Addison’s Disease: Symptoms, Causes, Diagnosis & Treatment

The adrenal glands are a part of the body’s endocrine system, an interconnected group of glands that work together to secrete hormones (chemical substances) that play an important role in all aspects of our body’s processes. When these glands are physically damaged and no longer function properly, we call this Addison’s Disease.

The adrenals are two triangular-shaped glands that lie above each kidney and are approximately the size of your thumb. Each adrenal gland consists of an outer part called the adrenal cortex and an inner part called the adrenal medulla. The hormones that are secreted from the adrenals include cortisol, adrenaline and aldosterone. These hormones help to regulate metabolism, blood pressure, and the body’s response to stress. Another hormone produced by the adrenal glands, dehydroepiandrosterone (DHEA), is used to make androgens and estrogens, the sex hormones.

This article will cover the following areas:
What is Addison’s Disease?
What are the symptoms of Addison’s Disease?
What are the causes of Addison’s Disease?
Diagnosing Addison’s Disease
How is Addison’s Disease Treated?

What is Addison’s Disease?

The adrenal glands in people who have Addison’s disease are not functioning properly. Adrenal insufficiency is a disorder that happens when the adrenals do not produce enough of these hormones. Addison’s is the name used to describe primary adrenal insufficiency when the glands are damaged and do not produce enough cortisol and aldosterone. Secondary adrenal insufficiency occurs when other glands such as the pituitary gland (a gland in the endocrine system located near the base of the brain) does not produce enough of its hormone (ACTH) that stimulates the adrenals to produce cortisol. If the ACTH is too low the adrenal glands can stop producing cortisol and may shrink in size. This secondary adrenal insufficiency is more common than Addison’s disease.

Approximately 140 people out of every million are affected by Addison’s disease. President John F. Kennedy had Addison’s disease as did his sister Eunice Kennedy Shriver. Other well-known people who had this rather rare disease include Dr. Thomas Addison (for whom the disease was named), singer Helen Reddy and artist Ferdinand Louis Schlemmer. Even writers Jane Austen and Charles Dickens were suspected of having the disease.

What are the main adrenal hormones and why are they important?

Cortisol is one of the glucocorticoid hormones produced by the adrenal glands. Cortisol is used by almost every single organ and tissue in the body. It helps the body respond to stress. It also takes care of and maintains heart and blood vessel function and keeps blood pressure controlled. It helps to regulate metabolism and use food efficiently in the body. Cortisol slows the immune system’s inflammatory response to help protect against bacteria, viruses, and harmful substances in the body.

Cortisol is ultimately controlled by the hypothalamus and the pituitary glands. The hypothalamus sends out CRH to the pituitary gland, which sends ACTH to the adrenal glands and stimulates cortisol production. Once cortisol levels have reached the required level, a message is then sent back to both the hypothalamus and the pituitary to decrease their hormones.

Aldosterone is a hormone belonging to the mineralocorticoid family that is also produced by the adrenal glands. This hormone helps with blood pressure control and at the same time helps to balance our sodium and potassium levels. When aldosterone is not secreted in the correct amounts, the body can lose too much sodium and retain too much potassium.

Sodium in the blood affects both blood volume and blood pressure. Having too little sodium in the body causes the condition hyponatremia, which usually leads to symptoms of feeling fatigued and confused with muscle twitches. Too much potassium can lead to hyperkalemia which has no symptoms but may sometimes produce irregular heartbeats, nausea, and a weak pulse.

Dehydroepiandrosterone (DHEA) is also produced by the adrenals and is used to make androgen and estrogen (male and female sex hormones). Men get most androgens from the testes and women get most of their estrogen from the ovaries. When adrenal insufficiency exists, the glands may not make enough DHEA.

What are the Symptoms of Addison’s Disease?

Addison’s usually develops slowly over many years’ time, and the symptoms may be vague or attributed to other reasons such as working too hard or not exercising. Many people do not contact their physicians until another illness, surgical procedure, pregnancy, or accident triggers an exacerbation of their symptoms.

