Addison's Disease

(Adrenal Insufficiency, Hypocortisolism, Primary Adrenal Insufficiency)

In this condition factsheet:

• The Facts
• Causes
• Symptoms and Complications
• Making the Diagnosis
• Treatment and Prevention

The Facts

Addison's disease, also known as primary adrenal insufficiency, is a rare condition that affects the body's hormonal activity. It is estimated that Addison's disease affects about 4 out of every 100,000 individuals, appearing in all age groups and affecting both genders equally. This disease is named after Dr. Thomas Addison, who discovered it in 1849.

Addison's disease occurs when the body's adrenal glands are not able to make enough of the hormones cortisol or aldosterone. Each hormone works differently and plays important roles in the human body.

Cortisol helps the body respond to stress. It also helps maintain blood pressure and blood sugar; slow the immune system's inflammatory response; and regulate the metabolism of proteins, carbohydrates, and fats. Aldosterone is involved in keeping adequate blood pressure and water and salt balance in the body.

The disease usually presents slowly, worsening over time, and is often diagnosed during an incident of trauma or stress.

Causes

Addison's disease is usually caused by an autoimmune reaction, where the body attacks its own adrenal glands and prevents them from functioning properly. Other possible causes of Addison's disease include tuberculosis, trauma with bleeding into the adrenal glands, surgery, fungal infections, inflammation, and cancer. Addison's disease may also be caused by genetic disorders.

A similar condition called secondary adrenal insufficiency occurs when the pituitary gland does not make enough adrenocorticotropin (ACTH), a hormone that stimulates the adrenal glands to produce cortisol and aldosterone. Possible causes of secondary adrenal insufficiency include pituitary tumours, brain surgery, reduced blood flow to the brain, or brain infections. It can also be caused by suddenly stopping corticosteroid medications after taking them for a prolonged period of time. In this case, the problem is usually temporary.

Symptoms and Complications

People with this condition may experience chronic fatigue and muscle weakness. Other symptoms include:

• salty food cravings
• lack of appetite
• nausea or vomiting
• weight loss
• constipation or diarrhea
• darkened skin on exposed and unexposed areas of the body (also called hyperpigmentation) – this is a symptom of primary adrenal insufficiency
• low blood pressure (which may lead to fainting)
• low blood sugar
• lower tolerance to cold

Making the Diagnosis

Physical examination, a discussion of symptoms, and medical tests are the best ways to determine if a person has Addison's disease.

The goal of the medical test is to first determine whether the levels of cortisol (in the blood) are sufficient, and then to identify the cause (primary or secondary) with the adrenocorticotropic hormone (ACTH) test and the corticotrophin-releasing hormone (CRH) stimulation test.

The ACTH stimulation test looks at the adrenal glands' ability to produce cortisol. Blood and urine cortisol samples are collected before and after an injection of synthetic (manmade) ACTH. Low or no cortisol in samples after the injection indicates Addison's disease or primary adrenal insufficiency.

When the response to the ACTH test is abnormal, a CRH stimulation test is helpful in determining the cause of adrenal insufficiency. CRH is produced by the hypothalamus in the brain to stimulate the pituitary gland to produce the ACTH, which then stimulates the adrenal gland to produce cortisol and aldosterone. A synthetic CRH is injected, and the blood cortisol is measured before and after the injection. Individuals with Addison's disease respond to the CRH test by producing high levels of ACTH but little cortisol. On the other hand, if CRH fails to stimulate the pituitary gland to produce ACTH, secondary adrenal insufficiency is suspected.

Other tests, such as imaging technologies (e.g., CT scan or MRI), are used to examine the size and shape of the adrenal glands, the pituitary gland, and the hypothalamus.

Treatment and Prevention

Hormone replacement therapy is the standard treatment for Addison's disease. In other words, these medications are supplementing or replacing the hormones that the adrenal glands are not making. Hydrocortisone or prednisone is used to replace cortisol, and fludrocortisone is used to replace aldosterone. The dose of each medication is adjusted to meet the individual's need.

Since the cortisol levels fluctuate throughout the day, multiple doses of hydrocortisone is required within 24 hours to best mimic the constant changes in this hormone level. Cortisol production normally increases under stressful situations – people with Addison's disease often require a higher dose of hydrocortisone when they are faced with acute physical stress, such as an infection or a surgery.

It is recommended that people with Addison's disease carry identification (like a bracelet or necklace) to let medical staff know of their condition. In the event of an Addisonian crisis (also known as adrenal crisis) where low blood pressure, low blood glucose, and high potassium levels may cause unconsciousness, identification alerts the medical staff to urgently administer hydrocortisone and other required supportive treatment.

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