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.
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.