title: Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology, Dokuz Eylul University Faculty of Medicine, Narlidere, 35340, Izmir, Turkey. serkanyenermd@gmail.com.
authors.forename: Serkan
authors.initials: S
authors.lastname: Yener
authors.affiliation: Department of Clinical Biochemistry, Katip Celebi University Faculty of Medicine, Izmir, Turkey.
authors.forename: Leyla
authors.initials: L
authors.lastname: Demir
authors.affiliation: Department of Endocrinology, Tepecik Education and Research Hospital, Konak, Izmir, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Demirpence
authors.affiliation: Department of Radiology, Dokuz Eylul University Faculty of Medicine, Narlidere, 35340, Izmir, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Mahmut Baris
authors.affiliation: Department of Endocrinology, Ege University Faculty of Medicine, Bornova, 35040, Izmir, Turkey.
authors.forename: Ilgin Yildirim
authors.initials: IY
authors.lastname: Simsir
authors.affiliation: Department of Endocrinology, Dokuz Eylul University Faculty of Medicine, Narlidere, 35340, Izmir, Turkey.
authors.forename: Secil
authors.initials: S
authors.lastname: Ozisik
authors.affiliation: Department of Endocrinology, Dokuz Eylul University Faculty of Medicine, Narlidere, 35340, Izmir, Turkey.
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Comlekci
authors.affiliation: Department of Endocrinology, Dokuz Eylul University Faculty of Medicine, Narlidere, 35340, Izmir, Turkey.
authors.forename: Tevfik
authors.initials: T
authors.lastname: Demir
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D000324:Adrenocorticotropic Hormone
keywords: Corticotropin; Interference; Subclinical Cushing's syndrome