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Adrenal Insufficiency

(Addison Disease)


Ashley B. Grossman

, MD, University of Oxford; Fellow, Green-Templeton College

Reviewed/Revised May 2022 | Modified Sep 2022
Topic Resources

In adrenal insufficiency, the adrenal glands do not produce enough adrenal hormones.

  • Adrenal insufficiency may be caused by a disorder of the adrenal glands, a disorder of the pituitary gland, or by certain drugs.

  • Adrenal insufficiency may be caused by an autoimmune reaction, cancer, an infection, or some other disease.

  • A person with adrenal insufficiency feels weak, tired, and dizzy when standing up after sitting or lying down, and may develop dark skin patches.

  • Doctors measure sodium and potassium in the blood and measure cortisol and adrenocorticotropic hormone (ACTH) levels to make the diagnosis.

  • People are given corticosteroids and fluids.

The Adrenal Glands

Adrenal insufficiency may be:

In both types of adrenal insufficiency, the adrenal glands produce an inadequate amount of one or more adrenal hormones.

Adrenal hormones

When the adrenal glands become underactive, they tend to produce inadequate amounts of all of the adrenal hormones, including corticosteroids (particularly cortisol) and mineralocorticoids (particularly aldosterone, which controls blood pressure and the levels of salt [sodium chloride] and potassium in the body). The adrenal glands also stimulate the production of small amounts of testosterone and estrogen and other similar sex hormones (androgens, such as dehydroepiandrosterone [DHEA]), levels of which also are reduced in people with adrenocortical insufficiency.

When the adrenal glands are destroyed by infection or cancer, the adrenal medulla and thus the source of epinephrine, is also lost. However, this loss does not cause symptoms.

Corticosteroid deficiency leads to an extreme sensitivity to insulin so that the level of sugar in the blood may fall dangerously low (hypoglycemia Hypoglycemia Hypoglycemia is abnormally low levels of sugar (glucose) in the blood. Hypoglycemia is most often caused by medications taken to control diabetes. Much less common causes of hypoglycemia include... read more ). The deficiency prevents the body from manufacturing carbohydrates, which are needed for cellular function, and protein, for fighting infections properly and controlling inflammation. Muscles weaken, and even the heart can become weak and unable to pump blood adequately. In addition, the blood pressure may become dangerously low.

People with adrenal insufficiency are not able to produce the additional corticosteroids that are needed when the body is stressed. People therefore are susceptible to serious symptoms and complications when confronted with illness, extreme fatigue, severe injury, surgery, or, possibly, severe psychologic stress.

Primary adrenal insufficiency (Addison disease)

Addison disease can start at any age and affects males and females about equally.

In 70% of people with Addison disease, the cause is not precisely known, but the adrenal glands are affected by an autoimmune reaction Autoimmune Disorders An autoimmune disorder is a malfunction of the body's immune system that causes the body to attack its own tissues. What triggers an autoimmune disorder is not known. Symptoms vary depending... read more in which the body’s immune system attacks and destroys the adrenal cortex (the outer part of the gland, which is distinct from the adrenal medulla, the inner part which produces different hormones).

In the other 30%, the adrenal glands are destroyed by cancer, an infection such as tuberculosis, or another identifiable disease. In infants and children, Addison disease may be due to a genetic abnormality of the adrenal glands (see Congenital adrenal hyperplasia Congenital adrenal hyperplasia Birth defects of the genitals can involve the penis, scrotum, or testes (testicles) in boys and the vagina and labia in girls. Sometimes the genitals are ambiguous, that is, not clearly female... read more Congenital adrenal hyperplasia ).

In Addison disease, the pituitary gland Overview of the Pituitary Gland The pituitary is a pea-sized gland that is housed within a bony structure (sella turcica) at the base of the brain. The sella turcica protects the pituitary but allows very little room for expansion... read more produces more adrenocorticotropic hormone (ACTH, also known as corticotropin) in an attempt to stimulate the adrenal glands. ACTH also stimulates melanin production, so the skin and the lining of the mouth often develop a dark pigmentation.

