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Patient education: Adrenal insufficiency (Addison's disease) (Beyond the Basics)

Lynnette K Nieman, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD
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The adrenal glands are located on top of each kidney (figure 1) and normally produce three classes of hormones: glucocorticoids, mineralocorticoids, and androgens. Adrenal insufficiency occurs when the adrenal glands produce an insufficient amount of one or more of these classes of hormones.

Early detection of adrenal insufficiency can be difficult, although treatment is usually successful once it is initiated. Treatment is tailored to the underlying cause and, in most cases, lifelong treatment is necessary. With appropriate treatment and a few added precautions, people with adrenal insufficiency can lead active lives and have a normal life expectancy.


Glucocorticoids — Cortisol is the main glucocorticoid produced by the adrenal gland. Corticotropin (ACTH) is made in the pituitary and stimulates the adrenal gland to produce cortisol. Cortisol has many important functions including:

Help to regulate glucose (blood sugar) levels

Increase fat in the body

Help to defend the body against infection

Help the body respond to stress

Mineralocorticoids — Aldosterone is the main mineralocorticoid produced by the adrenal glands. It helps to regulate the body's sodium and potassium levels, blood volume, and blood pressure.

Androgens — Androgen hormones, including testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate, are present in both men and women. In women, androgens are produced in the adrenal glands and the ovaries. In women, adrenal androgens promote the development of sex characteristics, such as underarm and pubic hair.

In men, most androgens (eg, testosterone) are produced in the testes. Androgens made by the adrenal glands are not as important for normal sexual function.


Cortisol levels are normally regulated by the hypothalamus and pituitary gland (figure 2). The hypothalamus sends corticotropin-releasing hormone (CRH) to the pituitary gland. The pituitary gland responds by producing several hormones, one of which is corticotropin (ACTH). ACTH stimulates the adrenal gland to produce cortisol. Cortisol levels help to control the pituitary's production of ACTH.


Primary adrenal insufficiency, also known as Addison's disease, occurs when the adrenal glands cannot produce an adequate amount of hormones despite a normal or increased corticotropin (ACTH) level (figure 2). This is a rare disease, occurring in approximately 35 to 120 people in every one million people.

Most patients with Addison's disease experience fatigue, generalized weakness, loss of appetite, and weight loss. The type and severity of symptoms depends upon the speed with which the condition develops, the severity of the hormone deficiency, the underlying cause of the condition, and other stresses on the body. Other common symptoms include:

Darkening of the skin, especially on the face, neck, and back of hands (picture 1 and picture 2 and picture 3)

Gastrointestinal symptoms such as nausea and vomiting (vomiting and abdominal pain may be a sign of an adrenal crisis) (see 'Adrenal crisis' below)

Low blood pressure with lightheadedness after standing or sitting up

Muscle and joint pain

Salt cravings

In women, decreased hair in the armpits and pubic area and decreased sexual desire


In secondary adrenal insufficiency, an insufficient amount of corticotropin (ACTH) is produced by the pituitary gland. In tertiary adrenal insufficiency, an insufficient amount of corticotropin-releasing hormone (CRH) is produced by the hypothalamus.

Symptoms — The symptoms of secondary and tertiary adrenal insufficiency are similar to those of primary insufficiency, with a few exceptions:

Darkening of the skin and dehydration do not occur

Gastrointestinal symptoms are less common

Symptoms of hypoglycemia (low blood sugar) are more common, including sweating, anxiety, shaking, nausea, or heart palpitations

A tumor or other growth in the pituitary or hypothalamus can cause other symptoms, including headaches and difficulty seeing objects in the periphery of vision (to the far left and right). Also, low levels of pituitary hormones can develop and may cause infertility, erectile dysfunction (impotence), fatigue, hoarseness, constipation, a delay in beginning puberty, or short stature in children.


The diagnosis of adrenal insufficiency is a four-part process:

The blood cortisol level is measured

Other tests are usually needed to confirm the diagnosis of adrenal insufficiency

The level of the defect is determined (primary versus secondary/tertiary) by measuring corticotropin (ACTH)

Once the level of the defect is known, further evaluation is done to determine the cause of the defect or to evaluate for other associated problems

Cortisol and ACTH level testing — To determine a person's cortisol and corticotropin (ACTH) level, a blood sample is taken early in the morning, usually at around 8 AM.

If the cortisol level is very low, the person is likely to have adrenal insufficiency

If the cortisol level is above a certain normal level, the person is very unlikely to have adrenal insufficiency

Many patients have cortisol results in an intermediate zone and need to have additional testing

A variety of other tests can be done to confirm the diagnosis of adrenal insufficiency.

Most often, an ACTH stimulation test is done to establish the diagnosis. To perform this test, a blood sample is taken at any time of day to measure the "baseline" cortisol level. A high dose of ACTH is then given into a vein. A blood sample is then taken again 30 to 60 minutes later to measure the cortisol level. A low cortisol level after a dose of ACTH confirms that the person has adrenal insufficiency.

