MANAGEMENT OF ENDOCRINE DISEASE: Immune check point inhibitors-induced hypophysitis

Eur J Endocrinol. 2019 Sep 1;181(3):R107-R118. doi: 10.1530/EJE-19-0169.


In recent years, the development of immunotherapy has constituted a revolution in the therapy for many cancers, with a specific toxicity profile including endocrine immune-related adverse events. Immune check point inhibitors (ICI)-induced hypophysitis is a common endocrine side effect, particularly with CTLA-4 antibodies and combination therapy, with frequent hormonal deficiencies at diagnosis. It can be difficult to evoke such diagnosis as the initial clinical symptoms are not specific (headache, asthenia…); thus, patients receiving such immunomodulatory therapies should be closely monitored by systematic hormone measurements, especially in the first weeks of treatment. Usually, hormonal deficiencies improve, except for corticotroph function. Despite a lack of large prospective studies on ICI-induced hypophysitis, some detailed longitudinal cohort studies have focused on such cases of hypophysitis and allow for optimal monitoring, follow-up and management of patients with this immune-related adverse event. In the case of ICI-induced hypophysitis, patients need long-term multidisciplinary follow-up, with specific education for those patients with corticotropin deficiency to allow them to be autonomous with their treatment. In this review, based on a clinical case, we detail the most relevant and novel aspects related to the incidence, diagnosis, treatment, evolution and management of hypophysitis induced by immunotherapy, with a focus on possible mechanisms and current recommendations and guidelines. Lastly, we emphasize several key points, such as the absence of indication to systematically treat with high-dose glucocorticoid and the pursuit of immunotherapy in such hypophysitis. These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • CTLA-4 Antigen / antagonists & inhibitors*
  • CTLA-4 Antigen / blood
  • Humans
  • Hypophysitis / blood
  • Hypophysitis / chemically induced*
  • Hypophysitis / diagnostic imaging*
  • Immunotherapy / adverse effects*
  • Male
  • Middle Aged


  • CTLA-4 Antigen
  • CTLA4 protein, human