Adrenal Insufficiency and Addison’s Disease Adrenal Insufficiency and Addison’s Disease
National Institute of Diabetes, Digestive and Kidney

What is adrenal insufficiency?

Adrenal insufficiency is an endocrine-or hormonal-disorder that occurs when the adrenal glands do not produce enough of certain hormones. The adrenal glands are located just above the kidneys. Adrenal insufficiency can be primary or secondary.

Primary adrenal insufficiency, also called Addison’s disease, occurs when the adrenal glands are damaged and cannot produce enough of the hormone cortisol and often the hormone aldosterone. Addison’s disease affects one to four of every 100,000 people, in all age groups and both sexes.1

Secondary adrenal insufficiency occurs when the pituitary gland-a bean-sized organ in the brain-fails to produce enough adrenocorticotropin (ACTH), a hormone that stimulates the adrenal glands to produce cortisol. If ACTH output is too low, cortisol production drops. Eventually, the adrenal glands can shrink due to lack of ACTH stimulation. Secondary adrenal insufficiency is much more common than Addison’s disease.

1Munver R, Volfson IA. Adrenal insufficiency: diagnosis and management. Current Urology Reports. 2006;7:80–85.

What do adrenal hormones do? Cortisol

Cortisol belongs to a class of hormones called glucocorticoids, which affect almost every organ and tissue in the body. Cortisol’s most important job is to help the body respond to stress. Among its many vital tasks, cortisol helps

maintain blood pressure and cardiovascular function slow the immune system’s inflammatory response maintain levels of glucose-a form of sugar used for energy-in the blood regulate the metabolism of proteins, carbohydrates, and fats

The amount of cortisol produced by the adrenals is precisely balanced. Like many other hormones, cortisol is regulated by the brain’s hypothalamus and the pituitary gland. First, the hypothalamus releases a "trigger" hormone called corticotropin-releasing hormone (CRH) that signals the pituitary gland. The pituitary responds by sending out ACTH, which in turn stimulates the adrenal glands. The adrenal glands respond by producing cortisol. Completing the cycle, cortisol then signals back to both the pituitary and hypothalamus to decrease these trigger hormones.

The hypothalamus sends CRH to the pituitary, which responds by sending out ACTH. ACTH then causes the adrenals to release cortisol into the bloodstream.


Aldosterone belongs to a class of hormones called mineralocorticoids, also produced by the adrenal glands. Aldosterone helps maintain blood pressure and water and salt balance in the body by helping the kidneys retain sodium and excrete potassium. When aldosterone production falls too low, the kidneys are not able to regulate water and salt balance, leading to a drop in both blood volume and blood pressure.

What are the symptoms of adrenal insufficiency?

The symptoms of adrenal insufficiency usually begin gradually. The most common symptoms are

chronic, worsening fatigue muscle weakness loss of appetite weight loss

Other symptoms can include

nausea vomiting diarrhea low blood pressure that falls further when standing, causing dizziness or fainting irritability and depression a craving for salty foods due to salt loss hypoglycemia, or low blood glucose headache sweating in women, irregular or absent menstrual periods

Hyperpigmentation, or darkening of the skin, can occur in Addison’s disease but not in secondary adrenal insufficiency. This darkening is most visible on scars; skin folds; pressure points such as the elbows, knees, knuckles, and toes; lips; and mucous membranes such as the lining of the cheek.

Because the symptoms progress slowly, they are often ignored until a stressful event like an illness or accident causes them to worsen. Sudden, severe worsening of symptoms is called an Addisonian crisis, or acute adrenal insufficiency. In most cases, symptoms of adrenal insufficiency become serious enough that people seek medical treatment before a crisis occurs. However, sometimes symptoms first appear during an Addisonian crisis.

Symptoms of an Addisonian or "adrenal" crisis include

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

If not treated, an Addisonian crisis can be fatal.

