Combined Hypophysitis and Type 1 Diabetes Mellitus Related to Immune Checkpoint Inhibitors

Abstract

Context The occurrence of multiple endocrinopathies due to immune checkpoint inhibitors (ICIs) is relatively common as an adverse event. However, the occurrence of a combination of hypophysitis and type 1 diabetes mellitus (T1DM) is extremely rare, and its clinical features are unclear. Objective To comparatively analyze the clinical features of this combination and each individual ICI-induced endocrinopathy. Methods We reported three cases that we encountered and reviewed previously reported cases of patients with combined hypophysitis and T1DM due to ICIs. Results Anti-programmed cell death-1 (anti-PD-1) antibodies were prescribed to all the three cases. The duration from ICI initiation to the onset of these endocrine disease was 12–48 weeks. Several human leukocyte antigen (HLA) haplotypes that have disease susceptibility to hypophysitis were detected in all three patients. Combining the 17 previously reported cases, combined endocrinopathies were more common in men (85%). The onset age was 60 s for both combined and single endocrinopathies. Anti-PD-1 antibodies were used in most of the cases (90%). The time from ICI initiation to the onset of endocrinopathies was 24 [8-76] weeks for hypophysitis and 32 [8-76] weeks for T1DM in patients with combined endocrinopathies, which was not significantly different from that for each single endocrinopathy. Conclusions We presented three cases of patients with combined endocrinopathies of hypophysitis and T1DM that may have been caused by anti-PD-1 antibodies. There was no difference in the time from ICI initiation to the onset of endocrinopathies between combined and single endocrinopathies. Further case accumulation and pathogenic investigations are required.