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    ACTH precursors characterize the ectopic ACTH syndrome.

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    Authors
    Stewart, P M
    Gibson, S
    Crosby, S R
    Penn, R
    Holder, R
    Ferry, D
    Thatcher, Nick
    Phillips, P
    London, D R
    White, A
    Affiliation
    Department of Medicine, University of Birmingham, UK.
    Issue Date
    1994-02
    
    Metadata
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    Abstract
    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'.
    Citation
    ACTH precursors characterize the ectopic ACTH syndrome. 1994, 40 (2):199-204 Clin. Endocrinol. (Oxf)
    Journal
    Clinical Endocrinology
    URI
    http://hdl.handle.net/10541/97020
    DOI
    10.1111/j.1365-2265.1994.tb02468.x
    PubMed ID
    8137518
    Type
    Article
    Language
    en
    ISSN
    0300-0664
    ae974a485f413a2113503eed53cd6c53
    10.1111/j.1365-2265.1994.tb02468.x
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