Clinical heterogeneity of hypophysitis secondary to PD-1/PD-l1 blockade: Insights from four cases

Isabella Lupi, Alessandro Brancatella, Mirco Cosottini, Nicola Viola, Giulia Lanzolla, Daniele Sgrò, Giulia Di Dalmazi, Francesco Latrofa, Patrizio Caturegli, Claudio Marcocci

Research output: Contribution to journalArticle

Abstract

Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy.

Original languageEnglish (US)
Article number19-0102
JournalEndocrinology, Diabetes and Metabolism Case Reports
Volume2019
Issue number1
DOIs
StatePublished - Jan 2019

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Lupi, I., Brancatella, A., Cosottini, M., Viola, N., Lanzolla, G., Sgrò, D., Di Dalmazi, G., Latrofa, F., Caturegli, P., & Marcocci, C. (2019). Clinical heterogeneity of hypophysitis secondary to PD-1/PD-l1 blockade: Insights from four cases. Endocrinology, Diabetes and Metabolism Case Reports, 2019(1), [19-0102]. https://doi.org/10.1530/EDM-19-0102