Simultaneous occurrence of acute-onset type 1 diabetes and Graves' disease; Genetic background of the autoimmune polyglandular syndrome type 3 variant

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 807-838-Diabetes - Diagnosis, Complications & Outcomes
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-838
Tetsuya Mizokami*, Ayumi Yamauchi, Yuichi Sato, Masae Toyonaga, Hirofumi Imoto and Kiyohide Nunoi
St Mary's Hospital, Kurume, Japan
BACKGROUND: Type 1 diabetes (T1D) and Graves’ disease (GD) are common organ-specific autoimmune endocrine disorders.  The occurrence of both T1D and GD in the same patient is one type of autoimmune polyglandular syndrome type 3 variant (APS3v).  Epidemiological evidence suggests a shared genetic background for the various autoimmune disorders of APS3v, and the human leukocyte antigen (HLA) is the most important disease susceptibility gene.  The simultaneous occurrence of acute-onset T1D and GD is rarely seen.  Herein, we describe two patients who developed acute-onset T1D and GD simultaneously with their HLA findings.  CLINICAL CASE: (Case 1) 41-year-old Japanese woman was admitted with a few week-history of thirst, weight loss and palpitations.  Her mother and uncle had type 2 diabetes (T2D).  (Case 2) 27-year-old Japanese woman was admitted with one month history of nausea and dizziness and a few week-history of thirst, polyuria and weight loss.  Her mother and aunt had GD, and her father had T2D.  Their serum glucose levels were 282 mg/dl (Case 1) and 342 mg/dl (Case 2), A1c 10.9% and 11.8%, GAD antibody 471 U/ml and 1,170 U/ml  (normal range; <1.5), IA-2 antibody >40 U/ml and 6.0 U/ml  (normal range; <0.4), urinary CPR 9 μg/day and 2 μg/day, respectively.  They had diffuse goiter, and 99mTcO4 uptake of the thyroid gland were elevated.  Serum free T4 levels were 4.4 ng/dl (Case 1) and 6.9 ng/dl (Case 2), TSH <0.01μIU/ml in both cases, TBII 6.0 IU/l and 131 IU/l (normal range; <1.0), TSAb 537% and 997% (normal range; <180), respectively.  They were diagnosed as having diabetic ketosis or ketoacidosis with acute-onset T1D and GD, and treated with intensive insulin therapy and anti-thyroid drugs.  Their HLA were A2, A24, B54, B67, DRB1*0405-DQA1*0303-DQB1*0401, DRB1*0101-DQA1*0101-DQB1*0501, DPB1*0402 or *0602, DPB1*0901 (Case 1) and A2, A24, B54, B60, DRB1*0405-DQA1*0303-DQB1*0401, DRB1*0405-DQA1*0303-DQB1*0303, DPB1*0501 (Case 2). DISCUSSION: They both had HLA-A2, A24, B54, and DRB1*0405-DQA1*0303-DQB1*0401. HLA class II haplotype DRB1*0405-DQA1*0303-DQB1*0401 is a major susceptibility haplotype for Japanese APS3v patients with both T1D and GD (Hashimoto K 2005).  HLA-A24 and B54 are susceptibility genes for acute-onset T1D, and HLA-A2 and DPB1*0501 have been reported to be factors in susceptibility to GD in Japanese subjects (Dong RP 1992).  Moreover, there exists a strong linkage disequilibrium between HLA-B54 and DRB1*0405 allele.  Thus, the present patients are genetically susceptible to not only APS3v but also both acute-onset T1D and GD.  CONCLUSION: Genetic background strongly contributes to the simultaneous development of acute-onset T1D and GD.

1) Hashimoto K et al 2005 Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population. Horm Res 64:253-260. 2) Dong RP et al 1992 HLA-A and DPB1 loci confer susceptibility to Graves' disease. Hum Immunol 35:165-172.

Nothing to Disclose: TM, AY, YS, MT, HI, KN

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