Analytical and clinical aspects of adrenocorticotrophin determination

Adrenocorticotrophin (ACTH) is formed from the cleavage of pro-opiomelanocortin. Measurement of plasma ACTH is a key step in the differential diagnosis of hypothalamic-pituitary-adrenal disorders. Prior to the development of radioimmunoassay, the bioassays employed 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 peak of ACTH could not be determined. The introduction of immunoassay methodology enabled the measurement of low normal ACTH concentrations. Immunological recognition of ACTH by the antibodies employed offered improvements with regard to specificity. The development of two-site immunometric assays further improved specificity and the ability to measure low normal ACTH concentrations without the need to extract large volumes of plasma. The quantification of ACTH is now routinely performed in clinical laboratories, with non-radioisotopic methods becoming increasingly popular. ACTH measurement is of limited value in distinguishing between the causes of Cushing's syndrome, as there is considerable overlap in circulating ACTH concentrations in subjects with either a pituitary or an ectopic tumour. The role of ACTH precursor and related peptides in normal and pathological states and the clinical utility of their measurement remain to be fully elucidated. However, there is evidence that measurement of ACTH precursors can be a useful diagnostic tool in identifying the aetiology of Cushing's syndrome. This review will primarily address methodological aspects of ACTH measurement in the diagnosis of clinical conditions.