title: Thyroid dysfunction as an unintended side effect of anticancer drugs.
abstract: BACKGROUND
  Several of the currently used anticancer drugs may variably affect thyroid function, with impairment ranging from modified total but not free concentration of thyroid hormones to overt thyroid disease.
  
  
  CONCLUSIONS
  Cytotoxic agents seem to alter thyroid function in a relatively small proportion of adult patients. Anticancer hormone drugs may mainly alter serum levels of thyroid hormone-binding proteins without clinically relevant thyroid dysfunction. Old immunomodulating drugs, such as interferon-α and interleukin-2, are known to induce variably high incidence of autoimmune thyroid dysfunction. Newer immune checkpoint inhibitors, such as anti-CTLA4 monoclonal antibodies, are responsible for a relatively low incidence of thyroiditis and may induce secondary hypothyroidism resulting from hypophysitis. Central hypothyroidism is a well-recognized side effect of bexarotene. Despite their inherent selectivity, tyrosine kinase inhibitors may cause high rates of thyroid dysfunction. Notably, thyroid toxicity seems to be restricted to tyrosine kinase inhibitors targeting key kinase-receptors in angiogenic pathways, but not other kinase-receptors (e.g., epidermal growth factor receptors family or c-KIT). In addition, a number of these agents may also increase the levothyroxine requirement in thyroidectomized patients.
  
  
  CONCLUSIONS
  The pathophysiology of thyroid toxicity induced by many anticancer agents is not fully clarified and for others it remains speculative. Thyroid dysfunction induced by anticancer agents is generally manageable and dose reduction or discontinuation of these agents is not required. The prognostic relevance of thyroid autoimmunity, overt and subclinical hypothyroidism induced by anticancer drugs, the value of thyroid hormone replacement in individuals with abnormal thyrotropin following anticancer systemic therapy, and the correct timing of replacement therapy in cancer patients need to be defined more accurately in well-powered prospective clinical trials.
authors.affiliation: 1 Department of Systems Medicine, Tor Vergata University of Rome , Rome, Italy .
authors.forename: Francesco
authors.initials: F
authors.lastname: Torino
authors.forename: Agnese
authors.initials: A
authors.lastname: Barnabei
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Paragliola
authors.forename: Roberto
authors.initials: R
authors.lastname: Baldelli
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Appetecchia
authors.forename: Salvatore Maria
authors.initials: SM
authors.lastname: Corsello
mesh_terms: D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077610:Bexarotene; D004167:Diphtheria Toxin / Q000009:adverse effects; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced; D016898:Interferon-alpha / Q000378:metabolism; D007376:Interleukin-2 / Q000009:adverse effects / Q000378:metabolism; D000077269:Lenalidomide; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D013764:Tetrahydronaphthalenes / Q000009:adverse effects; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives; D013959:Thyroid Diseases / Q000139:chemically induced*; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D016898:Interferon-alpha; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D013764:Tetrahydronaphthalenes; D013963:Thyroid Hormones; C078456:denileukin diftitox; D000074323:Alemtuzumab; D013792:Thalidomide; D000077610:Bexarotene; D000077269:Lenalidomide; D013974:Thyroxine