title: Thyroid hormone autoantibodies: are they a better marker to detect early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments?
abstract: BACKGROUND
  Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage that leads to dysfunction of the gland. To find a more reliable thyroid marker, we assessed the presence of antibodies binding thyroid hormones (thAbs) in a cancer population undergoing potentially thyrotoxic treatment.
  
  
  METHODS
  From April 2010 to September 2013, 82 patients with hematologic malignancies treated with tyrosine kinase inhibitors or immunoregulatory drugs were recruited. Healthy volunteers (n = 104) served as control subjects. Thyroid function, autoimmunity tests, thAbs, and thyroid sonography were assessed once during treatment.
  
  
  RESULTS
  Overall, thAb positivity was recorded in 13% of the entire cohort. In most cases, the thAbs were of a single type, with a predominance of T3 immunoglobulin G. More specifically, thAbs were detected in 11 cancer patients; and abnormal levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroperoxidase antibody were detected in 6 (p = 0.05), 0 (p = 0.0006), and 2 cancer patients (p = 0.001) respectively. Ultrasonographic alterations of the thyroid were observed in 12 cancer patients. In contrast, of the 104 healthy control subjects, only 1 was positive for thAbs (1%).
  
  
  CONCLUSIONS
  We have demonstrated for the first time that thAbs are a reliable marker of early thyroid dysfunction when compared with the widely used standard thyroid tests. A confirmatory prospective trial aiming at evaluating thAbs at various time points during treatment could clarify the incidence and timing of antibody appearance.
authors.affiliation: Department of Human Pathology, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy;; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy;; Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, U.S.A.;
authors.forename: P
authors.initials: P
authors.lastname: Mondello
authors.affiliation: Department of Hematology and CBMT, Hospital of Bolzano, Bolzano, Italy;
authors.forename: M
authors.initials: M
authors.lastname: Mian
authors.affiliation: Department of Human Pathology, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy;
authors.forename: V
authors.initials: V
authors.lastname: Pitini
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy;
authors.forename: S
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sindoni
authors.affiliation: Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Galletti
authors.affiliation: Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mandolfino
authors.affiliation: Department of Internal Medicine, University of Messina, Messina, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Santoro
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mondello
authors.affiliation: Department of Internal Medicine, University of Messina, Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Aloisi
authors.affiliation: Department of Human Pathology, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy;
authors.forename: G
authors.initials: G
authors.lastname: Altavilla
authors.affiliation: Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Benvenga
keywords: hematologic malignancies; immunoregulatory drugs; thAb; tyrosine kinase inhibitors