Endocrine Abstracts

Case history: A 61-year-old gentleman first presented to A&E following a collapse at work. After missing lunch, he became combative towards his colleagues and was found to be hypoglycaemic with capillary blood glucose of 2.5 mmol/l. Symptoms rapidly improved after oral glucose intake. The patient reported similar episodes in the past, usually occurring before meals and mainly if missing or delaying a meal. The patient did not have any past medical history of note, did not have diabetes and not taking any regular medications.

Investigations: Physical examination revealed a healthy male with BMI 28. Liver and renal functions as well as thyroid profile were normal, HbA1c 41 mmol/mol, 0900 h cortisol level at 401 nmol/l. Drug-induced hypoglycaemia and sulfonylurea use was excluded. During a fasting test the patient’s blood glucose dropped to 2.0 mmol/l at 4 h. Insulin was 10 800 pmol/l, C-peptide 671 pmol/l, discrepant for such a high insulin concentration. Because of this, the insulin concentration was measured using PEG precipitation – total insulin was 2930 pmol/l, PEG precipitated insulin 202 pmol/l, and the presence of anti-insulin antibodies was confirmed. Exogenous insulin administration was excluded by the use of two different insulin assay platforms. The patient underwent CT pancreas which revealed a possible 0.5 cm pancreatic lesion which was not demonstrated on MRCP, and determined to be vascular in nature.

Results and treatment: A diagnosis of Insulin Autoimmune Syndrome was made. He was advised to eat regularly and to stick to a low GI diet. Within 8 months follow up, he did not develop further hypoglycaemic episodes and his weight remained stable. He was not found to have other autoimmune conditions and remains under follow up.

Conclusions and points for discussion: The presence of anti-insulin antibodies is a very rare cause of hypoglycaemia. Anti-insulin antibodies delay insulin clearance, increasing receptor mediated insulin signalling. Recovery of plasma immunoreactive insulin after PEG precipitation of the plasma showed lower insulin concentration and confirmed the presence of anti-insulin antibodies. Insulin Autoimmune Syndrome may be related to use of exogenous insulin or associated with human leukocyte antigen DRB1*0406, more common in people of Japanese heritage. It has also been described in multiple myeloma. First-line treatment should be dietary management and patients need advice on emergency hypoglycaemia treatment. Acarbose may be of use, and in severe cases, treatment with corticosteroids or rituximab might be necessary. Although rare, the presence of anti-insulin antibodies should be considered in patients with recurrent hypoglycaemic episodes and inappropriately high insulin levels.