Endocrine Abstracts

IAS is common in Japanese but rare in Caucasians. Highlighting its aetiology is paramount in understanding its clinical and analytical variabilities and can help planning investigations and avoid mistakes in the interpretation of false pancreatic endocrine data commonly associated with this syndrome.

The underlying aetiology of IAS is the presence of high affinity/avidity endogenous insulin autoantibodies in significant amounts in non-diabetics. Clinically these autoantibodies could trigger pathology, namely hypoglycaemia and analytically it could interfere in immunoassays analyses causing erroneous pancreatic hormones data. Two types of insulin autoantibodies (different classes and subclasses) may develop separately, sequentially or in combination namely autoantibodies which bind insulin/proinsulin(s) and receptor autoantibodies (insulinmimetic). Binding of insulin/proinsulin(s) to autoantibodies increase considerably their t_1/2 and concentrations. The clinical manifestations are highly variable, ranging from mild and transient, to spontaneous, severe and protracted hypoglycaemia necessitating in extreme cases plasmapheresis for glycaemic control, dependent on the intrinsic nature of circulating autoantibodies (i.e. affinities/avidities, titres/concentrations and capacities/valency).

IAS appears to develop in genetically predisposed individuals with history of other autoimmune disorders and/or autoimmune polyendocrine syndromes. Major triggers are infection and drugs containing sulphydryl groups including the cyclic disulphide alpha-lipoic acid (ALA), sold over-the-counter and the internet as a universal antioxidant drug/free radical scavenger; it is also prescribed for conditions such as peripheral polyneuropathy. Recently, over a period of 22 months, seven cases in Caucasians (Italians) receiving ALA were diagnosed with IAS in single medical center in Sicily. It appears that the incidence of drug-induced IAS may not be after all insignificant in genetically predisposed Caucasians too.

Testing for insulin autoantibodies should be included among first line investigations in patients with indeterminate and/or unexplained hypoglycaemia; if present, pancreatic hormones data must be interpreted in the context of immunoassays cross-reactivities.