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Thyroid disorders induced by checkpoint inhibitors

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Abstract

Immune checkpoint inhibitors are drugs that inhibit the “checkpoint molecules”. Different types of cancer immune checkpoint inhibitors have been approved recently: CTLA-4 monoclonal antibodies (as ipilimumab); anti-PD-1 monoclonal antibodies (as pembrolizumab and nivolumab); and anti-PD-L1 monoclonal antibodies (as atezolizumab, avelumab, and durmalumab). The increased immune response induced by these agents leads to immune-related adverse events (irAEs), that can vary from mild to fatal, according to the organ system and severity. Immune-related endocrine toxicities are thyroid dysfunctions, hypophysitis, adrenal insufficiency, and type 1 diabetes mellitus, and are usually irreversible in 50%. In particular, hypophysitis is the most frequent anti-CTLA-4-antibodies-related irAE, while thyroid abnormalities (as hypothyroidism, thyrotoxicosis, painless thyroiditis, or even “thyroid storm”) are more frequently associated with anti-PD-1-antibodies. The combination of anti-CTLA-4-antibodies, with anti-PD-1-antibodies, is associated with about 30% of irAEs. Clinical signs and symptoms vary according to the influenced target organ. Endocrinopathies can often be managed by the treating oncologist. However in more severe cases (i.e. in the presence of insulin-dependent diabetes, adrenal insufficiency, or disorders of gonadal hormones, or severe hyperthyroidism, or hypothyroidism, or long-lasting management of hypophysitis) an endocrinological evaluation, and a prompt therapy, are needed.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, School of Medicine, Via Savi, 10, I-56126, Pisa, Italy

    Silvia Martina Ferrari, Fabio Galetta, Emanuele Citi & Alessandro Antonelli

  2. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126, Pisa, Italy

    Poupak Fallahi

  3. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    Salvatore Benvenga

  4. Master Program on Childhood, Adolescent and Women’s Endocrine Health, University of Messina, Messina, Italy

    Salvatore Benvenga

  5. Interdepartmental Program of Molecular and Clinical Endocrinology and Women’s Endocrine Health, Azienda Ospedaliera Universitaria Policlinico ‘G. Martino’, I-98125, Messina, Italy

    Salvatore Benvenga

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Ferrari, S.M., Fallahi, P., Galetta, F. et al. Thyroid disorders induced by checkpoint inhibitors. Rev Endocr Metab Disord 19, 325–333 (2018). https://doi.org/10.1007/s11154-018-9463-2

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