Measurement of a blood ACTH level helps to determine if the problem lies within the adrenal gland (causing primary adrenal insufficiency) or in the pituitary or hypothalamus (causing secondary adrenal insufficiency):

If the ACTH level is high, the person probably has primary adrenal insufficiency

If the ACTH level is low, the person probably has secondary or tertiary adrenal insufficiency

Determine the underlying cause

For primary adrenal insufficiency — To determine the cause of primary adrenal insufficiency, the clinician must consider the patient's age, gender, and other medical problems. Most clinicians recommend an abdominal computed tomography (CT) scan to evaluate the adrenal glands. In some cases, blood tests or a chest x-ray will also be recommended.

In the past, tuberculosis was the most common cause of primary adrenal insufficiency. Currently, the most common cause of Addison's disease is autoimmune adrenalitis (a disease that causes the body to develop antibodies against the adrenal gland, eventually destroying it).

For secondary/tertiary adrenal insufficiency — Possible causes of secondary and tertiary adrenal insufficiency include:

An abnormal growth in the pituitary or hypothalamus

Some people have deficiencies in ACTH and possibly other pituitary hormones (partial or panhypopituitarism) at birth; these are called congenital deficiencies

Long-term treatment with glucocorticoid medications (eg, taking prednisone for asthma); this can interfere with normal pituitary function and is the most common cause of secondary adrenal insufficiency

Previous radiation to the pituitary gland or brain

The clinician will usually obtain a magnetic resonance imaging (MRI) scan of the pituitary gland, as well as blood tests of pituitary hormones. The scan provides a detailed image, to determine if a mass or abnormal growth is present.


The treatment of adrenal insufficiency includes replacement of the deficient hormones. The goal of treatment is to relieve the symptoms of hormone deficiency without developing signs of hormone excess. Treatment usually requires lifelong hormone replacement. Correct use of these hormone medications is essential to minimize symptoms and the chance of adrenal crisis.

Primary adrenal insufficiency — Treatment of adrenal insufficiency requires a daily dose of a glucocorticoid and mineralocorticoid pill, usually for life. Androgen replacement may be recommended for women. The goal of treatment is to stabilize hormone levels and relieve symptoms.

Hormone levels must remain balanced to minimize symptoms and the chance of adrenal crisis (see 'Adrenal crisis' below). Fatigue and nausea usually begin to disappear within days of starting treatment.

Glucocorticoids — Several options are available for replacing glucocorticoids; a clinician will work with the patient to determine the regimen that is most effective, convenient, and that causes minimal side effects.

Many clinicians prescribe the short-acting preparation oral hydrocortisone (similar to cortisol produced normally), with two or three doses per day. The largest dose is taken in the early morning, and a smaller dose is taken in mid-morning and mid-afternoon; this mimics the normal variation in blood cortisol levels. Because hydrocortisone is available in a variety of doses, the amount of hydrocortisone can be adjusted easily, which may be an advantage over the longer acting glucocorticoids.

  • A longer-acting glucocorticoid like prednisone is sometimes preferred because it can be taken once per day. Occasionally, a small additional dose is needed in the afternoon. However, it can be more difficult to adjust the dose of these longer-acting medications to avoid overtreatment.

Monitoring during treatment – The development of weight gain or a puffy face is usually a sign of overtreatment, and the glucocorticoid dose is decreased as a result. Higher doses of glucocorticoids are of no benefit and may increase the risk of bone thinning (osteoporosis). A clinician will monitor closely for these complications.

Dosing – The dose of any of glucocorticoids is tailored to the patient's body weight and age; obese people may need a higher dose, while children and small adults may need a lower dose. Adjustments in dose are often necessary when starting treatment.

Mineralocorticoids — Mineralocorticoids are replaced with an oral, synthetic mineralocorticoid drug called fludrocortisone (sold as Florinef). The dose of this medication is tailored to manage blood pressure and fluid balance.

When the dose is adequate, there should be no problems with lightheadedness or dizziness when standing up. If the dose is too high, the person may notice swelling in the ankles, and the clinician may note hypertension (high blood pressure) or low blood potassium levels. In this case, the dose of fludrocortisone should be decreased.

Androgens — Androgen replacement is sometimes recommended for women with primary adrenal insufficiency. A daily dose of dehydroepiandrosterone (DHEA) may improve libido and provide an improved overall sense of well-being. However, there are potential side effects associated with DHEA that are related to elevated androgen levels (eg, acne, facial hair, deepened voice). In addition, DHEA is only available as a dietary supplement in the United States. Because it is not regulated by the US Food and Drug Administration (FDA), there are concerns about quality control and safety.

Secondary and tertiary adrenal insufficiency — People with secondary and tertiary adrenal insufficiency require only glucocorticoid (eg, hydrocortisone) replacement (not mineralocorticoid or androgen replacement). Doses may be adjusted frequently in the beginning. Treatment may also include replacement of other deficient pituitary hormones.


