Consideration Triggered By The Choice Of Heterophilic Antibody Interference Detection Tests In Measuring Acth For A Teenager Boy With A Rare Adrenal Disease

Background: Plasma ACTH is an important marker for Cushing syndrome; inaccurate measurement of ACTH concentrations due to the serum heterophile antibody may mislead diagnosis by physicians. We describe the case of a teenage boy with a rare adrenal disease who presented falsely increased ACTH concentrations (20.3 pg/ml; Siemens Immulite). Methods: Low dose dexamethasone inhibition test showed no inhibition of serum cortisol. While biochemical evidence suggested ACTH-dependent Cushing, the imaging tests suggested otherwise. Hence, further tests for interference identification, including test platform replacement, sample dilution, PEG precipitation, and use of blocking antibodies, were conducted. Results: The measurements of the same patient sample on three different analytical platforms suggested ACTH concentrations below 5 pg/ml. Serial dilutions of serum samples revealed nonlinearity, PEG recovery resulted in ACTH concentrations dropping to < 5 pg/ml, and interferences in plasma were blocked by a heterophilic blocking reagent (21.2 vs < 5 pg/ml), suggesting that assay interference performed on Siemens Immulite led to false-positive ACTH. Finally, the boy was diagnosed with a rare type of ACTH-independent Cushing syndrome. Conclusions: The inaccurate evaluation of ACTH misled the physicians, increasing treatment time and diagnostic testing. Thus, an anti-interference workflow should be established between physicians and laboratories to avoid such cases in the future.