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Addison’s disease or primary adrenal insufficiency is caused when the adrenal cortex is damaged leading to severe deficiency of the steroid hormones that are produced normally by the adrenal cortex.
In 70 to 80% of cases of Addison’s disease the underlying cause is autoimmunity.
Normally the immune system of the body is the primary defence against any infections and foreign organisms that enter the body. The immune system produces antibodies that destroy the disease carrying organisms and foreign invaders.
In persons with autoimmune disorders, the immune system fails to recognize self from foreign and attacks the body’s own cells and tissue leading to damage.
In Addison’s disease the immune system produces antibodies that attack the adrenal cortex cells and thus damage the cortex. The process may be gradual and when 90% of the adrenal cortex is destroyed the levels of cortical hormones like cortisol and aldosterone become very low and this gives rise to the symptoms of the disease.
There have been studies that show that some genetic mutations and changes may be responsible for inheritance of autoimmunity that raises the risk of autoimmune mechanisms leading to Addison’s disease.
The exact mechanism by which this defective gene causes Addison’s disease is not yet known.
The theory of inherited genetic changes that lead to Addison’s disease are further reinforced by the fact that certain inherited conditions are strongly associated with Addison’s disease. These conditions include vitiligo that is a long-term condition that causes whitish patches over the skin, type 1diabetes and underactive thyroid function or hypothyroidism.
Sometimes other endocrine glands are affected as well. This is called polyendocrine deficiency syndrome. In this condition there may be two forms - type 1 and type 2. Type 1 is inherited and is seen in children while type 2 (also called Schmidt’s syndrome) may affect young adults.
In type 1 polyendocrine deficiency syndrome there may be underactive parathyroid glands, retarded sexual development, pernicious anemia, fungal infections and liver disease. In type 2 there is an underactive thyroid gland, diabetes, vitiligo, retarded sexual development.
Some infections may lead to damage to the adrenal cortex. Tuberculosis is one of the most well known infections associated with Addison’s disease. Tuberculosis bacteria primarily affect the lungs but may spread to other organs like adrenals and destroy them.
HIV infection and AIDS and fungal infections may also be associated with Addison’s disease.
Some cancers either primarily in adrenals or spread from other organs can also cause Addison’s disease
Bleeding within the adrenal glands (may be caused due to whole body infections like sepsis or brain infections like meningitis) may also cause Addison’s disease. Surgery to remove the adrenal glands is also responsible for Addison’s disease in some cases.
Disease like amyloidosis that leads to the accumulation of amyloid protein in the adrenal glands may lead to Addison’s disease
There may be secondary adrenal insufficiency as well caused by a lack of ACTH. ACTH stimulates the adrenal to secrete its hormones. Without ACTH to stimulate the adrenal glands the cortisol production level falls. Aldosterone production is not usually affected.
This may be seen due to long term use of glucocorticoids, surgical removal of the benign or non cancerous ACTH-producing tumors of the pituitary gland that are causing Cushing’s disease.