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Addison's disease is a severe or total deficiency of the hormones made in the adrenal cortex, caused by the destruction of the adrenal cortex. It is basically a hormonal disorder that occurs in all age groups and afflicts men and women equally.

This hormonal disorder affects about 1 in 100,000 people, but there are no accurate statistics on the incidence of Addison's disease in the United States. Because these hormones produced by the adrenal gland give instructions to virtually every organ and tissue in your body, the effects of its’ deficiency are very serious!

 Adrenal glands and hormones

The adrenal glands are s

mall organs located on top of each kidney. They consist of the:

    * The outer portion –  the cortex and
    * The inner portion – the medulla

The cortex produces 3 types of hormones:

         1. sex hormones,
         2. glucocorticoid hormones, and
         3. mineralocorticoid hormones

Addison's disease, no matter what has caused it, occurs when the adrenal glands do not produce as much of the hormones as it should normally produce. The disease is also called adrenal insufficiency or hypocortisolism. The two main hormones that adrenal gland is producing are cortisone and aldosterone!

    * Cortisol

      Cortisol belongs to a class of hormones called glucocorticoids, which affect almost every organ and tissue in the body. Most of the experts believe that cortisol probably has hundreds of effects in the body.

      Cortisol is also called the stress-hormone because its most important job is to help the body respond to stress. Some of the main functions is to help:

          o maintain the blood pressure
          o support the cardiovascular function
          o slow the immune system's inflammatory response
          o balance the effects of insulin in breaking down sugar for energy
          o regulate the metabolism of proteins, carbohydrates, and fats
          o maintain the proper arousal and sense of well-being

    Adrenal glands have many mechanisms for the precise and balanced production of this hormone because it is so vital to health.
    The production of cortisone is regulated by the hypothalamus and the pituitary gland, similarly to the control of the thyroid hormones production.

    First, the hypothalamus sends hormones to the pituitary gland, which then responds by secreting hormones that regulate growth and thyroid and adrenal function, and also the sex hormones such as estrogen and testosterone. Pituitary hormone that controls the adrenal glands is called ACTH - Adrenocorticotopic hormone. 

    * Aldosterone

      Aldosterone belongs to a class of hormones called the mineralocorticoids. One of its most important functions is to help maintain the blood pressure and the water and salt balance in the body. It does so by helping the kidneys retain sodium and excrete potassium.

      We can easily understand that, when aldosterone production is too low, the kidneys are not be able to regulate salt and water balance, causing blood volume and blood pressure to decrease.

Symptoms of Addison’s disease

The symptoms of adrenal insufficiency usually begin gradually and some of the most common ones are:

    * chronic, worsening fatigue
    * muscle weakness
    * loss of appetite
    * weight loss
    * nausea
    * vomiting
    * diarrhea
    * darkening of the skin (hyper-pigmentation)
    * low blood pressure and even fainting
    * salt craving
    * irritability and depression

Addisonian crisis

The bad thing about this condition is that, because the symptoms progress slowly, they are usually ignored until some stressful event causes them to become worse.
This is called an Addisonian crisis, or acute adrenal insufficiency. Symptoms of an Addisonian crisis include:

    * sudden penetrating pain in the lower back, abdomen, or legs
    * severe vomiting and diarrhea
    * dehydration
    * low blood pressure
    * loss of consciousness

Causes of Addison’s disease

There are several possible causes of Addison’s disease and some of the most common are:

Primary Adrenal Insufficiency

Autoimmune theory tells that the most of the adrenal insufficiency cases are caused by the gradual destruction of the adrenal cortex by the body's own immune system. This means that the immune system makes antibodies that attack the body's own tissues or organs and slowly destroy them. Adrenal insufficiency occurs when at least 90 percent of the adrenal cortex has been destroyed. Possible causes of this type of deficiency are:

    * Tuberculosis
    * Other infections of the adrenal glands
    * Spreadind of the cancer to the adrenal glands
    * Bleeding into the adrenal glands;

Polyendocrine Deficiency Syndrome

This is a very complex syndrome which comes in two different forms:

    * Type I - affects children only and it is accompanied by the underactive parathyroid glands, slow sexual development, pernicious anemia, chronic Candida infections, chronic active hepatitis and, in rare cases, hair loss.
    * Type II - often called Schmidt's syndrome. It usually afflicts young adults and it is accompanied by an underactive thyroid gland, slow sexual development, diabetes, vitiligo and loss of pigment on areas of the skin.

