Corticotropin hormone assay interference: A case series

Donegan, Diane; Algeciras‐Schimnich, Alicia; Hamidi, Oksana; Young, William F.; Nippoldt, Todd B.; Bancos, Irina; Erickson, Dana

doi:10.1016/j.clinbiochem.2018.11.006

Cited by 30 publications

(44 citation statements)

References 14 publications

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“…A recent case series raised serious concerns about the performance of the Siemens Immulite ACTH assay [ACTH(Immulite)] [11]. The ACTH(Immulite) had yielded falsely elevated results, which had led to unnecessary testing and misdiagnosis [11]. Since 2012, we have been accumulating a series of cases highlighting serious issues with this assay.…”

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confidence: 99%

Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure—A Case Series

Greene

Geer

Page-Wilson

et al. 2019

Journal of the Endocrine Society

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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.

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confidence: 99%

Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure—A Case Series

Greene

Geer

Page-Wilson

et al. 2019

Journal of the Endocrine Society

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“…In all but one of the ACTH assay interference cases previously reported, the Siemens Immulite platforms were used [3][4][5][7][8][9][10] (Table 3), whereas in the present case, the Roche Diagnostics Elecsys ACTH assay yielded falsely elevated ACTH levels, for the first time to our knowledge. The Siemens Immulite platforms adopt a murine monoclonal anti-ACTH antibody and a rabbit polyclonal antibody that is considered capable of react-ing with unknown interference antibodies [9].…”

Section: Discussionmentioning

confidence: 56%

“…It is extremely rare that falsely high or low ACTH levels by a substance in the specimen interfering with the ACTH measurements are confirmed. There have been only 23 such cases, to our knowledge [3][4][5][6][7][8][9][10] (Table 3). Of the 23 cases, 22 exhibited erroneously elevated ACTH levels.…”

Section: Discussionmentioning

confidence: 99%

“…Of the 23 cases, 22 exhibited erroneously elevated ACTH levels. In some of these reports, the elevated ACTH levels measured on the Immulite platforms were proved to be false, either by pretreatment with heataggregated rabbit IgG, which is known to adsorb assayinterfering heterophilic antibodies [3], or by adoption of different assay platforms [4,[7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

“…In the field of endocrinology, falsely elevated levels of free thyroxine by anti-reagent or anti-analyte antibodies [1,2] and falsely elevated PRL or TSH levels due to formation of macromolecular complexes (such as "macro-PRL" or "macro-TSH") by anti-analyte antibodies [2] are well known. In the case of ACTH, however, there are extremely few reports only on the Siemens Immulite ACTH and the Abbott Architect ACTH [3][4][5][6][7][8][9][10].…”

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confidence: 99%

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Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency

et al. 2019

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A 49-year-old woman with membranous nephropathy was referred to our hospital during the tapering of oral prednisolone, because of suspicion of primary adrenal insufficiency based on a plasma ACTH level of 399.1 pg/mL in the Elecsys assay and a serum cortisol level of 3.1 μg/dL. A rapid ACTH stimulation test revealed a suboptimal response, whereas a prolonged ACTH simulation test showed a sufficient increase in her urinary free cortisol. Also, big ACTH was not detected by gel exclusion chromatography. Therefore, we speculated that ACTH levels were falsely elevated due to some interference substances. Pretreatment of her plasma with either polyethylene glycol precipitation or a heterophilic blocking tube substantially reduced her ACTH values. When either the Immulite ACTH II or the TOSOH II ACTH was tried instead of the Elecsys ACTH, her plasma ACTH values turned out to be lower and appropriate for her clinical status. These results indicated that heterophilic antibodies interfered only with the Elecsys ACTH assay presumably by bridging the capture and tracer antibodies. To our knowledge, this is the first case in which the Elecsys ACTH assay yielded falsely elevated results. Regardless of the measurement system used, if there is a discordance between assay results and clinical findings, it should be considered to adopt additional procedures and/or another assay.

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