Addison's disease develops when the adrenal glands, which are above the kidneys, are not able to make enough of the hormones cortisol and, sometimes, aldosterone.
Cortisol affects almost every organ in the body and is needed for your body to work as it should. The adrenal glands release cortisol to help the body cope withstress from illness, injury, surgery, childbirth, or other reasons. Aldosterone helps the body hold on to the salt it needs, and it keeps your blood pressure steady.
Normally, cortisol levels increase through a chain reaction of hormones:
- First, the hypothalamus in the brain makes a hormone called CRH (corticotropin-releasing hormone).
- Then, CRH tells the pituitary gland to make another hormone called ACTH(adrenocorticotropic hormone).
- ACTH then tells the adrenal glands to make cortisol. Cortisol affects almost every area of the body. It is especially important in regulating blood pressure and metabolism.
When your adrenal gland cannot make enough cortisol, you have Addison's disease.
The most common symptoms are:
- Extreme tiredness (fatigue).
- Losing weight without trying.
You may also have other symptoms, such as:
- Skin that looks darker than normal.
- Loss of appetite.
- Feeling lightheaded.
- Feeling sick to your stomach or vomiting.
- Craving salt.
And if you have diabetes, you may have low blood sugar more often, and it may be more severe than usual.
Symptoms usually start slowly. You may not even notice them until a stressful event such as a severe infection, trauma, surgery, or dehydration causes an adrenal crisis. An adrenal crisis means that your body can't make enough cortisol to cope with the stress.
In a few cases, Addison's disease gets worse quickly. These people may already be in an adrenal crisis when they see a doctor.
Symptoms of an adrenal crisis include:
- Severe vomiting and diarrhea.
- Sudden pain in the belly, low back, or legs.
- A high fever.
- Feeling very weak or lightheaded.
- Feeling restless, confused, or fearful.
- Having trouble staying awake.
Call your doctor right away if you have these symptoms. If an adrenal crisis is not treated, you could die of shock from a steep drop in blood pressure.
How is Addison's disease diagnosed?
To diagnose Addison's disease, the doctor will:
- Ask you questions about your symptoms and past health. He or she will want to know if this disease runs in your family and if you have had cancer or tuberculosis or have been infected with HIV.
- Do a physical exam. The doctor will check to see if your skin color is darker than normal, if you have low blood pressure, or if you are dehydrated.
- Order lab tests. Blood tests can show if you have high potassium or low sodium levels. These levels can be a sign of Addison's disease. You may also have a blood test to check your levels of cortisol and ACTH.
If the diagnosis is still not clear, you may have an ACTH stimulation test, which helps show how your hormone levels react to stress. You will be given a man-made form of ACTH to see if your body makes enough cortisol. Further tests will show if you have Addison's disease or another problem.
Your doctor may suggest some imaging tests, such as an MRI, after the problem area has been found.
If your doctor thinks you have Addison's disease, he or she may start treatment right away, even before you get your test results. If the test results later show that you don't have the disease, your doctor can stop the treatment.
Addison's disease most often occurs when the body's immune system kills off the part of the adrenal glands that makes cortisol and aldosterone.
It can also form when the adrenal glands are harmed by:
- Infections, such as tuberculosis, HIV, and other bacterial or fungal infections.
- Cancer that has spread to the adrenal glands. This is mostly seen in lung cancer.
- Bleeding into the adrenal glands as a side effect of using blood thinners.
- Some types of surgery or radiation treatments.
- The use of certain medicines, such as high doses of ketoconazole.
- Injury to the adrenal glands.
People can get Addison's disease at any age. Addison's disease can also form if you take a steroid medicine for a long time and then suddenly stop using it.
Tuberculosis (TB), an infection which can destroy the adrenal glands, accounts for about 20 percent of cases of primary adrenal insufficiency in developed countries. When adrenal insufficiency was first identified by Dr. Thomas Addison in 1849, TB was found at autopsy in 70 to 90 percent of cases.
As the treatment for TB improved, however, the incidence of adrenal insufficiency due to TB of the adrenal glands has greatly decreased.
Secondary adrenal insufficiency
This form of adrenal insufficiency is much more common than primary adrenal insufficiency and can be traced to a lack of ACTH. Without ACTH to stimulate the adrenals, the adrenal glands' production of cortisol drops, but not aldosterone. A temporary form of secondary adrenal insufficiency may occur when a person who has been receiving a glucocorticoid hormone such as prednisone for a long time abruptly stops or interrupts taking the medication.
Glucocorticoid hormones, which are often used to treat inflammatory illnesses like rheumatoid arthritis, asthma, orulcerative colitis, block the release of both corticotropin-releasing hormone (CRH) and ACTH. Normally, CRH instructs the pituitary gland to release ACTH. If CRH levels drop, the pituitary is not stimulated to release ACTH, and the adrenals then fail to secrete sufficient levels of cortisol.
Another cause of secondary adrenal insufficiency is the surgical removal of benign, or noncancerous, ACTH-producing tumors of the pituitary gland (Cushing's disease). In this case, the source of ACTH is suddenly removed, and replacement hormone must be taken until normal ACTH and cortisol production resumes.
Less commonly, adrenal insufficiency occurs when the pituitary gland either decreases in size or stops producing ACTH.
These events can result from:
- tumors or infections of the area,
- loss of blood flow to the pituitary,
- radiation for the treatment of pituitary tumors,
- surgical removal of parts of the hypothalamus,
- surgical removal of the pituitary gland.
Treatment of Addison's disease involves replacing, or substituting, the hormones that the adrenal glands are not making. Cortisol is replaced orally with hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day. If aldosterone is also deficient, it is replaced with oral doses of a mineralocorticoid called fludrocortisone acetate (Florinef), which is taken once a day.
Patients receiving aldosterone replacement therapy are usually advised by a doctor to increase their salt intake. Because patients with secondary adrenal insufficiency normally maintain aldosterone production, they do not require aldosterone replacement therapy. The doses of each of these medications are adjusted to meet the needs of individual patients.
During an addisonian crisis, low blood pressure, low blood glucose, and high levels of potassium can be life threatening. Standard therapy involves intravenous injections of hydrocortisone, saline (salt water), and dextrose (sugar). This treatment usually brings rapid improvement. When the patient can take fluids and medications by mouth, the amount of hydrocortisone is decreased until a maintenance dose is achieved. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.
Patients with chronic adrenal insufficiency who need surgery with general anesthesia are treated with injections of hydrocortisone and saline. Injections begin on the evening before surgery and continue until the patient is fully awake and able to take medication by mouth. The dosage is adjusted until the maintenance dosage given before surgery is reached.
Women with primary adrenal insufficiency who become pregnant are treated with standard replacement therapy. If nausea and vomiting in early pregnancy interfere with oral medication, injections of the hormone may be necessary. During delivery, treatment is similar to that of patients needing surgery; following delivery, the dose is gradually tapered and the usual maintenance doses of hydrocortisone and fludrocortisone acetate by mouth are reached by about 10 days after childbirth.