Secondary adrenal insufficiency

Adrenal insufficiency can also occur if the pituitary gland is affected and doesn’t produce hormones properly. This will result in the lack of ACTH hormone, which stimulates the adrenal cortex to produce its hormones.
So, even though adrenal glands aren't damaged, the inadequate production of ACTH can lead to insufficient production of hormones normally produced by adrenal glands. Secondary adrenal insufficiency can also occur when people are taking corticosteroids for treatment of some chronic conditions, such as asthma or arthritis, and then suddenly stop taking the medications.
Other possible reasons are:

    * tumors or infections of the area
    * loss of blood flow to the pituitary gland
    * radiation treatment of pituitary tumors
    * surgical removal of the parts of the hypothalamus
    * surgical removal of the pituitary gland

Diagnosis of Addison’s disease

Some of the most common diagnostic tools used for a proper diagnosis of Addison’s disease are:

Blood test

It is performed by measuring the blood levels of sodium, potassium, cortisol and ACTH. This method gives doctor an indication on whether adrenal insufficiency may be causing the signs and symptoms a patient is experiencing. The blood test can also measure the amount of antibodies associated with autoimmune caused Addison's disease.

ACTH Stimulation Test

This is the most specific test for diagnosing the Addison's disease. During this test, cortisol in the blood and urine are measured before and after a synthetic form of ACTH is given by injection. Measurement of cortisol in blood is repeated 30 to 60 minutes after this injection. The normal response after an injection of ACTH is a rise in blood and urine cortisol levels. It is logical to assume that patients with adrenal insufficiency will respond poorly or do not respond at all.

CRH Stimulation Test

In this test, a synthetic cortisone releasing hormone (CRH) is injected intravenously. The blood cortisol levels are measured before the injection and  then 30, 60, 90, and 120 minutes after the injection.
The problem with the patients with primary adrenal insufficiency is that they have high ACTH but do not produce cortisol at all. On the other hand, the patients with secondary adrenal insufficiency have deficient cortisol responses but absent or delayed ACTH responses. This is because the exact cause of deficiency are the pituitary gland and hypothalamus.

Imaging tests

Some doctors recommend computerized tomography (CT) scan of the abdomen to check the size of your adrenal glands and look for other abnormalities that may give them the insight into the cause of the adrenal insufficiency. CT is a diagnostic tool that is very similar to common X-ray but it involves computer processing of the images. Some doctors may also suggest a CT scan or the magnetic resonance imaging scan of the pituitary gland if testing indicates that the patient has secondary adrenal insufficiency.

Treatment of Addison’s disease

Since all of the manifestations of Addison's disease are caused by the lack of cortisol and aldosterone, the goal of the treatment is to replace or substitute these hormones with similar steroids.
Cortisol is replaced orally with Hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day. It is also replaced by using

    * Hydrocortisone (Cortef®),
    * Prednisone (Deltasone®) or
    * synthetic cortisone.

If aldosterone is deficient, it is replaced with oral doses of a mineralocorticoid called fludrocortisone acetate (Florinef®), which is taken once a day.
Since an Addisonian crisis may represent a life-threatening situation that results in low blood pressure and high levels of sugar and potassium in the blood, this situation requires immediate medical treatment which includes intravenous injections of:

    * Hydrocortisone
    * Saltwater solution
    * Sugar (dextrose)

Read More: Adrenalectomy surgical techniques and the reasons why


Special problems

Women with primary adrenal insufficiency who become pregnant are treated with standard replacement therapy. If nausea and vomiting, normally seen in early pregnancy, interfere with oral medication, injections of the hormone may be necessary and this cannot be avoided. During the delivery, the treatment is similar to that of the patients in need of a surgery. Following the delivery, the dose is gradually decreased and the usual doses of hormones given by mouth are reached in about 10 days after the childbirth.
As long as the proper dose of replacement medication is taken every day, people diagnosed with Addison’s disease can have a normal crisis-free life. Routine care includes

    * regular physician visits,
    * avoidance of dehydration, and
    * the use of extra medication during illness.