Insulin Autoimmune Syndrome Caused by an Adhesive Skin Patch Containing Loxoprofen-Sodium

Abstract

A 62-year-old woman complained of repeated hypoglycemic events. A 75g oral glucose tolerance test (75 gOGTT) showed a marked increase in the plasma insulin level and impaired glucose tolerance. The patient exhibited a high titer of plasma anti-insulin autoantibodies. Her diagnosis was insulin autoimmune syndrome (IAS). Following the cessation of loxoprofen-sodium (LOXs), she experienced no further hypoglycemic episodes. However, the hypoglycemic attacks recurred following the accidental readministration of LOXs in an adhesive skin patch. Considering the changes in the titer of anti-insulin autoantibodies, the repeated 75 gOGTT and the repeated Scatchard analysis, we determined LOXs to be the cause of the IAS and evaluated the characteristics of the autoantibodies. Case ReportA 62-year-old woman visited our hospital in April 2009. Her symptoms included repeated faintness, hunger, sweating, palpitations and finger tremors before lunch time. On the patient's first visit, her blood glucose level was 62 mg/ dL and her symptoms disappeared quickly after receiving an intravenous glucose injection. At that time, the symptoms were suspected to reflect hypoglycemic episodes. A few days later, a 75g oral glucose tolerance test (75gOGTT) showed a marked increase in the plasma insulin level and impaired glucose tolerance (Table 1: Onset of hypoglycemia). The plasma insulin level at 120 minutes was 2,995 μU/mL, which was more than 100 times the level observed at the time of the 75gOGTT before the administration of loxoprofen-sodium (LOXs) ( Table 1: Before hypoglycemia). The patient's past medical history included appendicitis at 20 years of age and sudden onset of deafness at 50 years of age. She denied having a history of a diagnosis of diabetes or receiving insulin therapy in the past. She had taken only -8 M (low affinity/high capacity site). The results of the Scatchard analysis matched the features of IAS; however, the diagnosis was not well grounded because the

Insulin autoimmune syndrome: from diagnosis to clinical management

“…It has recently been demonstrated that albumin has a cysteine residue (Cys34) with a strong reducing capacity, like ALA. Kamei et al described a case of IAS occurring in a patient who was taking no drugs containing a sulfhydryl group, but who was taking albumin (29). Loxoprofen-sodium is capable of inducing IAS even when administered through adhesive skin patches (30). It is fundamentally important to obtain a patient's detailed clinical history in this context.…”

Insulin autoimmune syndrome possibly caused by coenzyme Q10

“…The SH group activates T-cells by cleaving the S-S bond of insulin to produce an antibody against insulin 6 , 7 ) . Additionally, loxoprofen without SH also reportedly causes IAS 8 ) . In IAS caused by drugs, hypoglycemia occurs 4–6 weeks after drug ingestion 9 ) .…”

Methimazole‑induced insulin autoimmune syndrome in Graves' disease with hypokalemia: A case report and literature review

“…The plasma C-peptide levels in patients with IAS have also been indicated to be elevated, but it is much lower compared with the insulin concentration in the blood, showing a state of separation of C-peptide from insulin ( 8 ). IAA has a high titer; therefore, detection of IAA, serum insulin and C-peptide levels can assist with identification of this disorder ( 9 ).…”