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 79-year-old man who presented with a 3-year history of hyperglycemia and a 1-year history of polydipsia. At the time of presentation, he had been in a hypodynamic state for 15 days. Three years previously, he was diagnosed with impaired glucose tolerance without any symptoms, but no treatment was provided. One year earlier, he developed polydipsia, hyperuresis, and cutaneous pruritus, and lost weight. His random plasma glucose concentrations increased to as high as 20 mmol/L. Consequently, he was started on aspart 30 (21 units before breakfast and 8 units before dinner) and metformin (0.5 g twice a day). One month previously, he visited our hospital because of complaints of recurrent midnight hypoglycemia, particularly at approximately 02:00 am. During that period, although an insulin injection was gradually reduced and subsequently discontinued, his glucose concentration still dropped to 3 mmol/L. Laboratory tests showed that C-peptide and insulin concentrations were above the normal range, and the insulin autoantibody test was positive. At that time, non-classical IAS was considered as the probable cause of repeated hypoglycemia, and treatment was changed to acarbose (50 mg three times a day). After 15 days, blood tests showed the following: fasting plasma glucose level, 3.71 mmol/L; anti-insulin antibody, > 45.4 U/mL; and insulin concentrations were 1567.44/1493.06/1370.20/1616.43/1812.01 pmol/L at 0/30/60/120/180 min and C-peptide concentrations were 3.41/3.68/3.95/4.56/4.51 nmol/L at 0/30/60/120/180 min during the OGTT, respectively. For treatment of IAS, prednisone therapy was started at 12 mg daily (4 mg per dose three time daily) then reduced to 8 mg daily after 2 weeks and to 4 mg per night 1 week later. The diabetes treatment plan was changed to human biosynthetic insulin injection (16 units per day), sitagliptin (50 mg per day), and voglibose (0.3–0.2 mg twice a day). Repeated laboratory tests showed the following: C-peptide concentrations were 0.73/1.67 nmol/L at 0/2 h, respectively, and the insulin concentration was 728.14 pmol/L at 0 h during the OGTT. The glucose concentration fluctuated between 7 and 12.9 mmol/L.