The most common symptoms of adrenal insufficiency include:

Chronic fatigue
Muscle weakness
Abdominal pain
Loss of appetite
Weight loss

Other symptoms of the disease may include:

Diarrhea
Nausea, vomiting
Low blood pressure that may cause dizziness or fainting with standing
Irritability and depression
Headache
Sweating
Skin darkening on scars, skin folds, lips, elbows, knees, knuckles, toes, and mucous membranes of the cheek. This hyperpigmentation occurs only in Addison’s and not in secondary adrenal insufficiency.
Hypoglycemia (low blood sugar)
Craving salty foods
Irregular or nonexistent menstrual periods
Loss of interest in sex in women

When there is a sudden, severe worsening of these symptoms, it is called an adrenal crisis. Sometimes symptoms of adrenal crisis will occur during the adrenal crisis without warning. If your level of cortisol becomes very low, you can become ill in a short length of time. If you have adrenal insufficiency and experience these severe symptoms, it may signal an adrenal crisis, and you must seek immediate emergency treatment to prevent adrenal crisis and possible death.

Symptoms of adrenal crisis include:

Severe vomiting and diarrhea
Dehydration
Sudden and severe pain in lower back, abdomen, or legs
Low blood pressure
Loss of consciousness

What are the Causes of Addison’s Disease?

Autoimmune disorders

Most cases of Addison’s disease are caused by autoimmune disorders. Our body’s immune system makes antibodies that fight against germs, bacteria, and viruses that enter our bodies. When an autoimmune disease such as Addison’s exists, the immune system makes antibodies against a part of the body, which in this case would attach to the surface of the adrenals. These antibodies destroy the cells that make the cortisol and aldosterone. Whatever is causing the immune system to make these antibodies is not known.

Sometimes only the adrenals are affected, but other endocrine glands may be involved as well. If you have autoimmune Addison’s disease, you have a higher than likely chance of also having other autoimmune disorders such as pernicious anemia, vitiligo, and problems with your thyroid. Polyendocrine deficiency syndrome is divided into two groups, type 1 and type 2. Type 1 is inherited and occurs in children. Type 2 is sometimes called Schmidt’s syndrome and is also inherited. This usually affects young adults.

Infections

A disease that normally affects the lungs is tuberculosis (TB). This infection can also destroy the adrenal glands and cause Addison’s disease. When primary adrenal insufficiency was identified by Dr. Thomas Addison, TB was the most common culprit of the disease (in 1849). Although modern-day treatments of TB have improved the number of cases of Addison’s, it has recently been seen more with an increase in infections of TB and cytomegalovirus. People who have weakened immune systems and babies in the womb can contract cytomegalovirus due to HIV/AIDS.

Other less common causes

These include the following:

Other infections that can affect both adrenal glands
Cancer cells in the adrenal glands
Surgical removal of the adrenal glands
Genetic defects including abnormal development, defects in adrenal hormone production, and inability of the adrenal glands to acknowledge the ACTH from the pituitary
Medications which may interfere or react with hormone production such as anti-fungals and anesthetic drugs used during intubation in emergency situations.

What are the Causes of Secondary Adrenal Insufficiency?

The lack of CRH and ACTH hormones in the body cause secondary adrenal insufficiency. There are several reasons why this might happen.

Stopping corticosteroid medications

Steroid medications such as prednisolone are very similar to cortisol. These meds are used to treat inflammatory illnesses such as asthma, ulcerative colitis, rheumatoid arthritis, and some types of cancer. When a steroid medicine is used over a period of weeks or months, the pituitary and adrenal glands produce less of their natural hormones. If the medication is stopped, it takes a while for the pituitary and adrenal glands to begin producing the ACTH and cortisol in amounts adequate for the body’s needs. The steroids should never be stopped suddenly because you could quickly develop symptoms similar to those in adrenal crisis. A gradual tapering of the medication will give the glands adequate time to begin their normal function.

Pituitary tumors removed by surgery

Noncancerous tumors of the pituitary that overproduce ACTH (a condition called Cushing’s syndrome) are sometimes removed surgically to correct the condition. This source of ACTH is suddenly not available, and a replacement hormone must be taken until the adrenal glands can resume their normal production of cortisol. This may take time, and a person going off of steroids will need to be closely followed to prevent adrenal insufficiency.

