Adrenal insufficiency and Addison disease are hormonal or endocrine disorders caused by the body not producing enough of the adrenal hormones cortisol and aldosterone. This typically occurs when there is a malfunction in the system that maintains a close and timely balance of these hormones. This balance is achieved through a system of signaling and a feedback system. Signals sent and received among the hypothalamus in the brain, the pituitary gland in the brain, and the adrenal glands (located on top of each kidney) regulate adrenal hormone production.
The adrenal glands are multi-layered:
- The outer layer produces aldosterone, a salt-balancing hormone that has effects on blood pressure.
- The middle layer produces cortisol, a hormone with effects on blood sugar, blood pressure and inflammatory responses.
- The deepest layer produces hormones called androgens, which have effects on growth of sexual hair and acne, for example.
Normally, cortisol is produced and released by the adrenal cortex. Production of the hormone is regulated by the hypothalamus and the pituitary gland. When the blood cortisol level falls, the hypothalamus releases corticotropin-releasing hormone (CRH), which directs the pituitary gland to produce ACTH (adrenocorticotropic hormone). ACTH stimulates the adrenal glands to produce and release cortisol. In order for appropriate amounts of cortisol to be made, the hypothalamus and both the pituitary and adrenal glands must be functioning properly.
Without enough cortisol or aldosterone, people become weak and dehydrated, unable to maintain an adequate blood pressure or to respond properly to physical stress. Among its many roles, cortisol affects the metabolism of carbohydrates, proteins, and fats, affects glucose levels in the blood, acts as an anti-inflammatory agent, and helps the body react to stress such as infection or trauma. Aldosterone is produced by the adrenal cortex and manages the salt and potassium balance in the blood.
There are two different types of adrenal insufficiency and they depend on whether pituitary gland or adrenal dysfunction underlies hormone deficiencies:
- Primary adrenal insufficiency (Addison disease)—caused by underactive or damaged adrenal glands, which affect cortisol and aldosterone levels in the blood.
Addison disease is relatively rare. It affects about 1 person per 100,000 in the U.S. It is found in people of all ages and affects both males and females equally. Symptoms of insufficiency may not emerge until about 80% to 90% of the adrenal cortex has been destroyed.
In the U.S., the most common cause (about 75%) of primary adrenal insufficiency in adults is an autoimmune process. It may occur with other autoimmune conditions that affect other glands, such as the thyroid. The rest of the time, Addison disease is due to other causes, such as tuberculosis, a common cause in areas of the world where tuberculosis is more prevalent, other chronic infections, especially fungal infections, bleeding into the adrenal glands (hemorrhage) and the spread of cancer into the adrenal glands. Rarely, it may be due to a genetic abnormality of the adrenal glands.
In children, about 70% of cases are caused by a congenital disease termed congenital adrenal hyperplasia (CAH), while 30% of the time adrenal damage is due to autoimmune disease, the inherited disease adrenoleukodystrophy, or less common causes.
- Secondary adrenal insufficiency—a decrease in the production of the pituitary hormone ACTH (adrenocorticotropic hormone) is at the root of secondary adrenal insufficiency. ACTH is a pituitary messenger; it tells the adrenal cortex to produce cortisol. If there is insufficient ACTH, due to pituitary damage, a pituitary tumor, or some other cause, then cortisol production is not stimulated. Secondary adrenal insufficiency can also arise when corticosteroid therapy (such as prednisone, which may be given to relieve inflammation in conditions such as rheumatoid arthritis or high dose inhaled steroids, which may be given to treat asthma ) is abruptly halted. These treatments suppress natural cortisol production and it can take several weeks or months for normal production to resume.