Secondary adrenal insufficiency

Secondary adrenal insufficiency is a term given to a disorder that resembles Addison disease. In this disorder, the adrenal glands are underactive because the pituitary gland Overview of the Pituitary Gland The pituitary is a pea-sized gland that is housed within a bony structure (sella turcica) at the base of the brain. The sella turcica protects the pituitary but allows very little room for expansion... read more produces less ACTH, not because the adrenal glands have been destroyed or have otherwise directly failed. Lack of ACTH affects adrenal secretion of cortisol much more than secretion of aldosterone.

The pituitary gland may fail to produce ACTH because of a tumor, an infection, or injury. Also, taking corticosteroid drugs for more than a few weeks keeps the pituitary gland from producing enough ACTH, so the adrenal glands are not stimulated adequately.

Suppression of Adrenal Function by Corticosteroids

In people who take large doses of corticosteroids, such as prednisone, the function of the adrenal glands can become suppressed. This suppression occurs because large doses of corticosteroids signal the hypothalamus and pituitary gland to stop producing the hormones that normally stimulate adrenal function.

If the person abruptly stops taking corticosteroids, the body cannot restore adrenal function quickly enough, and temporary adrenal insufficiency (a type of secondary adrenal insufficiency) results. Also, when stress occurs, the body is not able to stimulate production of the additional corticosteroids that are needed.

Therefore, doctors never stop the use of corticosteroids abruptly if people have been taking them for more than 2 or 3 weeks. Instead, doctors gradually reduce (taper) the dose over weeks and sometimes months.

Also, the dose may need to be increased in people who become ill or otherwise severely stressed while taking corticosteroids. Corticosteroid use may need to be resumed in people who become ill or otherwise severely stressed within weeks of having the corticosteroid tapered and stopped.

Symptoms of secondary adrenal insufficiency are similar to those of Addison disease except that patches of dark skin are absent, and dehydration does not usually occur. Secondary adrenal insufficiency is diagnosed by blood tests. Unlike in Addison disease, sodium and potassium levels tend to be near normal in secondary adrenal insufficiency, and the ACTH level is low. Secondary adrenal insufficiency is treated with synthetic corticosteroids such as hydrocortisone or prednisone.

Symptoms of Adrenal Insufficiency

People with adrenal insufficiency feel weak, tired, and dizzy when standing up after sitting or lying down. These problems may develop gradually and insidiously. People with Addison disease develop patches of dark skin. The darkness may seem like tanning, but it appears on areas not even exposed to the sun. Even people with dark skin can develop excessive pigmentation, although the change may be harder to recognize. Black freckles may develop over the forehead, face, and shoulders, and a bluish black discoloration may develop around the nipples, lips, mouth, rectum, scrotum, or vagina. Dark skin patches usually do not occur in people with secondary adrenal insufficiency.

Most people lose weight, become dehydrated, have no appetite, and develop muscle aches, nausea, vomiting, and diarrhea. Many become unable to tolerate cold. Unless the disease is severe, symptoms tend to become apparent only during times of stress. Periods of hypoglycemia, with nervousness and extreme hunger for salty foods, can occur, particularly in children.

Adrenal crisis

If adrenal insufficiency is not treated, an adrenal crisis may occur. Severe abdominal pain, profound weakness, extremely low blood pressure, kidney failure, and shock may occur. An adrenal crisis often occurs if the body is subjected to stress, such as an accident, injury, surgery, or severe infection. If adrenal crisis is not treated, death may quickly follow.

Diagnosis of Adrenal Insufficiency

  • Blood tests

Because the symptoms may start slowly and subtly, and because no single laboratory test may give definitive results in the early stages, doctors often do not suspect adrenal insufficiency at the outset. Sometimes a major stress makes the symptoms more obvious and precipitates a crisis.

Blood tests may show low sodium and high potassium levels and usually indicate that the kidneys are not working well. Doctors who suspect adrenal insufficiency measure cortisol levels, which may be low, and ACTH levels. ACTH levels tend to be high in primary adrenal insufficiency and low in secondary adrenal insufficiency. However, doctors may need to confirm the diagnosis by measuring cortisol levels before and after an injection of a synthetic form of ACTH. If cortisol levels are low, further tests are needed to determine if the problem is Addison disease or secondary adrenal insufficiency.

