# Antibodies and distortion of insulin and C-peptide results in patients with hypoglycaemia of unknown origin

## TL;DR

Antibodies can cause misleading insulin and C-peptide test results in patients with unexplained low blood sugar, leading to incorrect diagnoses.

## Contribution

The paper highlights how insulin-binding and non-IAA autoantibodies can distort hypoglycaemia diagnosis and advocates for including antibody testing in initial investigations.

## Key findings

- Insulin-binding autoantibodies (IAA) can cause hypoglycaemia and distort insulin/C-peptide measurements.
- Non-IAA autoantibodies can also interfere with immunoassays, complicating hypoglycaemia diagnosis.
- Testing for antibodies using methods like PEG is not commonly used initially, leading to diagnostic delays.

## Abstract

Two types of antibody could confuse the differential diagnosis of hypoglycaemia. One is insulin-binding autoantibodies (IAA), a double hit causing hypoglycaemia of insulin autoimmune syndrome (IAS, also known as Hirata’s disease) as well as distorting measurements of insulin and/or C-peptide. The clinical manifestations and initial endocrine results in patients with IAS would mimic and masquerade as other common pathologies, as well as factitious hypoglycaemia in adults, children and newborns. The second type is non-IAA autoantibodies which, if fortuitously/incidentally present in patients with hypoglycaemia, could interfere with insulin and/or C-peptide immunoassay measurements, also confusing differential diagnosis. Currently, testing for antibodies (all classes/subclasses) by simple method such as polyethylene glycol (PEG) is not usually included among first-line investigations of hypoglycaemia, causing delayed diagnosis or diagnostic misapplication. Detection of antibodies, irrespective of their nature, warrants cautious and careful differential diagnosis, averting hospitalisation and curtailing unnecessary and expensive investigations.