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Related Experiment Videos

ACTH precursors characterize the ectopic ACTH syndrome

P M Stewart1, S Gibson, S R Crosby

  • 1Department of Medicine, University of Birmingham, UK.

Clinical Endocrinology
|February 1, 1994
PubMed
Summary

Ectopic ACTH syndrome is characterized by elevated ACTH precursors, not mature ACTH. These precursors, rather than ACTH, correlate with cortisol levels and dominate circulation.

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Area of Science:

  • Endocrinology
  • Oncology

Background:

  • Adrenocorticotropic hormone (ACTH) is secreted by the pituitary after processing of precursors like proopiomelanocortin (POMC).
  • Ectopic ACTH syndrome involves ACTH secretion by non-pituitary tumors, but the primary circulating peptide form is often unclear.

Purpose of the Study:

  • To investigate the predominant circulating form of ACTH and its precursors in ectopic ACTH syndrome.
  • To compare peptide profiles in ectopic ACTH syndrome with pituitary-dependent Cushing's syndrome and controls.

Main Methods:

  • Compared plasma ACTH and precursor levels in 15 ectopic ACTH syndrome patients, 20 Cushing's disease patients, 22 small cell lung carcinoma patients, and 25 controls.
  • Utilized specific monoclonal-based immunoradiometric assays for peptide measurement.
  • Performed serial measurements and chromatographic analysis in select cases.

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Main Results:

  • ACTH precursors were significantly elevated in ectopic ACTH syndrome compared to all other groups (P < 0.001).
  • ACTH levels were elevated but less so than precursors; secretion was non-pulsatile in ectopic cases, unlike Cushing's disease.
  • ACTH precursors, not ACTH, correlated with plasma cortisol in ectopic ACTH syndrome; chromatographic analysis confirmed precursors as the dominant circulating form.

Conclusions:

  • Ectopic ACTH secretion is marked by aberrant POMC processing, with precursors being the predominant circulating form.
  • The condition should be termed 'ectopic ACTH precursor syndrome' for greater accuracy.