Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know)

  • R. M. Ruggeri
  • A. Campennì
  • G. GiuffridaEmail author
  • P. Trimboli
  • L. Giovanella
  • F. Trimarchi
  • S. Cannavò
Review Article


Immune checkpoint inhibitors (ICIs) are novel anticancer agents, recently introduced with the aim of boosting the immune response against tumors. ICIs are monoclonal autoantibodies that specifically target inhibitory receptors on T cells: cytotoxic T lymphocyte antigen 4 (CTLA4), programmed death 1 (PD-1) and its ligand (PD-1L). ICIs also generate peculiar dysimmune toxicities, called immune-related adverse events (irAEs), that can potentially affect any tissue, and some may be life-threatening if not promptly recognized. The endocrine and metabolic side effects of ICIs are reviewed here, with a particular focus on their clinical presentation and management. They are among the most frequent toxicities (around 10%) and include hypophysitis, thyroid disorders, adrenalitis, and diabetes mellitus. Treatment is based on the replacement of specific hormone deficits, accompanied by immunosuppression (with corticosteroids or other drugs), depending on irAEs grade, often without the need of ICI withdrawal, except in more severe forms. Prompt recognition of endocrine and metabolic irAEs and adequate treatment allow the patients to continue a therapy they are benefiting from. Endocrinologists, as an integral part of the multidisciplinary oncologic team, need to be familiar with the unique toxicity profile of these anticancer agents. Practical recommendations for their management are proposed.


Immune checkpoint inhibitors Cancer treatment Endocrine side effects CTLA4 PD1/PD1-L Thyroid diseases Hypophysitis Hyponatremia 



This research did not receive any specific Grant from any funding agency in the public, commercial or not-for-profit sector.

Compliance with ethical standards

Conflict of interest

The authors declare they have no conflict of interest.

Ethical approval

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

Informed consent

Informed consent is not required.


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Copyright information

© Italian Society of Endocrinology (SIE) 2018

Authors and Affiliations

  • R. M. Ruggeri
    • 1
  • A. Campennì
    • 2
  • G. Giuffrida
    • 1
    Email author
  • P. Trimboli
    • 3
  • L. Giovanella
    • 3
  • F. Trimarchi
    • 4
  • S. Cannavò
    • 5
  1. 1.Unit of Endocrinology, Department of Clinical and Experimental MedicineBuilding H, Floor 4, “G. Martino” University Hospital, University of MessinaMessinaItaly
  2. 2.Unit of Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional ImagingUniversity of MessinaMessinaItaly
  3. 3.Nuclear Medicine, PET/CT CentreOncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  4. 4.Accademia Peloritana dei Pericolanti at the University of MessinaMessinaItaly
  5. 5.Department of Human Pathology of Adulthood and Childhood “Gaetano Barresi”University of MessinaMessinaItaly

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