Addison’s disease is a disease of the Adrenal Cortex caused by autoimmune destruction of the Adrenal gland with fibrosis and mononuclear cell infiltration. Symptoms become evident when more than 90% of the Adrenal gland is destroyed. Addison’s disease is characterised by increased production of adrenocorticotropic hormone (ACTH) and adrenal insufficiency with reduced production of corticosteroids and androgens. Patients present with hypotension, weakness, fatigue, light headedness when standing up, anorexia, nausea, salt craving and increased melanin pigmentation of the skin. Autoantibodies to 21-hydroxylase are present in 90% of cases.
Family studies have shown that Addison’s disease has a genetic component with HLA class II the most strongly associated genetic region. Addison’s disease is associated with DRB1*03:01-DQB1*02 (DR17, DQ2) and DRB1*04-DQB1*03:02 (DR4, DQ8). The most strongly associated DRB1*04 allele is DRB1*04:04. The major histocompatibility complex class I related chain – A (MICA) is an additional risk factor. MICA genes are highly polymorphic with over 70 alleles described. MICA is a ligand for the Natural Killer (NK) cell receptor NKG2D which is important for thymic maturation of T cells.
Autoantibody testing for anti-21-hydroxylase is more diagnostic in Addison’s disease than genetic testing. Genetic testing does however contribute to a better understanding of the aetiology of the disease.
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