disease in a patient with synchronous pituitary adenomas","volume":"304","author":"Blevins","year":"1992"},{"key":"b3-1100369","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1210\/jc.2003-030207","article-title":"The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing's syndrome","volume":"89","author":"Findling","year":"2004"},{"key":"b4-1100369","series-title":"J Clin Endocrinol Metab","first-page":"497","article-title":"Impaired processing of proopiomelanocortin in corticotroph macroadenomas","volume":"81","author":"Gibson","year":"1996"},{"key":"b5-1100369","series-title":"Neuroendocrinology","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1159\/000095524","article-title":"Pathology of acromegaly","volume":"83","author":"Horvath","year":"2006"},{"key":"b6-1100369","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"5299","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's syndrome","volume":"88","author":"Isidori","year":"2003"},{"key":"b7-1100369","series-title":"Endocr J","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1507\/endocrj.49.41","article-title":"A case of macroprolactinoma with subclinical growth hormone production","volume":"49","author":"Kageyama","year":"2002"},{"key":"b8-1100369","series-title":"Am J Med Sci","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1097\/00000441-200212000-00007","article-title":"A multihormonal pituitary adenoma with growth hormone and adrenocorticotropic hormone production, causing acromegaly and Cushing disease","volume":"324","author":"Kageyama","year":"2002"},{"key":"b9-1100369","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.3171\/jns.1998.88.6.1111","article-title":"Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study. Case report","volume":"88","author":"Kovacs","year":"1998"},{"key":"b10-1100369","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"874","DOI":"10.3171\/jns.2004.101.5.0874","article-title":"Secretion of highmolecular-weight adrenocorticotropic hormone from a pituitary adenoma in a patient without Cushing stigmata. Case report","volume":"101","author":"Matsuno","year":"2004"},{"key":"b11-1100369","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1056\/NEJMra062453","article-title":"Medical progress: acromegaly","volume":"355","author":"Melmed","year":"2006"},{"key":"b12-1100369","series-title":"Intern Med","doi-asserted-by":"publisher","first-page":"566","DOI":"10.2169\/internalmedicine.41.566","article-title":"Subclinical Cushing's disease accompanied by malignant hypertension and diabetes mellitus","volume":"41","author":"Nagai","year":"2002"},{"key":"b13-1100369","series-title":"Pituitary","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1023\/B:PITU.0000011172.26649.df","article-title":"Characterisation of ACTH related peptides in ectopic Cushing's syndrome","volume":"6","author":"Oliver","year":"2003"},{"key":"b14-1100369","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1210\/jcem-65-6-1296","article-title":"A pituitary adenoma secreting high molecular weight adrenocorticotropin without evidence of Cushing's disease","volume":"65","author":"Reincke","year":"1987"},{"key":"b15-1100369","series-title":"FEBS Lett","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/0014-5793(92)81339-N","article-title":"The cDNA structure of the porcine pro-hormone convertase PC2 and the comparative processing by PC1 and PC2 of the N-terminal glycopeptide segment of porcine POMC","volume":"310","author":"Seidah","year":"1992"},{"key":"b16-1100369","series-title":"Endocr J","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1507\/endocrj.52.743","article-title":"Malignant gastric carcinoid causing ectopic ACTH syndrome: discrepancy of plasma ACTH levels measured by different immunoradiometric assays","volume":"52","author":"Tsuchiya","year":"2005"},{"key":"b17-1100369","series-title":"Endocr J","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1507\/endocrj.K06-031","article-title":"A Case of acromegaly associated with subclinical Cushing's disease","volume":"53","author":"Tsuchiya","year":"2006"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/110\/2\/article-p369.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/110\/2\/article-p369.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/110\/2\/article-p369.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T04:38:37Z","timestamp":1664167117000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/110\/2\/article-p369.xml"}},"subtitle":["Case report"],"short-title":[],"issued":{"date-parts":[[2009,2]]},"references-count":17,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3171\/2008.8.jns08154","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2]]}}}