Immune checkpoint inhibitor related hypophysitis: Diagnostic criteria and recovery patterns

Ha Nguyen, Komal Shah, Steven G. Waguespack, Mimi I. Hu, Mouhammed Amir Habra, Maria E. Cabanillas, Naifa L. Busaidy, Roland Bassett, Shouhao Zhou, Priyanka C. Iyer, Garrett Simmons, Diana Kaya, Marie Pitteloud, Sumit K. Subudhi, Adi Diab, Ramona Dadu

Research output: Contribution to journalArticlepeer-review

Abstract

Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI)-related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with the occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted. IrH was defined as: (1) ACTH or TSH deficiency plus MRI changes or (2) ACTH and TSH deficiencies plus headache/fatigue in the absence of MRI findings. We found that of 83 patients followed for a median of 1.75 years (range 0.6-3), the proposed criteria used at initial evaluation accurately identified 61/62 (98%) irH cases. In the irH group (n = 62), the most common presentation was headache (60%), fatigue (66%), central hypothyroidism (94%), central adrenal insufficiency (69%) and MRI changes (77%). Compared with non-ipilimumab (ipi) regimens, ipi has a stronger association with irH occurrence (P = 0.004) and a shorter time to irH development (P < 0.01). Thyroid, gonadal and adrenal axis recovery occurred in 24, 58 and 0% pat ients, respectively. High-dose steroids (HDS) or ICI discontinuation was not associated with hormonal recovery. In the non-irH group (n = 19), one patient had isolated central hypothyroidism and six had isolated central adrenal insufficiency. All remained on hormone therapy at the last follow-up. We propose a strict definition of irH that identifies the vast majority of patients. HDS and ICI discontinuation is not always beneficial. Long-term follow-up to assess recovery is needed.

Original languageEnglish (US)
Pages (from-to)419-431
Number of pages13
JournalEndocrine-related cancer
Volume28
Issue number7
DOIs
StatePublished - Jun 2021

Keywords

  • Checkpoint inhibitors
  • Hypophysitis diagnostic criteria
  • Hypophysitis recovery
  • Immune hypophysitis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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