Poster Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Rituximab as a therapeutic agent for refractory Insulin Antibody Syndrome (#425)

Harsan Kanagaretnam 1 , Emily Hibbert 1 2
  1. Endocrinology Department, Nepean Hospital, Sydney, NSW, Australia
  2. Nepean Clinical School, University of Sydney, Sydney, NSW, Australia

Insulin autoimmune syndrome (IAS), or Hirata disease, is a rare cause of endogenous hyperinsulinaemic hypoglycaemia, estimated to affect 1 in 1 million people worldwide, characterised by elevated insulin and positive insulin autoantibodies1. Treatment is guided by scattered case reports without comparative trials, and refractory disease remains a clinical challenge.

We present a 78-year-old man who presented as a stroke call with slurred speech, on a background of six months of worsening hypoglycaemic episodes previously misattributed to TIAs. Capture of spontaneous hypoglycaemia (glucose 2.7 mmol/L) revealed grossly elevated insulin level (>6945 pmol/L) and C-peptide, with imaging excluding insulinoma. Strongly positive insulin antibodies (titre 1/1000) confirmed IAS. Diazoxide and corticosteroids reduced hypoglycaemia, complicated by severe immune thrombocytopenia requiring diazoxide cessation and IVIG, but symptomatic hypoglycaemia and persistent antibodies remained despite ongoing therapy.

Rituximab, a CD20-targeted monoclonal antibody that depletes B cells, was commenced for steroid-refractory disease, supported by TrialNet data showing sustained suppression of insulin autoantibodies after a single course2. Following two infusions, our patient's antibody titre fell from 1/4 to 1/2 within three weeks, hypoglycaemic episodes reduced, and diazoxide and prednisone doses were successfully weaned. A review of the rituximab literature identified at least eight published case reports in IAS (see Figure 1), all demonstrating complete or near-complete resolution of hypoglycaemia and successful steroid weaning, with only one reported adverse event (opportunistic infection on concurrent prednisone)3-10.

 This case adds to the growing evidence for rituximab as an effective, well-tolerated, steroid-sparing therapy in IAS.

 

Figure 1

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