Assay-specific spurious ACTH results lead to misdiagnosis, unnecessary testing, and surgical misadventure - A case series Journal Article


Authors: Wissner Greene, L.; Geer, E. B.; Page-Wilson, G.; Findling, J. W.; Raffa, H.
Article Title: Assay-specific spurious ACTH results lead to misdiagnosis, unnecessary testing, and surgical misadventure - A case series
Abstract: 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. Copyright (C) 2019 Endocrine Society
Keywords: diagnosis; immunoassay; disease; cushing syndrome; hypercortisolism; differential-diagnosis; cushings-syndrome; corticotropin-releasing hormone; distinguish; immunoradiometric assay; adrenocorticotropin; immunoassay interference; heterophilic antibody interference; internal jugular-vein
Journal Title: Journal of the Endocrine Society
Volume: 3
Issue: 4
ISSN: 2472-1972
Publisher: Endocrine Society  
Date Published: 2019-04-01
Start Page: 763
End Page: 772
Language: English
ACCESSION: WOS:000463993200008
DOI: 10.1210/js.2019-00027
PROVIDER: wos
PMCID: PMC6446888
PUBMED: 30963134
Notes: Article -- Source: Wos
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  1. Eliza Brevoort Geer
    49 Geer