ACTH precursors characterize the ectopic ACTH syndrome
| Autor: | R. Penn, S. Gibson, D Ferry, Anne White, Nick Thatcher, P Phillips, S. R. Crosby, D. R. London, Roger Holder, Paul M. Stewart |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
endocrine system medicine.medical_specialty Lung Neoplasms Pro-Opiomelanocortin Hydrocortisone Endocrinology Diabetes and Metabolism Prohormone Peptide hormone Endocrinology Adrenocorticotropic Hormone Proopiomelanocortin Internal medicine medicine Carcinoma Humans Carcinoma Small Cell Protein Precursors Lung cancer Cushing Syndrome Aged Immunoradiometric assay biology business.industry Antibodies Monoclonal Middle Aged medicine.disease Pathophysiology ACTH Syndrome Ectopic Monoclonal biology.protein Immunoradiometric Assay Secretory Rate business hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | University of Manchester-PURE Scopus-Elsevier |
| ISSN: | 1365-2265 0300-0664 |
| DOI: | 10.1111/j.1365-2265.1994.tb02468.x |
| Popis: | OBJECTIVE: ACTH is secreted by the pituitary following processing of larger molecular weight precursors, proopiomelanocortin and pro-ACTH. Ectopic ACTH syndrome refers to the secretion of ACTH by non-pituitary tumours, but the predominant circulating form of proopiomelanocortin-related peptides remains unclear. PATIENTS: Fifteen patients with ectopic ACTH syndrome were compared to 20 patients with pituitary-dependent Cushing's syndrome, 22 patients with small cell lung carcinoma but no evidence of Cushing's syndrome, and 25 controls. DESIGN AND MEASUREMENTS: Measurement of plasma ACTH and ACTH precursors using specific monoclonal-based immunoradiometric assays at 0900 h and, in five patients with ectopic ACTH syndrome, at 15-minute intervals for 6-24 hours. RESULTS: ACTH precursors were grossly elevated in patients with ectopic ACTH syndrome (median 2194, range 139-18000 pmol/l) compared to patients with Cushing's disease (median 33, 8-73 pmol/l, P < 0.001), patients with small cell lung carcinomas (38, 8-117 pmol/l, P < 0.001) and controls (26, 10-39 pmol/l, P < 0.001). ACTH levels were also elevated in ectopic ACTH syndrome (0900 h median 34, 11-152 pmol/l) compared to patients with Cushing's disease (0900 h median 8, 3-19 pmol/l), but not to the same degree as ACTH precursors. In contrast with Cushing's disease, ACTH was secreted in a non-pulsatile fashion. ACTH precursors but not ACTH itself correlated with plasma cortisol in patients with ectopic ACTH syndrome (r = 0.65, P < 0.05). Chromatographic analysis of plasma from a patient with ectopic ACTH syndrome confirmed ACTH precursors and not ACTH to be the predominant circulating form. With the cross-reactivity of proopiomelanocortin and pro-ACTH in the ACTH IRMA of < 1 and < 10% respectively, ACTH precursors could represent all the ACTH immunoreactivity in patients with ectopic ACTH syndrome. CONCLUSIONS: Ectopic 'ACTH' is characterized by aberrant processing of proopiomelanocortin and should be more accurately referred to as 'ectopic ACTH precursor syndrome'. |
| Databáze: | OpenAIRE |
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