This patient was a 71-year-old man who was admitted because of polydipsia and polyuria that had persisted for 8 years, as well as recurrent episodes of unconsciousness throughout this period. He was diagnosed with type 2 diabetes mellitus 8 years before admission. Acarbose was initially prescribed, but was switched to insulin aspart 30 (8–12 units twice a day) because of poor glucose control 5 years previously. Three months previously, the dose of insulin aspart 30 was gradually reduced to 4–10 units because of hypoglycemia. However, he had unexpected episodes of unconsciousness due to hypoglycemia 12 days before admission. Moreover, his symptoms were obviously relieved after food intake. He was subsequently treated with voglibose instead of insulin injections. However, the hypoglycemic symptoms continued to appear between 02:00 am and 03:00 am, despite the absence of other treatments. A laboratory examination showed the following: C-peptide values were 15.22/17.59/19.73/15.22 nmol/L at 0/1/2/3 h, and insulin concentrations were > 2089.5/> 2089.5/> 2089.5/> 2089.5 pmol/L at 0/1/2/3 h during the OGTT, respectively. The anti-insulin antibody test was also positive. His treatment regimen was changed to prednisone (5 mg three times a day), acarbose (50 mg three times a day), metformin (0.5 g twice a day), and glargine (12–18 units twice a day) for glucose control. Insulin injections were also gradually discontinued. Following this treatment, he showed improved glucose control. Laboratory tests during a recent follow-up showed the following: C-peptide levels of 0.77/2.40 nmol/L at 0/2 h and insulin levels of 430.13/1350.21 pmol/L at 0/2 h during the OGTT, respectively.
A 53-year-old woman visited the emergency room of our hospital complaining of headache, palpitation, and chest discomfort. She was diagnosed with Graves' disease at a different hospital 1 month prior to being admitted at our hospital and had been taking both methimazole 40 mg/day and β-blocker since her diagnosis. Prior to visiting our emergency room, she consumed breakfast and was measured with a serum glucose level of 294 mg/dL. Laboratory studies including complete blood cell count with differential, chemistry profile, and electrolytes were all within normal limits. The result of thyroid function tests were TSH <0.01 µIU/mL, free T4 2.74 ng/dL, and T3 184.8 ng/dL. The patient's symptoms were initially attributed to hyperthyroidism due to the lack of abnormal findings on neurologic exam and brain magnetic resonance imaging. However, 6 hours after discharge, the patient revisited our emergency room due to sweating and altered mental state, where it was noted that she had neither a history of diabetes mellitus nor previous exposure to insulin or oral antidiabetic agents. Furthermore, there was no family history of thyroid disease and diabetes mellitus. The patient's initial serum glucose level was 27 mg/dL, HbA1c was 5.8%, serum total insulin was 600 µIU/mL, and serum C-peptide was 15.3 ng/mL. The titer of insulin autoantibody was 84.8%, while detection of both insulin receptor antibody and islet cell antibody were negative. The percent of 125I-insulin binding was not measured. The titers of serum thyroid autoantibodies were high. Specifically, antithyroid peroxidase antibody was 2,876 U/mL (normal range, 0 to 100), antithyroglobulin antibody was 330 IU/mL (normal range, 0 to 115), and TSH receptor antibody was 2.95 IU/L (normal range, <1.22). A CT scan revealed no evidence of insulinoma or extrapancreatic neoplasm. The patient's fasting insulin level was more than 3,000 µIU/mL and C-peptide was 25.9 ng/mL on hospital day 7. A 75-g oral glucose tolerance test showed marked increase of total insulin level and subsequent hypoglycemia developed after 240 minutes (). HLA genotyping was performed by sequence based typing and the result was HLA-DRB1*0406 and *1501. Continuous intravenous glucose injection was needed due to recurrent fasting hypoglycemia. Methimazole-induced insulin autoimmune syndrome was diagnosed, and methimazole was subsequently discontinued. Hypoglycemic episodes disappeared after 1 month, with the patient consuming small frequent meals and a low carbohydrate diet. The concentration of serum total insulin, titer of insulin autoantibody, and serum C-peptide level decreased gradually after 5 months (). Radioactive iodine therapy with 131I 15 mCi was performed to address Graves' disease in the patient.