Analytical and clinical aspects of adrenocorticotrophin determination

Ann Clin Biochem 2003;40:453-471
© 2003 Association for Clinical Biochemistry

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Review Articles

JA Talbot,
JW Kane and
A White

Medeval Ltd, Manchester, UK;
Department of Clinical Biochemistry, Hope Hospital, Salford M6 8HD, UK;
Schools of Medicine and Biological Sciences, University of Manchester, Manchester M13 9PT, UK

Adrenocorticotrophin (ACTH) is formed from the cleavage of pro-opiomelanocortin.Measurement of plasma ACTH is a key step in the differentialdiagnosis of hypothalamic-pituitary-adrenal disorders.

Prior to the development of radioimmunoassay, the bioassaysemployed for the determination of ACTH were highly complex,time-consuming and costly in terms of number of animals used.Their sensitivity was such that the normal early morning peakof ACTH could not be determined. The introduction of immunoassaymethodology enabled the measurement of low normal ACTH concentrations.Immunological recognition of ACTH by the antibodies employedoffered improvements with regard to specificity. The developmentof two-site immunometric assays further improved specificityand the ability to measure low normal ACTH concentrations withoutthe need to extract large volumes of plasma. The quantificationof ACTH is now routinely performed in clinical laboratories,with non-radioisotopic methods becoming increasingly popular.

ACTH measurement is of limited value in distinguishing betweenthe causes of Cushing’s syndrome, as there is considerable overlapin circulating ACTH concentrations in subjects with either apituitary or an ectopic tumour. The role of ACTH precursor andrelated peptides in normal and pathological states and the clinicalutility of their measurement remain to be fully elucidated.However, there is evidence that measurement of ACTH precursorscan be a useful diagnostic tool in identifying the aetiologyof Cushing’s syndrome.

This review will primarily address methodological aspects ofACTH measurement in the diagnosis of clinical conditions.

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