title: Malignant gastric carcinoid causing ectopic ACTH syndrome: discrepancy of plasma ACTH levels measured by different immunoradiometric assays.
abstract: Discrepancy of plasma ACTH levels measured by different immunoradiometric assays (IRMA) in a case with malignant gastric carcinoid causing ectopic ACTH syndrome was examined by gel chromatography and immunohistochemical analysis. A 49-year-old male was found to have a large gastric tumor, with muscle wasting, hypertension, diabetes and hypokalemia caused by hypercortisolemia. His plasma ACTH levels, although initially elevated, were found to be almost in normal ranges. The discrepancy of plasma ACTH levels was proven to be due to different IRMA kits used; the initial assay was performed by a kit that could recognize high-molecular weight (HMW) form as well as ACTH(1-39), but the later assay by another kit that could recognize only ACTH(1-39). Pathological examination of the gastric tumor was consistent with the diagnosis of malignant carcinoid. Immunohistochemical study revealed that immunoreactivity of proopiomelanocortin (POMC) was positive within the tumor cells, whereas those of ACTH and prohormone convertase 1/3 were negative. Molecular sieving analysis of patient's plasma by gel chromatography coupled with ACTH radioimmunoassay which could recognize HMW form and ACTH(1-39) and two different IRMAs revealed that the predominant form of ACTH was HMW form with a minor peak of ACTH(1-39). This is a rare case of ectopic ACTH syndrome caused by malignant gastric carcinoid with preferential production of HMW form of ACTH, possibly due to unprocessed POMC.
authors.affiliation: Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo.
authors.forename: Kyoichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Isao
authors.initials: I
authors.lastname: Minami
authors.forename: Toru
authors.initials: T
authors.lastname: Tateno
authors.forename: Hajime
authors.initials: H
authors.lastname: Izumiyama
authors.forename: Masaru
authors.initials: M
authors.lastname: Doi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nemoto
authors.forename: Sunao
authors.initials: S
authors.lastname: Mae
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kasuga
authors.forename: R Yoshiyuki
authors.initials: RY
authors.lastname: Osamura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D002276:Carcinoid Tumor / Q000097:blood / Q000737:chemistry / Q000150:complications* / Q000175:diagnosis; D002850:Chromatography, Gel; D006801:Humans; D007150:Immunohistochemistry; D015592:Immunoradiometric Assay / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011333:Pro-Opiomelanocortin / Q000032:analysis / Q000502:physiology; D013274:Stomach Neoplasms / Q000097:blood / Q000737:chemistry / Q000150:complications* / Q000175:diagnosis
chemical_list: D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone