Thyroid Dysfunction from Antineoplastic Agents

• Published in: JNCI : Journal of the National Cancer Institute 2011-11, Vol.103 (21), p.1572-1587
• Main Authors: Hamnvik, Ole-Petter Riksfjord, Larsen, P. Reed, Marqusee, Ellen
• Format: Article
• Language: English
• Subjects: Alemtuzumab; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Neoplasm - adverse effects; Anticarcinogenic Agents - adverse effects; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Biological and medical sciences; Diphtheria Toxin - adverse effects; Drug toxicity and drugs side effects treatment; Humans; Hyperthyroidism - blood; Hyperthyroidism - chemically induced; Hyperthyroidism - diagnosis; Hypopituitarism - complications; Hypopituitarism - etiology; Hypothyroidism; Hypothyroidism - blood; Hypothyroidism - chemically induced; Hypothyroidism - diagnosis; Hypothyroidism - drug therapy; Hypothyroidism - etiology; Interferon-alpha - adverse effects; Interleukin-2 - adverse effects; Interleukin-2 - analogs & derivatives; Iodine Radioisotopes - administration & dosage; Ipilimumab; Medical diagnosis; Medical sciences; Medical treatment; Miscellaneous (drug allergy, mutagens, teratogens...); Molecular Targeted Therapy - methods; Neoplasms - drug therapy; Neoplasms - immunology; Pharmacology. Drug treatments; Protein-Tyrosine Kinases - antagonists & inhibitors; Quality of Life; Radioimmunotherapy; Recombinant Fusion Proteins - adverse effects; Recombinant Proteins - adverse effects; Review; Tetrahydronaphthalenes - adverse effects; Thalidomide - adverse effects; Thalidomide - analogs & derivatives; Thyroid diseases; Thyroid Function Tests; Thyroid Gland - drug effects; Thyroid Gland - metabolism; Thyroid Hormones - blood; Thyroiditis, Autoimmune - chemically induced; Tumors
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djr373

Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents.