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.