Insulin autoimmune syndrome in an occidental woman: a case report and literature review

Abstract

Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.

<p>Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description</p>

“…35 More recent papers describing case reports of IAS outside Asia did not uniformly confirm the linkage of the IAS with the above-mentioned immunodeterminants, suggesting that the genetic spectrum of the syndrome may be broader (especially outside Asia), and thus indicating the need of further studies to understand more deeply the genetic background of the syndrome. 24,36 Many different triggers have been advocated to induce the development of IAS when acting on an underlying predisposing background: among them, in order of importance, there are medications, viruses and hematological diseases.…”

“…8 Glycated hemoglobin concentrations may vary according to the frequency and severity of hypoglycemic attacks and to the presence of glucose concentrations swings, so normal or even increased HbA1c concentrations can be found. 36,86 An increase in body weight has been reported, especially in patients presenting with longlasting misrecognized IAS. 36 Whether this point could be due to the increased food intake as a corrective mechanism for hypoglycemia, or to the anabolic effects exerted by hyperinsulinemia, has not been investigated.…”

“…36,86 An increase in body weight has been reported, especially in patients presenting with longlasting misrecognized IAS. 36 Whether this point could be due to the increased food intake as a corrective mechanism for hypoglycemia, or to the anabolic effects exerted by hyperinsulinemia, has not been investigated.…”

“…However, proven that gel filtration chromatography with the addition of exogenous insulin may enhance the sensitivity for the identification of insulin immunocomplexes, 78 precipitation with PEG should be used cautiously when searching insulin-IAA complexes. 36 The measurement of IAA titer is mandatory for the diagnosis of IAS 99 since it is the only lab test that allows a reliable diagnosis of IAS. 4 However, the availability of IAA assay is not widespread and the results of this test are obtained with delay, therefore preliminary confirmatory tests are performed.…”

“…Scattered cases have proposed metformin in a combined therapeutic approach to IAS, with the aim to reduce insulin resistance (especially in patients affected by metabolic syndrome) and thus reducing insulin secretion and the consequent formation of insulin-IAA complexes. 36,117 The results of this treatment have not been evaluated systematically.…”