A Case of Type 1 Diabetes Followed by Methimazole-Induced Hypersensitivity Syndrome
- Nobuaki Ozaki, MD, PHD,
- Yoshitaka Miura, MD, PHD and
- Yutaka Oiso, MD, PHD
- From the Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Address correspondence to Nobuaki Ozaki, Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku, Nagoya 466-8550, Japan. E-mail: n-ozaki{at}med.nagoya-u.ac.jp
Viruses have generally been considered to be a major environmental factor in the etiology of type 1 diabetes. Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe drug eruption and multiorgan involvement, and reactivation of human herpesvirus-6 (HHV-6) may contribute to its pathology (1). This is the first reported case of type 1 diabetes followed by DIHS.
Recently, we have reported a case of DIHS induced by methimazole for Graves’ disease (2). This patient developed type 1 diabetes during treatment of DIHS. Briefly, a 50-year-old Japanese male subject was diagnosed as having DIHS caused by methimazole in November 2003, based on the physical manifestations and laboratory findings including elevated anti–HHV-6 IgG titer. The administration of glucocorticoids gradually improved his clinical manifestations.
In December 2003, fasting plasma glucose was 4.9 mmol/l. His glycemic control, thereafter, gradually worsened despite treatment with nateglinide (270 mg/day). In March 2004, laboratory studies showed fasting plasma glucose to be 14.4 mmol/l; HbA1c, 12.1%; fasting serum C-peptide, 0.35 ng/ml (normal range 0.5–2.73); and urinary excretion of C-peptide (which means integrated intrinsic insulin secretion), 17.24 mg/day (normal range 40–120). Basal level of serum C-peptide was finally undetectable. Anti-GAD antibody was 24.1 unit/ml (normal range <1.5). Response of serum C-peptide to glucagon was blunted. Thus, we diagnosed the patient as having type 1 diabetes. He started insulin injections immediately. His glycemic control gradually improved.
The coexistence of type 1 diabetes and Graves’ disease is not infrequent. The onset age of type 1 diabetes in this case is fairly later, and anti-GAD antibody titer is relatively low, although type 1 diabetes with autoimmune thyroid disease was reported to be clinically characterized as high titer (609 ± 166 units/ml) of anti-GAD antibody and later-onset age (∼30 years) compared with the general type 1 diabetic population (3). Therefore, these findings cannot exclude the possibility that the coexistence of type 1 diabetes and Graves’ disease may be not incidental.
It is possible that viral infections such as coxsackie B4 virus and cytomegalovirus can trigger autoimmune reactions against pancreatic β-cells, which leads to type 1 diabetes. Molecular mimicry has been considered as a pathogenetic mechanism for autoimmune disease (4). GAD65-reactive T-cells have been postulated to recognize the peptide derived by coxsackie B4 virus, leading to autoimmune type 1 diabetes (4). Furthermore, sequence homology between GAD65 and cytomegalovirus might participate in the onset of type 1 diabetes and stiff-man syndrome (5). Interestingly, HHV-6 is closely related to cytomegalovirus genomically and antigenically, and GAD65-reactive T-cells also recognize an epitope derived by HHV-6 (5), suggesting that reactivation of HHV-6 might contribute to the onset of autoimmune type 1 diabetes by the molecular mimicry.
