This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by CROSBY, S. R. Articles by WHITE, A. Search for Related Content PubMed PubMed Citation Articles by CROSBY, S. R. Articles by WHITE, A.

Direct Measurement of the Precursors of Adrenocorticotropin in Human Plasma by Two-Site Immunoradiometric Assay^*

University of Manchester, Department of Clinical Biochemistry, Hope Hospital, Clinical Sciences Building Salford M6 8HD, United Kingdom
Wolf son Research Laboratories (J.G.R.), Queen Elizabeth Medical Centre Edgbaston, Birmingham B15 2TH, United Kingdom

Address correspondence and requests for reprints to: Dr. A. White, University of Manchester, Department of Clinical Biochemistry, Hope Hospital, Clinical Sciences Building, Eccles Old Road, Salford M6 8HD, United Kingdom.

An immunoradiometric assay (IRMA) for the direct measurement of the precursors of ACTH in unextracted human plasma has been developed and evaluated clinically in normal subjects and patients with disorders of the hypothalamicpituitary-adrenal axis. The IRMA is based on an iodinated monoclonal antibody to ACTH and a monoclonal antibody to MSH coupled to Sephacryl S300. The assay detects only peptides containing both epitopes, i.e. POMC (31K) and pro-ACTH (22K). The reference standard was partially purified POMC from culture medium of human corticotroph adenoma cells. The detection limit (>+2.5SD of the 0 standard) was 2.0 pmol/L and the within-assay coefficient of variation was less than 10% between 29 and 2600 pmol/L.

Plasma concentrations of ACTH precursor peptides in 11 normal subjects sampled at 0930 h ranged from 5-34 pmol/L. The concentrations in the patient groups studied were: 260–2300 pmol/L in 5 patients with the ectopic ACTH syndrome associated with small cell lung cancer, less than 2.0–104 pmol/L in 10 patients with pituitary-dependent Cushing’s disease, 23 pmol/L in a patient with Nelson’s syndrome, and 3.0–230 pmol/L in 5 patients with Addison’s disease.

We conclude that this IRMA offers a simple and reliable method for measuring ACTH precursors in unextracted plasma. The proportionately greater elevation of ACTH precursors compared to ACTH in patients with the ectopic ACTH syndrome associated with small cell lung cancer but not in pituitarydependent Cushing’s syndrome, suggests that this assay may be clinically useful.

^* Financial support for this project was given by the Northwest Regional Health Authority and from Boots-Celltech Diagnostics.

Received February 2, 1988.

This article has been cited by other articles:

				J. W. M. Creemers, Y. S. Lee, R. L. Oliver, M. Bahceci, A. Tuzcu, D. Gokalp, J. Keogh, S. Herber, A. White, S. O'Rahilly, et al. Mutations in the Amino-Terminal Region of Proopiomelanocortin (POMC) in Patients with Early-Onset Obesity Impair POMC Sorting to the Regulated Secretory Pathway J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4494 - 4499. [Abstract] [Full Text] [PDF]

				I. S. Farooqi, K. Volders, R. Stanhope, R. Heuschkel, A. White, E. Lank, J. Keogh, S. O'Rahilly, and J. W. M. Creemers Hyperphagia and Early-Onset Obesity due to a Novel Homozygous Missense Mutation in Prohormone Convertase 1/3 J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3369 - 3373. [Abstract] [Full Text] [PDF]

				L. E. Pritchard and A. White Neuropeptide Processing and Its Impact on Melanocortin Pathways Endocrinology, September 1, 2007; 148(9): 4201 - 4207. [Abstract] [Full Text] [PDF]

				K. Rousseau, S. Kauser, L. E. Pritchard, A. Warhurst, R. L. Oliver, A. Slominski, E. T. Wei, A. J. Thody, D. J. Tobin, and A. White Proopiomelanocortin (POMC), the ACTH/melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis FASEB J, June 1, 2007; 21(8): 1844 - 1856. [Abstract] [Full Text] [PDF]

				B. G. Challis, A. P. Coll, G. S. H. Yeo, S. B. Pinnock, S. L. Dickson, R. R. Thresher, J. Dixon, D. Zahn, J. J. Rochford, A. White, et al. Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY3-36 PNAS, March 30, 2004; 101(13): 4695 - 4700. [Abstract] [Full Text] [PDF]

				L. E. Pritchard, R. L. Oliver, J. D. McLoughlin, S. Birtles, C. B. Lawrence, A. V. Turnbull, and A. White Proopiomelanocortin-Derived Peptides in Rat Cerebrospinal Fluid and Hypothalamic Extracts: Evidence that Secretion Is Regulated with Respect to Energy Balance Endocrinology, March 1, 2003; 144(3): 760 - 766. [Abstract] [Full Text] [PDF]

				S. F. Young and J. C. Rose Attenuation of Corticotropin-Releasing Hormone and Arginine Vasopressin Responsiveness During Late-Gestation Pregnancy in Sheep Biol Reprod, June 1, 2002; 66(6): 1805 - 1812. [Abstract] [Full Text] [PDF]

				N. Hiroi, G. P. Chrousos, B. Kohn, A. Lafferty, M. Abu-Asab, S. Bonat, A. White, and S. R. Bornstein Adrenocortical-Pituitary Hybrid Tumor Causing Cushing's Syndrome J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2631 - 2637. [Abstract] [Full Text] [PDF]

				M. Boscaro, L. Barzon, and N. Sonino The Diagnosis of Cushing's Syndrome: Atypical Presentations and Laboratory Shortcomings Arch Intern Med, November 13, 2000; 160(20): 3045 - 3053. [Abstract] [Full Text] [PDF]

				J. A. Ellison, L. Patel, D. W. Ray, and P. E. Clayton Hypothalamic-Pituitary-Adrenal Function and Glucocorticoid Sensitivity in Atopic Dermatitis Pediatrics, April 1, 2000; 105(4): 794 - 799. [Abstract] [Full Text]

				S. O'Rahilly, H. Gray, P. J. Humphreys, A. Krook, K. S. Polonsky, A. White, S. Gibson, K. Taylor, and C. Carr Impaired Processing of Prohormones Associated with Abnormalities of Glucose Homeostasis and Adrenal Function N. Engl. J. Med., November 23, 1995; 333(21): 1386 - 1391. [Full Text] [PDF]