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Differences in checkpoint-inhibitor-induced hypophysitis: mono- versus combination therapy induced hypophysitis.

Stephanie van der Leij1,2, Karijn P M Suijkerbuijk3, Medard F M van den Broek1,3

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Frontiers in Endocrinology
|August 13, 2024
PubMed
Summary

Immune checkpoint inhibitor (ICI) therapy can cause hypophysitis, a side effect. This study found that the type of ICI influences hypophysitis presentation and pituitary MRI findings, with varying recovery rates for hormone deficiencies.

Keywords:
IR-hypophysitisempty sellaimmune checkpoint inhibitorsimmune therapy toxicitytreatment corticosteroids

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Area of Science:

  • Oncology
  • Endocrinology
  • Immunology

Background:

  • Immune checkpoint inhibitors (ICIs) offer revolutionary cancer treatments but can cause immune-related adverse events (irAEs), including hypophysitis.
  • Hypophysitis, inflammation of the pituitary gland, is a known irAE of various ICIs, including anti-PD-(L)1, anti-CTLA-4, and combination therapies.
  • Understanding the distinct clinical presentations and management needs for ICI-induced hypophysitis is crucial for patient care.

Purpose of the Study:

  • To analyze and compare the clinical presentation, diagnostic findings, and endocrine recovery patterns of hypophysitis induced by different types of ICIs.
  • To identify specific differences in hypophysitis caused by anti-PD-(L)1, anti-CTLA-4, and combined anti-CTLA-4/PD-1 therapies.

Main Methods:

  • A retrospective analysis was conducted on 67 patients diagnosed with hypophysitis following ICI treatment.
  • Patient data included ICI type (anti-PD-(L)1, anti-CTLA-4, or anti-CTLA-4/PD-1), clinical symptoms, pituitary MRI findings, and endocrine function tests.
  • Outcomes such as time to onset, specific hormone deficiencies, MRI abnormalities, and endocrine recovery were compared across ICI treatment groups.

Main Results:

  • The median time to hypophysitis onset was longer with anti-PD-(L)1 therapy (22 weeks) compared to anti-CTLA-4 (11 weeks) and anti-CTLA-4/PD-1 (14 weeks).
  • Headache and deficiencies in TSH, LH/FSH, and ACTH were more frequent in hypophysitis induced by anti-CTLA-4 or anti-CTLA-4/PD-1 therapies.
  • Pituitary MRI abnormalities, including hypophysitis and secondary empty sella syndrome, were exclusively observed in patients treated with anti-CTLA-4 or anti-CTLA-4/PD-1.

Conclusions:

  • The clinical presentation and diagnostic findings of immune-related hypophysitis (IR-hypophysitis) differ significantly based on the specific type of immune checkpoint inhibitor used.
  • MRI abnormalities are more indicative of hypophysitis when associated with anti-CTLA-4 or anti-CTLA-4/PD-1 therapies.
  • While recovery from TSH and LH/FSH deficiencies is common, ACTH deficiency recovery is rare and not influenced by corticosteroid dosage.