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Assessment and management of anti-insulin autoantibodies in varying presentations of insulin autoimmune syndrome

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Title: Assessment and management of anti-insulin autoantibodies in varying presentations of insulin autoimmune syndrome
Authors: Church, D
Cardoso, L
Kay, RG
Williams, CL
Freudenthal, B
Clarke, C
Harris, J
Moorthy, M
Karra, E
Gribble, FM
Reimann, F
Burling, K
Williams, AJK
Munir, A
Jones, TH
Führer, D
Moeller, LC
Cohen, M
Khoo, B
Halsall, D
Semple, R
Item Type: Journal Article
Abstract: Context: Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia including surreptitious insulin administration. No standardized treatment regimen exists. Objectives: To evaluate an analytic approach to IAS and responses to different treatments. Design and Setting: Observational study in the UK Severe Insulin Resistance Service. Patients: 6 patients with hyperinsulinemic hypoglycemia and detectable circulating anti-insulin antibody (IA). Main outcome measures: Glycemia, plasma insulin and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), and IA were further characterized using radioligand binding studies. Results: All patients were diagnosed with IAS (5 IgG, 1 IgA) based on high insulin:C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. 1 patient was managed conservatively, 4 were treated with diazoxide without sustained benefit, and 4 were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis. Conclusions: IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin:C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response.
Issue Date: 1-Oct-2018
Date of Acceptance: 26-Jul-2018
URI: http://hdl.handle.net/10044/1/62314
DOI: https://dx.doi.org/10.1210/jc.2018-00972
ISSN: 0021-972X
Publisher: Oxford University Press (OUP)
Start Page: 3845
End Page: 3855
Journal / Book Title: Journal of Clinical Endocrinology and Metabolism
Volume: 103
Issue: 10
Copyright Statement: his article has been published under the terms of the Creative Commons AttributionLicense (CC BY;https://creativecommons.org/licenses/by/4.0/), which permits un-restricted use, distribution, and reproduction in any medium, provided the original authorand source are credited. Copyright for this article is retained by the author(s)
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
ANTIBODY STANDARDIZATION PROGRAM
C-PEPTIDE
HYPOGLYCEMIA
RESISTANCE
THERAPY
JAPAN
QUANTIFICATION
PROINSULIN
DIAGNOSIS
AFFINITY
1103 Clinical Sciences
1114 Paediatrics And Reproductive Medicine
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-07-31
Appears in Collections:Department of Medicine (up to 2019)