Malignant Gastric Carcinoid Causing Ectopic ACTH Syndrome: Discrepancy of Plasma ACTH Levels Measured by Different Immunoradiometric Assays

Abstract

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.

Clinical features and management of ectopic ACTH syndrome at a single institute in Japan

“…Diagnostic imaging test by SRS not available in Japan yet was approved by the Ethics Committee of TMDU Hospital; written informed consent was obtained from each patient. Some cases have been reported elsewhere [5][6][7][8][9][10].…”

“…A confirmed diagnosis of EAS (proven EAS) was made in 10 cases by demonstration of the presence of tumor debulking of advanced neuroendocrine carcinoma with multiple liver metastases, originated from the stomach (Case 5) [6], and the pancreas (Case 6) [7]. Multidisciplinary therapy, including transhepatic arterial embolization, systemic chemotherapy (adriamaycin, dacarbadine, streptozotocin, and fluorouracil), α-interferon, and finally liver transplantation was performed in Case 6 [7].…”

Small-cell Carcinoma of the Endometrium Presenting as Cushing's Syndrome

“…Furthermore, it was reported that expression of PC1/3 was investigated in various endocrine tumors [15]. in contrast, it was indicated that aberrant processing of PoMC might be observed in ectopic aCTH producing tumors [16]. immunohistochemical analysis in this study revealed that immunostaining for PoMC, PC1/3, and aCTH were positive in the tumor cells.…”

Defective Expression of Prohormone Convertase 1/3 in Silent Corticotroph Adenoma

“…Resected tumor tissues were subjected to immunohistochemical studies for ACTH by Envision method (DAKO: Carpinteria, CA) using anti-ACTH monoclonal antibody (1 : 200; DAKO) which could not recognize POMC [9], and PC1/3 by avidin-biotin peroxidase complex method using anti-PC1/3 polyclonal antibody (1 : 400; Chemicon Int,. CA) as previously reported [9].…”