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 speci city. The development of two-site immunometric assays further improved speci city and the ability to measure low normal ACTH concentrations without the need to extract large volumes of plasma. The quanti cation of ACTH is now routinely performed in clinical laboratories, with nonradioisotopic 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. Ann Clin Biochem 2003; 40: 453-471 Structure and nomenclature of ACTH and its related peptidesAdrenocorticotrophin (ACTH) and related peptides are derived by selective proteolytic cleavage of a common glycoprotein called pro-opiomelanocortin (POMC; MW 32 000) (see Fig. 1). Within human pituitary corticotrophs, POMC is cleaved by the enzyme prohormone convertase 1 (PC1) into an N-terminal terminal glycopeptide (N-POC, 76 aa), joining peptide (JP, 30 aa), ACTH (39 aa) and a C-terminal fragment called b-lipotrophin (bLPH, 89 aa). There is no further processing in the adult human pituitary and therefore the ACTH-related peptides in the circulation are N-POC, JP, ACTH and bLPH. However, in addition, the ACTH precursors POMC and pro-ACTH are present in the human circulation at concentrations of 5-40 pmol/L, which is ¢ve-fold greater than that of ACTH (54.1-51.4 ng/L, 50.9-11.3 pmol/L) (see Fig. 2). 1 ACTH concentrations are lower than those of N-POC (5.6-16.8 pmol/ L) and approximately equimolar with those of bLPH (2.5-6.7 pmol/L). However, b-endorphin concentrations (41.7 pmol/ L) are consistently lower than those of the other peptides. Further processing can occur in animals that have neurointermediate lobes in the pituitary. These cells contain prohormone convertase 2 (PC2), which can cleave ACTH to a-melanocyte-stimulating hormone (aMSH, 13 aa) and corticotrophin-like intermediat...

We compared results of five sensitive immunometric assays of serum thyrotropin (TSH) in controls and in different groups of patients with hyperthyroidism, untreated or treated; secondary hypothyroidism; nonthyroidal illness (NTI); or depression; or who were being treated with amiodarone. With most kits, measured TSH concentrations did not overlap between controls and hyperthyroid patients. In untreated secondary hypothyroidism TSH was not always undetectable. Patients with NTI and depression showed many low TSH values, and among these categories of patients, we observed large discrepancies among the kits. This lack of specificity at low concentration means that one cannot assess hyperthyroidism by TSH measurement alone, but it can be used as the first screening test. Similarly, TSH determination cannot be used alone in monitoring therapy (e.g., with carbimazole, thyroxin, amiodarone) to assess the presence of hyperthyroidism. Nonetheless, this assay plays a well-established role in hypothyroidism detection. Four of the five kits were found useful for clinical evaluation, the fifth less so.

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