Endocrine Abstracts

Introduction: Hirata disease (or Insulin autoimmune syndrome) is characterized by the presence of high concentrations of insulin autoantibodies leading to hyperinsulinemic hypoglycemia in individuals with no history of prior exposure to exogenous insulin. Etiopathogenesis is not completely elucidated, it’s considered to result from the interaction of genetic predisposition and environmental triggers such as: medications (methimazole, carbimazole, alpha-lipoic acid, captopril, diltiazem, clopidogrel, diclofenac, pantoprazole, omeprazole), viral infections (mumps, rubella, varicella zoster, hepatitis C virus), and hematological disorders (multiple myeloma, monoclonal gammopathy).

Case report: A 67-year-old female was referred to our clinic with frequent, daily episodes of unpredictable hypoglycemia (fasting, postprandial, and during physical activity) with autonomic and neuroglycopenic symptoms for about six months. Hypoglycemia (capillary blood glucose 42-55 mg/dl) was documented during these episodes with remission of symptoms and signs of hypoglycemia after glucose administration. She had a history of toxic multinodular goiter treated by surgery, prediabetes treated with lifestyle change, arterial hypertension, chronic ischemic heart disease, and old myocardial infarction. She was taking Indapamide, Amlodipine, Valsartan, Betaxolol, Clopidogrel and Pantoprazole. In addition, the patient did not previously use oral hypoglycemic drugs or exogenous insulin. Laboratory tests revealed normal thyroid and adrenal function, and normal chromogranin A (with prior interruption of Pantoprazole). We observed normal basal glucose level, HbA1c 6.99%, and very high insulin levels (19600 uU/ml). After 72-h fasting test, results revealed low glucose (55 mg/dl) with high insulin levels (8673 uU/ml), elevated C-peptide levels (9.44 ng/ml, NR: 0.8-3.85), high insulin/peptide-C molar ratio (>1), and high level of proinsulin (31 pmol/l, NR<11). Measurement of anti-insulin antibodies revealed high titers (>100 U/ml, NR<10). Abdominal CT scan showed no pancreatic or extra-pancreatic lesions. Regarding the presence of hypoglycemic hyperinsulinemia, high titers of insulin autoantibodies, and the use of medications associated with this disease, the diagnosis of insulin autoimmune syndrome was established. The treatment with Pantoprazole was stopped and Clopidogrel was switched to another drug, and the patient was advised to eat frequent and small meals with low carbohydrate content. After six months, our patient reported a decrease in the frequency of hypoglycemic episodes until complete remission.

Conclusions: Hirata disease is still an underdiagnosed condition with increasing incidence. Diagnosis of the disease is a challenge and differential diagnosis from other forms of hypoglycemia is mandatory to avoid unnecessary and high costs imaging examinations. In most cases is self-limited, but in severe cases, pharmacologic therapy is indicated.