Adrenal crisis refers to overwhelming and life-threatening adrenal insufficiency. The most common signs of adrenal crisis are shock (very low blood pressure with a loss of consciousness), dehydration, and an imbalance of sodium and potassium levels in the body. In some cases, shock is preceded by fever; nausea, vomiting, and abdominal pain; weakness or fatigue; and confusion. Adrenal crisis usually occurs after an infection, trauma, or another stressor.

Adrenal crisis is a life-threatening condition that requires emergency medical treatment. The patient or a family member or friend should immediately give an emergency injection of a glucocorticoid at the first signs of adrenal crisis (see 'Emergency precautions' below). In the emergency department or ambulance, treatment usually includes giving several liters of a salt solution (saline) and an injection of a glucocorticoid (dexamethasone or another form of cortisol) into a vein. Mineralocorticoid treatment (if needed) is usually started at a later time, when the saline treatment is completed.

Following treatment, it is important look for and treat any factors that may have triggered the crisis, such as infection.


People with adrenal insufficiency should learn as much as possible about their condition and should be aware of early warning signs of hormone deficiency. It is also wise to share this information with family, friends, and any caregivers, so that they can also identify signs of trouble and be prepared to act in case of adrenal crisis.

General precautions — People with adrenal insufficiency should wear a medical alert bracelet or necklace. They should also carry an emergency medical information card that lists the names and doses of their daily medications and the clinician and family member(s) to call in case of emergency. It is extremely important to identify early symptoms of adrenal deficiency and adrenal crisis; a clinician can describe subtle symptoms that should not be ignored.

Emergency precautions — Even with careful use of medications and medical monitoring, some people with primary adrenal insufficiency will experience adrenal crisis. As a safety measure, the patient should always carry a syringe and a vial of dexamethasone (or another glucocorticoid). This system should be stored at home, at work or school, and in the patient's handbag or backpack.

The patient or a family member or friend should give the injection into a muscle (usually the thigh) if any of the following occurs:

After a major injury with substantial blood loss, fracture, or shock

During an episode of nausea and vomiting if oral medications are thrown up

If there are any signs or symptoms of adrenal crisis

If a person is found unconscious

Most people with adrenal insufficiency go years without needing an injection. However, the injection is recommended if there is any reason to believe it might be needed. There is little to no risk of being given an extra dose of a glucocorticoid injection, while there are significant risks of having a low glucocorticoid level.

After the injection is given, the patient should seek medical care immediately. After a major injury or if the person is found unconscious, it is best to call for emergency medical services. In the United States, most people can access emergency care by calling 911.

Illnesses, medical procedures, and surgery — The adrenal glands normally increase cortisol output when the body is stressed by illness, major medical procedures, or surgery. People with adrenal insufficiency do not have this ability. The risk of adrenal crisis can be minimized by adjusting the dose of medications.

During symptoms of a cold or flu, it is safe to double or triple the daily dose of glucocorticoid for three days without calling the doctor. However, if symptoms become worse during that time, or if it is not possible to return to the usual glucocorticoid dose on the fourth day, the health care provider should be called for advice.

It is important to call the provider if there are any signs of a stomach illness with nausea, diarrhea, or vomiting. It is also important to call before any medical procedures or surgery. The provider will usually recommend temporarily increasing the glucocorticoid dose for these types of stresses.

Pregnancy — Most women who have primary adrenal insufficiency are able to have a healthy pregnancy, labor, and delivery. Women should be monitored by an obstetrician and endocrinologist with expertise in adrenal insufficiency.

During this time, it is important to take medications on schedule and have careful monitoring of the growing fetus, as well as the woman's adrenal insufficiency. Some women require changes in glucocorticoid doses, especially during the third trimester and during labor. Women who have severe morning sickness may need to switch from oral medication to injected medication until the morning sickness subsides.


The long-term outlook is good for most people with adrenal insufficiency who are treated and monitored. Most people can lead an active life and have a normal life expectancy. Children with adrenal insufficiency who are treated and monitored carefully can grow normally and experience puberty without difficulty.


Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Addison's disease (The Basics)
Patient education: Cushing's syndrome (The Basics)
Patient education: Adrenal crisis (The Basics)
Patient education: Panhypopituitarism (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

This topic has no corresponding Beyond the Basics information.

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Causes of primary adrenal insufficiency (Addison's disease)
Causes of secondary and tertiary adrenal insufficiency in adults
Clinical manifestations of adrenal insufficiency in adults
Diagnosis of adrenal insufficiency in adults
Evaluation of the response to ACTH in adrenal insufficiency
Hyponatremia and hyperkalemia in adrenal insufficiency
Pathogenesis of autoimmune adrenal insufficiency
Treatment of adrenal insufficiency in adults
Treatment of adrenal insufficiency in children

The following organizations also provide reliable health information.

National Library of Medicine


National Institute of Diabetes and Digestive and Kidney Diseases


Hormone Health Network


National Adrenal Diseases Foundation


Literature review current through: Nov 2017. | This topic last updated: Tue Mar 07 00:00:00 GMT+00:00 2017.
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