Novel anti-neoplastic agents, including targeted therapies and immunotherapies, show promising results in managing both solid and hematological malignancies: their mechanisms of action include direct effect on signaling of tumor cells, anti-angiogenetic effects and host's immune system activation leading to enhanced anti-tumor response. However new typical side effects have emerged including thyroid dysfunction, which can manifest as development of thyroid auto-immunity, primary hypothyroidism, and thyrotoxicosis.

Immune checkpoint inhibitors (monoclonal antibodies targeting different ligands on T-cells and tumor cells), have shown striking results in improving prognosis of patients with metastatic melanoma and are now under investigation for several malignancies. These drugs lead to T-cell reactivation against tumor cells and host cells, causing both anti-neoplastic response and autoimmune adverse events. Autoimmune thyroid disease includes primary hypothyroidism, thyrotoxicosis and euthyroid Graves’ ophtalmopathy. In this setting, hypothyroidism may be a consequence of autoimmune hypophysitis as well. Tyrosine-kinase inhibitors, currently used for gastrointestinal stromal tumors, renal carcinoma and other malignancies, frequently lead to thyroid dysfunction and many mechanisms have been advocated, including capillary regression within the thyroid gland, direct toxic effects on thyrocytes and peripheral effects on thyroid hormone metabolism. Other immunotherapies, such as denileukin diftitox, alemtuzumab and lenalidomide can cause thyroid adverse effect as well.

Thyroid dysfunction can be associated with non specific signs and symptoms which can overlap with the effects of either anti-cancer therapies or the underlying disease. Therefore clinicians should be aware of thyroid adverse effects of novel anti-neoplastic agents, in order not to overlook a condition that potentially affects patients’ morbidity and mortality.