From the Guidelines
Addison's disease is a rare endocrine disorder characterized by insufficient production of adrenal hormones, primarily cortisol and aldosterone, resulting from progressive destruction of the adrenal cortex, typically affecting more than 90% of the gland before clinical symptoms appear. The pathophysiology of Addison's disease involves the destruction of the adrenal cortex, leading to inadequate production of glucocorticoids (cortisol) and mineralocorticoids (aldosterone) [ 1 ]. The most common cause (about 80-90% of cases) is autoimmune adrenalitis, where the body's immune system attacks and damages the adrenal glands [ 1 ]. Other causes include tuberculosis, fungal infections, metastatic cancer, adrenal hemorrhage, and certain medications like ketoconazole or etomidate that inhibit cortisol synthesis. Genetic disorders such as adrenoleukodystrophy can also lead to adrenal insufficiency.
Causes of Addison's Disease
- Autoimmune adrenalitis (80-90% of cases)
- Tuberculosis
- Fungal infections
- Metastatic cancer
- Adrenal hemorrhage
- Certain medications (e.g. ketoconazole, etomidate)
- Genetic disorders (e.g. adrenoleukodystrophy)
Pathophysiology
The destruction of the adrenal cortex results in inadequate production of glucocorticoids (cortisol), which regulate metabolism and stress response, and mineralocorticoids (aldosterone), which maintain electrolyte balance and blood pressure [ 2 ]. This hormonal deficiency leads to the classic symptoms of fatigue, weakness, weight loss, hyperpigmentation, salt craving, hypotension, and electrolyte imbalances. In autoimmune Addison's disease, patients often have circulating adrenal antibodies and may develop other autoimmune conditions as part of polyglandular autoimmune syndromes. The disease typically develops gradually, with symptoms appearing only after significant adrenal destruction has occurred.
From the Research
Pathophysiology of Addison's Disease
- Primary adrenal insufficiency (PAI) occurs when the adrenal glands are damaged, leading to a deficiency in the production of cortisol and aldosterone hormones [ 3 ].
- The adrenal glands play a crucial role in regulating various bodily functions, including blood pressure, electrolyte balance, and metabolism.
- In Addison's disease, the adrenal glands are unable to produce sufficient amounts of cortisol and aldosterone, leading to a range of symptoms and complications.
Causes of Addison's Disease
- Autoimmune Addison's disease (AAD) is the major cause of primary adrenal insufficiency (PAI) [ 3 ].
- AAD is characterized by the presence of 21-hydroxylase autoantibodies (21OHAb), which identify subjects with ongoing clinical or pre-clinical adrenal autoimmunity [ 3 ].
- AAD is a major component of autoimmune polyendocrine syndrome type 1 (APS1) and type 2 (APS2) [ 3 ].
- Other causes of Addison's disease may include infections, tumors, and genetic disorders, although these are less common [no specific reference available].