Pituitary gland changes

Secondary adrenal insufficiency may also occur but with less frequency when the pituitary gland stops producing ACTH or when it decreases in size. This can be caused by an infection or tumor in the pituitary, loss of blood flow to the gland, radiation treatment to the gland (for tumors), removal of part of the hypothalamus, or surgical removal of the pituitary itself.

Diagnosing Addison’s disease

Because adrenal insufficiency may be hard to diagnose, the physician will take a detailed medical history and review the symptoms. Hormonal blood and urine tests will be taken to check the cortisol levels, and if they are too low, imaging studies of the adrenal and pituitary glands may also be useful in establishing a cause.

Blood and urine tests used to diagnose Addison’s

The following tests are used:

ACTH stimulation test. The patient is given an IV injection of synthetic ACTH with samples of blood and urine taken both before and after the injection. Cortisol levels are measured. The normal response after ACTH is introduced would be a rise in blood and urine cortisol levels. Patients who have Addison’s or secondary adrenal insufficiency would have little or no increase in cortisol level.
CRH stimulation test. When the result of the ACTH test is abnormal, it may be followed by a CRH stimulation test to determine the cause of the adrenal insufficiency. In this test the patient is given synthetic CRH, and the blood is sampled at 30, 60, 90, and 120 minutes after the CRH administration. The cortisol levels are again measured at each interval. People with Addison’s respond with high levels of ACTH, but no cortisol. People with secondary adrenal insufficiency do not produce ACTH or have a delayed response. If the pituitary is damaged, CRH will not stimulate ACTH, so no ACTH being produced points the finger to the pituitary as the culprit. Delayed ACTH response points to the hypothalamus as the cause.

Other testing performed after diagnosis of adrenal insufficiency

These tests help to pinpoint if the disease is related to TB and to look at the adrenal glands. They are also used to identify antibodies associated with autoimmune Addison’s disease:

Ultrasound of the abdomen
Tuberculin skin test
Antibody blood tests

Other testing performed after diagnosis of secondary adrenal insufficiency

These are used to gather details of the pituitary gland and determine how it is functioning.

CT (computerized tomography) scan
MRI (magnetic resonance imaging)
Hormonal blood tests

How is Addison’s Disease Treated?

Hormone replacement

When the adrenal glands are not making necessary hormones needed by the body, the condition is treated by substituting or replacing the hormones and must be adjusted to meet each individual’s needs. Cortisol is replaced with a corticosteroid such as hydrocortisone, dexamethasone, or prednisone, and is taken orally one to three times a day (depending on which replacement is used).

Aldosterone is replaced with a mineralocorticoid called fludrocortisone acetate taken orally once or twice a day. Patients with secondary adrenal insufficiency usually do not require aldosterone replacement as their adrenals still produce aldosterone.

During adrenal crisis because the low levels of blood pressure, sodium, blood glucose, and high levels of potassium can cause great danger, immediate IV injections of steroids along with IV saline solutions of sugars in the form of dextrose may be administered for quick improvement.

Adrenal insufficiency stress must be monitored

When people have adrenal insufficiency they must be sure to pay special attention to times of increased stress on the body such as those undergoing surgery, those suffering from an illness or severe injury, and those who are pregnant. Even taking part in strenuous sports or exercise or working night shifts can affect cortisol levels. Some of these types of stress would require additional treatment to recover including “stress” dosages of corticosteroids, which may be given either intravenously or orally. When the person recovers from the stress situation, they can usually return to their usual amounts of medications.

Diet and nutrition

When people with Addison’s disease are aldosterone deficient, they can benefit from a high sodium diet. Their physicians will be able to give them specific suggestions and guidelines on the amount of sodium required.

Treatment with steroids is associated with an increased risk of osteoporosis which is a condition which may cause bones to fracture or become less dense. By consuming enough calcium in their diet along with vitamin D, they may help protect against this condition and maintain good bone health.