Assessment of ACTH assay variability: a multicenter study

Objective: Measurement of plasma ACTH plays a pivotal role in the diagnosis and treatment of several endocrine disorders. Little is known, however, on the variability of ACTH assay results and its impact on clinical practice. The aim of the present study was to assess the performance of routine plasma ACTH measurements. Design: Twenty-five fresh-frozen plasma samples collected from patients with either high, low, or normal ACTH concentrations were measured using seven different assays by 35 different laboratories. Assay precision, method agreement, and result classification were estimated. Results: Inter- and intra-assay coefficient of variation varied considerably with some assays achieving <10%, others consistently achieving >20%. Overall method agreement was good (mean ratio versus target value 1.02) but subject to exceedingly large excursion (lower and upper limits of agreement at 0.13 and 1.91 respectively). Both differences between assays and between laboratories contributed to variability of method agreement. Assays correctly classified most patients with normal and high ACTH concentrations (90% (95% CI 82-97%) and 95% (95% CI 86-100%) respectively), whereas only 60% (95% CI 52-67%) of measurements from patients with low ACTH values were assigned correctly. Conclusions: Field ACTH assays have to be interpreted with caution as they are burdened by high variability and often fail to correctly identify patients with suppressed ACTH secretion. The endocrine community has to include ACTH assays among those requiring standardization.