What causes Addison’s disease? Autoimmune Disorders

The gradual destruction of the adrenal cortex, the outer layer of the adrenal glands, by the body’s immune system causes up to 80 percent of Addison’s disease cases.2 In autoimmune disorders, 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. As a result, often both cortisol and aldosterone are lacking. Sometimes only the adrenal glands are affected. Sometimes other endocrine glands are affected as well, as in polyendocrine deficiency syndrome.

Polyendocrine deficiency syndrome is classified into two separate forms, type 1 and type 2. Type 1 is inherited and occurs in children. In addition to adrenal insufficiency, these children may have

underactive parathyroid glands, which produce a hormone that regulates calcium and phosphorus balance in the body slow sexual development pernicious anemia, a severe type of anemia chronic candida infections, a type of fungal infection chronic active hepatitis, a liver disease

Type 2, sometimes called Schmidt’s syndrome, usually affects young adults and may include

an underactive thyroid gland, which produces hormones that regulate metabolism slow sexual development diabetes vitiligo, a loss of pigment on areas of the skin

Scientists think type 2 polyendocrine deficiency syndrome is also inherited because often more than one family member has one or more endocrine deficiencies.

2Martorell PM, Roep BO, Smit JWA. Autoimmunity in Addison’s disease. The Netherlands Journal of Medicine. 2002;60(7):269-275


Tuberculosis (TB), an infection that can destroy the adrenal glands, accounts for less than 20 percent of cases of Addison’s disease in developed countries.3 When adrenal insufficiency was first identified by Dr. Thomas Addison in 1849, TB was the most common cause of the disease. As TB treatment improved, the incidence of adrenal insufficiency due to TB of the adrenal glands greatly decreased.

3Munver R, Volfson IA. Adrenal insufficiency: diagnosis and management.Current Urology Reports. 2006;7:80-85.

Other Causes

Less common causes of Addison’s disease are

chronic infection, mainly fungal infections cancer cells spreading from other parts of the body to the adrenal glands amyloidosis, a disease that causes abnormal protein buildup in, and damage to, various organs surgical removal of the adrenal glands AIDS-associated infections bleeding into the adrenal glands genetic defects including abnormal adrenal gland development, an inability of the adrenal gland to respond to ACTH, or a defect in adrenal hormone production

What causes secondary adrenal insufficiency?

Secondary adrenal insufficiency can be traced to a lack of ACTH. Without ACTH to stimulate the adrenal glands, the adrenals’ production of cortisol drops. Aldosterone production is not usually affected.

A temporary form of secondary adrenal insufficiency may occur when a person who has been taking a synthetic glucocorticoid hormone such as prednisone for a long time stops taking the medication, either abruptly or gradually. Glucocorticoid hormones, which are often used to treat inflammatory illnesses such as rheumatoid arthritis, asthma, and ulcerative colitis, block the release of both CRH and ACTH. As a result, the adrenals may begin to atrophy—or shrink—from lack of ACTH stimulation and then fail to secrete sufficient levels of cortisol.

A person who stops taking a synthetic glucocorticoid hormone may have enough ACTH to function when healthy. However, when a person is under the stress of an illness, accident, or surgery, the person’s body may not have enough ACTH to stimulate the adrenal glands to produce cortisol.

Another cause of secondary adrenal insufficiency is surgical removal of the noncancerous, ACTH-producing tumors of the pituitary gland that cause Cushing’s disease. Cushing’s disease is another disorder that leads to excess cortisol in the body. 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 glan

How is adrenal insufficiency diagnosed?

In its early stages, adrenal insufficiency can be difficult to diagnose. A review of a patient’s medical history and symptoms may lead a doctor to suspect Addison’s disease.

A diagnosis of adrenal insufficiency is confirmed through laboratory tests. The aim of these tests is first to determine whether levels of cortisol are insufficient and then to establish the cause. Radiologic exams of the adrenal and pituitary glands also are useful in helping to establish the cause.