This patient was a 79-year-old man who had a 10-year history of hyperglycemia in addition to fluctuating glucose concentrations for more than 1 year. This was accompanied by diabetic nephropathy as well as a history of gout for more than 30 years. His glucose concentrations were initially well controlled with metformin after diagnosis of type 2 diabetes mellitus. A subcutaneous insulin pump (lispro) was recently added to his treatment regimen for renal insufficiency, and metformin was gradually changed to Humulin R (6–4-4 units, three times a day) combined with glargine 12 units a day. Thereafter, he had recurrent midnight hypoglycemia and daytime hyperglycemia, with blood glucose concentrations up to 20 mmol/L. Therefore, he was treated with acarbose (50 mg three times a day) instead of insulin injections. At this time, his C-peptide values were 5.45/6.94/6.94/7.89/7.17 nmol/L at 0/0.5/1/2/3 h, respectively (normal range: 0.27–1.28 nmol/L). His insulin concentrations were > 1000.00/> 1000.00 pmol/L at 0/2 h, respectively (normal range: 13–161 pmol/L), during an oral glucose tolerance test (OGTT), his HbA1c concentration was 10.2%, and an anti-insulin antibody test was positive (reference level: < 0.4). His glucose concentrations still fluctuated between 11 mmol/L and 22 mmol/L in the daytime, while hypoglycemia occurred at night. Subsequently, acarbose (100–100-50 mg three times a day) and sitagliptin (50 mg per day) were prescribed for symptom management, and his glucose concentrations returned to the normal range. Laboratory findings at a 1-year follow-up showed an HbA1c concentration of 7.0%, insulin concentrations of 138.53/733.40 pmol/L at 0/2 h, and C-peptide concentrations of 1.35/2.21 nmol/L at 0/2 h, 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.