Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: Addison's disease in a high-risk population.
Individuals with type 1 diabetes mellitus (T1D) at risk for Addison's disease (AD) can be identified with RIAs for autoantibodies to the adrenal antigen 21-hydroxylase (21-OHAA). Screening individuals with T1D for 21OH-AA shows a relatively high prevalence of positive autoantibodies (1.4%, 38 of 2696 subjects). After detection of 21-OHAA, individuals were evaluated with endocrine testing, including baseline cortisol, ACTH, and plasma renin activity and low (1 mug) and high (250 mug) dose cortrosyn stimulation. Typing for DR and DQ alleles and for the major histocompatibility complex class I-related chain A (MICA) gene polymorphisms was performed. Six individuals were diagnosed with AD; five were identified on initial endocrine evaluation. Follow-up over 2.9 yr yielded one additional diagnosis of AD. Endocrine testing showed a correlation between baseline ACTH and peak cortisol (r = -0.61; P < 0.0001), baseline and peak cortisol (r = 0.70; P < 0.0001), and stimulated cortisol after low- and high-dose testing (r = 0.92; P < 0.0001). DR3-DQ2/DR4-DQ8 with DRB1* 0404 was associated with expression of 21-OHAA. At 2 yr, individuals homozygous for MICA5.1 had AD-free survival of 60% compared with 100% AD-free survival in those who were not homozygous for MICA5.1. Homozygosity for MICA5.1 may increase progression to overt AD among 21-OHAA-positive individuals.
Barker
Jennifer M
JM
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Avenue, B-140, Denver, Colorado 80262, USA. jennifer.barker@uchsc.edu
Ide
Akane
A
Hostetler
Corey
C
Yu
Liping
L
Miao
Dongmei
D
Fain
Pamela R
PR
Eisenbarth
George S
GS
Gottlieb
Peter A
PA
D000224:Addison Disease / Q000209:etiology*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I; D006650:Histocompatibility Testing; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis; D012680:Sensitivity and Specificity; D013255:Steroid 21-Hydroxylase / Q000276:immunology*
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D011506:Proteins; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone