Endocrine Abstracts

JOINT460

Introduction: Insulin autoimmune syndrome (IAS), a condition mostly prevalent in East Asia, is a rare cause of spontaneous hypoglycaemic episodes, occurring in the late post-prandial phase and driven by the production of insulin autoantibodies (IAAs). The soaring popularity of food supplements containing Alpha-Lipoic Acid (ALA) and the concomitant surge in the reported cases of IAS have led the European Food Safety Authority to raise a safety concern about this association, especially in the presence of certain genetic polymorphisms in the Human Leukocyte Antigen HLA-DR4.

Case report: A 48-year-old female of Caucasian origin was referred on an urgent basis to an endocrine clinic in Athens, Greece, with a 5-day history of recurrent pre-syncopal episodes occurring two hours after meal ingestion. She had no history of diabetes mellitus and fulfilled the criteria of Whipple’s triad on several occasions, with capillary blood glucose as low as 36-43 mg/dl (2.0-2.4 mmol/l). On hospital admission, baseline laboratory evaluation showed hypoglycaemia due to endogenous hyperinsulinism, as evidenced by very high serum insulin (189 mIU/l) and C-peptide concentrations. Its commonest cause, insulinoma, was excluded following detailed imaging. Grossly elevated IAAs of 175 IU/ml (normal range < 20 IU/ml) indicated IAS which, in the absence of exposure to other offending drugs, was attributed to an ALA-containing supplement initiated two months ago for the management of arthralgia. Her management included dietary modification with small, frequent meals of low glycaemic index, oral prednisolone 40 mg, and diazoxide 150 mg daily. She responded rapidly without experiencing further hypoglycaemic episodes on this strict dietary regimen. In the following months, the IAA titre remained significantly elevated despite high-dose glucocorticoids, whilst she developed severe resting tremor, insomnia and depressive symptoms. Three months after the initial presentation, prednisolone was tapered and eventually discontinued, leading to resolution of these neuropsychiatric symptoms. One month later and despite prednisolone withdrawal, a significant decline in the IAA titre was first noted. Six months after presentation, the patient remained symptom-free with gradually declining, albeit still positive, IAA titres, despite discontinuation of both prednisolone and diazoxide, alongside a significant relaxation of dietary restrictions.

Conclusion: IAS is a severe, albeit rare, adverse event of ALA intake, which should discourage the overuse of ALA-containing supplements, and lead to inclusion of a clear warning about this risk in their labelling. This case report also illustrates the challenges in the management of IAS, as well as the often underappreciated neuropsychiatric side effects of glucocorticoids.