Proopiomelanocortin interference in the measurement of adrenocorticotrophic hormone: a United Kingdom National External Quality Assessment Service study

Abstract

Objective: It is recognized that measurement of ACTH-precursor peptides including proopiomelanocortin (POMC) has clinical utility in identifying the aetiology of Cushing's syndrome. Recent data have also demonstrated cross-reactivity of POMC in ACTH immunoassays used in clinical laboratories. The aim of this study was to assess the cross-reactivity of POMC in the main commercial immunoassays for ACTH and to survey the awareness of laboratory professionals to this potential interference.

Method: To assess cross-reactivity, specimens containing ACTH and/or POMC were prepared by the UK National External Quality Assessment Service (UK NEQAS) [Edinburgh]. A separate interpretative exercise was also sent to participating laboratories.

Results: Eighty-seven laboratories measured 'total' ACTH (i.e. ACTH and/or POMC) in their assays. Cross-reactivity of POMC varied from a mean of 1·6-4·7% (reflected in a large percentage increase in measured ACTH of up to 261% due to POMC cross-reactivity) depending on the manufacturer. Major differences in the clinical interpretation of test results were observed in returned responses to the interpretative exercise.

Conclusion: An appraisal of POMC cross-reactivity in currently available ACTH immunoassays has been achieved. Cross-reactivity was sufficient to detect ACTH precursors at concentrations that could be found in patients with ectopic ACTH syndrome. These data will assist laboratories in interpreting results when assessing the hypothalamic-pituitary-adrenal axis. Endocrinologists and laboratory professionals should be aware of the degree of cross-reactivity in ACTH immunoassay in order to minimize the risk of misinterpretation of results and/or potentially delayed treatment.