The proper clinical evaluation of pituitary and adrenal disorders depends on the accurate measurement of plasma
ACTH. The modern two-site sandwich
ACTH immunoassay is a great improvement compared with older methods but still has the potential for interferences such as
heterophile antibodies and
pro-opiomelanocortin (
POMC) and
ACTH fragments. We report the cases of five patients in whom the diagnosis or differential diagnosis of
Cushing syndrome was confounded by erroneously elevated results from the Siemens
ACTH Immulite assay [
ACTH(Immulite)] that were resolved using the Roche Cobas or Tosoh AIA [
ACTH(Cobas) and
ACTH(AIA), respectively]. In one case, falsely elevated
ACTH(Immulite) results owing to interfering
antibodies resulted in several invasive differential diagnostic procedures (including inferior petrosal sinus sampling), MRI, and unnecessary pituitary surgery.
ACTH(Cobas) measurements were normal, and further studies excluded the diagnosis of
Cushing syndrome. In three cases, either
Cushing disease or occult ectopic
ACTH were suspected owing to elevated
ACTH(Immulite) results. However, adrenal (
ACTH-independent) Cushing syndrome was established using
ACTH(AIA) or
ACTH(Cobas) and proved surgically. In one case, ectopic
ACTH was suspected owing to elevated
ACTH(Immulite) results; however, the
ACTH(Cobas) findings led to the diagnosis of alcohol-induced
hypercortisolism that resolved with abstinence. We have concluded that
ACTH(Immulite) results can be falsely increased and alternate
ACTH assays should be used in the diagnosis or differential diagnosis of clinical disorders of the hypothalamic-pituitary-adrenal axis.