A case of autoimmune polyendocrine syndrome type I with strong positive GAD antibody titer, followed up with glucose tolerance measured by oral glucose tolerance test.
A 26-year-old Japanese woman presented with adrenal insufficiency, and treatment was started with cortisone and fludrocortisone in 1975. A few years later, she presented with hypoparathyroidism and was diagnosed with autoimmune polyendocrine syndrome type I (APS I), and treatment with calcium and alfacalcidol was started. She was found to have subacute thyroiditis and relative adrenal failure in 2006. Her condition remained stable under treatment with cortisone, fludrocortisone, levothyroxine, calcium lactate, precipitated calcium carbonate and alfacalcidol. While antibodies against pancreatic glutamic acid decarboxylase (GAD) were strongly positive (7,690 U/ml), fasting glucose level was 4.9 mmol/L and HbA1c was 6.3% on admission. As GAD antibody showed a high-titer of >10,000 U/ml and fasting plasma glucose level showed a rising trend, we performed 75-g oral glucose tolerance test (OGTT) 6 years after discharge. Whereas OGTT in 2012 showed impaired glucose tolerance, glucose tolerance had reverted to normal in 2014. A patient with a high-titer GAD antibody does not always have progressive glucose intolerance. GAD antibody positivity is common in not only type 1 diabetes, but also APS I and stiff-person syndrome (SPS). There are differences in recognized epitopes among the three disorders. Epitopes for GAD65 antibody associated with type 1 diabetes are located in the middle region and the COOH-terminal of the GAD65 protein, whereas epitopes associated with SPS reside in the NH2-terminal in addition to the middle region and COOH-terminal. The present case suggests that these differences in epitopes may be related to various pathogenic mechanisms including glucose intolerance.
Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Rie
R
Murakami
Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Toshihide
T
Kawai
Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Shu
S
Meguro
Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Matsuhiko
M
Hayashi
Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Hiroshi
H
Itoh
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D000939:Epitopes / Q000276:immunology; D005260:Female; D005951:Glucose Tolerance Test; D005968:Glutamate Decarboxylase / Q000097:blood*; D006801:Humans; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D016750:Stiff-Person Syndrome / Q000097:blood / Q000175:diagnosis
D001323:Autoantibodies; D001786:Blood Glucose; D000939:Epitopes; D005968:Glutamate Decarboxylase