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Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism

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Abstract

Purpose

Low plasma corticotropin is considered a useful parameter for the diagnosis of subclinical hypercortisolism in patients with an adrenal incidentaloma. However, immunoassays are vulnerable to interference from endogenous antibodies. In this study, subjects who underwent Hypothalamus-pituitary-adrenal axis evaluation for the assessment of subclinical hypercortisolism were evaluated. The objective of the study was to ascertain whether antibody interference in corticotropin immunoassay affected the diagnostic work-up and clinical decisions.

Methods

The 437 consecutive patients with incidentally discovered adrenal adenomas were included in this single centre study. Patients who had a combination of a nonsuppressed corticotropin concentration (>4.4 pmol/L) and a non-suppressed cortisol concentration after 1 mg overnight dexamethasone suppression test (>50 nmol/L) were selected. Eight eligible subjects without specific features of Cushing's syndrome were identified and recruited for interference studies and follow-up. Nine controls including one patient with unilateral adrenalectomy and one patient with Cushing's disease were recruited as well.

Measurements

Eligible subjects and controls were subjected to hormonal tests and investigations for suspected interference. Interference studies included measurement of corticotropin on a different analytical platform, serial dilutions, polyethylene glycol precipitation and heterophilic antibody analysis. Patients were followed with clinical and laboratory parameters for a median duration of 30 (12–90) months.

Results

Antibody interference was identified in four patients. Rheumatoid factor was responsible for the interference in one patient. Clinical management of the patients was affected by the erroneous results. Interference tests were negative in control subjects.

Conclusions

Erroneous results associated with analytical interference negatively impacted on clinical decision making in this patient group. This should be considered particularly in conditions such as subclinical hypercortisolism which decisions depend on laboratory investigations mainly. Analytical interference could explain the high variability observed both in field measurements from patients who were expected to have lower corticotropin concentrations and in subclinical hypercortisolism prevalence reported by different studies. Many problems can be resolved by ensuring good communication between clinical and laboratory staff.

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Author notes

    Authors and Affiliations

    1. Department of Endocrinology, Dokuz Eylul University Faculty of Medicine, Narlidere, 35340, Izmir, Turkey

      Serkan Yener, Secil Ozisik, Abdurrahman Comlekci & Tevfik Demir

    2. Department of Clinical Biochemistry, Katip Celebi University Faculty of Medicine, Izmir, Turkey

      Leyla Demir

    3. Department of Endocrinology, Tepecik Education and Research Hospital, Konak, Izmir, Turkey

      Mustafa Demirpence

    4. Department of Radiology, Dokuz Eylul University Faculty of Medicine, Narlidere, 35340, Izmir, Turkey

      Mustafa Mahmut Baris

    5. Department of Endocrinology, Ege University Faculty of Medicine, Bornova, 35040, Izmir, Turkey

      Ilgin Yildirim Simsir

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    1. Serkan Yener
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    Correspondence to Serkan Yener.

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    Authors declare that they have no competing interests

    Ethical approval

    All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Dokuz Eylul University Research Ethics Committee approved the study

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    Informed consent was obtained from all individual participants included in the study

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    Serkan Yener and Tevfik Demir contributed equally to this work.

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    Yener, S., Demir, L., Demirpence, M. et al. Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism. Endocrine 56, 308–316 (2017). https://doi.org/10.1007/s12020-017-1268-7

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    • DOI: https://doi.org/10.1007/s12020-017-1268-7

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