Immunological Aspects in the Pathogenesis of Primary Adrenocortical Insufficiency (Addison’s disease)

Author: Feyzullova-Sopadzhieva, Aylin G.1, Robeva, Ralitsa N.1, Elenkova, Atanaska P.1, Zacharieva, Sabina Z.1

1 USHATE “Acad. Ivan Penchev”, Department of Endocrinology, Faculty of Medicine, Medical University, Sofia

Abstracts:

Primary adrenocortical insufficiency was first described by Dr. Thomas Addison in 1885. At that time the main cause of Addison’s disease (AD) was tuberculosis infection. After 1950, autoimmune adrenalitis took precedence.

The aim of this review is to consider some new immunological aspects in the pathogenesis of AD. Serum autoantibodies directed against steroidogenic enzymes in the adrenal cortex, most frequently 21-hydroxylase antibodies and less frequently against 17-alpha- and 11-alpha-hydroxylases, are found in nearly 90% of affected patients. In addition, antibodies against interleukin-17F and interleukin-22 can be detected in AD within autoimmune polyglandular syndrome (APS) type 1. A number of studies have shown that other organ-specific autoantibodies are detected in a large proportion of atients with autoimmune adrenalitis, predisposing to the development of concomitant endocrine and extraendocrine autoimmune diseases. Systemic connective tissue diseases may also be seen in association with AD, and it has been hypothesized that, for example, antiphospholipid syndrome may not only be a marker for APS in AD patients but also an etiologic factor for the onset of the disease due to vascular damage to the kidneys. In recent years, immunotherapy with new classes of cancer drugs, immune checkpoint inhibitors (ICIs), which probably mediate autoimmune activation, has been an important cause of AD.

In conclusion, the heterogeneous antibody profile against steroidogenic adrenal and gonadal enzymes likely modulates the phenotypic expression of AD. The elevated titer of many organ-specific and cytokine antibodies in patients may predispose to different co-morbidities and treatment needs that should be considered in clinical practice.

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Journal of the Bulgarian Society of Endocrinology

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