A 52-year-old woman presented at our hospital with heat intolerance, palpitation, and chest discomfort persisting for 2 months. Physical examination revealed thyroid gland enlargement but no exophthalmos. Thyroid function test indicated hyperthyroidism with thyroid stimulating hormone (TSH) <0.05 µIU/mL (normal range, 0.4 to 4.1), free thyroxine (free T4) 5.71 ng/dL (normal range, 0.70 to 1.80), and triiodothyronine (T3) 375 ng/dL (normal range, 87 to 184). The level of thyroid stimulating immunoglobulin was 60.8% (normal range, 0 to 15). A thyroid scan demonstrated an increase of 20-minute thyroid uptake of 99mTc. A diagnosis of Graves' disease was made and the patient was started on methimazole 30 mg/day. Four weeks after beginning methimazole treatment, she suffered general weakness and sweating that disappeared with food intake. The patient visited the emergency room because of confusion, irritability, and inappropriate verbal responses. She had no history of diabetes mellitus or exposure to insulin or oral antidiabetic agents. The patient's younger brother had a medical history of hyperthyroidism; however, there was no family history of diabetes mellitus. The patient's initial serum glucose level was 34 mg/dL. Laboratory studies including complete blood cell count with differential, chemistry profile, and electrolytes were all within normal limits. Thyroid function study revealed TSH <0.05 µIU/mL, free T4 0.77 ng/dL, and T3 146 ng/dL. Hemoglobin A1c (HbA1c) was 5.8%. The total serum insulin concentration was 119 µIU/mL (normal range, 2 to 25) and serum C-peptide was 14.7 ng/mL (normal range, 0.8 to 4.0). Insulin autoantibody was measured by radioimmunoassay at 84.7% (normal range, 0 to 7). Percent 125I-insulin binding was not measured. A computed tomography (CT) scan revealed a small cyst of the pancreas tail, which had no contrast enhancement. There was no evidence of insulinoma or extrapancreatic neoplasm. The result of 75-g oral glucose tolerance test showed an abnormal increase of total serum insulin levels with delayed hypoglycemia developing after 240 minutes with symptoms of sweating and dizziness (). A diagnosis of methimazole-induced insulin autoimmune syndrome was made based on the high serum concentration of total insulin, fasting hypoglycemia, and the presence of insulin autoantibodies. Methimazole was discontinued, and consumption of six or more small meals throughout the day with low carbohydrate was recommended. Hypoglycemic attacks subsided within 1 week and there were no further hypoglycemic episodes after discharge. Total serum insulin, titer of insulin autoantibody, and level of serum C-peptide decreased gradually after 5 months (). Treatment with 131I 20 mCi was performed to address Graves' disease in the patient.
This patient was a 52-year-old man diagnosed with type 2 diabetes mellitus at the local hospital according to a fasting glucose test that showed a concentration of 16 mmol/L. His postprandial glucose concentration was 27 mmol/L. However, the patient was asymptomatic. He was then treated with a 50/50 Mixture Recombinant Human Insulin Injection (Gansulin 50R) of 12–16 units twice a day, and the dose had been adjusted to 6–10 units 2 months previously. During this period, his glucose was well controlled. One month previously, he developed dizziness and was flustered again. He also started sweating excessively, and at that time, his fasting plasma glucose concentration was 2.8 mmol/L. One week previously, the treatment was changed to acarbose 0.1 mg three times a day because of repeated occurrence of hypoglycemic symptoms. His insulin concentrations were 1294.01/1303.77/1456.7/2057.11/2032.41 pmol/L at 0/30/60/120/180 min and C-peptide concentrations were 1.30/1.80/2.21/2.87/2.55 nmol/L at 0/30/60/120/180 min during the OGTT, respectively. The anti-insulin antibody test was positive. He was prescribed metformin (0.5 g twice a day), acarbose (0.05 g three times a day), aspart (6–5-5 units three times a day), and methylprednisolone (4 mg three times a day) for glucose control. After these changes, hypoglycemia syndrome did not recur (Table ).