Treatment of Adrenal Insufficiency

  • Corticosteroids

Regardless of the cause, adrenal insufficiency can be life threatening and must be treated with corticosteroids and intravenous fluids. Usually, treatment can be started with hydrocortisone (the drug form of cortisol) or prednisone (a synthetic corticosteroid) taken by mouth. However, people who are severely ill may be given hydrocortisone intravenously or intramuscularly at first and then hydrocortisone tablets. Because the body normally produces most cortisol in the morning, replacement hydrocortisone should also be taken in divided doses, with the largest dose in the morning. Hydrocortisone will need to be taken every day for the rest of the person’s life. Larger doses of hydrocortisone are needed when the body is stressed, especially as a result of an illness, and may need to be given by injection if the person has severe diarrhea or vomiting.

Most people with primary adrenal insufficiency also need to take fludrocortisone tablets every day to help restore the body’s normal excretion of sodium and potassium. Supplemental testosterone is not usually needed, although there is some evidence that replacement with DHEA improves the quality of life in some people. Although treatment must be continued for life, the outlook is excellent.

People with adrenal insufficiency should carry a card or wear a bracelet or necklace that identifies them as having the disorder and that lists their drugs and doses in case they become ill and cannot communicate that information. They should also carry an injection of hydrocortisone for use in an emergency.

Drugs Mentioned In This Article

Generic Name Select Brand Names
4-Way Saline, Adsorbonac, Altamist, Ayr Allergy & Sinus, Ayr Baby Saline, Ayr Saline Nasal, BD Posiflush Normal Saline, BD Posiflush Sterile Field Normal Saline, BD Posiflush SureScrub Normal Saline, Blairex Broncho Saline, Breathe Free Saline, Deep Sea , Entsol, HyperSal, Hyper-Sal, Hypertears, Little Remedies for Noses, Little Remedies Stuffy Nose, Monoject Sodium Chloride, Muro 128, NebuSal , Ocean, Ocean Complete, Ocean For Kids, Pediamist, PULMOSAL, Rhinaris, Rhinaris Lubricating, Saljet , Saljet Rinse, SaltAire, Sea Soft, Trichotine, Wound Wash, XYNASE, ZARBEE'S Soothing Saline Nasal Mist
A-Hydrocort, Ala-Cort, Ala-Scalp, Alkindi, Anucort-HC, Anumed-HC, Anusol HC, Aquaphor Children's Itch Relief, Aquaphor Itch Relief, Balneol for Her, Caldecort , Cetacort, Colocort , Cortaid, Cortaid Advanced, Cortaid Intensive Therapy, Cortaid Sensitive Skin, CortAlo, Cortef, Cortenema, Corticaine, Corticool, Cortifoam, Cortizone-10, Cortizone-10 Cooling Relief, Cortizone-10 External Itch Relief, Cortizone-10 Intensive Healing, Cortizone-10 Plus, Cortizone-10 Quick Shot, Cortizone-5 , Dermarest Dricort, Dermarest Eczema, Dermarest Itch Relief, Encort, First - Hydrocortisone, Gly-Cort , GRx HiCort, Hemmorex-HC, Hemorrhoidal-HC, Hemril , Hycort, Hydro Skin, Hydrocortisone in Absorbase, Hydrocortone, Hydroskin , Hydroxym, Hytone, Instacort, Lacticare HC, Locoid, Locoid Lipocream, MiCort-HC , Monistat Complete Care Instant Itch Relief Cream, Neosporin Eczema, NuCort , Nutracort, NuZon, Pandel, Penecort, Preparation H Hydrocortisone, Proctocort, Proctocream-HC, Procto-Kit, Procto-Med HC , Procto-Pak, Proctosert HC , Proctosol-HC, Proctozone-HC, Rectacort HC, Rectasol-HC, Rederm, Sarnol-HC, Scalacort, Scalpicin Anti-Itch, Solu-Cortef, Texacort, Tucks HC, Vagisil Anti-Itch, Walgreens Intensive Healing, Westcort
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
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