Reviews in Endocrine and Metabolic Disorders

, Volume 19, Issue 4, pp 325–333 | Cite as

Thyroid disorders induced by checkpoint inhibitors

  • Silvia Martina Ferrari
  • Poupak Fallahi
  • Fabio Galetta
  • Emanuele Citi
  • Salvatore Benvenga
  • Alessandro AntonelliEmail author


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.


Immune checkpoint inhibitors CTLA-4 PD-1 PD-L1 Thyroid disorders Hypophysitis 


Compliance with ethical standards

Research involving human participants

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Silvia Martina Ferrari
    • 1
  • Poupak Fallahi
    • 2
  • Fabio Galetta
    • 1
  • Emanuele Citi
    • 1
  • Salvatore Benvenga
    • 3
    • 4
    • 5
  • Alessandro Antonelli
    • 1
    Email author
  1. 1.Department of Clinical and Experimental MedicineUniversity of Pisa, School of MedicinePisaItaly
  2. 2.Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
  3. 3.Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
  4. 4.Master Program on Childhood, Adolescent and Women’s Endocrine HealthUniversity of MessinaMessinaItaly
  5. 5.Interdepartmental Program of Molecular and Clinical Endocrinology and Women’s Endocrine HealthAzienda Ospedaliera Universitaria Policlinico ‘G. Martino’MessinaItaly

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