Two Contrasting Cases of Spontaneous Severe Hypoglycaemia Secondary to Anti-Insulin Antibodies (Insulin Autoimmune Syndrome / Hirata disease)

Presentation Number: MON 602
Date of Presentation: April 3rd, 2017

Myuri Moorthy1, Bernard Freudenthal2, David Church3, Robert Kenneth Semple3, Judith Kisalu2, Emma Woolman4, Amy Hale2, Huw Beynon2, Efthimia Karra5, Mark A Cohen5 and Bernard Chong Eu Khoo*6
1Royal Free London NHS Trust, London, United Kingdom, 2Royal Free London NHS Foundation Trust, London, United Kingdom, 3University of Cambridge, Cambridge, United Kingdom, 4Health Services Laboratories, London, United Kingdom, 5Royal Free London NHS Foundation Trust, London, UNITED KINGDOM, 6UCL Medical School, London, United Kingdom

Abstract

Insulin Autoimmune Syndrome is a very rare condition in which anti-insulin antibodies accumulate high concentrations of insulin in complexes in circulation. Hypoglycaemia occurs when insulin is released from the antibodies during fasting. We present two cases and contrast their management.

Patient A is a 52-year old obese Thai female, with acanthosis nigricans and a strong family history of T2DM. Patient B is a 28 year-old Caucasian female of normal BMI. None of the patients received any regular medication or had history of autoimmunity. Both presented with symptomatic hypoglycaemia.

Whipple’s triad was noted at 10hr of a supervised fast for patient A. Nadir laboratory glucose was 1.8mmol/L, and coupled with hyperinsulinaemia and a non-physiological ratio of insulin-to-C-peptide (insulin=58854 pmol/L, C-peptide=3690 pmol/L, insulin:C-peptide ratio=15.9).

Patient B developed hypoglycaemia at 4hr during a supervised fast, with hyperinsulinaemia and a high ratio of insulin-to-C-peptide (plasma glucose=2.2mmol/L, insulin=17800 pmol/L, C-peptide=409 pmol/L, insulin:C-peptide ratio=43.5).

In both patients, hook-effect phenomena were excluded with insulin/C-peptide recovery as expected post serial dilutions. Insulin was lower post-PEG precipitation, indicating that much of the measured insulin was complexed in macromolecular aggregates. Sulphonylurea screen was negative, imaging unremarkable. Anti-insulin-receptor Abs were negative, whereas anti-insulin IgG were positive. Antinuclear antibody and anti-dsDNA antibodies negative. Chromatography demonstrated insulin sequestration by anti-insulin antibodies, identifying monomeric and antibody-bound insulin.

Pending final diagnosis, both patients received diazoxide with no efficacy. In light of positive insulin Ab, prednisolone and mycophenolate mofetil (MMF) treatment were initiated in patient A, later euglycaemia was maintained on MMF monotherapy. In patient B dexamethasone and add-on MMF only induced partial response; thus, CD20 depletion by Rituximab steroid adjuvant treatment strategy was adopted with partial efficacy. Patient B is currently undergoing plasmapheresis with adjuvant Rituximab therapy.

We discuss the diagnostic challenges in IAS, the diverse phenotype and treatment responses in our two cases.

 

Nothing to Disclose: MM, BF, DC, RKS, JK, EW, AH, HB, EK, MAC, BCEK