corticotropin-like-intermediate-lobe-peptide and Lung-Neoplasms

The increases in the level of plasma lipotropin (LPH) and in the LPH/ACTH ratio are considered diagnostic tools in ectopic ACTH syndrome. However, plasma ACTH is also elevated in this syndrome. We report a case of a small carcinoid tumor with an increase in both ACTH and LPH in plasma before surgery. Eight months after the tumoral resection, plasma LPH alone was increased again, whereas plasma ACTH and plasma and urinary cortisol remained normal in this apparently cured patient. This repeated abnormality was the only available feature that allowed successful removal of the occult tumoral residue.

Topics: Adrenocorticotropic Hormone; Adult; beta-Lipotropin; Carcinoid Tumor; Chromatography, High Pressure Liquid; Corticotropin-Like Intermediate Lobe Peptide; Corticotropin-Releasing Hormone; Female; Humans; Hydrocortisone; Lung Neoplasms; Peptide Fragments; Tomography, X-Ray Computed

POMC processing is frequently altered in ACTH-secreting nonpituitary tumors in which intermediate lobe-like peptides such as corticotropin-like intermediate lobe peptide (CLIP) are occasionally generated. In rodent pituitaries, the exclusive presence of prohormone convertase PC2 in the melanotrophs of the intermediate lobe is responsible for the specific conversion of ACTH to alpha MSH and CLIP, by contrast with corticotrophs of the anterior lobe, which do not contain PC2 and, therefore, only produce ACTH. The goal of our study was to look for PC2 expression in ACTH-secreting nonpituitary tumors in man. Using Northern blot analysis, PC2 transcripts were detected in five nonpituitary tumors that contained large proportions of CLIP (from 40-95% of the total C-terminal immunoreactive ACTH). A predominant PC2 messenger ribonucleic acid migrated with an apparent mol wt of 5 kilobases, and a minor signal at 3 kilobases was also detected. No PC2 messenger ribonucleic acid could be detected in the small cell carcinoma of the lung-derived DMS-79 human cell line, which produces unprocessed POMC, or in three pituitary tumors responsible for Cushing's disease or Nelson's syndrome, which produced intact ACTH, but no CLIP. These data strongly suggest that, as in rodents, PC2 is responsible for the production of smaller POMC end products, such as CLIP, frequently observed in ACTH-secreting nonpituitary tumors in man.

Topics: Adrenocorticotropic Hormone; Base Sequence; Bronchial Neoplasms; Carcinoid Tumor; Carcinoma, Small Cell; Corticotropin-Like Intermediate Lobe Peptide; DNA, Neoplasm; Humans; Lung Neoplasms; Molecular Sequence Data; Peptide Fragments; Pituitary Neoplasms; Proprotein Convertase 2; Subtilisins; Thymus Neoplasms; Tumor Cells, Cultured