Large-scale comparison of two immunoassays for adrenocorticotropic hormone in human plasma

Accurate measurement of plasma adrenocorticotropic hormone (ACTH) is critical in the diagnosis and management of conditions that affect pituitary or adrenal gland function. Herein, we assessed the agreement and the extent of discordance between immunoassays from Roche and Siemens in two large collections of specimens. In a collection of 602 de-identified specimens (n = 561 from patients and n = 41 from healthy volunteers), the ACTH results were highly correlated with a Spearman correlation coefficient of 0.87. For all specimen comparisons, 56 (9.3%; 95% confidence interval [CI], 7.2%-11.9%) had a discordance with > 50% difference in the ACTH levels (including 2 healthy donors). In Bland-Altman analysis, 37 (6.1%; 95%CI, 4.5%-8.4%) specimens fell outside the limits of agreement (lower limit: -82% in difference, and upper limit: 75%), the majority of which (33 [89.2%]) had higher ACTH results (including 2 healthy donors) using the Siemens assay than the Roche assay (p < 0.05). Similar results were observed in another collection of 100 de-identified patient specimens. HAMA/heterophile absorption experiments did not explain these phenomena. These observations demonstrate that a substantial fraction of patient specimens had significant differences in the ACTH results using the Roche and Siemens assays (p < 0.001), primarily due to higher levels from the Siemens assay. Therefore, abnormally high levels of ACTH should be interpreted with caution, particularly when the Siemens assay is used.