Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry.
OBJECTIVE
Primary adrenal insufficiency [Addison's disease (AD)] is rare, and systematic studies are few, mostly conducted on small patient samples. We aimed to determine the clinical, immunological, and genetic features of a national registry-based cohort.


METHODS
Patients with AD identified through a nationwide search of diagnosis registries were invited to participate in a survey of clinical features, health-related quality of life (HRQoL), autoantibody assays, and human leukocyte antigen (HLA) class II typing.


RESULTS
Of 664 registered patients, 64% participated in the study. The prevalence of autoimmune or idiopathic AD in Norway was 144 per million, and the incidence was 0.44 per 100,000 per year (1993-2007). Familial disease was reported by 10% and autoimmune comorbidity by 66%. Thyroid disease was most common (47%), followed by type 1 diabetes (12%), vitiligo (11%), vitamin B12 deficiency (10%), and premature ovarian insufficiency (6.6% of women). The mean daily treatment for AD was 40.5 mg cortisone acetate and 0.1 mg fludrocortisone. The mean Short Form 36 vitality scores were significantly diminished from the norm (51 vs. 60), especially among those with diabetes. Concomitant thyroid autoimmunity did not lower scores. Anti-21-hydroxylase antibodies were found in 86%. Particularly strong susceptibility for AD was found for the DR3-DQ2/ DRB1*0404-DQ8 genotype (odds ratio, 32; P = 4 x 10(-17)), which predicted early onset.


CONCLUSIONS
AD is almost exclusively autoimmune, with high autoimmune comorbidity. Both anti-21-hydroxylase antibodies and HLA class II can be clinically relevant predictors of AD. HRQoL is reduced, especially among diabetes patients, whereas thyroid disease did not have an impact on HRQoL. Treatment modalities that improve HRQoL are needed.
Erichsen
Martina M
MM
Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway. martina.moter.erichsen@helse-bergen.no
Løvås
Kristian
K
Skinningsrud
Beate
B
Wolff
Anette B
AB
Undlien
Dag E
DE
Svartberg
Johan
J
Fougner
Kristian J
KJ
Berg
Tore J
TJ
Bollerslev
Jens
J
Mella
Bjarne
B
Carlson
Joyce A
JA
Erlich
Henry
H
Husebye
Eystein S
ES
D000224:Addison Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004651:Employment; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006680:HLA Antigens / Q000235:genetics; D006306:Health Surveys; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011788:Quality of Life; D012042:Registries; D011795:Surveys and Questionnaires; D055815:Young Adult
D001323:Autoantibodies; D005938:Glucocorticoids; D006680:HLA Antigens; D004247:DNA