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 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.